The effect of ixekizumab treatment on MRI sacroiliac joint structural lesions in patients with radiographic axial spondyloarthritis: post-hoc analysis of a 52-week, randomised, placebo-controlled trial with an active reference arm.

Background: The effect of biological disease-modifying antirheumatic drugs (DMARDs) on sacroiliac joint lesions over 52 weeks in biological DMARD-naive patients with radiographic axial spondyloarthritis is unknown. This post-hoc analysis evaluated the effect of ixekizumab and adalimumab versus placebo on structural lesions in sacroiliac joints assessed by MRI in patients naive to biological DMARDs with radiographic axial spondyloarthritis from the COAST-V study.

Methods: COAST-V was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial with an active reference arm done over 52 weeks at 84 sites in 12 countries. Eligible patients were adults (aged ≥18 years) naive to biological DMARDs with active radiographic axial spondyloarthritis, radiographic evidence of sacroiliitis, and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1:1:1) to 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W), 40 mg adalimumab Q2W, or placebo. At week 16, patients receiving placebo or adalimumab were randomly assigned (1:1) again to ixekizumab Q2W or ixekizumab Q4W. Post-hoc analyses of patients with MRI available at baseline, 16 weeks, and 52 weeks are reported. MRIs were scored using the Spondyloarthritis Research Consortium of Canada sacroiliac joint structural scores for erosion, backfill, fat lesions, and ankylosis. ANCOVA was used for treatment comparisons in observed cases adjusting for baseline values, bone marrow oedema, and stratification factors. Subgroup analyses by sex, HLA-B27, and baseline bone marrow oedema were done.

Findings: Between June 20, 2016, and Aug 22, 2017, 341 patients were enrolled in the COAST-V study. MRI scans were available for 325 (95%) of 341 patients at baseline and week 16, and for 301 (88%) patients at week 52. 264 (81%) of 325 patients were male and 61 (19%) were female, and the mean age was 41·5 years (SD 11·6). At week 16, erosion significantly decreased versus placebo in the ixekizumab Q2W group (least squares mean -0·91 [SE 0·19] vs 0·10 [0·18]; p<0·0001) and the ixekizumab Q4W group (-0·57 [SE 0·19]; p=0·0086]); the effect of adalimumab was similar. Backfill significantly increased from baseline to week 16 in ixekizumab Q2W versus placebo (0·52 [0·12] vs 0·04 [0·12]; p=0·0042). At week 16, decreases in erosion differed significantly between the placebo group and ixekizumab Q2W or Q4W groups, and differences were seen by sex, HLA-B27 status, and baseline bone marrow oedema score. At week 52, at both ixekizumab doses, further changes were observed in erosion and backfill, which were greatest with continuous ixekizumab Q2W (mean erosion -1·50 [SD 2·70], mean backfill 0·76 [SD 2·09]). A decrease in erosion was also noted in patients switching from adalimumab to ixekizumab at week 16. COAST-V was registered with ClinicalTrials.gov (NCT02696785).

Interpretation: A decrease in erosion and increase in backfill were observed at week 16 with further reductions in erosion and increases in backfill occurring at week 52 in patients receiving ixekizumab. Ixekizumab, like adalimumab, modifies structural lesions that is consistent with a rapid tissue response in patients with radiographic axial spondyloarthritis. However, the effect on the development of ankylosis in sacroiliac joints or the spine requires further analysis.

Funding: Eli Lilly.