Continuous long-term treatment with dupilumab is associated with sustained improvements in skin inflammation, pruritus, and quality of life, as well as manageable toxicity in patients with moderate to severe atopic dermatitis (AD), a study in the Journal of the American Academy of Dermatology reports.
The study was an efficacy and safety analysis of the ongoing OLE (ClinicalTrials.gov identifier: NCT01949311) multicenter randomized trial. In the trial analysis, 1587 adult patients with moderate to severe AD were enrolled at 319 sites and received subcutaneous 300 mg dupilumab per week, including a loading dose of 600 mg dupilumab on day 1. Early-stage enrollees received 200 mg weekly dupilumab with a 400 mg initial loading dose. Treatment was administered for up to 3 years. In this analysis, researchers only assessed safety (ie, adverse events [AEs]) and efficacy outcomes in patients who received 300 mg weekly doses of dupilumab for up to 76 weeks.
In the overall cohort, a total of 4384 AEs were reported. Exposure-adjusted AE and serious AE (SAE) rates were 420.4 events/100 person-years and 8.5 events/100 person-years, respectively. The majority of patients (70.7%) experienced ≥1 AE, whereas only 5.0% experienced ≥1 SAE. Only 0.5% (n=7) of patients had 8 SAEs deemed related to the study drug. Up to 10.7% of patients had conjunctivitis (20.8 events/100 person-years), most of which was mild to moderate in severity. Rates of new injection site reactions and conjunctivitis events dropped from weeks 0 to 12 (8.5% and 5.8%, respectively) and weeks 48 to 60 (0.7% and 1.8%, respectively).
Severity of AD skin lesions and AD-related symptoms mostly improved during the OLE trial. A continual improvement in the mean Eczema Area and Severity Index was observed from weeks 2 to 24, and the score at 76 weeks was 3.11. The researchers also observed improvements in Peak Pruritus numerical rating scale, Dermatology Life Quality Index, and Patient-Oriented Eczema Measure at 76 weeks.
Approximately 2.8% of patients had treatment-emergent antidrug antibodies in the trial. The proportions of treatment-emergent anti-drug antibodies were 5.2%, 2.2%, and 1.0% in the re-treatment subgroup, interrupted treatment group, and dupilumab-naive subgroups, respectively.
Limitations of the study include the low proportion of patients who reached 76 weeks of treatment by time of data cutoff, results that may not fully characterize the consequences of multiple retreatments, and a 300 mg per week regimen that is higher than the 300 mg every 2 weeks approved in most countries.
The findings from this trial suggest a long-term role of dupilumab “for patients with moderate-to-severe AD and demonstrates that blocking IL-4 and IL-13 signaling can achieve sustained control of AD signs and symptoms with an acceptable safety profile in patients with significant disease burden and for whom conventional topical treatments are inadequate.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures. This clinical trial was supported by Sanofi and Regeneron Pharmaceuticals, Inc. Please see the original reference for a full list of authors’ disclosures.
Deleuran M, Thaçi D, Beck LA, et al. Dupilumab shows long-term safety and efficacy in moderate-to-severe atopic dermatitis patients enrolled in a phase 3 open-label extension study [published online July 30, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.07.074