Efficacy, Tolerability, and Pharmacodynamics of Apremilast in Recalcitrant Plaque Psoriasis: A Phase II Open-Label Study
August 2013 | Volume 12 | Issue 8 | Original Article | 888 | Copyright © August 2013
Alice B. Gottlieb MD PhD,a Robert T. Matheson MD,b Alan Menter MD,c Craig L. Leonardi MD,d Robert M. Day PhD,e ChiaChi Hu EdM,e Peter H. Schafer PhD,e and James G. Krueger MD PhDf
aDepartment of Dermatology, Tufts Medical Center, Boston, MA
bOregon Medical Research Center, PC, Portland, OR
cDermatology Research Center, Baylor University Medical Center, Dallas, TX
dDepartment of Dermatology, Saint Louis University School of Medicine, St. Louis, MO
eCelgene Corporation, Summit, NJ
fLaboratory for Investigative Dermatology, Rockefeller University, New York, NY
METHODS: This multicenter, open-label study comprised four phases: pre-treatment (≤35 days), treatment (12 weeks), extension (12 weeks), and observational follow-up (4 weeks). Patients with recalcitrant plaque psoriasis received apremilast 20 mg BID for 12 weeks. Responders (≥75% improvement in Psoriasis Area and Severity Index [PASI-75]) continued treatment and non-responders (< PASI-75) were titrated to apremilast 30 mg BID through week 24. Efficacy assessments included change in static Physician's Global Assessment, PASI, and body surface area, and proportion of patients achieving PASI-50, PASI-75, and PASI-90. Other assessments included adverse events, lesional skin biopsies to assess changes in epidermal thickness, and immunohistochemistry to assess changes in peripheral blood subsets.
RESULTS: A total of 30 patients were enrolled. At week 12, 67% of patients had a ≥1-point improvement in static Physician’s Global Assessment, meeting treatment effect criterion. Mean percent decreases (improvements) from baseline were –59% for PASI score and –53% for body surface area. Most adverse events were mild. Median reduction in epidermal thickness was 34% at week 12 (P=0.083); five patients showed absence of keratin 16. Significant reductions in CD11c, CD3, and CD56 indicate that apremilast reduced myeloid dendritic cell, T-cell, and NK-cell or NK–T-cell infiltration into the epidermis and dermis. Reduced inflammatory leukocytes, with a pattern of broad, partial inhibition, suggested reduced IL-23/Th17 and Th22 response pathways.
CONCLUSIONS: These results confirm apremilast's biological and clinical activity and support ongoing studies in psoriasis. Clinicaltrials.gov Identifier: NCT00521339.
J Drugs Dermatol. 2013;12(8):888-897.