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  • Secukinumab, a human anti-i...
    McInnes, Iain B, Prof; Mease, Philip J, Prof; Kirkham, Bruce, MD; Kavanaugh, Arthur, Prof; Ritchlin, Christopher T, Prof; Rahman, Proton, Prof; van der Heijde, Désirée, Prof; Landewé, Robert, Prof; Conaghan, Philip G, Prof; Gottlieb, Alice B, Prof; Richards, Hanno, MD; Pricop, Luminita, MD; Ligozio, Gregory, MSc; Patekar, Manmath, MD; Mpofu, Shephard, MD

    Lancet, 09/2015, Letnik: 386, Številka: 9999
    Journal Article

    Summary Background Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. Methods In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01752634. Findings Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 54% patients; odds ratio versus placebo 6·81, 95% CI 3·42–13·56; p<0·0001), 150 mg (51 51% patients; 6·52, 3·25–13·08; p<0·0001), and 75 mg (29 29% patients; 2·32, 1·14–4·73; p=0·0399) versus placebo (15 15% patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four 4%, eight 8%, ten 10%, and seven 7% with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six 6%, four 4%, six 6%, and eight 8%, respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Interpretation Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder. Funding Novartis.