Atopic dermatitis and skin diseaseIL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis
Section snippets
Study design and subjects
A total of 46 subjects with chronic moderate-to-severe plaque psoriasis participated in a phase I, randomized, subject- and investigator-blinded, placebo-controlled, dose-escalation study of ixekizumab, an anti–IL-17 mAb. Subjects were randomized to groups receiving subcutaneous injections of 5 mg (n = 8), 15 mg (n = 8), 50 mg (n = 8), or 150 mg (n = 8) of ixekizumab or placebo (n = 8) or to groups receiving intravenous infusions of 15 mg (n = 5) of ixekizumab or placebo (n = 1; intravenous
Results
Ixekizumab was administered to 32 subjects with plaque psoriasis by means of subcutaneous injection across a range of doses from 5 to 150 mg at weeks 0, 2, and 4. Eight subjects received placebo injections at the same time points. Baseline characteristics for these patients are presented in Table E1. Skin biopsies for IL-17 pathway and other disease-related biomarkers and histopathology were performed before treatment (baseline) and again at weeks 2 and 6 after starting the study drug.
Discussion
Although autoimmune inflammation was long considered to be driven by TH1 T-cell activation and associated cytokines (ie, IFN-γ), the discovery of TH17 T cells and the causality of TH17 T cells in inducing experimental autoimmune encephalitis greatly altered this concept.44, 45, 46
In turn, this then raised the question of whether TH17 T cells have an important pathogenic contribution in human immune-mediated inflammatory diseases. Psoriasis vulgaris is a strong candidate disease for pathogenic
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Supported by Eli Lilly and Company.
Disclosure of potential conflict of interest: J. G. Krueger is a consultant for Centocor/Janssen, Pfizer, Boehringer-Ingelheim, and Merck and has received research support from Amgen, Novartis, Eli Lilly, and Merck. P. A. Haslett is a former employee of Eli Lilly and Company. K. M. Phipps, J. McColm, and R. W. Hoffman hold stock in Eli Lilly and Company. G. S. Cameron is employed by Eli Lilly and Company. S. Banerjee is an employee of and holds stock in Eli Lilly and Company. The rest of the authors declare that they have no relevant conflicts of interest.