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Review article
Deflazacort in rheumatoid arthritis: A scoping review
Deflazacort en artritis reumatoide: revisión panorámica de la literatura (scoping review)
Diana Guavita-Navarroa,
Corresponding author
dianakt08@hotmail.com

Corresponding author.
, Laura Gallegoa, Jhon Buitragoa, Diana Guevaraa, Ana María Arredondoa, Héctor Cubidesa, Alejandro Escobara, Adriana Rojas-Villarragab, Jairo Cajamarca-Baróna
a Rheumatology Service, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital San José, Bogotá, Colombia
b Research Institute, Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Corticosteroids are hormones released by the adrenal gland&#44; which are divided into 2 groups according to their biological activity&#58; glucocorticoids &#40;regulation of the metabolism of carbohydrates&#41; and mineralocorticoids &#40;balance of fluids and electrolytes&#44; mainly sodium&#41;&#46; The potency of these hormones is given by their activity on sodium&#44; glucose metabolism and their anti-inflammatory properties&#59; the latter 2 are closely related since they share the same receptor&#46; Although these concepts are important when talking about synthetic corticosteroids&#44; it should be taken into account that they share characteristics of one group or another&#46; For example&#44; although prednisone is considered a glucocorticoid&#44; it also has mineralocorticoid activity&#46; This property of acting on different pathways depends on the structure of the drug and the metabolism carried out by the enzyme 11-beta-hydroxydehydrogenase&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The first synthetic corticosteroids developed were prednisolone and prednisone&#44; which&#44; as mentioned above&#44; have a predominantly glucocorticoid effect&#46; Subsequently&#44; other drugs were developed such as dexamethasone and more recently deflazacort&#44; a derivative of prednisolone with a methyl-oxazoline ring that differentiates it from the original compound and gives it its attractive pharmacological properties&#58; lack of activity on loss of sodium&#44; potent anti-inflammatory and immunosuppressant activity and little interference with glucose and phosphocalcic metabolism&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> This explains why&#44; when compared with corticosteroids such as prednisolone or methylprednisolone&#44; it exhibits fewer adverse effects&#58; less decrease in bone mineral density &#40;BMD&#41;&#44; no alteration of the lipid profile and prevention of fat accumulation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Ganapati et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> conducted a study in which they compared the adverse effects of deflazacort and prednisolone in patients with systemic lupus erythematosus&#44; and confirmed these benefits&#58; lower weight gain&#44; less hirsutism and low cushingoid severity index&#44; as well as less impact on blood glucose&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">It has been demonstrated that deflazacort inhibits the inflammatory exudative phase&#44; as well as the development of chronic granulomatous inflammation&#46; It has been seen in experimental models that it also exerts its effect on the joints and&#44; although the majority of patients treated with deflazacort are those with muscular dystrophies&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6&#44;7</span></a> there are several disorders in which its use has been tested with satisfactory results&#44; such as sarcoidosis&#44; juvenile idiopathic arthritis&#44; polymyalgia rheumatica&#44; systemic lupus erythematosus&#44; and rheumatoid arthritis &#40;RA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8&#44;9</span></a> However&#44; its use is infrequent in rheumatological practice and there are some gaps such as the dose ranges and de-escalation&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">After considering the previous points and with the purpose of examining the extent and nature of the existing literature in this area&#44; summarizing and disseminating its results and identifying gaps in the current literature around the use of deflazacort in RA&#44; we have decided to carry out this panoramic literature review &#40;scoping review<span class="elsevierStyleItalic">&#41;&#44;</span> which aims to describe the effect of deflazacort compared with other corticosteroids in RA&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">For the scoping review&#44; a literature search was conducted in the different databases &#40;PubMed&#44; Cochrane&#44; BVS&#41; and in the grey literature as sources of information&#44; including articles published until June 2021 and limited to English and Spanish languages&#44; with no limits on the type of publication&#46; The PRISMA extension for scoping reviews &#91;PRISMA-ScR&#93; guideline was followed &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> &#40;Appendix A Supplementary material 1 Appendix annex 1&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The related search terms &#171;deflazacort&#187;&#44; &#171;rheumatoid arthritis&#187; were used&#46; In the construction of the search equations&#44; each of the MeSH terms was crossed with the respective keywords using different Boolean operators &#40;OR&#44; AND&#41;&#46; The full search strategy is presented in the Appendix B Supplementary material 2 &#40;Appendix B annex 2&#41;&#46; Two reviewers conducted the search independently and clarified disagreements by