Letter to the Editor
Apremilast, beyond psoriasis as a therapeutic target
Apremilast, más allá de la psoriasis como diana terapéutica
Ricardo Ruiz-Villaverde
, Ahinoa Bueno-Rodriguez, Jesús Tercedor-Sánchez
Corresponding author
Unidad de Dermatología, Complejo Hospitalario de Granada, Granada, Spain
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It increases intracellular levels of cAMP, which in turn decrease the inflammatory response by modulating the expression of TNF-α, IL-23, IL-17 and other inflammatory cytokines.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 16-year-old girl with a family history of psoriasis (maternal great-grandmother), suffering from psoriasis from the age of 6 and under biological treatment with etanercept 50<span class="elsevierStyleHsp" style=""></span>mg/week since the age of 8, meeting criteria for moderate-severe psoriasis (DLQI 16, BSA 13, PASI 10) resistant to methotrexate, acitretin and cyclosporine. At the age of 12 years she developed alopecia areata universalis with 100% compromise of scalp, eyebrows and eyelashes hair. After unsuccessful topical treatments (5% minoxidil solution and high potency topical corticosteroids) it was decided to add methotrexate 7.5<span class="elsevierStyleHsp" style=""></span>mg weekly, without improvement in her alopecic process. Eight months later the patient developed aversion to subcutaneous injection, which forced the withdrawal of etanercept, so it was decided to increase the dose of methotrexate to 20<span class="elsevierStyleHsp" style=""></span>mg/week. Once etanercept was withdrawn and methotrexate was increased, the patient's body mass index (BMI) rose from 27.3 to 30.1, in addition to experiencing a worsening of her psoriasis (PASI from 0.5 to 10.8), with Renbök phenomenon on scalp, onset of psoriatic arthritis observed by the Rheumatology Service, development of mild atopic dermatitis (SCORAD 7) in antecubital fossa and absence of improvement in alopecia areata, without abnormalities in laboratory parameters. Therefore, it was proposed to start treatment with apremilast according to the guidelines indicated in the summary of product characteristics and after the approval by the biological committee of our center. Six months after starting treatment, the patient is in remission of her psoriasis (PASI 0.2, BSA 0.5 and DLQI 2), without exacerbations of her atopic dermatitis (SCORAD 0), asymptomatic from her psoriatic arthritis, with repopulation of the eyebrows and eyelashes and 40% of the hair of the scalp, in addition to a reduction of 4 points in her BMI, up to the value of 26.1.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the pivotal studies of psoriasis and psoriatic arthritis (ESTEEM 1 and 2<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> and PALACE 1 and 2, respectively), its efficacy may be evidenced from the second week, showing a significantly greater average percentage improvement with respect to the baseline value in the PASI score between apremilast 30<span class="elsevierStyleHsp" style=""></span>mg twice/day and placebo (22.3 vs 6.5%).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In relation to alopecia areata, it has proven effective in its treatment when it has been induced in murine models with preservation of hair follicles and a significant reduction of proinflammatory cytokines (INF-γ and TNF-α). This fact has led to the initiation of clinical trials to demonstrate the efficacy and safety of apremilast in alopecia areata (ClinicalTrials.com <a href="ctgov:NCT02684123">NCT02684123</a>).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The use of apremilast in atopic dermatitis and contact eczema has shown a reduction of the EASI score by 50% in at least 20% of the treated patients. This reduction appears to be directly proportional to the dose used and is simultaneously accompanied by a decrease in the dermatology life quality index (DLQI), with a significant improvement in pruritus associated with the disease.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> There is currently a clinical trial underway to determine the degree of efficacy and safety of apremilast in atopic dermatitis (ClinicalTrials.com <a href="ctgov:NCT02087943">NCT02087943</a>).</p><p id="par0030" class="elsevierStylePara elsevierViewall">In pivotal studies,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> the percentage of weight change has a low incidence, 1.4% (compared to 0.2% in the placebo group), with no gastrointestinal intolerance association (nausea and diarrhea). It is known that in murine models the absence of PDE4B expression is associated with a reduction of adipose tissue.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Whether the reduction of BMI in our patient is associated with the effect of apremilast remains to be determined, as well as whether it is maintained over time, since her mother has not reported changes in the patient's life habits.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, although the current progression time is short, only 6 months from treatment initiation, apremilast has achieved psoriasis control in our patient without psoriatic arthritis involvement or new atopic dermatitis exacerbations, and with a substantial improvement in her alopecia areata universalis and BMI.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ruiz-Villaverde R, Bueno-Rodriguez A, Tercedor-Sánchez J. Apremilast, más allá de la psoriasis como diana terapéutica. Med Clin (Barc). 2017;149:42–43.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Papp" 1 => "K. Reich" 2 => "C.L. Leonardi" 3 => "L. Kircik" 4 => "S. Chimenti" 5 => "R.G. 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