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An IL-4 and IL-13 Biologic Inhibitor for Atopic Dermatitis

Summary and Comment |
July 9, 2014

An IL-4 and IL-13 Biologic Inhibitor for Atopic Dermatitis

  1. Craig A. Elmets, MD

Dupilumab may prevent atopic flares as well as treating the disease.

  1. Craig A. Elmets, MD

The type 2 helper T-cell (Th2) cytokines interleukin (IL)-4 and IL-13 have been implicated in the pathogenesis of atopic dermatitis (AD). Dupilumab is a fully human monoclonal antibody that binds to a subunit of the IL-4 receptor and inhibits both IL-4 and IL-13 signaling to cells that express the receptor. Investigators conducted four multicenter, randomized, double-blind, placebo-controlled clinical trials to evaluate dupilumab treatment of moderate-to-severe AD.

Two 4-week trials examined three doses of weekly subcutaneous dupilumab (75 mg, 150 mg, and 300 mg). Treatment produced significant dose-dependent reductions in clinical severity. A continuation trial of the 300-mg dose to 12 weeks produced at least 50% improvement on the Eczema Area and Severity Index (EASI-50) in 85% of dupilumab recipients versus 35% of placebo recipients — a significant improvement. Pruritus also improved significantly with treatment (mean decrease, 56% vs. 15% with placebo). Finally, dupilumab combined with topical steroids produced significantly better EASI-50 scores than topical steroids plus placebo; other parameters of clinical activity also improved with dupilumab/steroids, despite a decrease in topical corticosteroid use by the dupilumab recipients.

In all clinical trials, dupilumab treatment was associated with reductions in serum IgE and TARC (thymus and activation-regulated chemokine) levels. Transcriptome analyses of lesional skin showed a trending return to the profile of nonlesional skin in dupilumab recipients and exacerbation in placebo recipients. Nasopharyngitis and headache were the most frequent adverse events occurring equally in treatment and placebo groups. Skin infections and atopic dermatitis flares, the most common serious adverse events, were more common in placebo recipients.

Comment

The introduction of biologics that target cytokines and other immunological elements has substantially improved treatment options and quality of life for psoriasis patients. It is exciting to see that a new biologic is on the horizon for AD, another immunological skin disease with suboptimal treatment options. Particularly promising is the safety profile, which showed that dupilumab may prevent atopic flares as well as treat the disease.

  • Disclosures for Craig A. Elmets, MD at time of publication Consultant / Advisory board Astellas Pharmaceuticals Grant / Research support NIH; NIH/NCI; Veteran’s Administration; Ferndale Laboratories; Abbvie Editorial boards Cancer Prevention Research; Photodermatology, Photoimmunology, & Photomedicine; UpToDate; eMedicine; Journal of Dermatological Sciences Leadership positions in professional societies American Academy of Dermatology (Chair, Clinical Guidelines and Research Committee); Photomedicine Society (Board of Directors)

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Reader Comments (2)

Mozelle Lee Other

Treated for Atopic Dermatitis since 4 months old. on-going Cortisone injections caused osteoporosis.
would like to know if clinical trials are available.

PhD Other, Allergy/Immunology, RETAIRED

VERY INTERESTUING ARTICLE.

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