A randomized placebo-controlled single-center pilot study of the safety and efficacy of apremilast in subjects with moderate-to-severe alopecia areata
Alopecia areata (AA) is a common autoimmune disease that results in non-scarring hair loss. AA pathogenesis is thought to involve multiple inflammatory cytokines. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that reduces pro-inflammatory cytokine production. Recent studies demonstrate upregulation of PDE4 in human scalp lesions of AA patients and hair regrowth in a humanized AA mouse model upon apremilast treatment, suggesting a possible potential of apremilast in AA. To assess the efficacy and safety of apremilast in AA, we conducted a double-blind, placebo-controlled single-center pilot study in 30 moderate-to-severe AA patients (≥ 50% scalp involvement) that were randomized 2:1 to receive apremilast (n = 20) or placebo (n = 10) orally for 24 weeks. The primary endpoint was the percentage of patients achieving 50% reduction in severity of alopecia tool (SALT) score (SALT50) at 24 weeks compared to baseline, and the secondary endpoints included the percent change in SALT score at weeks 24 and 48. Eight patients in the apremilast arm withdrew prior to week 24 along with two patients in the placebo group, mostly due to lack of efficacy and adverse events. At 24 weeks, only 1 of 12 apremilast-treated subjects achieved SALT50, and similarly 1 of 8 placebo-treated subjects achieved SALT50. The difference between the mean percent improvement in SALT score at week 24 compared to baseline of the two study arms was not statistically significant (p = 0.38). The lack of treatment response in most of our patients argues against a pathogenic role for PDE4 specifically in moderate-to-severe AA, but targeting this pathway may still be of value in patients with mild AA as there is less of an inflammatory burden in this population. However, future larger studies may be needed to conclude apremilast’s lack of efficacy in moderate-to-severe AA.
KeywordsAlopecia areata Apremilast PDE4 inhibitor Placebo-controlled trial Moderate-to-severe AA
Severity of alopecia tool
This study was funded by Celgene (Grant number AP-CL-ALOP-PI-005776).
Compliance with ethical standards
Conflict of interest
Daniela Mikhaylov, Ana Pavel, Christopher Yao, Giselle Singer, Mark Taliercio, Rachel Karalekas, John Nia, Peter Hashim, Grace Kimmel, Danielle Baum, Yasaman Mansouri, and Anjali S. Vekaria have no conflicts of interest to disclose. Dr. Emma Guttman-Yassky is a board member of Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Celsus, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae and Leo Pharma; has received consultancy fees from Regeneron, Sanofi, MedImmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, Drais, AbbVie, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, LEO Pharma, Novartis, Pfizer, Vitae, Mitsubishi Tanabe and Eli Lilly; and has received research support from Janssen, Regeneron, Celgene, BMS, Novartis, Merck, LEO Pharma and Dermira. Dr. Mark Lebwohl is an employee of Mount Sinai, which receives research funds from Amgen, Anacor Pharmaceuticals Inc, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen Biotech, Kadmon Corporation, LEO Pharmaceuticals, MedImmune, Novartis Pharmaceuticals Corporation, Pfizer, Sun Pharmaceuticals Industries Ltd, and Valeant Pharmaceuticals. The authors did not receive any form of compensation, either directly or indirectly, from any company or agency related to the development, authorship, or publication of this article.
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