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.

• Authors: Emma Guttman-Yassky, Patrick M Brunner, Avidan U Neumann, Saakshi Khattri, Ana B Pavel, Kunal Malik, Giselle K Singer, Danielle Baum, Patricia Gilleaudeau, Mary Sullivan-Whalen, Sharon Rose, Shelbi Jim On, Xuan Li, Judilyn Fuentes-Duculan, Yeriel Estrada, Sandra Garcet, Claudia Traidl-Hoffmann, James G Krueger, Mark G Lebwohl
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 78 Issue 5 Pg. 872-881.e6 (05 2018) ISSN: 1097-6787 [Electronic] United States
• PMID: 29353025 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukins
• fezakinumab
• interleukin-22

Topics

• Adult
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Dermatitis, Atopic (diagnosis, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infusions, Intravenous
• Interleukins (immunology)
• Male
• Middle Aged
• Severity of Illness Index
• Treatment Outcome