Lupus erythematosus 2020 | Medicina Clínica (English Edition)

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In patient 1, the appearance was that of a lobar consolidative pneumonia (image a). Subsequent CT scan of this patient (image f) also revealed ground-glass opacities suggesting organizing pneumonia." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "David Cucchiari, Juan M. Pericàs, Josep Riera, Roberto Gumucio, Emmanuel Coloma Md, David Nicolás" "autores" => array:7 [ 0 => array:2 [ "nombre" => "David" "apellidos" => "Cucchiari" ] 1 => array:2 [ "nombre" => "Juan M." 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With a prevalence in Spain of 210 cases per 100,000 inhabitants according to data from 2016,<a class="elsevierStyleCrossRef" href="#bib0285">1</a> it should cease to be considered a rare disease.<a class="elsevierStyleCrossRef" href="#bib0290">2</a>New classification criteriaAlthough the diagnosis of SLE should always be based on expert clinical judgment, the diagnostic suspicion frequently conflicts with the disease's classification criteria.<a class="elsevierStyleCrossRef" href="#bib0295">3</a> In September 2019, new criteria was jointly developed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).<a class="elsevierStyleCrossRef" href="#bib0300">4</a> It has a sensitivity similar to that of the previous criteria of the Systemic Lupus International Collaborating Clinics (SLICC)<a class="elsevierStyleCrossRef" href="#bib0305">5</a> group but a much higher specificity (93.4 vs. 83.6%), so it is hoped that correct patient classification will improve, especially in the early stages of the disease (the main defect in the SLICC criteria).According to these criteria, the entry point for classifying an SLE patient is the presence of antinuclear antibodies (ANA) positive by titer ≥1/80 at least once (mandatory criterion), to which 7 clinical and 3 immunologic domains are added (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Although this represents progress, we must not forget that these criteria have not been designed for diagnostic purposes, but rather their sole purpose is to have criteria to enrich the selection of homogeneous patients in research studies. These criteria are not validated for application to individual cases in clinical practice.The occurrence or not of the SLE classification criteria does not allow the disease to be confirmed or ruled out with total certainty, since diagnostic errors can occur (for example, 2–3% of SLE patients with negative ANA could not be classified as such according to the new criteria). This is confirmed by various studies<a class="elsevierStyleCrossRefs" href="#bib0310">6–10</a> which show that the use of the ACR 1987 or SLICC 2012 criteria for the diagnosis of SLE entails a non-negligible percentage of diagnostic errors that can reach as high as 30% of cases, with its performance being especially poor in juvenile forms and in early stages of the disease (with consequent diagnostic delay).Search for new biomarkersIn the search for new biomarkers to help us diagnose SLE, the possible role of anti-DFS70 antibodies (Ab) stands out, not because of their diagnostic value, but because of their possible usefulness in ruling out the disease.<a class="elsevierStyleCrossRef" href="#bib0335">11</a> These Ab are a subgroup of ANA that present a fine dense speckled pattern by indirect immunofluorescence. It has been observed that they are much more common in healthy individuals than in patients with SLE (prevalence of 0.7–1.1% monospecific Ab), and that healthy individuals with these Ab do not develop any systemic autoimmune disease after a clinical follow-up of ≥4 years.<a class="elsevierStyleCrossRef" href="#bib0335">11</a> For this reason its validity to discriminate those with positive ANA who will not end up developing SLE is being evaluated.There is also a search for non-invasive biomarkers that reflect an early onset of lupus activity or are better predictors of it than those currently used in clinical practice. Genomic studies have shown that 70% of adults and up to 95% of children with SLE have a pattern of overexpression of type 1 IFN-related genes.<a class="elsevierStyleCrossRef" href="#bib0340">12</a> This pattern of gene expression is called type 1 IFN “signature”. One of the type 1 INFs, specifically the IFN-α, is a key mediator in the SLE pathogenesis, with high serum concentrations found in disease flares. Elevated levels of IFN-α are closely associated with the production of autoantibodies and with the appearance of renal, hematologic and central nervous system manifestations.<a class="elsevierStyleCrossRef" href="#bib0340">12</a> The presence of an elevated INF-α signature appears to be a good biomarker of disease activity, both for its biological effects and the genetic argument. There is also hope in the measurement of cell-bound complement activation products, specifically those bound to erythrocytes (E-C4d), reticulocytes (R-C4d), platelets (P-C4d), and T and B lymphocytes (T-C4d and B-C4d).<a class="elsevierStyleCrossRef" href="#bib0345">13</a> E-C4d reflects of SLE activity during the preceding 120 days. Other promising biomarkers of activity are S100A12 calcium-binding proteins, and serum concentrations of soluble tumor necrosis factor receptor-2α (soluble TNF receptor 2: sTNF-R2).<a class="elsevierStyleCrossRef" href="#bib0350">14</a>The search for a marker comparable to kidney biopsy has lead to the evaluation of serum and urinary biomarkers, with the latter generally achieving better results. From among the different urinary biomarkers evaluated, the most promising are the urine neutrophil gelatinase-associated lipocalin (uNGAL), TNF-like weak inducer of apopotosis (TWEAK), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1).<a class="elsevierStyleCrossRef" href="#bib0350">14</a> The determination of urinary T lymphocytes has also shown its usefulness in monitoring the activity of lupus nephritis (LN) (increase in CD4+ and CD8+ only during disease activity phases).<a class="elsevierStyleCrossRef" href="#bib0350">14</a>Latest achievements in the general treatment strategySince 2014, SLE treatment with a therapeutic objective (treat to target strategy) has been advocated, with the target necessarily being the induction of sustained clinical remission or, failing that, a state of low inflammatory activity of the disease.<a class="elsevierStyleCrossRef" href="#bib0355">15</a> It means that all the treatment is aimed at achieving the pre-established results in the shortest possible time. To achieve this, the disease activity must be measured and documented at each visit and, if the patient has not reached the desired goal, then therapeutic adjustments must be made to achieve it. Anything other than reaching the therapeutic target must be interpreted as an insufficient response and requires complementary measures to achieve it. The current, most widely accepted definitions of remission (DORIS Group),<a class="elsevierStyleCrossRef" href="#bib0360">16</a> and low activity (Asia-Pacific group),<a class="elsevierStyleCrossRef" href="#bib0365">17</a> as well as complete and partial renal response in LN,<a class="elsevierStyleCrossRefs" href="#bib0370">18,19</a> are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>In addition to this strategy, the new approach to SLE is fundamentally specified in aspects shown as follows:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1)The multidimensional assessment of the disease when planning treatment and evaluating the response: control perceived or verifiable clinical lupus activity, preventing activity flares, avoiding secondary irreversible damage both to the actual disease and to its treatment (the damage produced by chronic treatment with glucocorticoids [GCs] is often greater than that of SLE) and minimize the impact on the patient's quality of life and survival.</li><li class="elsevierStyleListItem" id="lsti0010">2)Treatment with hydroxychloroquine (HCQ) at doses of 5mg/kg/day in all patients (provided there is no absolute contraindication for its use) due to its beneficial pleiotropic effects in SLE.</li><li class="elsevierStyleListItem" id="lsti0015">3)The use of GCs should always be at the lowest dose and for the shortest time possible.</li><li class="elsevierStyleListItem" id="lsti0020">4)An early association of immunosuppressants in severe cases with major organ involvement, or if needed to restrict GC-use. The most widely used immunosuppressants are mycophenolate (MMF), azathioprine, and methotrexate. In some clinical settings, cyclophosphamide and tacrolimus or cyclosporine A are used, as are the biological therapies directed against B-cells.</li><li class="elsevierStyleListItem" id="lsti0025">5)Make an early diagnosis and treatment of kidney disease. In patients with LN, after remission induction treatment, the immunosuppressant should be maintained for a minimum of 3 years to improve prognosis.</li><li class="elsevierStyleListItem" id="lsti0030">6)Adequate control of the disease comorbidities (antiphospholipid syndrome, cardiovascular risk, osteoporosis and prevention of infections) and maintain optimal levels of vitamin D.</li></ul>These and other general principles can be consulted in the latest update of the EULAR recommendations for the treatment of SLE published in 2019,<a class="elsevierStyleCrossRef" href="#bib0370">18</a> and in the new EULAR/ERA-EDTA recommendations for the management of lupus nephritis published in 2020.<a class="elsevierStyleCrossRef" href="#bib0375">19</a>Regarding treatment with antimalarial drugs, in addition to HCQ, we have chloroquine (CQ) and quinacrine. CQ (dose 250mg/day) is 2–3 times more potent than HCQ, so its use carries a higher risk of retinal toxicity (bull's eye maculopathy) which is often irreversible. Screening for this adverse effect should be carried out systematically in all patients receiving HCQ and CQ. According to the new recommendations,<a class="elsevierStyleCrossRef" href="#bib0380">20</a> if the patient does not have any risk factor for this complication and the ophthalmological evaluation (fundus examination, visual campimetry and optical coherence tomography) at the beginning of the treatment is normal, no new controls will be necessary until after the first 5 years.<a class="elsevierStyleCrossRef" href="#bib0380">20</a> If the patient has risk factors (previous maculopathy, kidney failure, concomitant treatment with tamoxifen or receives a dose >5mg/kg/day), the ophthalmological examination will be annual or biannual.<a class="elsevierStyleCrossRefs" href="#bib0380">20,21</a> Any patient previously treated with HCQ and who has received a total cumulative dose >1000g at the time of restarting treatment should also be considered at risk.<a class="elsevierStyleCrossRefs" href="#bib0385">21,22</a>Due to its long half-life, the determination of HCQ plasma levels has proven to be useful in the control of therapeutic compliance, since it allows the non-compliant patients to be identified.<a class="elsevierStyleCrossRef" href="#bib0385">21</a>Quinacrine has the advantage of not producing retinal toxicity, so it can be a therapeutic alternative to HCQ and CQ when they are contraindicated due to ocular toxicity. It is also used (at doses of 100mg/day) in combination with HCQ in patients with resistant skin and/or joint involvement, achieving a synergistic beneficial effect.<a class="elsevierStyleCrossRef" href="#bib0385">21</a>Today it is known that GCs exert their anti-inflammatory action via 2 mechanisms: the genomic, classic pathway and the non-genomic pathway.<a class="elsevierStyleCrossRef" href="#bib0390">22</a> The genomic pathway is slower in onset with a persistent effect, and it is responsible for the adverse effects of GCs. It is activated 100% with a prednisone dose of 30mg/day. Therefore, with doses greater than 30mg/day (the guidelines state 1mg/kg/day) the only achievement is increased toxicity without a substantial increase in its anti-inflammatory effect. In contrast, the nongenomic pathway exerts an anti-inflammatory action which is much more intense and quicker. This pathway begins to be noticeably activated after 100mg/day, with a maximum effect at over 250mg/day.<a class="elsevierStyleCrossRefs" href="#bib0385">21,22</a> Intravenous pulse therapy above 100–250mg/day for 3 days has greater efficacy and less toxicity than prolonged treatment with high doses of prednisone.<a class="elsevierStyleCrossRefs" href="#bib0385">21,22</a>According to this knowledge, current advise is not to exceed 30mg/day of prednisone regardless of the patient's clinical condition.