SAN FRANCISCO– Dupilumab met its safety endpoints and significantly outperformed placebo for adults with moderate to severe atopic dermatitis, according to final results of a multicenter, international phase IIb study.
At all five doses tested, the biologic significantly improved atopic dermatitis (AD) compared with placebo based on multiple clinical measures, Dr. Lisa A. Beck said at the annual meeting of the American Academy of Dermatology. The highest dose of 300 mg given either weekly or every two weeks provided the most consistent benefits, added Dr. Beck of the University of Rochester Medical Center, Rochester, New York.
Atopic dermatitis (eczema) is caused by immune dysregulation and altered skin barrier function, though the relative contribution of each process is still under debate, Dr. Beck said. Dupilumab is a monoclonal antibody designed to block intracellular signaling by the interleukin 4 and IL-13 cytokines, which are thought to mediate many features of AD.
The study included 380 patients in Europe, the United States, Canada, and Japan who had moderate to severe AD that was inadequately controlled by topical corticosteroids or calcineurin inhibitors. At baseline, patients had been living with AD for more than three years and at least 10% of their body surface area was affected. Patients were randomized to weekly, biweekly, or monthly subcutaneous injections of dupilumab at doses of 300 mg, 200 mg, or 100 mg, or to placebo. The groups were demographically similar.
After 16 weeks of treatment, a linear regression model of Eczema Area and Severity Index (EASI) scores strongly favored dupilumab over placebo and indicated a dose-response trend, Dr. Beck reported. Based on the model, EASI scores dropped by about 45% for the low-dose group, by 63% to 65% for the intermediate-dose groups, by 68% for the high-dose group treated every two weeks, and by almost 74% for patients treated with 300 mg weekly. In contrast, the placebo group improved by about 18% (all P-values < .0001).
About 80% of patients who received the most intensive regimen (300 mg dupilumab weekly) achieved EASI-50, while about 60% achieved EASI-75 and close to 40% achieved EASI-90 (all P-values < .0001 compared with placebo). Responses for the lower-dose cohorts again indicated a dose-response trend. “Even the lowest dose showed an improvement, but it tended to lose that effect through the treatment phase,” Dr. Beck said.
Dupilumab also beat placebo on the Scoring Atopic Dermatitis (SCORAD) assessment, with estimated improvements in AD ranging from 26% for the low-dose group to the 57% for the high-dose group treated weekly, compared with about 14% for placebo (P < .05). Analyses of body surface area (BSA) ranged from about a 26% improvement for the low-dose group to more than 65% for the highest-dose, compared with about 8% for placebo (P < .05).
“We saw really significant drops in BSA with the highest dose group, and the BSA response was very much in line with the response in terms of signs of the disease,” Dr. Beck said. During every week of treatment, patients on dupilumab also reported significant improvements in pruritus compared with placebo based on a numerical rating scale.
Researchers assessed dupilumab’s safety through week 32, and found no dose-limiting adverse events. The dupilumab groups had slightly greater rates of headache, injection site reactions, and conjunctivitis. “We did see a trend of slightly greater herpes infections in the dupilumab-treated patients,” Dr. Beck said. “But if you look at other viral infections, there was no difference, and also herpes infections were highest in the lowest dose group. More studies need to be done to ferret out whether that’s real.”
Regeneron Pharmaceuticals is the maker of dupilumab. Dr. Beck reported having been the principal investigator at her site for the Regeneron trials of dupilumab in AD, and having consulted with the company on study design. She reported having no other relevant disclosures.