Ixekizumab Improves Patient-Reported Outcomes in Non-Radiographic Axial Spondyloarthritis: Results from the Coast-X Trial

Abstract

Introduction: Ixekizumab, an interleukin-17A antibody, has shown efficacy in non-radiographic axial spondyloarthritis (nr-axSpA). The objectives of this analysis were (a) to measure improvement in ixekizumab-treated patients in Assessment of Spondyloarthritis International Society (ASAS) response domains and other patient-reported outcomes (PROs) and (b) to determine how ASAS responses were associated with changes in patient global disease activity (PtGA), spinal pain, function, stiffness, fatigue, and spinal pain at night.

Methods: COAST-X was a phase 3, 52-week multicenter, randomized, controlled trial investigating the efficacy and safety of 80-mg ixekizumab every 2 weeks (Q2W) and every 4 weeks (Q4W) in patients with active nr-axSpA. Changes from baseline in PROs were analyzed via mixed-effects models for repeated measures. Association analyses for ASAS responses used analysis of covariance with Scheffé's method.

Results: Patients treated with ixekizumab Q2W and Q4W reported significantly greater improvements in PtGA, spinal pain, function, and stiffness at week 1, when these measures were first assessed, compared with placebo (p < 0.05). ASAS40 responders, in comparison to ASAS20 non-responders, had the highest correlations with improvements in all response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night (p < 0.001). ASAS40 responses were associated with 3.5- to 48.0-fold greater improvements in these PROs, with the highest values for PtGA and function, compared to ASAS20 non-achievement.

Conclusions: As early as week 1, patients with nr-axSpA treated with ixekizumab reported significant improvements in PtGA, spinal pain, function, and stiffness compared with those taking placebo. ASAS40 responders reported significantly greater improvements in all ASAS response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night than ASAS20 non-responders. Improvements in PtGA and function appear to be major drivers in achieving ASAS40 response in patients with nr-axSpA.

Trial registration: NCT02757352.

Keywords: Assessment of Spondyloarthritis International Society (ASAS) response; Biological therapy; Ixekizumab; Non-radiographic axial spondyloarthritis; Patient-reported outcomes.

Figures

Fig. 1

Changes from baseline in patient global disease activity (a), spinal pain (b), function (BASFI) (c), and stiffness (BASDAI questions 5 and 6) through week 52 (d). Values are LSM from MMRM. Week 1: PBO, Nx = 103; IXE Q4W, Nx = 95; IXE Q2W, Nx = 99. Week 2: PBO, Nx = 102; IXE Q4W, Nx = 96; IXE Q2W, Nx = 102. Weeks 4 and 8: PBO, Nx = 101; IXE Q4W, Nx = 96; IXE Q2W, Nx = 101. Weeks 12 and 16: PBO, Nx = 99; IXE Q4W, Nx = 96; IXE Q2W, Nx = 98. Week 20: PBO, Nx = 55; IXE Q4W, Nx = 68; IXE Q2W, Nx = 73. Week 24: PBO, Nx = 50; IXE Q4W, Nx = 64; IXE Q2W, Nx = 64. Week 28: PBO, Nx = 43; IXE Q4W, Nx = 63; IXE Q2W, Nx = 61. Week 32: PBO, Nx = 43; IXE Q4W, Nx = 59; IXE Q2W, Nx = 60. Week 36: PBO, Nx = 39; IXE Q4W, Nx = 56; IXE Q2W, Nx = 58. Week 44: PBO, Nx = 36; IXE Q4W, Nx = 54; IXE Q2W, Nx = 56. Week 52: PBO, Nx = 34; IXE Q4W, Nx = 53; IXE Q2W, Nx = 52. P values were from MMRM (treatment vs. placebo). *p < 0.05, ‡p < 0.01, †p < 0.001. BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, IXE Q2W = 80-mg ixekizumab every 2 weeks, IXE Q4W 80-mg ixekizumab every 4 weeks, IXE Q2W 80-mg ixekizumab every 2 weeks, LSM least squares mean, MMRM mixed-effect model for repeated measures, Nx number of patients with non-missing values, PBO placebo

Fig. 2

Changes from baseline in fatigue as measured by Fatigue NRS (a) and BASDAI fatigue (b), as well as spinal pain at night through week 52 (c). Values are LSM from MMRM. Fatigue NRS—week 8: PBO, Nx = 101; IXE Q4W, Nx = 95; IXE Q2W, Nx = 101. Week 16: PBO, Nx = 99; IXE Q4W, Nx = 96; IXE Q2W, Nx = 98. Week 36: PBO, N = 39; IXE Q4W, Nx = 56; IXE Q2W, Nx = 58. Week 52: PBO, Nx = 34; IXE Q4W, Nx = 53; IXE Q2W; Nx = 52. BASDAI Fatigue and Spinal Pain at Night—week 1: PBO, Nx = 103; IXE Q4W, Nx = 95; IXE Q2W, Nx = 99. Week 2: PBO, Nx = 102; IXE Q4W, Nx = 96; IXE Q2W, Nx = 102. Weeks 4 and 8: PBO, Nx = 101; IXE Q4W, Nx = 96; IXE Q2W, Nx = 101. Weeks 12 and 16: PBO, Nx = 99; IXE Q4W, Nx = 96; IXE Q2W, Nx = 98. Week 20: PBO, Nx = 55; IXE Q4W, Nx = 68; IXE Q2W, Nx = 73. Week 24: PBO, Nx = 50; IXE Q4W, Nx = 64; IXE Q2W, Nx = 64. Week 28: PBO, Nx = 43; IXE Q4W, Nx = 63; IXE Q2W, Nx = 61. Week 32: PBO, Nx = 43; IXE Q4W, Nx = 59; IXE Q2W, Nx = 60. Week 36: PBO, Nx = 39; IXE Q4W, Nx = 56; IXE Q2W, Nx = 58. Week 44: PBO, Nx = 36; IXE Q4W, Nx = 54; IXE Q2W, Nx = 56. Week 52: PBO, Nx = 34; IXE Q4W, Nx = 53; IXE Q2W, Nx = 52. P values were from MMRM (treatment vs. placebo). *p < 0.05, ‡p < 0.01, †p < 0.001. BASDAI Bath Ankylosing Spondylitis Disease Activity Index, IXE Q2W 80-mg ixekizumab every 2 weeks, IXE Q4W 80-mg ixekizumab every 4 weeks, LSM least squares mean, MMRM mixed-effect model for repeated measures, NRS numeric rating scale, Nx number of patients with non-missing values, PBO placebo

Fig. 3

Association between ASAS response and changes from baseline in measures of patient global disease activity (a), spinal pain (b), function (c), and stiffness (d) (BASDAI questions 5 and 6) at weeks 16 and 52. Values are LSM (SE) from ANCOVA. Only observed data were used in this analysis. P values were from ANCOVA after correcting for baseline value, age, gender, and ASAS response category. §p < 0.001, ASAS20 responder vs. ASAS20 non-responder; **p < 0.001, ASAS40 responder vs. ASAS20 non-responder; †p < 0.001, ASAS40 responder vs. ASAS20 responder. ANCOVA analysis of covariance, ASAS Assessment of Spondyloarthritis International Society, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, LSM least squares mean, Nx number of non-missing observations, SE standard error