<a class="elsevierStyleCrossRefs" href="#bib0370">18,21</a> If necessary due to an acute flare or major organ involvement, the administration of pulses of methylprednisolone (125 or 250mg daily for 3 days, or 500mg/day in the most severe cases) can be considered, which would achieve greater and faster efficacy than prolonged treatment with doses of 1mg/kg/day.<a class="elsevierStyleCrossRefs" href="#bib0370">18,19,21</a> The subsequent decrease in the prednisone dose must be done quickly (every 2 weeks), with the aim of reaching a maintenance dose ≤7.5mg/day and, if possible, discontinuing it.New treatmentsThe search for new treatments continues to be a universally recognized need in SLE. We herein provide a review of the current research in this field, which includes only those drugs whose research has reached phase II CT at least (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>B-cell targeting therapiesThe depletion of B lymphocytes has been attempted in 2 ways: by Ab against their surface receptors (CD20 and CD22) or by inhibiting their survival factors BAFF (BLyS) or APRIL.Within this group, the currently available drugs are rituximab (RTX), chimeric anti-CD20 monoclonal Ab, and belimumab, a human monoclonal Ab that specifically binds to the soluble form of BAFF. Belimumab has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of SLE. The results of the open-label extension phase of the patients included in the pivotal BLISS-52 and BLISS-76 trials, as well as the results of observational studies of real clinical practice (OBSERVE studies), show a response rate close to 50%, which remains relatively stable over time.<a class="elsevierStyleCrossRefs" href="#bib0400">24,25</a> In addition, medium- and long-term treatment achieves a progressive decrease in disease activity flares, a significant saving in GCs (around 50%), and an improvement or negativisation of the immunological markers of activity, confirming its efficacy in preventing accumulated damage.<a class="elsevierStyleCrossRefs" href="#bib0400">24,25</a> Although initially belimumab had not been tested (nor approved) in patients with LN, the results of the phase III CT – BLISS-LN, have recently been released and they demonstrate its superiority over placebo in patients with active LN, plus standard therapy with MMF and GC (percentage of responders 43 vs. 32%, p=0.031).<a class="elsevierStyleCrossRef" href="#bib0410">26</a> With these results, the company will request approval from the health authorities for this indication.Neither of the CTs that have evaluated the efficacy of RTX in SLE (LUNAR in patients with proliferative LN and EXPLORER) demonstrated superiority of the drug over placebo plus standard therapy, except in the improvement of the immunological activity parameters.<a class="elsevierStyleCrossRefs" href="#bib0415">27,28</a> Despite this, real-life data from open studies and national registries of biological therapies demonstrate its clinical efficacy in patients refractory to conventional treatment.<a class="elsevierStyleCrossRef" href="#bib0395">23</a> For example, in a meta-analysis that included 1243 patients from 30 observational studies, the complete response rates reached 46.7% according to BILAG and 56.6% according to SLEDAI; for LN, the percentages of complete (CR) or partial (PR) renal response were 36.1% and 37.4%, respectively.<a class="elsevierStyleCrossRef" href="#bib0425">29</a> This lack of agreement has given rise to an endless controversy and detailed analysis of the methodologies used. Regardless of the explanations given to justify the discrepancies, the ACR contemplates its use as a rescue treatment in LN,<a class="elsevierStyleCrossRef" href="#bib0430">30</a> and EULAR, in patients with severe renal or extrarenal involvement (mainly hematological or neurological) and when there is inadequate response or contraindication to standard treatment and/or belimumab.<a class="elsevierStyleCrossRef" href="#bib0370">18</a>A strategy in the evaluation phase is the sequential double blocking of B-cells with RTX followed by belimumab (RTCs: BEAT Lupus and BLISS-BELIEVE).<a class="elsevierStyleCrossRefs" href="#bib0435">31,32</a> The scientific rationale behind this strategy is to try to avoid the elevated BAFF production that occurs after B-cell depletion by RTX and that facilitates the activation, differentiation, and proliferation of autoreactive B-cells.In addition to RTX, two other anti-CD20s have been evaluated, namely ocrelizumab and obinutuzumab (OBI), with mixed success. The development of ocrelizumab in SLE was discontinued due to an increase in the incidence of severe infections in phase III CTs conducted (namely BELONG in patients with proliferative LN and BEGIN). The efficacy analysis showed a trend toward improvement in the activity compared to the placebo group, but without significant differences.<a class="elsevierStyleCrossRefs" href="#bib0445">33,34</a> OBI is a humanised, monoclonal, type II Ab, modified by glycoengineering in it Fc portion. This modification is more effective in eliminating CD20+ B-cells than RTX. At the ACR 2019 congress, the results of NOBILITY, a phase II CT were disseminated. This CT has evaluated the safety and efficacy of OBI in adults with proliferative LN in combination with standard treatment.<a class="elsevierStyleCrossRef" href="#bib0455">35</a> The study results show superiority of the drug compared to placebo both in the primary efficacy endpoint (CR at week 76: 40 vs. 18%, p=0.007) and in the secondary endpoints, without observing differences in terms of safety. With these results, the FDA has granted OBI the designation of breakthrough therapy. This designation is granted to expedite the development and review of drugs for severe diseases, when there is evidence to suggest that they can provide substantial benefit over currently available treatments. phase III of the CT was programmed to start in 2020.Within this treatment strategy, epratuzumab, a monoclonal Ab directed against CD22, has also been tested. Despite the favorable differences in the BICLA response observed in several of the doses (but not in all) in the EMBLEN phase II CT, the superiority of epratuzumab over placebo plus standard treatment could not be demonstrated in the phase III EMBODY 1 and -2, as neither of the doses tested achieved the primary efficacy endpoint.<a class="elsevierStyleCrossRef" href="#bib0460">36</a> Qualifying these results, in a post hoc analysis, the drug has been shown to be especially effective in the subgroup of patients with secondary Sjögren's syndrome and positive for anti-Ro/SSA Ab.Apart from belimumab, other therapies directed against BAFF and APRIL factors have not been successful. Treatment with atacicept, a BAFF/APRIL dual inhibitor, increased the incidence of severe infections and hypogammaglobulinaemia without observing large significant differences in efficacy compared to placebo (ADDRESS II), so the expectations which had been generated with this drug have fizzled out.<a class="elsevierStyleCrossRef" href="#bib0465">37</a> Neither has it been possible to demonstrate superiority over placebo in the primary efficacy endpoint in the pivotal phase III CTs with two other BAFF inhibitors, blisibimod (CHABLIS-SC1)<a class="elsevierStyleCrossRef" href="#bib0470">38</a> and tabalumab (ILLUMINATE-1 and ILLUMINATE-2).<a class="elsevierStyleCrossRefs" href="#bib0475">39,40</a> While the development of tabalumab appears to have been permanently abandoned, the destiny of blisibimod remains to be seen. Although it did not achieve significant differences in the primary efficacy endpoint, it did demonstrate a substantial saving of GCs and an improvement in the markers of immune activity and proteinuria in patients with LN.<a class="elsevierStyleCrossRef" href="#bib0470">38</a>Block T-cell activationAbatacept is a fusion protein that inhibits the activation of T-cells by selectively blocking the specific binding of CD80/CD86 receptors to CD28. In phase IIb/III studies in SLE patients, abatacept did not achieve any of the preset primary efficacy endpoints, but it demonstrated some beneficial secondary effects, such as improvement of immunological parameters, reduction in the number of flares compared to placebo in arthritic patients, and it achieved faster (but not more numerous) CRs compared to standard treatment in patients with proliferative LN (ALLURE study).<a class="elsevierStyleCrossRef" href="#bib0485">41</a>Another researched strategy has been the blockade of CD40/CD40L. Both ruplizumab and toralizumab, two humanised anti-CD40 ligand monoclonal antibodies, showed a tendency to improve SLE activity, but their development was interrupted by the appearance of thrombotic phenomena.<a class="elsevierStyleCrossRef" href="#bib0490">42</a> This adverse effect has been resolved with the development of dapirolizumab pegol. The results of a CT IIb CT at 24 weeks has shown that treatment with dapirolizumab pegol achieves numerically higher SRI-4 and BICLA responses than placebo, but without reaching statistical significance.<a class="elsevierStyleCrossRef" href="#bib0495">43</a> Its safety profile is good, with no serious adverse effects or changes in coagulation factors being detected. During 2020 an CT in phase III is scheduled to be started.α interferon antagonistsDue to both its biological effects and the genetic argument, IFN-α is one of the most sought after therapeutic targets today. To date, three fully human monoclonal antibodies have been developed that block its action: sifalimumab, rontalizumab, and anifrolumab.The first two are anti-IFN-α antibodies. Both demonstrated a modest efficacy in phase II CTs, so the study has been discontinued (although sifalimumab was shown to be effective for skin manifestations).<a class="elsevierStyleCrossRef" href="#bib0500">44</a> However, anifrolumab is an Ab that binds to the type 1 INF receptor subunit 1, blocking the activity of all INF, including IFN-α, IFN-β and IFN-ω. After achieving encouraging results in phase II (MUSO), two clinical trials have been conducted in phase III (TULIP 1 and 2) with conflicting results.<a class="elsevierStyleCrossRefs" href="#bib0505">45,46</a> This discrepancy exemplifies what appears to be the main problem with many of the CTs conducted to date in SLE: the response measurement instruments. Thus, while in TULIP-1 anifrolumab did not achieve the primary efficacy endpoint which was the SRI-4 response, it went beyond achieving it in the TULIP-2 study, where the efficacy endpoint was the BICLA response. BICLA and SRI clearly differ. While BICLA is based on the 2004 BILAG, which can record both partial and complete improvements in each organ-system, SRI focuses on the SLEDAI, which only captures complete improvements in each organ-system.In the recently published TULIP-2 study, the response rate achieved with anifrolumab at doses of 300mg every 4 weeks was much higher than the placebo (47.8% vs. 31.5%, p=0.001) at the end of 48 weeks.<a class="elsevierStyleCrossRef" href="#bib0510">46</a> The differences in response were constant regardless of the intensity of the IFN signature. Differences were also observed in favor of anifrolumab in the reduction of the GC dose and in the improvement of the cutaneous manifestations, but not in those of the joints. When considering the global SRI and BICLA responses of all the patients included in the anifrolumab trials (MUSE, TULIP 1 and 2), the results in 5 of the 6 domains demonstrate the superiority of the drug over placebo. With these data, the promoting laboratory will request the approval of anifrolumab from the FDA at the beginning of this year.TolerogensThe deficient clearance of apoptotic residues with nucleic content, together with a loss of tolerance, are considered the factors that determine the formation of antibodies against nuclear components in SLE. A target that has attracted the attention of researchers has been the search for tolerogens, that is, agents capable of restoring tolerance to nuclear autoantigens. The first drugs evaluated within this group were edratide and abetimus, both with unsuccessful results, since despite decreasing the production of autoantibodies, they did not demonstrate clinical benefits.<a class="elsevierStyleCrossRefs" href="#bib0515">47,48</a> In contrast, lupuzor, also called rigerimod, showed encouraging results in the phase IIb CT.<a class="elsevierStyleCrossRef" href="#bib0525">49</a> So, the FDA granted it fast track designation to facilitate its development and review. However, the recently released results of the phase III study, have not been able to demonstrate its superiority over placebo due to the high response rate observed in this group (SRI-4 response: 52.5% vs. 44.6%, p=0.263).