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.