consensus&#46; The following eligibility criteria were considered&#58; controlled clinical trials or equivalence studies with a comparator&#44; developed in adult patients with RA &#40;confirmed according to validated criteria&#41; and use of deflazacort compared with other corticosteroids for control of the disease&#46; The articles that did not clearly mention the dose of deflazacort and of the comparator used were excluded&#46; The articles related to the topic were selected and the data were subsequently extracted from a database created in the Excel&#174; software&#44; evaluating as main variables&#58; type of study&#44; sample size&#44; age of the participants in both arms &#40;years&#41;&#44; disease &#40;in the case of others evaluated in addition to RA&#41; dose of deflazacort and comparator&#44; and follow-up time&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In accordance with Colombian regulations &#40;Resolution 008430 of 1993 of the Ministry of Health&#41; this systematic review is considered a risk-free investigation&#44; because no intervention or intentioned modification of the biological&#44; physiological&#44; psychological or social variables of the individuals was made&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">The initial search yielded a total of 166 studies coming from the 3 databases&#46; After excluding duplicates in the identification&#44; screening and assessing eligibility through the review of the abstract and the full text&#44; 5 studies &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; that met the eligibility criteria were included&#44; which are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The results are exposed in detail below&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Deflazacort vs&#46; prednisolone</span><p id="par0045" class="elsevierStylePara elsevierViewall">The effects of deflazacort and prednisone are usually diverse&#44; considering the dose&#44; the underlying disease&#44; and concomitant medications&#46; There are particular modifications that may influence their choice based on the clinical benefit to the patients&#46; These differences are related to the chemical transformation that prednisone undergoes&#44; which gives way to the constitution of the C-17 nanoxazoline group&#44; which reduces its solubility in lipids and exerts an effect on blood components that limits or excludes the tissues&#44; particularly the osteoblasts&#44; without interfering in the clinical response&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding the use of prednisolone in patients with RA&#44; the harmful effects on bone metabolism&#44; with induction of osteoporosis&#44; have been widely described&#44; and the use of deflazacort has been proposed as a therapy that could reduce this effect&#46; In a study conducted by Messina et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> both drugs were compared for 12 months &#8212; deflazacort 12&#8239;mg&#47;day vs&#46; prednisolone 10&#8239;mg&#47;day &#8212; finding equal rates of synovitis and body bone mineral count&#46; However&#44; at the level of Ward&#8217;s triangle&#44; the drop in BMD was lower with deflazacort&#44; which suggests a possible lower impact on the bone with the use of this drug in patients with RA&#46; In the study conducted by Gray et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> in patients with RA&#44; participants received titratable doses of prednisolone and deflazacort for 2 months&#46; At 90 days&#44; the reduction in the erythrocyte sedimentation rate and activity indices were similar&#44; with an increase in urinary calcium excretion and greater inhibition of endogenous secretion of cortisol in the deflazacort group&#44; and it was demonstrated a therapeutic potency of 83&#37; with respect to prednisolone&#44; so that it may be better tolerated&#44; in addition to showing fewer adverse effects in the long term&#46; Montecucco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> supported this statement in their study&#44; in which they compared the serum levels of osteocalcin &#40;a marker of osteoblastic activity&#41; after management with prednisone or deflazacort&#46; At 6 months&#44; the serum concentration of osteocalcin was reduced in the 2 groups&#44; but the decrease was more significant with prednisolone&#44; even more so when the doses were higher than 10&#8239;mg&#47;day&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">A double-blind study compared the efficacy of deflazacort and prednisolone in patients with systemic lupus erythematosus and RA&#46; The 2 drugs induced clinical remission within one month&#44; which was maintained until the sixth month&#46; Likewise&#44; immunological modifications persisted with deflazacort for 1&#8211;1&#46;5 months&#44; including the significant reduction in T lymphocytes and CD4&#47;CD8 ratio&#44; with an apparent lower effect on calcium and glucose metabolism compared with prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In addition&#44; del Rosso et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> evaluated the effects of the administration of deflazacort on the synoviocytes of healthy and RA patients&#44; and documented <span class="elsevierStyleItalic">in vitro</span> that the expression and activity of the fibrinolytic system are reduced&#46; This system plays a leading role in the invasion and proliferation of synoviocytes in RA&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Deflazacort vs&#46; methylprednisolone</span><p id="par0065" class="elsevierStylePara