<a class="elsevierStyleCrossRef" href="#bib0530">50</a> The efficacy of the drug appears to be better in the subgroup of patients who had anti-dsDNA autoantibodies (61.5% vs. 47.3%, p=0.09, with statistically significant differences if we only consider the selected population in Europe: 71.1% vs. 48.8%, p=0.02), achieving remission in 7.6% of cases.UstekinumabUstekinumab is a fully human monoclonal Ab that binds to the p40 protein subunit of the cytokines IL-12 and IL-23, inhibiting their activity by preventing these cytokines from interacting with the IL-12Rβ1 receptor that is expressed on the surface of T-cells. The IL-12/23 pathway allows the differentiation and clonal proliferation of the Th1 and Th17 lymphocyte subpopulations that are involved in the pathogenesis of SLE. The results of a phase II CT have shown the superiority of ustekinumab over placebo plus standard treatment at 24 and 48 weeks,<a class="elsevierStyleCrossRefs" href="#bib0535">51,52</a> both in global disease endpoints (SRI-4 response) and organ-specific endpoints, as well as a reduction in severe flares. The phase III trial is currently underway.JAK inhibitorsAs with other autoimmune diseases, hopes have also been pinned on the inhibition of intracellular signaling pathways. There are currently four JAK kinase inhibitors available, two of which are being evaluated in SLE. Baricitinib is a selective and reversible inhibitor of JAK 1 and 2 that with the dose of 4mg/day has shown superiority to placebo in a phase II CT lasting 24 weeks, conducted with patients with skin and/or joint activity (SLEDAI-2K response: 67 vs. 53%, p=0.04)<a class="elsevierStyleCrossRef" href="#bib0545">53</a>. The FDA has also granted it the fast track designation to facilitate its development and review, and the phase III trials (BRAVE I, II and X) are in progress.Upadacitinib is a recently approved selective JAK 1 inhibitor for the treatment of rheumatoid arthritis. A current phase II CT in being conducted for SLE that assesses its efficacy in monotherapy and in combination with a Bruton tyrosine kinase inhibitor.<a class="elsevierStyleCrossRef" href="#bib0550">54</a>VoclosporinIt is a next generation calcineurin inhibitor that has been evaluated in adults with proliferative LN in combination with standard treatment. The results of the phase III CT (AURORA) released at the end of 2019 have demonstrated its superiority over placebo both in the main efficacy endpoint (CR at week 52: 40.8 vs. 22.5% in the placebo group; p<0.001) as in all the secondary endpoints analyzed (CR at week 24, PR at weeks 24 and 52, and reduction in proteinuria by more than 50%), without observing differences in terms of safety.<a class="elsevierStyleCrossRefs" href="#bib0555">55,56</a> Based on these results, the sponsor laboratory will request its approval from the FDA for the treatment of LN at the beginning of this year. Since the FDA had also granted it the fast track designation in 2016, the decision on its authorization is likely to be favorable and quick.ConclusionsIn recent years, there has been an important improvement in the prognosis of SLE thanks to new strategies for approaching the disease, the better use of GCs and immunosuppressants, the systematic use of HCQ, the use of targeted biological therapies against B-cells in refractory cases and an adequate control of the comorbidities. However, we are still far from its final cure and we still face unmet needs. It is foreseeable that in a short time new treatments will be approved that will allow the rescue of refractory patients or those with insufficient control of disease activity. When looking at the new treatments evaluated, anifrolumab (for the global activity of SLE) and voclosporin (for LN) are the options that today have the best guarantees of success, without forgetting baricitinib and OBI.Conflict of interestsThe author declares that he has no conflict of interest in relation to this publication." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1435011" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1309970" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1435012" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1309971" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "New classification criteria" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Search for new biomarkers" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Latest achievements in the general treatment strategy" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "New treatments" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "B-cell targeting therapies" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Block T-cell activation" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "α interferon antagonists" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Tolerogens" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Ustekinumab" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "JAK inhibitors" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Voclosporin" ] ] ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-11" "fechaAceptado" => "2020-05-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1309970" "palabras" => array:5 [ 0 => "Systemic lupus erythematosus" 1 => "Update" 2 => "Classification criteria" 3 => "Biomarkers" 4 => "New treatments" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1309971" "palabras" => array:5 [ 0 => "Lupus eritematoso sistémico" 1 => "Actualización" 2 => "Criterios de clasificación" 3 => "Biomarcadores" 4 => "Nuevos tratamientos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Systemic lupus erythematosus (SLE) is a complex autoimmune multisystemic disease of great clinical heterogeneity and significant potential morbidity and mortality. Although the outlook for patients with SLE has greatly improved, many unmet needs remain. In this review we aim to summarize the most relevant data on SLE that have emerged in recent years. In particular we discuss the new classification criteria from the European League Against Rheumatism and American College of Rheumatology, new biomarkers, novel definitions of remission and low lupus disease activity and what has emerged on new drugs and new therapeutic strategies." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El lupus eritematoso sistémico (LES) es una enfermedad autoinmunitaria multisistémica compleja, con una gran heterogeneidad en su presentación clínica y una alta morbimortalidad. Aunque su pronóstico ha mejorado de forma notable a lo largo de las últimas décadas, aún siguen existiendo necesidades no cubiertas en esta enfermedad. En esta actualización realizamos una puesta al día de los principales avances en esta enfermedad en los últimos años. Concretamente revisamos los nuevos criterios de clasificación propuestos por la Liga Europea de Reumatología y el Colegio Americano de Reumatología, la búsqueda de nuevos biomarcadores, las nuevas definiciones de remisión y de baja actividad de la enfermedad, así como las estrategias actuales de abordaje y tratamiento del LES y la situación actual de las nuevas terapias." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Narváez J. Revisión: lupus eritematoso sistémico 2020;155:494–501." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ACR: American College of Rheumatology; EULAR: European League Against Rheumatology.Classifying a patient for systemic lupus erythematosus requires at least one clinical criterion and a score ≥10 points.Considerations:The existence of a criterion or clinical manifestation on at least one occasion during the clinical course is sufficient to score.The criteria do not have to be simultaneous.Within each domain, only the criterion with the highest score is counted for the total score." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Entry criterionPositive antinuclear antibodies ≥1/80 by indirect immunofluorescence using HEp-2 cell line substrate (at any time)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical domains \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Points \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Constitutional</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cutaneous</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-scarring alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral thrush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Subacute cutaneous lupus or discoid lupus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute cutaneous lupus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Joints</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Synovitis or pain in ≥2 joints with morning joint stiffness >30min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neurological</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Delirium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psychosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Convulsions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serositis</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pleural or pericardial effusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute pericarditis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hematological</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leukopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoimmune hemolysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Proteinuria >0.5mg/24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lupus nephritis class II or V \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lupus nephritis class III or IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2468654.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Immunological domains \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Points \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiphospholipid antibodies</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anticardiolipin at medium or high titer or anti-β2 glycoprotein 1 or positive lupus anticoagulant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complement</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low C3 or low C4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low C3 and low C4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antibodies</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-dsDNA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-Sm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2468652.png" ] ] ] ] "descripcion" => array:1 [ "en" => "New EULAR/ACR classification criteria for systemic lupus erythematosus." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Ab: antibody; BILAG: British Isles Lupus Assessment Group Index; ECLAM: European Consensus Lupus Activity Measurement; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Low activity<a class="elsevierStyleCrossRef" href="#bib0365">17</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Remission<a class="elsevierStyleCrossRef" href="#bib0360">16</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SLEDAI-2K ≤4, no major organ activity, hemolytic anemia, fever or gastrointestinal symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A validated index must be used: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No new activity data compared to the previous assessment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SLEDAI<2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assessment of disease activity by the doctor ≤1 (0–3 scale) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SLEDAI symptoms=0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucocorticoid maintenance dose: ≤7.5mg/day prednisone or equivalent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ECLAM symptoms=0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immunosuppressive or biological treatment at stable doses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Only BILAG D and E \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assessment of disease activity by the doctor <0.5 (0–3 scale) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serological remission (negative anti-dsDNA Ab and normal complement) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment with antimalarial drugs and prednisone only ≤5mg/day or equivalent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of remission not yet defined (minimum ≥6 months to ≥5 years) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lupus nephritis</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Therapeutic objective: complete renal response<a class="elsevierStyleCrossRef" href="#bib0375">19</a> defined by a protein/creatinine ratio <500–700mg/g with normalization or stabilization (±10%) of serum creatinine with respect to baseline, at 12 months after starting treatment (expected improvement in proteinuria: at least 25% at 3 months and 50% at 6 months after starting treatment).