Mechanisms Underlying the Clinical Effects of Apremilast for Psoriasis

August 2018 | Volume 17 | Issue 8 | Original Article | 835 | Copyright © August 2018

Carlo Pincelli MD,a Peter H. Schafer PhD,b Lars E. French MD,c Matthias Augustin MD,d James G. Krueger MD PhDe

aLaboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy bDepartment of Translational Development, Celgene Corporation, Summit, NJ cDepartment of Dermatology, Zurich University Hospital, Zurich, Switzerland dInstitute and German Center for Health Services Research in Dermatology, University Medical Center of Hamburg, Hamburg, Germany eLaboratory of Investigative Dermatology, The Rockefeller University, New York, NY

Figure3clinical efficacy that was maintained with continued treatment for up to 52 weeks,27-29 and some patients enrolled in the ESTEEM trials will continue to receive apremilast therapy for up to 5 years. In the more recent Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL) study, the efficacy of apremilast was demonstrated in systemic-naive, post-topical patients with moderate plaque psoriasis (ie, 5% to 10% body surface area involvement and static Physician’s Global Assessment score of 3 [moderate] on a 6-point scale) and was consistent with results from the ESTEEM trials in patients with moderate to severe plaque psoriasis.31


Psoriasis involves chronic, systemic dysregulation of pro-inflammatory and anti-inflammatory cytokines that leads to the symptoms of psoriasis and underlying systemic inflammation. Apremilast is an oral PDE4 inhibitor that has demonstrated safety and efficacy in the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. Apremilast exhibits pleiotropic, synergistic attenuating effects on a key group of cytokines involved in the pathology of psoriasis, most notably IL-17A/F, IL-22, and TNF-α, and these effects correlate with reduced skin manifestations.24 Newly available pharmacodynamic data from clinical study patients further clarify the link between clinical efficacy and the beneficial effects of apremilast on these known inflammatory mediators.


Dr. Pincelli reports grants from Expascience, Lilly, and Mylan; nonfinancial support from Celgene Corporation; and personal fees from Sienna. Dr. Schafer is an employee of and has stocks/stock options in Celgene Corporation. Dr. French has received a grant from Celgene Corporation and has served as a consultant for Celgene Corporation. Dr. Augustin has served as a consultant to or paid speaker for clinical trials sponsored by companies that manufacture drugs for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Eli Lilly, GSK, Janssen-Cilag, LEO Pharma, Medac, Merck, MSD, Novartis, Pfizer, UCB, and XenoPort. Dr. Krueger reports grants paid to institution and/or personal fees from AbbVie, Acros, Allergan, Amgen, Asana, Aurigne, Biogen-Idec, BiogenMA, BMS, Boehringer Ingelheim, Escalier, Innovaderm, Janssen, Kineta, LEO Pharma, Lilly, Novan, Novartis, Paraxel, Pfizer, Regeneron, Roche, Vitae, Sienna, UCB, and Valeant.


This work was sponsored by Celgene Corporation. The authors received editorial support in the preparation of this review from Amy Shaberman, PhD, of Peloton Advantage, LLC, funded by Celgene Corporation. The authors, however, directed and are fully responsible for all content and editorial decisions for this review.


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Peter H. Schafer PhD