elsevierViewall">Methyl prednisolone&#44; administered orally or intravenously&#44; is a member of the group of glucocorticoids that has a great anti-inflammatory activity&#44; which is why it has been used in several inflammatory and autoimmune disorders&#44; such as inflammatory bowel disease&#44; vasculitis&#44; systemic lupus erythematosus and RA&#44; among others&#46; Likewise&#44; it shares the undesirable effects generated by the use of prednisolone&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding the use of methylprednisolone in patients with RA&#44; Grassi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> evaluated its frequency of use and found that it was the main corticosteroid prescribed in patients with RA &#40;63&#46;2&#37;&#41;&#44; with an average dose of 5&#46;7&#177;3&#46;6&#8239;mg&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Saviola et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> evaluated the equivalence of correct clinical efficacy in low doses of deflazacort and methylprednisolone in a 12-month clinical trial&#44; and as a secondary objective they considered the bone metabolic effects of such doses in the treatment of RA and psoriatic arthropathy&#46; There were no significant differences in achieving ACR20 response at 6 and 12 months&#46; Regarding bone metabolism&#44; measurements of bone-specific alkaline phosphatase&#44; osteocalcin and osteoprotegerin &#40;OPG&#41; were made&#44; without finding statistically significant differences&#44; even though there was a trend towards a more marked decrease in OPG levels in the methylprednisolone group at 3 months &#40;6&#37; with deflazacort vs&#46; 24&#37; with methylprednisolone&#41;&#46; Although it was not the main objective of the research and the conclusions in favor of the use of deflazacort are not strong&#44; it does open a path to conduct studies in which the formulated hypothesis is evaluated&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the rheumatology setting&#44; glucocorticoids are frequently used&#44; however&#44; unfortunately&#44; they are not innocuous drugs and can trigger side effects&#44; such as loss of bone mineral density&#44; osteoporosis&#44; weight gain&#44; hypertension&#44; diabetes mellitus&#44; or neuropsychiatric alterations&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Deflazacort and prednisolone are corticosteroids with the same therapeutic effects&#44; used in different clinical scenarios&#44; mainly in muscular dystrophies in the case of deflazacort&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> with limited use in systemic autoimmune diseases&#44; perhaps due to lack of evidence&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The drugs studied show pharmacological differences&#44; such as the methyl-oxazoline ring in the chemical structure of deflazacort&#44; which influence the generation of adverse effects&#44; as we have observed in our narrative review&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The majority of the studies had prednisolone as comparator&#44; in relation to which there appear to be no difference in terms of therapeutic efficacy&#44; as documented by Montecucco et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Gray et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and other authors&#46; However&#44; the negative impact of deflazacort on bone and glucose metabolism is lower than that of its comparator&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Studies comparing deflazacort and methylprednisolone were also found&#44; with results similar to those that compared it with prednisolone&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The present study has some limitations&#44; since as it is a panoramic literature review &#40;scoping review&#41; it has been focused on 3 main search databases&#44; without doing a quantitative analysis of the data of meta-analysis type&#46; In addition&#44; due to the type of studies obtained&#44; it was not possible to perform a quantitative analysis thereof&#46; However&#44; in order to avoid biases&#44; the extension of the PRISMA guide for panoramic reviews has been followed&#44; thanks to which more objective results have been obtained&#46; Like all panoramic reviews&#44; the results of the present review could serve as input for decision-making and to determine the need and feasibility of conducting a systematic review subsequent to the present panoramic review&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Deflazacort is a promising drug in rheumatology clinical practice&#44; due to its apparent safety for long-term use and comparable efficacy to that of prednisolone&#59; However&#44; questions remain to be answered&#44; such as the scheme of use and&#44; specifically&#44; de-escalation&#46; Studies with a broader statistical power and that include a larger sample of patients with rheumatological diseases are required to consider the standard use of deflazacort in our practice&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">The study did not receive any funding from agencies in the public&#44; commercial or nonprofit sectors&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Deflazacort vs&#46; prednisolone"
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              "titulo" => "Deflazacort vs&#46; methylprednisolone"
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            0 => "Deflazacort"
            1 => "Prednisolone"
            2 => "Methylprednisolone"
            3 => "Dexamethasone"