</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Partial response<a class="elsevierStyleCrossRef" href="#bib0370">18</a> defined as reduction ≥50% proteinuria compared to baseline (with values below 3.5g/24h) with stabilization (±10%) of serum creatinine with respect to baseline, at 12 months after starting treatment.</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2468655.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Definitions of low activity and remission in systemic lupus erythematosus and therapeutic objective in lupus nephritis." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "APRIL: A proliferation-inducing ligand; BAFF: B-cell Activating Factor, also called BLyS; IFN: interferon; IL: interleukin; JAK=janus kinases; SLE: systemic lupus erythematosus." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Target \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical trial \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Status \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary efficacy endpoint achieved \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rituximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EXPLORER phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LUNAR phase III lupus nephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ocrelizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BEGIN phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Discontinued \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BELONG phase III lupus nephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Discontinued due to infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Obinituzumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NOBILITY phase II lupus nephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epratuzumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EMBLEM phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EMBODY 1 and 2 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finished \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Belimumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BAFF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BLISS-52 and 76 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finished \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BLISS-LN phase III lupus nephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tabalumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BAFF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ILLUMINATE-1 and 2 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blisibimod \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BAFF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PEARL sc phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finished \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CHABLIS SC1 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atacicept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BAFF and APRIL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADDRESS II phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abatacept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Costimulation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT00119678 phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T-cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALLURE 3 phase III lupus nephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IM101-330 phase II arthritis in SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dapirolizumab pegol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT02804763 phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Selection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+/− \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD40L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sifalimumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IFN-α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT01283139 phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rontalizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IFN-α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ROSE phase II active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anifrolumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 1 IFN \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MUSE phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TULIP-1 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TULIP-2 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lupuzor (rigerimod) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tolerogen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT01240694 phase IIb active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT02504645 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ustekinumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-12/23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT02349061 phase IIa active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT03517722 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Selection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baricitinib \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">JAK 1 and 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT02708095 phase II active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BRAVE-1 and 2 phase III active SLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Selection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Voclosporin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Calcineurin inhibitor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AURORA phase III lupus nephritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Finalized \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2468653.png" ] ] ] ] "descripcion" => array:1 [ "en" => "New treatments evaluated in systemic lupus erythematosus." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:56 [ 0 => array:3 [ "identificador" => "bib0285" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of systemic lupus erythematosus in Spain: higher than previously reported in other countries?" 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Lupus erythematosus 2020

Revisión: lupus eritematoso sistémico 2020

Javier Narváez

Servicio de Reumatología, Hospital Universitario de Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic lupus erythematosus &#40;SLE&#41; is a chronic&#44; multisystemic and complex autoimmune disease&#44; with great heterogeneity in its clinical presentation&#44; transitionary course&#44; and prognosis&#46; With a prevalence in Spain of 210 cases per 100&#44;000 inhabitants according to data from 2016&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a> it should cease to be considered a rare disease&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">New classification criteria</span><p id="par0010" class="elsevierStylePara elsevierViewall">Although the diagnosis of SLE should always be based on expert clinical judgment&#44; the diagnostic suspicion frequently conflicts with the disease&#39;s classification criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">3</span></a> In September 2019&#44; new criteria was jointly developed by the <span class="elsevierStyleItalic">European League Against Rheumatism</span> &#40;EULAR&#41; and the <span class="elsevierStyleItalic">American College of Rheumatology</span> &#40;ACR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">4</span></a> It has a sensitivity similar to that of the previous criteria of the <span class="elsevierStyleItalic">Systemic Lupus International Collaborating Clinics</span> &#40;SLICC&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">5</span></a> group but a much higher specificity &#40;93&#46;4 vs&#46; 83&#46;6&#37;&#41;&#44; so it is hoped that correct patient classification will improve&#44; especially in the early stages of the disease &#40;the main defect in the SLICC criteria&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">According to these criteria&#44; the entry point for classifying an SLE patient is the presence of <span class="elsevierStyleItalic">antinuclear antibodies</span> &#40;ANA&#41; positive by titer &#8805;1&#47;80 at least once &#40;mandatory criterion&#41;&#44; to which 7 clinical and 3 immunologic domains are added &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Although this represents progress&#44; we must not forget that these criteria have not been designed for diagnostic purposes&#44; but rather their sole purpose is to have criteria to enrich the selection of homogeneous patients in research studies&#46; These criteria are not validated for application to individual cases in clinical practice&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The occurrence or not of the SLE classification criteria does not allow the disease to be confirmed or ruled out with total certainty&#44; since diagnostic errors can occur &#40;for example&#44; 2&#8211;3&#37; of SLE patients with negative ANA could not be classified as such according to the new criteria&#41;&#46; This is confirmed by various studies<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">6&#8211;10</span></a> which show that the use of the ACR 1987 or SLICC 2012 criteria for the diagnosis of SLE entails a non-negligible percentage of diagnostic errors that can reach as high as 30&#37; of cases&#44; with its performance being especially poor in juvenile forms and in early stages of the disease &#40;with consequent diagnostic delay&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Search for new biomarkers</span><p id="par0030" class="elsevierStylePara elsevierViewall">In the search for new biomarkers to help us diagnose SLE&#44; the possible role of anti-DFS70 antibodies &#40;Ab&#41; stands out&#44; not because of their diagnostic value&#44; but because of their possible usefulness in ruling out the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> These Ab are a subgroup of ANA that present a fine dense speckled pattern by indirect immunofluorescence&#46; It has been observed that they are much more common in healthy individuals than in patients with SLE &#40;prevalence of 0&#46;7&#8211;1&#46;1&#37; monospecific Ab&#41;&#44; and that healthy individuals with these Ab do not develop any systemic autoimmune disease after a clinical follow-up of &#8805;4 years&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> For this reason its validity to discriminate those with positive ANA who will not end up developing SLE is being evaluated&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">There is also a search for non-invasive biomarkers that reflect an early onset of lupus activity or are better predictors of it than those currently used in clinical practice&#46; Genomic studies have shown that 70&#37; of adults and up to 95&#37; of children with SLE have a pattern of overexpression of type 1 IFN-related genes&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">12</span></a> This pattern of gene expression is called type 1 IFN &#8220;signature&#8221;&#46; One of the type 1 INFs&#44; specifically the IFN-&#945;&#44; is a key mediator in the SLE pathogenesis&#44; with high serum concentrations found in disease flares&#46; Elevated levels of IFN-&#945; are closely associated with the production of autoantibodies and with the appearance of renal&#44; hematologic and central nervous system manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">12</span></a> The presence of an elevated INF-&#945; signature appears to be a good biomarker of disease activity&#44; both for its biological effects and the genetic argument&#46; There is also hope in the measurement of cell-bound complement activation products&#44; specifically those bound to erythrocytes &#40;E-C4d&#41;&#44; reticulocytes &#40;R-C4d&#41;&#44; platelets &#40;P-C4d&#41;&#44; and T and B lymphocytes &#40;T-C4d and B-C4d&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">13</span></a> E-C4d reflects of SLE activity during the preceding 120 days&#46; Other promising biomarkers of activity are S100A12 calcium-binding proteins&#44; and serum concentrations of soluble tumor necrosis factor receptor-2&#945; &#40;soluble TNF receptor 2&#58; sTNF-R2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The search for a marker comparable to kidney