TY - JOUR
T1 - A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis
AU - Simpson, Eric L.
AU - Imafuku, Shinichi
AU - Poulin, Yves
AU - Ungar, Benjamin
AU - Zhou, Lisa
AU - Malik, Kunal
AU - Wen, Huei Chi
AU - Xu, Hui
AU - Estrada, Yeriel D.
AU - Peng, Xiangyu
AU - Chen, Mindy
AU - Shah, Nilam
AU - Suarez-Farinas, Mayte
AU - Pavel, Ana B.
AU - Nograles, Kristine
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2019/5
Y1 - 2019/5
N2 - A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis. Patients were randomly assigned to receive placebo, apremilast 30 mg twice daily (APR30), or apremilast 40 mg twice daily (APR40) for 12 weeks. During weeks 12–24, all patients received APR30 or APR40. A biopsy substudy evaluated atopic dermatitis-related biomarkers. Among 185 randomly assigned intent-to-treat patients at week 12, a dose-response relationship was observed; APR40 (n = 63), but not APR30 (n = 58), led to statistically significant improvements (vs. placebo, n = 64) in Eczema Area and Severity Index (mean [standard deviation] percent change from baseline = −31.6% [44.6] vs. −11.0% [71.2], P < 0.04; primary endpoint). mRNA expression of T helper type 17/T helper type 22-related markers (IL-17A, IL-22, and S100A7/A8; P < 0.05) showed the highest reductions with APR40, with minimal changes in other immune axes. Safety with APR30 was largely consistent with apremilast's known profile (common adverse events: nausea, diarrhea, headache, and nasopharyngitis). With APR40, adverse events were more frequent, and cellulitis occurred (n = 6). An independent safety monitoring committee discontinued the APR40 dosage. APR40 showed modest efficacy and decreased atopic dermatitis-related biomarkers in moderate to severe atopic dermatitis patients. Adverse events, including cellulitis, were more frequent with APR40, which was discontinued during the trial. Clinical Trial Registration Number: NCT02087943 (clinicaltrials.gov).
AB - A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis. Patients were randomly assigned to receive placebo, apremilast 30 mg twice daily (APR30), or apremilast 40 mg twice daily (APR40) for 12 weeks. During weeks 12–24, all patients received APR30 or APR40. A biopsy substudy evaluated atopic dermatitis-related biomarkers. Among 185 randomly assigned intent-to-treat patients at week 12, a dose-response relationship was observed; APR40 (n = 63), but not APR30 (n = 58), led to statistically significant improvements (vs. placebo, n = 64) in Eczema Area and Severity Index (mean [standard deviation] percent change from baseline = −31.6% [44.6] vs. −11.0% [71.2], P < 0.04; primary endpoint). mRNA expression of T helper type 17/T helper type 22-related markers (IL-17A, IL-22, and S100A7/A8; P < 0.05) showed the highest reductions with APR40, with minimal changes in other immune axes. Safety with APR30 was largely consistent with apremilast's known profile (common adverse events: nausea, diarrhea, headache, and nasopharyngitis). With APR40, adverse events were more frequent, and cellulitis occurred (n = 6). An independent safety monitoring committee discontinued the APR40 dosage. APR40 showed modest efficacy and decreased atopic dermatitis-related biomarkers in moderate to severe atopic dermatitis patients. Adverse events, including cellulitis, were more frequent with APR40, which was discontinued during the trial. Clinical Trial Registration Number: NCT02087943 (clinicaltrials.gov).
UR - http://www.scopus.com/inward/record.url?scp=85061620113&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061620113&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2018.10.043
DO - 10.1016/j.jid.2018.10.043
M3 - Article
C2 - 30528828
AN - SCOPUS:85061620113
SN - 0022-202X
VL - 139
SP - 1063
EP - 1072
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -