Michele G. Sullivan, Skin & Allergy News
DENVER – The investigational drug REGN668, a monoclonal antibody that modulates interleukins 4 and 13, significantly improved overall quality of life and pruritus in patients with severe, longstanding atopic dermatitis.
Improvements for patients in the REGN668 (dupilumab) group were obvious in the first week of treatment and achieved statistical significance by week 2 of the placebo-controlled trial, Dr. Thomas Luger said at the annual meeting of the American Academy of Dermatology.
The drug probably works in two ways, said Dr. Luger of the University of Munster, Germany.
“It can be explained by its down-regulation of the immune mediators IL 4 and IL 13, but another issue is also important. IL4 has been shown to impair barrier function by down-modulating filaggrin expression,” he noted.
The 12-week, multi center trial randomized 109 patients to weekly injections of 300 mg dupilumab or placebo. The primary endpoint was the percent change in the Eczema Area and Severity Index (EASI) scale. Secondary endpoints were change from baseline in measures of pruritus and the proportion of patients who reached the EASI 50-75 level.
On the primary endpoint of change in EASI, dupilumab was associated with significantly greater improvement than placebo. By the end of week 1, the EASI had already dropped 10%, Dr. Luger said. By week 2, it had decreased 40% from baseline compared with placebo, and the improvement continued each week, then plateaued at about 7 weeks, with a mean decrease of 74%.
Changes in pruritus and overall quality of life were secondary endpoints for 65 patients who completed the quality of life portion. The validated survey was only available in French and German, and some of the study participants did not speak those languages.
The secondary exploratory endpoint was the change in baseline on the Quality of Life Index for Atopic Dermatitis, a 25-question survey, and its association with clinical outcomes. A higher score indicates worse quality of life; a two- to three-point change is considered clinically significant.
All of the patients were white; mean age was about 40 years and the mean disease duration was 28 years. The mean baseline EASI score was 27, indicating moderate severity. Scores on measures of pruritus indicated severe itching. The mean QoLIAD score was 12, with 25 being the worst.
The quality of life score followed the same pattern as the primary endpoint, Dr. Luger said. The average quality of life score had improved by approximately 25% after 1 week and by approximately 45% after 2 weeks. The score continued to drop, plateauing at an 80% decrease by week 7 and maintaining that level through the end of the treatment period. Almost all treated patients (91%) achieved at least at 50% reduction in symptoms, with 69% achieving at least a 75% reduction.
Pruritus was measured in two QoLIAD subscales: the numeric rating scale (NRS) and the 5–D itch scale. Itching began to improve early and continued to do so until it reached a maximum reduction of 65% in week 8 on the NRS. By week 12, the mean reduction in itching was 60%.
The 5-D scale followed a similar pattern, with early improvement that reached a maximum 50% reduction by week 8. By week 12, the mean reduction from baseline was 45%.
The overall QoLIAD score reflected these changes, improving by a mean of 6.5 points by week 12. In the placebo group, this score remained virtually unchanged. QoLIAD improvements strongly correlated with clinical improvements, Dr. Luger added.
Dupilumab was well tolerated overall. The most frequent adverse events were nasopharyngitis, headache, and conjunctivitis. Skin infections occurred in significantly fewer patients taking the drug, compared with placebo (5.5% vs. 24%). There were no infection-related serious adverse events or eczema herpeticum occurrences in the dupilumab group.
Sanofi and Regeneron, which are jointly developing dupilumab, sponsored the study. Dr. Luger is a consultant for numerous pharmaceutical companies but not for Sanofi or Regeneron.