Atopic dermatitis and inflammatory skin diseaseBaseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab
Section snippets
Study patients and skin samples
Skin biopsy specimens were obtained from adults with moderate-to-severe chronic AD in a randomized, placebo-controlled, multicenter, phase 2a clinical trial (NCT01941537) of IL-22 blockade with the mAb fezakinumab (ILV-094).27 Patients were randomized 2:1 to either intravenous drug (nĀ =Ā 40) or placebo (nĀ =Ā 20), with a loading drug dose of 600Ā mg at baseline (day 0), followed by 300Ā mg at weeks 2, 4, 6, 8, and 10 (last dose).
Lesional and nonlesional biopsy specimens were obtained before
Study population
As recently reported, clinical scores (SCORAD, Investigator Global Assessment, and body surface area scores) significantly improved in patients with severe AD (baseline SCORAD scoreĀ ā„Ā 50) starting at 6 to 8Ā weeks of IL-22 antagonism (administered intravenously every other week between 0 and 10Ā weeks), with progressive improvements for another 10Ā weeks after the last dose until end of study (week 20) compared with placebo.27 Baseline patients' characteristics are shown in Table I.
Improvement of the AD transcriptome
We performed
Discussion
IL-22āproducing cells have been suggested to be pathogenically linked to AD, with increased IL-22 expression in both skin and blood compartments.11, 12 Increased IL-22 levels have also been shown in patients with other inflammatory diseases, including psoriasis, inflammatory bowel diseases, and rheumatoid arthritis.15 In patients with Crohn disease, greater baseline serum IL-22 levels were associated with greater likelihood of an antiāIL-23 therapeutic response.58
Our study is the first to
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Supported by National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grant no. 1UM1AR063917. P.M.B. was supported in part by grant no. UL1 TR0001866 from the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program. Fezakinumab was provided by Pfizer (New York, NY).
Disclosure of potential conflict of interest: P.M.B. is an employee of the Rockefeller University and has received personal fees from LEO Pharma, Sanofi Genzyme, and Pfizer. C.T.-H. is an employee of the Technical University Munich and the Helmholtz Zentrum MĆ¼nchen and has received research support from Danone Nutricia and personal fees from Novartis and La Roche Posay. M.G.L. is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/Astra Zeneca, Novartis, Pfizer, Valeant, and ViDac, and is also a consultant for Allergan, Aqua, LEO Pharma, and Promius. J.G.K. 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. E.G.-Y. 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 and 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. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.