Improvement of Functioning and Health With Ixekizumab in the Treatment of Active Nonradiographic Axial Spondyloarthritis in a 52-Week, Randomized, Controlled Trial

Abstract

Objective: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA).

Methods: COAST-X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self-reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF-36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility descriptive system.

Results: Compared to placebo, ixekizumab treatment resulted in improvement of SF-36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P < 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P < 0.01); the greatest improvements were observed in the domains of physical functioning, role-physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported ≥3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P < 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in "good health status" on the ASAS health index (ASAS score of ≤5) at weeks 16 and 52 (P < 0.05). Patients receiving ixekizumab reported improvements on the EQ-5D-5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P < 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks.

Conclusion: In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self-reported functioning and health at weeks 16 and 52.

Trial registration: ClinicalTrials.gov NCT02757352.

Figure 1

Medical Outcomes Study Short Form 36 (SF‐36) health survey domain scores at baseline, week 16, and week 52 in the intent‐to‐treat population of the COAST‐X trial. Subgroups included patients who received 80 mg of ixekizumab every 2 weeks (IXE Q2W), patients who received 80 mg of ixekizumab every 4 weeks (IXE Q4W), and patients who received placebo (PBO). Spydergrams depict modified baseline observation carried forward SF‐36 domain scores (0–100 scale) and US age‐ and gender‐matched normative values (A/G Matched Norm). SF‐36 age‐ and gender‐matched norms are based on the 1998 US population norms and patient counts for each age and gender distribution of the protocol population. BP = bodily pain; GH = general health MH = mental health; PF = physical functioning; RE = role‐emotional; RP = role‐physical; SF = social functioning; VT = vitality.

Figure 2

Medical Outcomes Study Short Form 36 health survey physical component summary scores, with least squares mean change from baseline observed in the intent‐to‐treat population of the COAST‐X trial. Subgroups included patients who received 80 mg of ixekizumab every 2 weeks (IXE Q2W), patients who received 80 mg of ixekizumab every 4 weeks (IXE Q4W), and patients who received placebo (PBO). Comparisons between the ixekizumab treatment groups and the placebo group were made using a mixed‐effects model for repeated measures. * = P < 0.05; ** = P < 0.01; *** = P < 0.001.

Figure 3

Assessment of Spondyloarthritis International Society health index least squares mean change from baseline in the intent‐to‐treat population of the COAST‐X trial. Subgroups included patients who received 80 mg of ixekizumab every 2 weeks (IXE Q2W), patients who received 80 mg of ixekizumab every 4 weeks (IXE Q4W), and patients who received placebo (PBO). Comparisons between the ixekizumab treatment groups and the placebo group were made using a mixed‐effects model for repeated measures. * = P < 0.05.

Figure 4

Percentage of patients achieving an Assessment of Spondyloarthritis International Society health index (ASAS HI) score of ≤5, indicating “good health status,” in the intent‐to‐treat population of the COAST‐X trial. Missing data were imputed with a nonresponder imputation. Subgroups included patients who received 80 mg of ixekizumab every 2 weeks (IXE Q2W), patients who received 80 mg of ixekizumab every 4 weeks (IXE Q4W), and patients who received placebo (PBO). Comparisons between the ixekizumab treatment groups and the placebo group were made using a logistic regression model. * = P < 0.05; ** = P < 0.01; *** = P < 0.001.

Figure 5

European Quality of Life‐5 Dimensions‐5 Level (EQ‐5D‐5L) UK population–based index scores, with the least squares mean change from baseline in the intent‐to‐treat population of the COAST‐X trial. Missing data were imputed using modified baseline observation carried forward. Subgroups included patients who received 80 mg of ixekizumab every 2 weeks (IXE Q2W), patients who received 80 mg of ixekizumab every 4 weeks (IXE Q4W), and patients who received placebo (PBO). Comparisons between the ixekizumab treatment groups and the placebo group were made using a logistic regression model. * = P < 0.05.