Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis

作者：Philip J. Mease, Iain B. McInnes, Bruce Kirkham, Arthur Kavanaugh, Proton Rahman, Désirée van der Heijde, R. Landewé, Peter Nash, Luminita Pricop, Jiacheng Yuan, Hanno B. Richards, Shephard Mpofu · 发表于：New England Journal of Medicine · 年份：2015 · DOI：10.1056/nejmoa1412679 · 被引用次数：748 · 研究领域：Spondyloarthritis Studies and Treatments、Psoriasis: Treatment and Pathogenesis、Rheumatoid Arthritis Research and Therapies

BACKGROUND: In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in such patients. METHODS: In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains. RESULTS: ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout...