Ixekizumab Halts Bone Damage in Axial Spondyloarthritis

TOPLINE:

Ixekizumab reduced erosion and increased backfill in the sacroiliac joints of biologic disease-modifying antirheumatic drug (bDMARD)–naive patients with radiographic axial spondyloarthritis (r-axSpA) by week 16, with further improvements observed up to week 52. Male patients and human leukocyte antigen B27 (HLA-B27)–positive patients showed more pronounced structural changes.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the COAST-V trial to compare the effects of ixekizumab with both placebo and an active control, adalimumab, on structural lesions in the sacroiliac joints of patients with r-axSpA; the lesions were evaluated using MRI at baseline, 16 weeks, and 52 weeks.
• In the COAST-V trial, 341 bDMARD-naive patients with inadequate response to nonsteroidal anti-inflammatory drugs were randomly assigned to receive either 8src mg ixekizumab every 2 or 4 weeks (Q2W or Q4W), 4src mg adalimumab Q2W, or a matching placebo.
• Those who completed 16 weeks of treatment entered an extended treatment period for up to 52 weeks; among these patients, those initially receiving placebo or adalimumab were randomly reassigned to receive either ixekizumab Q2W or Q4W.
• MRI scans were available for 325 patients (mean age, 41.5 years; 19% women) at baseline and week 16 and for 3src1 patients at week 52; structural lesions were assessed using Spondyloarthritis Research Consortium of Canada MRI sacroiliac joint structural scores.
• Least squares mean (LSM) changes in erosion, backfill, fat lesions, and ankylosis in the sacroiliac joints were measured from baseline to week 16 and week 52.

TAKEAWAY:

• Erosion scores decreased to a greater extent with ixekizumab Q2W (LSM change, −src.91; P <.srcsrcsrc1) or ixekizumab Q4W (LSM change, −src.57; P=.srcsrc86) than with placebo (LSM change, src.1src) at week 16; the decrease in erosion scores was also more prominent with adalimumab than with placebo.
• Backfill significantly increased from baseline to week 16 with ixekizumab Q2W compared with placebo (LSM increase, src.52 vs src.src4; P=.srcsrc42).
• At week 52, further improvements in erosion and backfill were observed with both ixekizumab doses, with the most notable effects seen in the continuous ixekizumab Q2W group (mean change in erosion score, −1.5src; mean change in backfill score, src.76); those who switched from adalimumab to ixekizumab also experienced benefits.
• Effects were more pronounced in men, those with HLA-B27 positivity, and those with concomitant inflammation in the sacroiliac joints.

IN PRACTICE:

“This finding underlines the potential of biological DMARDs and other inflammation-targeting therapies to produce lasting benefits for structural lesions,” experts wrote in an accompanying editorial.

SOURCE:

The study was led by Walter P. Maksymowych, MD, University of Alberta, Edmonton, Alberta, Canada. It was published online on February 18, 2src25, in The Lancet Rheumatology.

LIMITATIONS:

The primary limitation was the relatively short 52-week period for examining structural changes, which may have led to unresolved uncertainty about the treatment’s effect on the development of ankylosis, especially in the spine. The sample size was small across treatment groups, particularly for subgroup analyses, and the placebo and adalimumab groups only progressed to week 16, making comparison at week 52 impossible. Additionally, the applicability of this study to the general population of patients with axial spondyloarthritis remains unknown.

DISCLOSURES:

This study was funded by Eli Lilly and Company. Four authors were employees and shareholders of Eli Lilly and Company. Other authors declared receiving speaker fees, honoraria, research grants, financial support, and reading fees; serving as consultants; and having other ties with many sources, including Eli Lilly and Company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.