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

Abstract

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.

Keywords: IL-22; atopic dermatitis; fezakinumab; moderate-to-severe AD; placebo-controlled trial.

Figure 1.. Patient disposition.

SAE – Serious adverse event; ITT – intention to treat.

Figure 2.. Time course of efficacy variables in the entire study population.

Clinical responses for SCORAD (A), BSA (B), and IGA (C) are shown for the fezakinumab (red) and placebo (blue) arms. All panels depict the mean ±SEM change from baseline. Data was analyzed by MMRM: red and blue asterisks by each curve indicate significant change from baseline for each arm (*p<0·05, **p<0·01, ***p<0·001); black asterisks at the bottom indicate significant differences between drug and placebo arm; green asterisks indicate the significance of the combined factor: baseline severity and treatment arm.

Figure 3.. Time course of efficacy variables stratified for moderate and severe patients.

Patients were stratified as having moderate (SCORAD between 25 and 50) or severe (SCORAD ≥50) AD at baseline (week 0). Panels depict the mean ±SEM change from baseline for SCORAD (A, B), BSA (C, D), and IGA (E, F). Data was analyzed by MMRM: red and blue asterisks by each curve indicate significant change from baseline for each arm (*p<0·05, **p<0·01, ***p<0·001); black asterisks at the bottom indicate significant differences between drug and placebo arm.