biopsy has lead to the evaluation of serum and urinary biomarkers&#44; with the latter generally achieving better results&#46; From among the different urinary biomarkers evaluated&#44; the most promising are the urine neutrophil gelatinase-associated lipocalin &#40;uNGAL&#41;&#44; TNF-like weak inducer of apopotosis &#40;TWEAK&#41;&#44; kidney injury molecule-1 &#40;KIM-1&#41; and monocyte chemoattractant protein-1 &#40;MCP-1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">14</span></a> The determination of urinary T lymphocytes has also shown its usefulness in monitoring the activity of lupus nephritis &#40;LN&#41; &#40;increase in CD4&#43; and CD8&#43; only during disease activity phases&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Latest achievements in the general treatment strategy</span><p id="par0045" class="elsevierStylePara elsevierViewall">Since 2014&#44; SLE treatment with a therapeutic objective &#40;<span class="elsevierStyleItalic">treat to target</span> strategy&#41; has been advocated&#44; with the target necessarily being the induction of sustained clinical remission or&#44; failing that&#44; a state of low inflammatory activity of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">15</span></a> It means that all the treatment is aimed at achieving the pre-established results in the shortest possible time&#46; To achieve this&#44; the disease activity must be measured and documented at each visit and&#44; if the patient has not reached the desired goal&#44; then therapeutic adjustments must be made to achieve it&#46; Anything other than reaching the therapeutic target must be interpreted as an insufficient response and requires complementary measures to achieve it&#46; The current&#44; most widely accepted definitions of remission &#40;DORIS Group&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a> and low activity &#40;Asia-Pacific group&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> as well as complete and partial renal response in LN&#44;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">18&#44;19</span></a> are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">In addition to this strategy&#44; the new approach to SLE is fundamentally specified in aspects shown as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The multidimensional assessment of the disease when planning treatment and evaluating the response</span>&#58; control perceived or verifiable clinical lupus activity&#44; preventing activity flares&#44; avoiding secondary irreversible damage both to the actual disease and to its treatment &#40;the damage produced by chronic treatment with glucocorticoids &#91;GCs&#93; is often greater than that of SLE&#41; and minimize the impact on the patient&#39;s quality of life and survival&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#41;</span><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment with hydroxychloroquine &#40;HCQ&#41; at doses of 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day in all patients</span> &#40;provided there is no absolute contraindication for its use&#41; due to its beneficial pleiotropic effects in SLE&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The use of GCs should always be at the lowest dose and for the shortest time possible&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">An early association of immunosuppressants in severe cases with major organ involvement&#44; or if needed to restrict GC-use&#46;</span> The most widely used immunosuppressants are mycophenolate &#40;MMF&#41;&#44; azathioprine&#44; and methotrexate&#46; In some clinical settings&#44; cyclophosphamide and tacrolimus or cyclosporine A are used&#44; as are the biological therapies directed against B-cells&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Make an early diagnosis and treatment of kidney disease&#46;</span> In patients with LN&#44; after remission induction treatment&#44; the immunosuppressant should be maintained for a minimum of 3 years to improve prognosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Adequate control <span class="elsevierStyleItalic">of the disease comorbidities &#40;antiphospholipid syndrome&#44; cardiovascular risk&#44; osteoporosis and prevention of infections&#41; and maintain optimal levels of vitamin D&#46;</span></p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">These and other general principles can be consulted in the latest update of the EULAR recommendations for the treatment of SLE published in 2019&#44;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">18</span></a> and in the new EULAR&#47;ERA-EDTA recommendations for the management of lupus nephritis published in 2020&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">19</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Regarding treatment with antimalarial drugs&#44; in addition to HCQ&#44; we have chloroquine &#40;CQ&#41; and quinacrine&#46; CQ &#40;dose 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; is 2&#8211;3 times more potent than HCQ&#44; so its use carries a higher risk of retinal toxicity &#40;bull&#39;s eye maculopathy&#41; which is often irreversible&#46; Screening for this adverse effect should be carried out systematically in all patients receiving HCQ and CQ&#46; According to the new recommendations&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">20</span></a> if the patient does not have any risk factor for this complication and the ophthalmological evaluation &#40;fundus examination&#44; visual campimetry and optical coherence tomography&#41; at the beginning of the treatment is normal&#44; no new controls will be necessary until after the first 5 years&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">20</span></a> If the patient has risk factors &#40;previous maculopathy&#44; kidney failure&#44; concomitant treatment with tamoxifen or receives a dose &#62;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41;&#44; the ophthalmological examination will be annual or biannual&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">20&#44;21</span></a> Any patient previously treated with HCQ and who has received a total cumulative dose &#62;1000<span class="elsevierStyleHsp" style=""></span>g at the time of restarting treatment should also be considered at risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Due to its long half-life&#44; the determination of HCQ plasma levels has proven to be useful in the control of therapeutic compliance&#44; since it allows the non-compliant patients to be identified&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">21</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Quinacrine has the advantage of not producing retinal toxicity&#44; so it can be a therapeutic alternative to HCQ and CQ when they are contraindicated due to ocular toxicity&#46; It is also used &#40;at doses of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; in combination with HCQ in patients with resistant skin and&#47;or joint involvement&#44; achieving a synergistic beneficial effect&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">21</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Today it is known that GCs exert their anti-inflammatory action via 2 mechanisms&#58; the genomic&#44; classic pathway and the non-genomic pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">22</span></a> The genomic pathway is slower in onset with a persistent effect&#44; and it is responsible for the adverse effects of GCs&#46; It is activated 100&#37; with a prednisone dose of 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; Therefore&#44; with doses greater than 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;the guidelines state 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41; the only achievement is increased toxicity without a substantial increase in its anti-inflammatory effect&#46; In contrast&#44; the nongenomic pathway exerts an anti-inflammatory action which is much more intense and quicker&#46; This pathway begins to be noticeably activated after 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; with a maximum effect at over 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">21&#44;22</span></a> Intravenous pulse therapy above 100&#8211;250<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days has greater efficacy and less toxicity than prolonged treatment with high doses of prednisone&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">According to this knowledge&#44; current advise is not to exceed 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone regardless of the patient&#39;s clinical condition&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">18&#44;21</span></a> If necessary due to an acute flare or major organ involvement&#44; the administration of pulses of methylprednisolone &#40;125 or 250<span class="elsevierStyleHsp" style=""></span>mg daily for 3 days&#44; or 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day in the most severe cases&#41; can be considered&#44; which would achieve greater and faster efficacy than prolonged treatment with doses of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">18&#44;19&#44;21</span></a> The subsequent decrease in the prednisone dose must be done quickly &#40;every 2 weeks&#41;&#44; with the aim of reaching a maintenance dose &#8804;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day and&#44; if possible&#44; discontinuing it&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">New treatments</span><p id="par0115" class="elsevierStylePara elsevierViewall">The search for new treatments continues to be a universally recognized need in SLE&#46; We herein provide a review of the current research in this field&#44; which includes only those drugs whose research has reached phase II CT at least &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">B-cell targeting therapies</span><p id="par0120" class="elsevierStylePara elsevierViewall">The depletion of B lymphocytes has been attempted in 2 ways&#58; by Ab against their surface receptors &#40;CD20 and CD22&#41; or by inhibiting their survival factors BAFF &#40;BLyS&#41; or APRIL&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Within this group&#44; the currently available drugs are rituximab &#40;RTX&#41;&#44; chimeric anti-CD20 monoclonal Ab&#44; and belimumab&#44; a human monoclonal Ab that specifically binds to the soluble form of BAFF&#46; Belimumab has been approved by the <span class="elsevierStyleItalic">Food and Drug Administration</span> &#40;FDA&#41; and the European Medicines Agency for the treatment of SLE&#46; The results of the open-label extension phase of the patients included in the pivotal BLISS-52 and BLISS-76 trials&#44; as well as the results of observational studies of real clinical practice &#40;OBSERVE studies&#41;&#44; show a response rate close to 50&#37;&#44; which remains relatively stable over time&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">24&#44;25</span></a> In addition&#44; medium- and long-term treatment achieves a progressive decrease in disease activity flares&#44; a significant saving in GCs &#40;around 50&#37;&#41;&#44; and an improvement or negativisation of the immunological markers of activity&#44; confirming its efficacy in preventing accumulated damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">24&#44;25</span></a> Although initially belimumab had not been tested &#40;nor approved&#41; in patients with LN&#44; the results of the phase III CT &#8211; BLISS-LN&#44; have recently been released and they demonstrate its superiority over placebo in patients with active LN&#44; plus standard therapy with MMF and GC &#40;percentage of responders 43 vs&#46; 32&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;031&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">26</span></a> With these results&#44; the company will request approval from the health authorities for this indication&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Neither of the CTs that have evaluated the efficacy of RTX in SLE &#40;LUNAR in patients with proliferative LN and EXPLORER&#41; demonstrated superiority of the drug over placebo plus standard therapy&#44; except in the improvement of the immunological activity parameters&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">27&#44;28</span></a> Despite this&#44; real-life data from open studies and national registries of biological therapies demonstrate its clinical efficacy in patients refractory to conventional treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">23</span></a> For example&#44; in a meta-analysis