Journal Article

Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial

Wollenhaupt, Jürgen, Bertolino, Arthur P, Schulze-Koops, Hendrik, van der Heijde, Désirée, Kogan, Joseph, Tak, Paul P, Schumacher, Martin M, McInnes, Iain B, Ma, Shenglin, Hueber, Wolfgang, Dahmen, Georg, Braun, Jürgen, Isaacs, John D, Sieper, Joachim, Emery, Paul

2014

Overview

Objective To evaluate the efficacy and safety of secukinumab, a fully human, anti-interleukin (IL)-17A monoclonal antibody, in patients with psoriatic arthritis (PsA). Methods 42 patients with active PsA fulfilling ClASsification for Psoriatic ARthritis (CASPAR) criteria were randomly assigned (2:1) to receive two intravenous secukinumab doses (10 mg/kg; n=28) or placebo (n=14) 3 weeks apart. The primary endpoint was the proportion of American College of Rheumatology (ACR) 20 responses at week 6 for secukinumab versus placebo (one-sided p<0.1). Results Primary endpoint: ACR20 responses at week 6 were 39% (9/23) for secukinumab versus 23% (3/13) for placebo (p=0.27). ACR20 responses were greater with secukinumab versus placebo at week 12 (39% (9/23) vs 15% (2/13), p=0.13) and week 24 (43% (10/23) vs 18% (2/11), p= 0.14). At week 6, ‘good’ European League Against Rheumatism response was seen in 21.7% (5/23) secukinumab versus 9.1% (1/11) placebo patients. Compared with placebo at week 6, significant reductions were observed among secukinumab recipients for C reactive protein (p=0.039), erythrocyte sedimentation rate (p=0.038), Health Assessment Questionnaire Disability Index (p=0.002) and Short Form Health Survey (SF-36; p=0.030) scores. The overall adverse event (AE) frequency was comparable between secukinumab (26 (93%)) and placebo (11 (79%)) recipients. Six serious AEs (SAEs) were reported in four secukinumab patients and one SAE in one placebo patient. Conclusions Although the primary endpoint was not met, clinical responses, acute-phase reactant and quality of life improvements were greater with secukinumab versus placebo, suggesting some clinical benefit. Secukinumab exhibited satisfactory safety. Larger clinical trials of secukinumab in PsA are warranted.

• Publisher: Elsevier Limited
• Subject: Adult / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Antirheumatic Agents - administration & dosage / Antirheumatic Agents - adverse effects / Antirheumatic Agents - therapeutic use / Arthritis, Psoriatic - blood / Arthritis, Psoriatic - drug therapy / Biomarkers - blood / Blood Sedimentation / C-Reactive Protein - metabolism / Classification / Cytokines / Disease / Double-Blind Method / Drug Administration Schedule / Female / Hepatitis / HIV / Human immunodeficiency virus / Humans / Interleukin-17 - antagonists & inhibitors / Male / Middle Aged / Patients / Pharmaceutical industry / Psoriasis / Response rates / Rheumatoid arthritis / Severity of Illness Index / TNF inhibitors / Treatment Outcome / Tumor necrosis factor-TNF