            4 => "Corticosteroids"
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            2 => "Metilprednisolona"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Corticosteroids are hormones released by the adrenal gland that act on sodium and glucose metabolism and have anti-inflammatory properties&#46; The first synthetic corticosteroids were prednisolone and prednisone&#46; Deflazacort is the most recent of the synthetic corticosteroids&#44; with molecular differences that bestow benefits such as&#44; for example&#44; in relation to sodium loss&#44; anti-inflammatory potency and immunosuppressive activity&#44; and lower interference on glucose and phosphocalcium metabolism&#46;</p></span> <span id="abst1010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1015">Objective</span><p id="spar1030" class="elsevierStyleSimplePara elsevierViewall">We decided to conduct this study to describe the effect of deflazacort compared to other corticosteroids in rheumatoid arthritis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We conducted a scoping review&#46; A literature search was conducted in Pubmed&#44; Cochrane and BVS databases&#44; and in grey literature&#44; for controlled clinical trials or equivalence studies conducted in adult patients with rheumatoid arthritis and the use of deflazacort versus other corticosteroids&#46; We excluded articles that did not clearly mention the dose of deflazacort&#44; or the comparator used&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The search of the 3 databases yielded 166 studies&#44; of which 5 met the eligibility criteria and were included&#46; Four studies evaluated deflazacort versus prednisolone&#44; and one versus methylprednisolone&#46; The results were similar for all 5&#58; less decline in bone mineral density and glucose metabolism&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Deflazacort and prednisolone have pharmacological differences that influence adverse effects at the level of bone and glucose metabolism&#46; However&#44; further studies are required for deflazacort to be used routinely in our practice&#44; especially in diseases such as rheumatoid arthritis&#46;</p></span>"
        "secciones" => array:5 [
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            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
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            "titulo" => "Objective"
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          2 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
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          3 => array:2 [
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            "titulo" => "Results"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los corticoides son hormonas liberadas por la gl&#225;ndula suprarrenal&#44; con actividad sobre el sodio y el metabolismo de la glucosa&#44; as&#237; como propiedades antiinflamatorias&#46; Los primeros corticoides sint&#233;ticos fueron la prednisolona y la prednisona&#46; El deflazacort es el m&#225;s reciente de los corticoides sint&#233;ticos&#44; con diferencias moleculares que le confieren beneficios como&#44; por ejemplo&#44; en relaci&#243;n con la p&#233;rdida de sodio&#44; una potente actividad antiinflamatoria e inmunosupresora y poca interferencia en el metabolismo de la glucosa y el fosfoc&#225;lcico&#46;</p></span> <span id="abst2010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect2015">Objectivo</span><p id="spar2030" class="elsevierStyleSimplePara elsevierViewall">Decidimos llevar a cabo este estudio con el fin de describir el efecto del deflazacort&#44; comparado con otros corticoides en artritis reumatoide&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y m&#233;todos</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Llevamos a cabo una revisi&#243;n panor&#225;mica de la literatura &#40;del ingl&#233;s <span class="elsevierStyleItalic">scoping review</span>&#41;&#46; Se realiz&#243; una b&#250;squeda de la literatura en las bases de datos Pubmed&#44; Cochrane y BVS&#44; como tambi&#233;n en la literatura gris&#44; de ensayos cl&#237;nicos controlados o estudios de equivalencia desarrollados en pacientes adultos con artritis reumatoide y uso de deflazacort&#44; en comparaci&#243;n con otros corticoides&#46; Se excluyeron art&#237;culos que no mencionaran claramente la dosis de deflazacort y del comparador utilizadas&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La b&#250;squeda en las 3 bases de datos arrojo 166 estudios&#44; de los cuales se incluyeron 5 que cumpl&#237;an con los criterios de elegibilidad&#46; Cuatro estudios evaluaron deflazacort comparado con prednisolona&#44; en tanto que uno lo compar&#243; con metilprednisolona&#46; Los resultados fueron similares para los 5&#58; menor ca&#237;da en la densidad mineral &#243;sea y en el metabolismo de la glucosa&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">El deflazacort y la prednisolona tienen diferencias farmacol&#243;gicas que influyen en la generaci&#243;n de efectos adversos a nivel del metabolismo &#243;seo y de la glucosa&#59; sin embargo&#44; se requieren m&#225;s estudios para considerar el uso est&#225;ndar del deflazacort en nuestra pr&#225;ctica&#44; especialmente en enfermedades como la artritis reumatoide&#46;</p></span>"
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            "apendice" => "<p id="par0120" class="elsevierStylePara elsevierViewall">The following are Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia></p>"
