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Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis.

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Hueber, Wolfgang [] Patel, Dhavalkumar D [] Dryja, Thaddeus [] Wright, Andrew M [] Koroleva, Irina [] Durez, Patrick [UCL] Di Padova, Franco []

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

Document type Article de périodique (Journal article) – Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2010
Language Anglais
Journal information "Science Translational Medicine" - Vol. 2, no. 52, p. 52ra72 (2010)
Peer reviewed yes
Publisher American Association for the Advancement of Science
issn 1946-6234
e-issn 1946-6242
Affiliations UCL - (SLuc) Service de rhumatologie
UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales
MESH Subject Adolescent ; Adult ; Middle Aged ; Placebos - therapeutic use ; Psoriasis - drug therapy, immunology, pathology ; Treatment Outcome ; Uveitis - drug therapy, immunology, pathology ; Young Adult ; Aged ; Animals ; Antibodies - immunology, therapeutic use ; Antibodies, Monoclonal - immunology, therapeutic use ; Arthritis, Rheumatoid - drug therapy, immunology, pathology ; Double-Blind Method ; Humans ; Interleukin-17 - immunology
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Bibliographic reference Hueber, Wolfgang ; Patel, Dhavalkumar D ; Dryja, Thaddeus ; Wright, Andrew M ; Koroleva, Irina ; et. al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis.. In: Science Translational Medicine, Vol. 2, no. 52, p. 52ra72 (2010)
Permanent URL http://hdl.handle.net/2078.1/105548