A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis

Eric Simpson, Shinichi Imafuku, Yves Poulin, Benjamin Ungar, Lisa Zhou, Kunal Malik, Huei Chi Wen, Hui Xu, Yeriel D. Estrada, Xiangyu Peng, Mindy Chen, Nilam Shah, Mayte Suarez-Farinas, Ana B. Pavel, Kristine Nograles, Emma Guttman-Yassky

Research output: Contribution to journalArticle

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Abstract

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).

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Atopic Dermatitis
Cellulitis
Placebos
Biomarkers
Safety
Nasopharyngitis
Pharmacodynamics
Interleukin-17
Biopsy
Eczema
Nausea
Headache
Diarrhea
Clinical Trials
Messenger RNA
apremilast
Monitoring

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis. / Simpson, Eric; Imafuku, Shinichi; Poulin, Yves; Ungar, Benjamin; Zhou, Lisa; Malik, Kunal; Wen, Huei Chi; Xu, Hui; Estrada, Yeriel D.; Peng, Xiangyu; Chen, Mindy; Shah, Nilam; Suarez-Farinas, Mayte; Pavel, Ana B.; Nograles, Kristine; Guttman-Yassky, Emma.

In: Journal of Investigative Dermatology, 01.01.2019.

Research output: Contribution to journalArticle

Simpson, E, Imafuku, S, Poulin, Y, Ungar, B, Zhou, L, Malik, K, Wen, HC, Xu, H, Estrada, YD, Peng, X, Chen, M, Shah, N, Suarez-Farinas, M, Pavel, AB, Nograles, K & Guttman-Yassky, E 2019, 'A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis', Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2018.10.043
Simpson, Eric ; Imafuku, Shinichi ; Poulin, Yves ; Ungar, Benjamin ; Zhou, Lisa ; Malik, Kunal ; Wen, Huei Chi ; Xu, Hui ; Estrada, Yeriel D. ; Peng, Xiangyu ; Chen, Mindy ; Shah, Nilam ; Suarez-Farinas, Mayte ; Pavel, Ana B. ; Nograles, Kristine ; Guttman-Yassky, Emma. / A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis. In: Journal of Investigative Dermatology. 2019.
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AU - Xu, Hui

AU - Estrada, Yeriel D.

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AU - Chen, Mindy

AU - Shah, Nilam

AU - Suarez-Farinas, Mayte

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