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 - 19/04/18
, Patrick M. Brunner, MD b, Avidan U. Neumann, PhD c, d, e, Saakshi Khattri, MD a, Ana B. Pavel, PhD a, Kunal Malik, BA a, Giselle K. Singer, BS a, Danielle Baum a, Patricia Gilleaudeau b, Mary Sullivan-Whalen b, Sharon Rose, MD a, Shelbi Jim On, MD a, Xuan Li, BA b, Judilyn Fuentes-Duculan, MD b, Yeriel Estrada, BS a, Sandra Garcet, PhD b, Claudia Traidl-Hoffmann, MD c, f, James G. Krueger, MD, PhD b, Mark G. Lebwohl, MD aAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : atopic dermatitis, fezakinumab, IL-22, placebo-controlled trial, moderate-to-severe AD
Abbreviation used : AD, BSA, BMI, EASI, IGA, ITT, MMRM, SCORAD
Plan
| Funding sources: Supported by National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Disease (grant no. 1UM1AR063917). Dr Brunner was supported in part by grant no. UL1 TR0001866 from the National Center for Advancing Translational Sciences, National Institutes of Health, Clinical and Translational Science Award program. Fezakinumab was provided by Pfizer Inc (New York, NY). |
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| Conflicts of interest: Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from Abbvie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB. Dr Guttman-Yassky is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, Abbvie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. Dr Brunner has received personal fees from LEO Pharma and Sanofi. Dr Traidl-Hoffmann has received research support from Danone Nutricia and personal fees from Novartis and La Roche Posay. Dr Krueger is an employee of the Rockefeller University and has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. Dr Lebwohl is an employee of Mount Sinai who receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/Astra Zeneca, Novartis, Pfizer, and ViDac. Dr Lebwohl is also a consultant for Allergan and Promius. The rest of the authors have no relevant conflicts of interest to disclose. |
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| Reprints not available from the authors. |
Vol 78 - N° 5
P. 872 - mai 2018 Retour au numéro
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