Journal Article

Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W)

Zhao, Fangyi, Maksymowych, Walter P, Wei, James Cheng-Chung, Walsh, Jessica A, Van den Bosch, Filip, van der Heijde, Désirée, Baraliakos, Xenofon, Li, Xiaoqi, Dougados, Maxime, Bertram, Clinton C, Gallo, Gaia, Carlier, Hilde, Landewé, Robert, Sieper, Joachim, Deodhar, Atul, Ermann, Joerg, Gensler, Lianne S, Tomita, Tetsuya

2020

Overview

ObjectivesTo investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W).MethodsAdults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52.ResultsIn COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks.ConclusionThe significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab.Trial registration number NCT02696785/NCT02696798.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Adalimumab - administration & dosage / ankylosing spondylitis / Antibodies, Monoclonal, Humanized - administration & dosage / Antirheumatic Agents - administration & dosage / Arthritis / Clinical trials / DMARDs (biologic) / Double-Blind Method / Drug dosages / Drug Substitution / Female / Humans / Inflammatory bowel disease / Inflammatory diseases / Male / Monoclonal antibodies / Patients / Psoriasis / Radiography / Rheumatic diseases / Safety / Severity of Illness Index / Spondylarthritis - diagnostic imaging / Spondylarthritis - drug therapy / Spondyloarthritis / Studies / Time Factors / Treatment Outcome / Tumor necrosis factor / Tumor Necrosis Factor Inhibitors - administration & dosage / Tumor necrosis factor-TNF / Tumors