Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial

Background: Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective: Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods: We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. Results: At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 +/- 2.7 in the fezakinumab arm and 8.0 +/- 3.1 in the placebo arm (P=.134). In the severe AD patient subset (with a baseline SCORAD of >= 50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 +/- 3.8 vs 9.6 +/- 4.2, P=.029) and 20 weeks (27.4 +/- 3.9 vs 11.5 +/- 5.1, P=.010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% +/- 2.4 vs 6.2% +/- 2.7; P=.009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 +/- 0.2 vs 0.3 +/- 0.1; P=.034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. Limitations: The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. Conclusion: Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.