Baeten, Dominique, Baraliakos, Xenofon, Braun, Juergen, Sieper, Joachim, Emery, Paul, Van der Heijde, Desiree, McInnes, Iain, Van Laar, Jacob, Landewé, Robert, Wordsworth, Paul, Wollenhaupt, Jürgen, Kellner, Herbert, Paramarta, Jacqueline, Wei, Jiawei, Brachat, Arndt Holger, Bek, Stephan, Laurent, Didier, Li, Yali, Bertolino, Arthur, Gsteiger, Sandro, Wright, Andrew and Hueber, Wolfgang (2013) Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: A randomised, double-blind, placebo-controlled trial. The Lancet, 382 (9906). pp. 1705-1713. ISSN 01406736

Abstract

Background Ankylosing spondylitis is a chronic immune-mediated infl ammatory disease characterised by spinal infl ammation, progressive spinal rigidity, and peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key infl ammatory cytokine in the development of ankylosing spondylitis, the prototypical form of spondyloarthritis. We assessed the effi cacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis. Methods We did a randomised double-blind proof-of-concept study at eight centres in Europe (four in Germany, two in the Netherlands, and two in the UK). Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either intravenous secukinumab (2 × 10 mg/kg) or placebo, given 3 weeks apart. Randomisation was done with a computergenerated block randomisation list without a stratifi cation process. The primary effi cacy endpoint was the percentage of patients with a 20% response according to the Assessment of SpondyloArthritis international Society criteria for improvement (ASAS20) at week 6 (Bayesian analysis). Safety was assessed up to week 28. This study is registered with ClinicalTrials.gov, number NCT00809159. Findings 37 patients with moderate-to-severe ankylosing spondylitis were screened, and 30 were randomly assigned to receive either intravenous secukinumab (n=24) or placebo (n=6). The fi nal effi cacy analysis included 23 patients receiving secukinumab and six patients receiving placebo, and the safety analysis included all 30 patients. At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99•8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group. Interpretation Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated. It is the fi rst targeted therapy that we know of that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial.

Item Type:	Article
Date Deposited:	25 Oct 2017 00:45
Last Modified:	25 Jan 2019 00:46
URI:	https://oak.novartis.com/id/eprint/9243