A Phase 2, Open-Label, Investigator-Initiated Study to Evaluate the Safety and Efficacy of Apremilast in Subjects With Recalcitrant Allergic Contact or Atopic Dermatitis

March 2012 | Volume 11 | Issue 3 | Original Article | 341 | Copyright © March 2012


Eva M. Volf MD,a Shiu-Chung Au MD,b Nicole Dumont,b Pamela Scheinman MD,b Alice B. Gottlieb MD PhDa,b

aTufts University School of Medicine, Boston, MA bTufts Medical Center, Boston, MA

Abstract
Objective: Evaluate the efficacy and safety of apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, in subjects with recalcitrant moderate to severe atopic dermatitis (AD) or allergic contact dermatitis (ACD).
Research design and methods: This was a proof-of-concept, phase 2, open-label, single institution trial that evaluated the efficacy and safety of apremilast, 20 mg twice daily, for twelve weeks, in ten subjects with either AD and/or ACD. The primary endpoint was a ≥2 point improvement in Investigator Global Assessment (IGA) score after 12 weeks of treatment. Secondary endpoints included a 75% reduction in the Eczema Assessment Severity Index (EASI-75), EASI-50, and the maximum EASI response.
Results: The primary endpoint of improvement in IGA by two or more points was met by 20% of subjects. Ten percent of subjects achieved EASI-75 and another 10% reached EASI-50. All subjects tolerated apremilast well with no serious adverse events or withdrawal due to side effects. Common adverse events associated with apremilast included headache, nausea, and soft stool.
Limitations: This study was limited by its small sample size and lack of a comparison group to serve as a control.
Conclusions: Apremilast was well tolerated in all subjects. Apremilast was minimally effective in AD and ACD and results were inferior to previous trials of apremilast in psoriasis.

J Drugs Dermatol. 2012;11(3):341-346.

INTRODUCTION

Atopic dermatitis (AD) affects 1-3% of the adult population and is associated with asthma and allergic rhinitis. 1 While onset and resolution typically occur in childhood, the condition may persist into adulthood or even be newly diagnosed in adults. Both hereditary and environmental factors contribute to the development of AD but a precise understanding of the complex interplay between genes and the environment is unknown.
Allergic contact dermatitis (ACD) is an acquired inflammatory condition in response to an environmental allergen that usually presents in adulthood.2 ACD has a high prevalence in North America and Western Europe, where over 20% of people in the general population have a contact allergy to at least one allergen.1 In patch testing results, the most common allergens include nickel, neomycin sulfate, and fragrance.3
Patients with moderate to severe AD and ACD often require systemic treatments such as cyclosporine, systemic steroids, methotrexate, azathioprine, and mycophenolate mofetil. These treatments have multiple adverse side effects.
Apremilast is an oral agent that modulates multiple anti-inflammatory pathways through PDE4 inhibition. PDE4 inhibitors increase intracellular cyclic adenosine monophosphate (cAMP), which activates protein kinase A and other downstream effectors resulting in the inhibition of pro-inflammatory cytokines. In human cellular models, apremilast has been shown to decrease tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-2, IL-8, IL-12, IL-23, and leukotriene B4 (LTB4).4 In a phase 2 clinical trial, apremilast, 20 mg once daily, demonstrated efficacy in subjects with severe psoriasis where epidermal thickness was reduced by a mean of 20.5% and fourteen out of nineteen subjects demonstrated improvement in PASI scores after 29 days of treatment.5 In this study, apremilast treatment was associated with a significant decrease in inducible nitric oxide synthase (iNOS) mRNA expression within the psoriatic lesions.5 In a recent press release, it was reported that 41% of subjects achieved PASI-75 with 30 mg BID apremilast compared to 6% on placebo (P<0.001) after 16 weeks of treatment.6
A topical PDE4 inhibitor has previously been studied for the treatment of atopic dermatitis, with positive results. CP-80633
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