that included 1243 patients from 30 observational studies&#44; the complete response rates reached 46&#46;7&#37; according to BILAG and 56&#46;6&#37; according to SLEDAI&#59; for LN&#44; the percentages of complete &#40;CR&#41; or partial &#40;PR&#41; renal response were 36&#46;1&#37; and 37&#46;4&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">29</span></a> This lack of agreement has given rise to an endless controversy and detailed analysis of the methodologies used&#46; Regardless of the explanations given to justify the discrepancies&#44; the ACR contemplates its use as a rescue treatment in LN&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">30</span></a> and EULAR&#44; in patients with severe renal or extrarenal involvement &#40;mainly hematological or neurological&#41; and when there is inadequate response or contraindication to standard treatment and&#47;or belimumab&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">18</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">A strategy in the evaluation phase is the sequential double blocking of B-cells with RTX followed by belimumab &#40;RTCs&#58; BEAT Lupus and BLISS-BELIEVE&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">31&#44;32</span></a> The scientific rationale behind this strategy is to try to avoid the elevated BAFF production that occurs after B-cell depletion by RTX and that facilitates the activation&#44; differentiation&#44; and proliferation of autoreactive B-cells&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In addition to RTX&#44; two other anti-CD20s have been evaluated&#44; namely ocrelizumab and obinutuzumab &#40;OBI&#41;&#44; with mixed success&#46; The development of ocrelizumab in SLE was discontinued due to an increase in the incidence of severe infections in phase III CTs conducted &#40;namely BELONG in patients with proliferative LN and BEGIN&#41;&#46; The efficacy analysis showed a trend toward improvement in the activity compared to the placebo group&#44; but without significant differences&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">33&#44;34</span></a> OBI is a humanised&#44; monoclonal&#44; type II Ab&#44; modified by glycoengineering in it Fc portion&#46; This modification is more effective in eliminating CD20&#43; B-cells than RTX&#46; At the ACR 2019 congress&#44; the results of NOBILITY&#44; a phase II CT were disseminated&#46; This CT has evaluated the safety and efficacy of OBI in adults with proliferative LN in combination with standard treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">35</span></a> The study results show superiority of the drug compared to placebo both in the primary efficacy endpoint &#40;CR at week 76&#58; 40 vs&#46; 18&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41; and in the secondary endpoints&#44; without observing differences in terms of safety&#46; With these results&#44; the FDA has granted OBI the designation of <span class="elsevierStyleItalic">breakthrough therapy&#46;</span> This designation is granted to expedite the development and review of drugs for severe diseases&#44; when there is evidence to suggest that they can provide substantial benefit over currently available treatments&#46; phase III of the CT was programmed to start in 2020&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Within this treatment strategy&#44; epratuzumab&#44; a monoclonal Ab directed against CD22&#44; has also been tested&#46; Despite the favorable differences in the BICLA response observed in several of the doses &#40;but not in all&#41; in the EMBLEN phase II CT&#44; the superiority of epratuzumab over placebo plus standard treatment could not be demonstrated in the phase III EMBODY 1 and -2&#44; as neither of the doses tested achieved the primary efficacy endpoint&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">36</span></a> Qualifying these results&#44; in a post hoc analysis&#44; the drug has been shown to be especially effective in the subgroup of patients with secondary Sj&#246;gren&#39;s syndrome and positive for anti-Ro&#47;SSA Ab&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Apart from belimumab&#44; other therapies directed against BAFF and APRIL factors have not been successful&#46; Treatment with atacicept&#44; a BAFF&#47;APRIL dual inhibitor&#44; increased the incidence of severe infections and hypogammaglobulinaemia without observing large significant differences in efficacy compared to placebo &#40;ADDRESS II&#41;&#44; so the expectations which had been generated with this drug have fizzled out&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">37</span></a> Neither has it been possible to demonstrate superiority over placebo in the primary efficacy endpoint in the pivotal phase III CTs with two other BAFF inhibitors&#44; blisibimod &#40;CHABLIS-SC1&#41;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">38</span></a> and tabalumab &#40;ILLUMINATE-1 and ILLUMINATE-2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">39&#44;40</span></a> While the development of tabalumab appears to have been permanently abandoned&#44; the destiny of blisibimod remains to be seen&#46; Although it did not achieve significant differences in the primary efficacy endpoint&#44; it did demonstrate a substantial saving of GCs and an improvement in the markers of immune activity and proteinuria in patients with LN&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Block T-cell activation</span><p id="par0155" class="elsevierStylePara elsevierViewall">Abatacept is a fusion protein that inhibits the activation of T-cells by selectively blocking the specific binding of CD80&#47;CD86 receptors to CD28&#46; In phase IIb&#47;III studies in SLE patients&#44; abatacept did not achieve any of the preset primary efficacy endpoints&#44; but it demonstrated some beneficial secondary effects&#44; such as improvement of immunological parameters&#44; reduction in the number of flares compared to placebo in arthritic patients&#44; and it achieved faster &#40;but not more numerous&#41; CRs compared to standard treatment in patients with proliferative LN &#40;ALLURE study&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">41</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Another researched strategy has been the blockade of CD40&#47;CD40L&#46; Both ruplizumab and toralizumab&#44; two humanised anti-CD40 ligand monoclonal antibodies&#44; showed a tendency to improve SLE activity&#44; but their development was interrupted by the appearance of thrombotic phenomena&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">42</span></a> This adverse effect has been resolved with the development of dapirolizumab pegol&#46; The results of a CT IIb CT at 24 weeks has shown that treatment with dapirolizumab pegol achieves numerically higher SRI-4 and BICLA responses than placebo&#44; but without reaching statistical significance&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">43</span></a> Its safety profile is good&#44; with no serious adverse effects or changes in coagulation factors being detected&#46; During 2020 an CT in phase III is scheduled to be started&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">&#945; interferon antagonists</span><p id="par0165" class="elsevierStylePara elsevierViewall">Due to both its biological effects and the genetic argument&#44; IFN-&#945; is one of the most sought after therapeutic targets today&#46; To date&#44; three fully human monoclonal antibodies have been developed that block its action&#58; sifalimumab&#44; rontalizumab&#44; and anifrolumab&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The first two are anti-IFN-&#945; antibodies&#46; Both demonstrated a modest efficacy in phase II CTs&#44; so the study has been discontinued &#40;although sifalimumab was shown to be effective for skin manifestations&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">44</span></a> However&#44; anifrolumab is an Ab that binds to the type 1 INF receptor subunit 1&#44; blocking the activity of all INF&#44; including IFN-&#945;&#44; IFN-&#946; and IFN-&#969;&#46; After achieving encouraging results in phase II &#40;MUSO&#41;&#44; two clinical trials have been conducted in phase III &#40;TULIP 1 and 2&#41; with conflicting results&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">45&#44;46</span></a> This discrepancy exemplifies what appears to be the main problem with many of the CTs conducted to date in SLE&#58; the response measurement instruments&#46; Thus&#44; while in TULIP-1 anifrolumab did not achieve the primary efficacy endpoint which was the SRI-4 response&#44; it went beyond achieving it in the TULIP-2 study&#44; where the efficacy endpoint was the BICLA response&#46; BICLA and SRI clearly differ&#46; While BICLA is based on the 2004 BILAG&#44; which can record both partial and complete improvements in each organ-system&#44; SRI focuses on the SLEDAI&#44; which only captures complete improvements in each organ-system&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">In the recently published TULIP-2 study&#44; the response rate achieved with anifrolumab at doses of 300<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks was much higher than the placebo &#40;47&#46;8&#37; vs&#46; 31&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; at the end of 48 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">46</span></a> The differences in response were constant regardless of the intensity of the IFN signature&#46; Differences were also observed in favor of anifrolumab in the reduction of the GC dose and in the improvement of the cutaneous manifestations&#44; but not in those of the joints&#46; When considering the global SRI and BICLA responses of all the patients included in the anifrolumab trials &#40;MUSE&#44; TULIP 1 and 2&#41;&#44; the results in 5 of the 6 domains demonstrate the superiority of the drug over placebo&#46; With these data&#44; the promoting laboratory will request the approval of anifrolumab from the FDA at the beginning of this year&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Tolerogens</span><p id="par0180" class="elsevierStylePara elsevierViewall">The deficient clearance of apoptotic residues with nucleic content&#44; together with a loss of tolerance&#44; are considered the factors that determine the formation of antibodies against nuclear components in SLE&#46; A target that has attracted the attention of researchers has been the search for tolerogens&#44; that is&#44; agents capable of restoring tolerance to nuclear autoantigens&#46; The first drugs evaluated within this group were edratide and abetimus&#44; both with unsuccessful results&#44; since despite decreasing the production of autoantibodies&#44; they did not demonstrate clinical benefits&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">47&#44;48</span></a> In contrast&#44; lupuzor&#44; also called rigerimod&#44; showed encouraging results in the phase IIb CT&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">49</span></a> So&#44; the FDA granted it fast track designation to facilitate its development and review&#46; However&#44; the recently released results of the phase III study&#44; have not been able to demonstrate its superiority over placebo due to the high response rate observed in this group &#40;SRI-4 response&#58; 52&#46;5&#37; vs&#46; 44&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;263&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">50</span></a> The efficacy of the drug appears to be better in the subgroup of patients who had anti-dsDNA autoantibodies &#40;61&#46;5&#37; vs&#46; 47&#46;3&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;09&#44; with statistically significant differences if we only consider the selected population in Europe&#58; 71&#46;1&#37; vs&#46; 48&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; achieving remission in 7&#46;6&#37; of cases&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ustekinumab</span><p id="par0185" class="elsevierStylePara elsevierViewall">Ustekinumab is a fully human monoclonal Ab that binds to the p40 protein subunit of the cytokines IL-12 and IL-23&#44; inhibiting their activity by preventing these cytokines from interacting with the IL-12R&#946;1 receptor that is expressed on the surface of T-cells&#46; The IL-12&#47;23 pathway allows the differentiation and clonal proliferation of the Th1 and Th17 lymphocyte subpopulations that are involved in the pathogenesis of SLE&#46; The results of a phase II CT have shown the superiority of ustekinumab over placebo plus standard treatment at 24 and 48 