Good news for sleep in patients with axial spondyloarthritis – ixekizumab effectively reduces night-time back pain

Treatment in the COAST-V study

This international phase III clinical trial was open to patients with radiographic axial spondyloarthritis who had not been treated with biologics before and were candidates for this therapy. Participants were randomized to receive ixekizumab every 4 (IXE4W) or 2 weeks (IXE2W) or to control arms with adalimumab (ADA) administered every 2 weeks or placebo. At week 16, patients in the control arms were re-randomized to continue the study with IXE4W or IXE2W treatment. A total of 341 patients were monitored for 52 weeks.

Methodology for assessing the analgesic effect

One of the research objectives was to evaluate how IXE alleviates night-time back pain and whether its analgesic effect correlates with laboratory signs of inflammation (C-reactive protein [CRP] level) and the duration or intensity of morning joint stiffness (questions 5 and 6 in the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]).

For data analysis, patients were divided into a group with stable reduction (i.e., CRP < 5 mg/l between weeks 4 and 16 of the study) and a group with fluctuating levels (CRP ≥ 5 mg/l at any measurement between weeks 4 and 16). A similar division was applied based on improvements in scores for questions 5 and 6 in the BASDAI. Patients were categorized into a group with stable improvement in joint stiffness (i.e., improvement by ≥ 2 points between weeks 12 and 16 of the study) and a group with fluctuating results (improvement by < 2 points at any assessment during weeks 12 and 16).

Results – relief from night-time pain

In the initial phase of the study (up to week 16), night-time back pain decreased more significantly in patients on IXE4W than in patients on ADA, regardless of CRP levels.

• In the group with fluctuating CRP levels, IXE4W performed better than ADA (causing a more significant reduction in night-time pain) when comparing both treatments to placebo (p < 0.001 for IXE4W). The ADA result, in this case, was not statistically different from placebo (p = 0.4).
• In patients with stable CRP reduction, both treatments were more effective than placebo (IXE: p = 0.002; ADA: p = 0.02), with IXE4W showing a more significant reduction in night-time pain than ADA.

Similar results were observed when correlating with morning joint stiffness, although there was markedly worse efficacy of both treatments in patients with fluctuating results. However, even in these patients, IXE4W was more effective than ADA when compared to placebo (IXE4W: p < 0.05; ADA: p > 0.05).

Patients initially taking ADA showed further reduction in night-time back pain after switching to IXE4W, and the analgesic effect was maintained until the end of the study.

Conclusion

Ixekizumab treatment significantly and durably reduced night-time back pain regardless of CRP levels and the degree of morning joint stiffness. In patients with a stable response to therapy, ixekizumab was similarly or slightly more analgesically effective than adalimumab. In patients with a variable response, ixekizumab showed significantly better analgesic efficacy than adalimumab. After switching from adalimumab to ixekizumab, patients reported continued relief from night-time pain.

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Sources:
1. Ramiro S., Nikiphorou E., Sepriano A. et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis 2022 Oct 21; ard-2022-223296, doi: 10.1136/ard-2022-223296 [Epub ahead of print].
2. De Vlam K., Gallo G., Mease P. J. et al. Ixekizumab shows a distinct pattern of pain improvement beyond inflammation in radiographic axial spondyloarthritis. Ann Rheum Dis 2021; 80 (Suppl. 1): 707‒708, doi: 10.1136/annrheumdis-2021-eular.211.