Ixekizumab in radiographic axial spondyloarthritis with and without elevated C-reactive protein or positive magnetic resonance imaging

Abstract

Objective: To evaluate response rates at week 16 with ixekizumab in patients with radiographic axial SpA (r-axSpA) and elevated or normal/low baseline inflammation measured by serum CRP or spinal MRI using data from two randomized, double-blind, placebo (PBO)-controlled phase III trials.

Methods: Biologic-naïve (COAST-V) or TNF inhibitor-experienced (COAST-W) adults with active r-axSpA received 80 mg ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) or PBO or active reference [40 mg adalimumab every 2 weeks (ADAQ2W) in COAST-V. At week 16, patients receiving ixekizumab continued as assigned and patients receiving PBO or ADA were rerandomized 1:1 to IXEQ2W or IXEQ4W through week 52. Assessment of SpondyloArthritis international Society 40% (ASAS40) response rates were examined by baseline CRP (≤5 or >5 mg/l) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine inflammation score (<2 or ≥2).

Results: In the COAST-V/W integrated dataset (N = 567), significantly more patients treated with ixekizumab achieved ASAS40 response at week 16 by CRP ≤5 mg/l (27% IXEQ4W, P < 0.05; 35% IXEQ2W, P < 0.01 vs 12% PBO), CRP >5 mg/l (39% IXEQ4W, P < 0.001; 43% IXEQ2W, P < 0.001 vs 17% PBO), SPARCC MRI spine score <2 (40% IXEQ4W P < 0.01, 52% IXEQ2W P < 0.001 vs 16% PBO), and SPARCC MRI spine score ≥2 (44% IXEQ4W P < 0.001, 47% IXEQ2W P < 0.001 vs 19% PBO). ASAS40 response was observed with CRP ≤5 mg/l and SPARCC MRI spine score <2 with IXEQ4W (29%) and was significant with IXEQ2W (48%; P < 0.05) vs PBO (13%).

Conclusion: Ixekizumab demonstrated efficacy in the treatment of AS/r-axSpA in patients with and without elevated CRP or evidence of spinal inflammation on MRI.

Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov): NCT02696785, NCT02696798.

Keywords: AS; CRP; MRI; inflammation; ixekizumab; randomized clinical trials.

Fig. 1

ASAS40 response by baseline CRP and relationship based on a logistic regression model ASAS40 response at week 16 by baseline CRP ≤5 or >5 mg/L (A–F) and the relationship between ASAS40 response at week 16 and baseline CRP levels based on a logistic regression model for (G) COAST-V and (H) COAST-W. The analysis was performed on the full range of baseline values. Baseline values of 0–50 are shown. n: number of patients with ASAS40 response; Ns: number of patients in the subgroup; Nx: number of patients with non-missing values; ADA: active reference, adalimumab; ASAS40: 40% improvement in disease activity by ASAS criteria; IXE: ixekizumab; PBO: placebo. *P < 0.05, †P < 0.01, ‡P < 0.001 vs placebo.

Fig. 2

ASAS40 response by baseline MRI inflammation ASAS40 response at week 16 by baseline SPARCC MRI spine score <2 or ≥2 (A, B, E–H) and baseline SPARCC MRI SI joint score <2 or ≥2 (C, D). n: number of patients with ASAS40 response; Ns: number of patients in the subgroup. *P < 0.05, †P < 0.01, ‡P < 0.001 vs placebo.

Fig. 3

Relationship between ASAS40 response and baseline MRI inflammation based on a logistic regression model Relationship between ASAS40 response at week 16 and baseline SPARCC MRI spine score in (A) COAST-V and (C) COAST-W and (B) the relationship between ASAS40 response at week 16 and baseline SPARCC MRI SI joint score in COAST-V based on a logistic regression model. The analysis was performed on the full range of baseline values. Baseline values of 0–50 are shown. Nx: number of patients with non-missing values.

Fig. 4

ASAS40 response by baseline CRP and MRI spine inflammation ASAS40 response at week 16 by (A) absence of inflammation as measured by baseline CRP ≤5 mg/L and SPARCC MRI spine score <2 and by (B) elevated inflammation as measured by baseline CRP >5 mg/l and/or SPARCC MRI spine score ≥2. n: number of patients with ASAS40 response; Ns: number of patients in the subgroup. *P < 0.05, ‡P < 0.001 vs placebo.