Patients with axial spondyloarthritis receiving ixekizumab showed reduced sacroiliac joint erosion and increased fat lesions and backfill compared with those receiving placebo, according to findings published in The Lancet Rheumatology.
Researchers conducted a randomized, double-blind, placebo-controlled, parallel-group trial at 107 sites in 15 countries in Europe, North America, South America, and Asia between August 2, 2016, and January 29, 2018. They included 303 patients diagnosed with nonradiographic axial spondyloarthritis who were randomly assigned to the treatment group and the placebo group. They subdivided the study patients in the treatment group into 2 groups — those who received ixekizumab 80 mg every 4 weeks (Q4W) and those who received ixekizumab 80 mg every 2 weeks (Q2W).
The researchers confirmed structural changes in the sacroiliac joint indicating progression from nonradiographic to radiographic axial spondyloarthritis by comparing magnetic resonance imaging (MRI) scans at baseline and after 16 weeks of ixekizumab therapy. Approximately 290 (96%) of study patients completed the follow-up visit at week 16, and 266 patients had MRI scans available from both baseline and week 16.
Compared with the placebo group (mean change from baseline, 0.16), patients in the ixekizumab treatment groups demonstrated reduced sacroiliac joint erosions at week 16 (Q4W: mean change, -0.39; 95% CI, -0.92 to -0.19; P =.003 and Q2W: mean change, -0.40; 95% CI, -0.92 to -0.20; P =.002).
Increased presence of fat lesions (Q4W: mean change, 0.16; 95% CI, 0.04 to 0.37; P =.013 and Q2W: mean change, 0.10; 95% CI, -0.01 to 0.31; P =.067) and backfill (Q4W: mean change, 0.21; 95% CI, 0.07 to 0.55; P =.011 and Q2W: mean change, 0.22; 95% CI, 0.09 to 0.56; P =.006) occurred in the ixekizumab group compared with the placebo group. These radiographic changes suggested that ixekizumab stimulates early repair processes in the sacroiliac joint.
Men and patients who tested positive for human leukocyte antigen-B27 (HLA-B27) demonstrated more pronounced effects of ixekizumab on structural changes than women and patients who tested negative for HLA-B27.
Decreased erosions of the sacroiliac joint correlated with increased fat lesions and backfill. While all of the joint changes slightly corresponded to improved Spondyloarthritis Research Consortium of Canada (SPARCC) Bone Marrow Edema scores, the researchers observed no other correlations between the changes and other outcome measures, including the Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, and SPARCC sacroiliac joints structural score.
Limitations of the study include the short 16-week follow-up period, the absence of an erosion-specific MRI sequence, and the inability to correlate treatment-related changes with clinically relevant outcomes such as function and mobility.
“Although the clinical relevance is not yet clear, patients with [nonradiographic] axial spondyloarthritis receiving ixekizumab had significant reductions in erosions and increases in fat lesions and backfill in the sacroiliac joints versus placebo at week 16, suggesting an early repair process with ixekizumab treatment,” the study authors conclude.
Maksymowych WP, Baraliakos X, Lambert RG, et al. Effects of ixekizumab treatment on structural changes in the sacroiliac joint: MRI assessments at 16 weeks in patients with non-radiographic axial spondyloarthritis. The Lancet Rheumatology. 2022;4(9):e626-e634. doi:10.1016/S2665-9913(22)00185-0