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            "titulo" => "Supplementary data"
            "identificador" => "sec0050"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">RA&#58; rheumatoid arthritis&#59; DFZ&#58; deflazacort&#59; RCT&#58; randomized clinical trial&#59; MCTD&#58; mixed connective tissue disease&#59; SLE&#58; systemic lupus erythematosus&#59; mg&#58; milligrams&#59; NA&#58; not available&#59; PD&#58; prednisone&#59; PMR&#58; polymyalgia rheumatica&#59; PsA&#58; psoriatic arthritis&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Source&#58; own elaboration&#46;</p>"
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                  <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
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                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&#44; DFZ&#47;PD &#40;years&#41;&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pathology&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose of deflazacort&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comparator&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Follow-up time&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">Messina &#40;1992&#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">RCT&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">16 &#40;women&#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">36&#46;5&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">RA&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">12&#8239;mg&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">10&#8239;mg of prednisolone or its 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">12 months&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">Gray &#40;1991&#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">RCT&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">26 &#40;14 men&#44; 12 women&#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">56&#47;55&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">RA&#44; PMR&#44; MCTD&#44; eczema&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">12&#44; 24 and 36&#8239;mg&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">10&#44; 20 and 30&#8239;mg of prednisolone&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">90 days&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">Montecucco &#40;1988&#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">RCT&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">41 &#40;women&#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">62&#46;0&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">RA&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">6&#8211;30&#8239;mg&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">5&#8211;25&#8239;mg of prednisolone&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">6 months&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">Scudeletti &#40;1993&#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">RCT&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">30 &#40;NA&#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">&#60;60&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">RA&#44; 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">6&#8211;30&#8239;mg&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">5&#8211;25&#8239;mg&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">24 months&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">Saviola &#40;2007&#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">Equivalence&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">21 &#40;men&#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">60&#46;0&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">RA PsA&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">7&#46;5&#8239;mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#8239;mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                      "titulo" => "Adrenocorticotropic hormone&#44; adrenal steroids&#44; and the adrenal cortex"
                      "autores" => array:1 [
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                            0 => "B&#46;P&#46; Schimmer"
                            1 => "J&#46;W&#46; Funder"
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                        "titulo" => "Goodman &#38; Gilman&#8217;s&#58; the pharmacological basis of therapeutics"
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                      "titulo" => "A review of its pharmacological properties and therapeutic efficacy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "A&#46; Markham"
                            1 => "H&#46;M&#46; Bryson"
                            2 => "Deflazacort"
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                      "doi" => "10.2165/00003495-199550020-00008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drugs"
                        "fecha" => "1995"
                        "volumen" => "50"
                        "paginaInicial" => "317"
                        "paginaFinal" => "333"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8521761"
                            "web" => "Medline"
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                      "doi" => "10.1186/s40360-016-0111-8"
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                        "tituloSerie" => "BMC Pharmacol Toxicol"
                        "fecha" => "2017"
                        "volumen" => "18"
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