weeks&#44;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">51&#44;52</span></a> both in global disease endpoints &#40;SRI-4 response&#41; and organ-specific endpoints&#44; as well as a reduction in severe flares&#46; The phase III trial is currently underway&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">JAK inhibitors</span><p id="par0190" class="elsevierStylePara elsevierViewall">As with other autoimmune diseases&#44; hopes have also been pinned on the inhibition of intracellular signaling pathways&#46; There are currently four JAK kinase inhibitors available&#44; two of which are being evaluated in SLE&#46; Baricitinib is a selective and reversible inhibitor of JAK 1 and 2 that with the dose of 4<span class="elsevierStyleHsp" style=""></span>mg&#47;day has shown superiority to placebo in a phase II CT lasting 24 weeks&#44; conducted with patients with skin and&#47;or joint activity &#40;SLEDAI-2K response&#58; 67 vs&#46; 53&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">53</span></a>&#46; The FDA has also granted it the fast track designation to facilitate its development and review&#44; and the phase III trials &#40;BRAVE I&#44; II and X&#41; are in progress&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Upadacitinib is a recently approved selective JAK 1 inhibitor for the treatment of rheumatoid arthritis&#46; A current phase II CT in being conducted for SLE that assesses its efficacy in monotherapy and in combination with a Bruton tyrosine kinase inhibitor&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">54</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Voclosporin</span><p id="par0200" class="elsevierStylePara elsevierViewall">It is a next generation calcineurin inhibitor that has been evaluated in adults with proliferative LN in combination with standard treatment&#46; The results of the phase III CT &#40;AURORA&#41; released at the end of 2019 have demonstrated its superiority over placebo both in the main efficacy endpoint &#40;CR at week 52&#58; 40&#46;8 vs&#46; 22&#46;5&#37; in the placebo group&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; as in all the secondary endpoints analyzed &#40;CR at week 24&#44; PR at weeks 24 and 52&#44; and reduction in proteinuria by more than 50&#37;&#41;&#44; without observing differences in terms of safety&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">55&#44;56</span></a> Based on these results&#44; the sponsor laboratory will request its approval from the FDA for the treatment of LN at the beginning of this year&#46; Since the FDA had also granted it the fast track designation in 2016&#44; the decision on its authorization is likely to be favorable and quick&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusions</span><p id="par0205" class="elsevierStylePara elsevierViewall">In recent years&#44; there has been an important improvement in the prognosis of SLE thanks to new strategies for approaching the disease&#44; the better use of GCs and immunosuppressants&#44; the systematic use of HCQ&#44; the use of targeted biological therapies against B-cells in refractory cases and an adequate control of the comorbidities&#46; However&#44; we are still far from its final cure and we still face unmet needs&#46; It is foreseeable that in a short time new treatments will be approved that will allow the rescue of refractory patients or those with insufficient control of disease activity&#46; When looking at the new treatments evaluated&#44; anifrolumab &#40;for the global activity of SLE&#41; and voclosporin &#40;for LN&#41; are the options that today have the best guarantees of success&#44; without forgetting baricitinib and OBI&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0210" class="elsevierStylePara elsevierViewall">The author declares that he has no conflict of interest in relation to this publication&#46;</p></span></span>"
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          "titulo" => "New classification criteria"
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          "identificador" => "sec0010"
          "titulo" => "Search for new biomarkers"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Latest achievements in the general treatment strategy"
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          "titulo" => "New treatments"
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            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "B-cell targeting therapies"
            ]
            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Block T-cell activation"
            ]
            2 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "&#945; interferon antagonists"
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              "identificador" => "sec0040"
              "titulo" => "Tolerogens"
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              "identificador" => "sec0045"
              "titulo" => "Ustekinumab"
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              "identificador" => "sec0050"
              "titulo" => "JAK inhibitors"
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            6 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Voclosporin"
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          "titulo" => "Conclusions"
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          "titulo" => "Conflict of interests"
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          "titulo" => "References"
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    "fechaRecibido" => "2020-03-11"
    "fechaAceptado" => "2020-05-13"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1309970"
          "palabras" => array:5 [
            0 => "Systemic lupus erythematosus"
            1 => "Update"
            2 => "Classification criteria"
            3 => "Biomarkers"
            4 => "New treatments"
          ]
        ]
      ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:5 [
            0 => "Lupus eritematoso sist&#233;mico"
            1 => "Actualizaci&#243;n"
            2 => "Criterios de clasificaci&#243;n"
            3 => "Biomarcadores"
            4 => "Nuevos tratamientos"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic lupus erythematosus &#40;SLE&#41; is a complex autoimmune multisystemic disease of great clinical heterogeneity and significant potential morbidity and mortality&#46; Although the outlook for patients with SLE has greatly improved&#44; many unmet needs remain&#46; In this review we aim to summarize the most relevant data on SLE that have emerged in recent years&#46; In particular we discuss the new classification criteria from the European League Against Rheumatism and American College of Rheumatology&#44; new biomarkers&#44; novel definitions of remission and low lupus disease activity and what has emerged on new drugs and new therapeutic strategies&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El lupus eritematoso sist&#233;mico &#40;LES&#41; es una enfermedad autoinmunitaria multisist&#233;mica compleja&#44; con una gran heterogeneidad en su presentaci&#243;n cl&#237;nica y una alta morbimortalidad&#46; Aunque su pron&#243;stico ha mejorado de forma notable a lo largo de las &#250;ltimas d&#233;cadas&#44; a&#250;n siguen existiendo necesidades no cubiertas en esta enfermedad&#46; En esta actualizaci&#243;n realizamos una puesta al d&#237;a de los principales avances en esta enfermedad en los &#250;ltimos a&#241;os&#46; Concretamente revisamos los nuevos criterios de clasificaci&#243;n propuestos por la Liga Europea de Reumatolog&#237;a y el Colegio Americano de Reumatolog&#237;a&#44; la b&#250;squeda de nuevos biomarcadores&#44; las nuevas definiciones de remisi&#243;n y de baja actividad de la enfermedad&#44; as&#237; como las estrategias actuales de abordaje y tratamiento del LES y la situaci&#243;n actual de las nuevas terapias&#46;</p></span>"
      ]
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Narv&#225;ez J&#46; Revisi&#243;n&#58; lupus eritematoso sist&#233;mico 2020&#59;155&#58;494&#8211;501&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ACR&#58; American College of Rheumatology&#59; EULAR&#58; European League Against Rheumatology&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Classifying a patient for systemic lupus erythematosus requires at least one clinical criterion and a score &#8805;10 points&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Considerations&#58;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The existence of a criterion or clinical manifestation on at least one occasion during the clinical course is sufficient to score&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The criteria do not have to be simultaneous&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Within each domain&#44; only the criterion with the highest score is counted for the total score&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Entry criterionPositive antinuclear antibodies &#8805;1&#47;80 by indirect immunofluorescence using HEp-2 cell line substrate &#40;at any time&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical domains&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Points&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Constitutional</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Cutaneous</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Non-scarring alopecia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Oral thrush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subacute cutaneous lupus or discoid lupus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute cutaneous lupus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Joints</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Synovitis or pain in &#8805;2 joints with morning joint stiffness &#62;30<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Neurological</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Delirium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Psychosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Convulsions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Serositis</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pleural or pericardial effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute pericarditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hematological</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Leukopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Autoimmune hemolysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Renal</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Proteinuria &#62;0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lupus nephritis class II or V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lupus nephritis class III or IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Immunological domains&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Points&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anticardiolipin at medium or high titer or anti-&#946;2 glycoprotein 1 or positive lupus anticoagulant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Complement</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low C3 or low C4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low C3 and low C4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-dsDNA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-Sm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">New EULAR&#47;ACR classification criteria for systemic lupus erythematosus&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Ab&#58; antibody&#59; BILAG&#58; <span class="elsevierStyleItalic">British Isles Lupus Assessment Group Index</span>&#59; ECLAM&#58; <span class="elsevierStyleItalic">European Consensus Lupus Activity Measurement&#59;</span> SLEDAI&#58; <span class="elsevierStyleItalic">Systemic Lupus Erythematosus Disease Activity Index&#46;</span></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Low activity<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Remission<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLEDAI-2K &#8804;4&#44; no major organ activity&#44; hemolytic anemia&#44; fever or gastrointestinal symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A validated index must be used&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No new activity data compared to the previous assessment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLEDAI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assessment of disease activity by the doctor &#8804;1 &#40;0&#8211;3 scale&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLEDAI