medwireNews: Treatment with ixekizumab rapidly reduces sacroiliac joint erosion and promotes backfill in patients with radiographic axial spondyloarthritis (r-axSpA), according to a 52-week post-hoc analysis of the COAST-V trial.
Writing in The Lancet Rheumatology, Walter Maksymowych, from the University of Alberta in Edmonton, Canada, and colleagues examined magnetic resonance imaging (MRI) data from the multicenter, phase 3, randomized, placebo-controlled study conducted in 12 countries between 2016 and 2017.
The study evaluated the effects of the interleukin-17 inhibitor ixekizumab compared with placebo or adalimumab in patients with active r-axSpA that had an inadequate response to nonsteroidal anti-inflammatory drugs but was naïve to biologic disease-modifying antirheumatic drugs (DMARDs).
A total of 341 patients were randomly assigned to receive the targeted DMARD ixekizumab 80 mg every 2 weeks (Q2W; n=78) or every 4 weeks (Q4W; n=78), placebo (n=85), or adalimumab Q2W (active placebo, n=84). At week 16, patients in the placebo and adalimumab groups were reassigned to receive ixekizumab Q2W or Q4W. The participants were aged a mean of 41.5 years, and the majority (81%) were men.
MRI assessments were performed at baseline (n=325), week 16 (n=325), and week 52 (n=301) using the Spondyloarthritis Research Consortium of Canada sacroiliac joint structural scoring system (SPARCC SSS) to evaluate changes in erosion, backfill, fat lesions, and ankylosis.
Mean erosion scores at baseline ranged from 2.2 out of a possible 40 points for the adalimumab group to 4.1 in the ixekizumab group, where higher scores indicate greater erosion.
At 16 weeks, patients taking ixekizumab Q2W had a least squares mean (LSM) reduction in erosion of 0.91 points, which was significantly less than the LSM increase of 0.10 points among patients taking placebo, after taking into account confounding factors such as baseline lesion severity and bone marrow edema. Smaller, but still significant, reductions compared with placebo were also observed for ixekizumab Q4W and adalimumab, at a respective 0.57 points and 0.56 points.
These decreases in erosion scores correlated with an increase in backfill scores at 16 weeks, which were measured out of a possible 20 points on the SPARCC SSS. Treatment differences compared with placebo were only significant for the ixekizumab Q2W group, with LSM changes of 0.52 versus 0.04 points from baseline values of 1.53 and 1.11, respectively.
The treatment groups did not differ significantly with regard to changes in fat lesions or ankylosis.
“This decrease in erosion was associated with resolution of inflammation and the development of fat metaplasia in the erosion cavity, which reflects the tissue response that is typical of axial spondyloarthritis, as previously reported in patients receiving [tumor necrosis factor] inhibitor therapy,” observe the investigators.
They also report that subanalyses showed that “[t]hese changes in structural lesions were more prominent in male patients with [human leukocyte antigen]-B27 positivity and inflammation in the sacroiliac joints on MRI at baseline,” compared with other patients.
Erosion was further reduced in the whole patient group at week 52, particularly in patients who continued to receive ixekizumab Q2W, with a 1.50-point reduction from baseline. For those who received ixekizumab Q4W for the 52 weeks, the mean reduction was 0.88 points. A similar reduction in erosion was also seen at 52 weeks in patients who switched from placebo or adalimumab to ixekizumab at 16 weeks, with respective mean reductions from baseline of 0.95 and 0.58 points.
Backfill further increased between weeks 16 to 52, by means of 0.76 points among patients in the ixekizumab Q2W group, 0.30 points among those taking ixekizumab Q4W, and 0.38 points among those who switched from placebo. Additionally, fat lesions increased by a mean of 0.56, 0.31, and 0.50 points, respectively, out of a possible 40 points on the SPARCC SSS, from corresponding mean baseline scores of 7.3, 5.9, and 7.8 points. For patients who switched from adalimumab, there was a slight decrease in backfill score and a slight increase in fat lesion score.
The authors suggest that the results “are consistent with the hypothesis that inflammation is associated with structural lesions.” However, they caution that larger, longer-term studies are needed to determine whether these changes prevent the development of spinal ankylosis – the primary driver of functional impairment in axial spondyloarthritis.
In an accompanying commentary, Torsten Diekhoff and Sevtap Tugce Ulas, both from Freie Universität Berlin in Germany, conclude that the study “offers valuable insights into the long-term structural lesion development in axial spondyloarthritis at the sacroiliac joint during biological DMARD therapy,” but emphasize that “[w]hether these findings will translate into improved patient outcomes remains an open question and a crucial area for future research.”
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