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AIN457, a fully human anti-interleukin-17A antibody, for the treatment of psoriasis, rheumatoid arthritis, and uveitis

Hueber, Wolfgang, Patel, Dhavalkumar, Dryja, Thaddeus, Wright, Andrew, Koroleva, Irina, Bruin, Gerardus, Antoni, Christian, Draelos, Zoe, Gold, Michael M, Durez, Patrick, Tak, Paul-Peter, Gomez-Reino, Juan, Foster, C Stephen, Kim, Rosa Y, Samson, Michael C, Falk, Naomi S, Chu, David S, Callanan, David, Nguyen, Quan Dong, Haider, Asifa and Di Padova, Franco E. (2010) AIN457, a fully human anti-interleukin-17A antibody, for the treatment of psoriasis, rheumatoid arthritis, and uveitis. Science Translational Medicine, 2 (52). 52ra72. ISSN 1946-6234


Background: To determine whether interleukin (IL)-17A mediates human inflammatory diseases, three proof-of-concept studies investigated the efficacy and safety of AIN457, a human anti-IL-17A antibody, in psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis.
Methods: Patients with moderate to severe 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 intravenous infusion of AIN457 at doses of 3 to 10 mg/kg. The efficacy endpoints were psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20), or the number of responders, respectively.
Results: AIN457 treatment reduced the PASI versus placebo at week 4 (58% vs 4%; p=0.0001) in psoriasis patients, and this difference was sustained at week 12. In patients with rheumatoid arthritis, ACR20 response rates were higher with AIN457 vs placebo at Week 6 (46% vs 27%, p=0.12) and were maintained at Week 16 (54% vs 31%; p=0.08). By Week 8, 11 of 16 AIN457-treated patients with uveitis were responders, defined by either vision improvement or reductions in ocular inflammation or corticosteroid dose. Overall, the rates of adverse events, including infections, were similar in the AIN457 and placebo groups.
Conclusion: Inhibition of IL-17A with AIN457 has encouraging safety and efficacy outcomes in three distinct immune-mediated diseases. These results support the potential role of IL-17A in the physiopathology of these disorders. numbers: NCT00669916 (psoriasis); NCT00669942 (rheumatoid arthritis); NCT00685399 (uveitis)

Item Type: Article
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Keywords: IL-17A, psoriasis, rheumatoid arthritis, uveitis, AIN457
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16


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