symptoms<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucocorticoid maintenance dose&#58; &#8804;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day prednisone or equivalent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ECLAM symptoms<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunosuppressive or biological treatment at stable doses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Only BILAG D and E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assessment of disease activity by the doctor &#60;0&#46;5 &#40;0&#8211;3 scale&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serological remission &#40;negative anti-dsDNA Ab and normal complement&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment with antimalarial drugs and prednisone only &#8804;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day or equivalent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Duration of remission not yet defined &#40;minimum &#8805;6 months to &#8805;5 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lupus nephritis</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Therapeutic objective&#58; complete renal response</span><a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">19</span></a> defined by a protein&#47;creatinine ratio &#60;500&#8211;700<span class="elsevierStyleHsp" style=""></span>mg&#47;g with normalization or stabilization &#40;&#177;10&#37;&#41; of serum creatinine with respect to baseline&#44; at 12 months after starting treatment &#40;expected improvement in proteinuria&#58; at least 25&#37; at 3 months and 50&#37; at 6 months after starting treatment&#41;&#46;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Partial response</span><a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">18</span></a> defined as reduction &#8805;50&#37; proteinuria compared to baseline &#40;with values below 3&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41; with stabilization &#40;&#177;10&#37;&#41; of serum creatinine with respect to baseline&#44; at 12 months after starting treatment&#46;</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2468655.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Definitions of low activity and remission in systemic lupus erythematosus and therapeutic objective in lupus nephritis&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">APRIL&#58; <span class="elsevierStyleItalic">A proliferation-inducing ligand</span>&#59; BAFF&#58; <span class="elsevierStyleItalic">B-cell Activating Factor</span>&#44; also called BLyS&#59; IFN&#58; interferon&#59; IL&#58; interleukin&#59; JAK<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>janus kinases&#59; SLE&#58; systemic lupus erythematosus&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary efficacy endpoint achieved&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EXPLORER phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LUNAR phase III lupus nephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ocrelizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BEGIN phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discontinued&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BELONG phase III lupus nephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discontinued due to infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obinituzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NOBILITY phase II lupus nephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epratuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EMBLEM phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EMBODY 1 and 2 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finished&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Belimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BAFF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BLISS-52 and 76 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finished&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BLISS-LN phase III lupus nephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tabalumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BAFF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ILLUMINATE-1 and 2 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blisibimod&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BAFF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PEARL sc phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finished&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CHABLIS SC1 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atacicept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BAFF and APRIL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ADDRESS II phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abatacept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Costimulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT00119678 phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T-cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALLURE 3 phase III lupus nephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IM101-330 phase II arthritis in SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dapirolizumab pegol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02804763 phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Selection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD40L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sifalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN-&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT01283139 phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rontalizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN-&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROSE phase II active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anifrolumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Type 1 IFN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MUSE phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TULIP-1 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TULIP-2 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lupuzor &#40;rigerimod&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tolerogen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT01240694 phase IIb active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02504645 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-12&#47;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02349061 phase IIa active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT03517722 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Selection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baricitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1 and 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02708095 phase II active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BRAVE-1 and 2 phase III active SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Selection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Voclosporin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Calcineurin inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AURORA phase III lupus nephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2468653.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">New treatments evaluated in systemic lupus erythematosus&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:56 [
            0 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of systemic lupus erythematosus in Spain&#58; higher than previously reported in other countries&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Cort&#233;s Verd&#250;"
                            1 => "J&#46;M&#46; Pego-Reigosa"
                            2 => "D&#46; Seoane-Mato"
                            3 => "M&#46; Morcillo Valle"
                            4 => "D&#46; Palma S&#225;nchez"
                            5 => "M&#46;J&#46; Moreno Mart&#237;nez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/kez668"
                      "Revista" => array:2 [
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                      ]
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                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
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                ]
              ]
            ]
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              "identificador" => "bib0295"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Practice variations in the diagnosis&#44; monitoring&#44; and treatment of systemic lupus erythematosus in Canada"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;O&#46; Keeling"
                            1 => "A&#46; Bissonauth"
                            2 => "S&#46; Bernatsky"
                            3 => "B&#46; Vandermeer"
                            4 => "P&#46;R&#46; Fortin"
                            5 => "D&#46;D&#46; Gladman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.171307"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2018"
                        "volumen" => "45"
                        "paginaInicial" => "1440"
                        "paginaFinal" => "1447"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30068762"
                            "web" => "Medline"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2019 European League Against Rheumatism&#47;American College of Rheumatology classification criteria for systemic lupus erythematosus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Aringer"
                            1 => "K&#46; Costenbader"
                            2 => "D&#46; Daikh"
                            3 => "R&#46; Brinks"
                            4 => "M&#46; Mosca"
                            5 => "R&#46; Ramsey-Goldman"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2018-214819"
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                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2019"
                        "volumen" => "78"
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                        "paginaFinal" => "1159"
                        "link" => array:1 [
                          0 => array:2 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Petri"
                            1 => "A&#46;M&#46; Orbai"
                            2 => "G&#46;S&#46; Alarc&#243;n"
                            3 => "C&#46; Gordon"
                            4 => "J&#46;T&#46; Merrill"
                            5 => "P&#46;R&#46; Fortin"
                          ]
                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.34473"
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                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "2677"
                        "paginaFinal" => "2686"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22553077"
                            "web" => "Medline"
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              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "How do patients with newly diagnosed systemic lupus erythematosus present&#63; A multicenter cohort of early systemic lupus erythematosus to inform the development of new classification criteria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Mosca"
                            1 => "K&#46;H&#46; Costenbader"
                            2 => "S&#46;R&#46; Johnson"
                            3 => "V&#46; Lorenzoni"
                            4 => "G&#46;D&#46; Sebastiani"
                            5 => "B&#46;F&#46; Hoyer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.40674"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2019"
                        "volumen" => "71"
                        "paginaInicial" => "91"
                        "paginaFinal" => "98"
                        "link" => array:1 [
                          0 => array:2 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Performance of the 2012 Systemic Lupus International Collaborating Clinics classification criteria versus the 1997 American College of Rheumatology classification criteria in adult and juvenile systemic lupus erythematosus&#46; A systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;A&#46;R&#46; Hartman"
                            1 => "A&#46; van Royen-Kerkhof"
                            2 => "J&#46;W&#46;G&#46; Jacobs"
                            3 => "P&#46;M&#46;J&#46; Welsing"
                            4 => "R&#46;D&#46;E&#46; Fritsch-Stork"
                          ]
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                  "host" => array:1 [
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