3/17/2025
Biologic disease-modifying antirheumatic drugs (DMARDs) are commonly used to treat radiographic axial spondyloarthritis (r-AxSpA), but their impact on structural damage in the sacroiliac joints over time is not fully understood. A recent study, COAST-V, examined how ixekizumab and adalimumab affect joint damage in patients who had never taken biologic DMARDs before.
COAST-V was a large, international phase 3 study that enrolled 341 adults with active r-AxSpA who had not responded well to NSAIDs. Participants were randomly assigned to receive either ixekizumab (every two or four weeks), adalimumab (every two weeks), or a placebo. MRI scans taken at the start of the study, at 16 weeks, and at 52 weeks tracked changes in bone erosion (a sign of joint damage), backfill (a sign of bone regrowth and healing), fat lesions, and ankylosis (joint fusion).
By week 16, patients taking ixekizumab every two weeks showed a significant reduction in erosion compared to those on placebo. To measure these changes, researchers used least squares mean (LSM), a statistical method that accounts for differences between patients to provide a more precise estimate of treatment effects. In this case, a larger negative LSM change indicates greater reduction in erosion (which is beneficial), while a higher positive LSM change means more progression of damage (which is undesirable). The LSM change in erosion was -0.91 in this group, while the placebo group showed a slight increase of 0.10 (p<0.0001). Patients on ixekizumab every four weeks also had a reduction in erosion (LSM change of -0.57, p=0.0086), and adalimumab produced a similar effect. Additionally, backfill, which indicates early bone repair, increased significantly in the ixekizumab every-two-weeks group (LSM change of 0.52 vs. 0.04 with placebo, p=0.0042).
At week 52, even greater improvements were observed, particularly in patients who remained on ixekizumab every two weeks. In this group, the LSM change in erosion was -1.50, and backfill increased to 0.76. Patients who switched from adalimumab to ixekizumab at week 16 also experienced a decrease in erosion, suggesting continued benefits with treatment.
These findings suggest that ixekizumab, like adalimumab, not only helps reduce inflammation but also slows structural damage in the sacroiliac joints. However, more research is needed to determine whether these changes can prevent long-term joint fusion (ankylosis) in r-AxSpA.
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