Dupilumab and the dawn of the biologic era for atopic dermatitis
Aug. 28, 2016
I have a list of patients with severe, recalcitrant atopic dermatitis (AD) eagerly awaiting the release of dupilumab. I first became aware of this biologic from the article by Beck et al, who noted that dupilumab, a fully humanized monoclonal antibody that blocks IL-4 and IL-13, previously reported to be efficacious in patients with asthma and eosinophilia, could also be beneficial for atopic dermatitis. They performed randomized, double-blind, placebo-controlled trials in adults with moderate-to-severe atopic dermatitis recalcitrant to topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator’s global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome. The authors concluded that patients treated with dupilumab had marked and rapid improvement in all evaluated measures of atopic dermatitis disease activity. This was based on the statistically significant findings that in the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (1).
In a study of 380 adults (older than 18 years) with moderate-to-severe AD, Simpson et al compared different dosing regimens (see methods section) of dupilumab and found that either 300 mg subcutaneously each week or every 2 weeks were most beneficial. At these doses, there was statistical improvement on all scales, including those for the patient oriented eczema measure (POEM), pruritus, sleep, anxiety, depression, and quality of life. Adverse reactions noted in > 5% of treated patients included nasopharyngitis, upper respiratory infections, headaches, and injection site reactions (2).
If you visit the Regeneron website, you will read the following: “Dupilumab/REGN668 (IL4-R Antibody) – An antibody against the interleukin-4 receptor, through which both interleukin-4 and interleukin-13 signal, that is being evaluated in atopic dermatitis, asthma, nasal polyps and eosinophilic esophagitis in collaboration with Sanofi.” It is in the pipeline, and with the ample advertising I see explaining the Th2 pathogenesis of AD, I will assume that release of the drug cannot be in the very distant future, pending FDA regulation.
I recall my eager anticipation fifteen years ago for the release of alefacept (Amevive) after reading how it improved psoriasis after 12 weeks of therapy, with some patients having a sustained clinical remission (3). While that drug was nearly valueless for my patients, there is no doubt that the initial foray into biologics paved the path for subsequent life-altering biologics. Perhaps dupilumab won’t be the game changing biologic that patients are pining for. At the least, it represents the dawn of the biologic era for AD. That alone offers hope for our long-suffering patients as next-generation drugs will surely follow.
1. Beck LA, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 2014; 371: 130-9.
2. Simpson EL, et al. Dupilumab therapy provides clinically meaningful improvement in patient outcome (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate-to-severe atopic dermatitis. J Am Acad Dermatol 2016; 75: 506-15.
3. Ellis CN, et al. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 354: 248-55.
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