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)

Abstract

Objectives: To 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).

Methods: Adults 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.

Results: In 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.

Conclusion: The 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.

Keywords: DMARDs (biologic); ankylosing spondylitis; spondyloarthritis.

Figure 1

Patient disposition: (A) COAST-V; (B) COAST-W. ADA, adalimumab; bDMARD, biological disease-modifying antirheumatic drug; extended treatment period, dose double-blind extended treatment period; IXE Q4W, ixekizumab 80 mg every 4 weeks; IXE Q2W, ixekizumab 80 mg every 2 weeks; PBO, placebo; TNFi, tumour necrosis factor inhibitor.

Figure 2

Proportion of patients achieving ASAS40, ASAS20 and ASDAS <2.1 responses through 52 weeks in COAST-V (A, C, E) and COAST-W (B, D, F). ITT population. Missing data were imputed using NRI. ADA represents an active reference group; the study was not powered to test equivalence or non-inferiority of the active treatment groups to each other, including ixekizumab versus ADA. *ASDAS <2.1 indicates low disease activity. ADA, adalimumab; ASAS, Assessment of SpondyloArthritis international Society; ASDAS, Ankylosing Spondylitis Disease Activity Score; bDMARD, biological disease-modifying antirheumatic drug; ITT, intent to treat; IXE Q4W, ixekizumab 80 mg every 4 weeks; IXE Q2W, ixekizumab 80 mg every 2 weeks; NRI, non-responder imputation; PBO, placebo; TNFi, tumour necrosis factor inhibitor.

Figure 3

Proportion of patients initially randomised to PBO or ADA achieving ASAS40 responses on treatment with ixekizumab from week 16 through week 52 in COAST-V (A) and COAST-W (B). ETP population. Missing data were imputed using NRI. ADA, adalimumab; ASAS, Assessment of SpondyloArthritis international Society; bDMARD, biological disease-modifying antirheumatic drug; ETP, dose double-blind extended treatment period; IXE, ixekizumab; NRI, non-responder imputation; PBO, placebo; TNFi, tumour necrosis factor inhibitor.