de Vlam Kurt, Maksymowych Walter P, Gallo Gaia, Rahman Proton, Mease Philip, Krishnan Venkatesh, McVeigh Conor J, Lisse Jeffrey, Zhu Danting, Bolce Rebecca J, Conaghan Philip G
University Hospital Leuven, Leuven, Belgium.
Department of Medicine, Division of Rheumatology at the University of Alberta, Edmonton, Alberta, Canada.
Rheumatol Ther. 2024 Jun;11(3):691-707. doi: 10.1007/s40744-024-00660-7. Epub 2024 Apr 18.
The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS).
The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers.
In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = - 3.9, p < 0.001, adalimumab mean = - 2.6, p < 0.05) compared to placebo (mean = - 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = - 3.7, p < 0.001) versus placebo (mean = - 1.7), improvement with adalimumab did not reach significance (mean = - 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab.
This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation.
NCT02696785.
本分析的目的是基于强直性脊柱炎（AS）患者炎症反应的客观指标，评估ixekizumab、安慰剂和阿达木单抗对脊柱疼痛的改善情况。
COAST-V为期52周的双盲、安慰剂对照、随机III期试验研究了ixekizumab对活动性AS患者的疗效；阿达木单抗作为活性对照组。通过可控性和持续性炎症的客观指标（由磁共振成像[MRI]、C反应蛋白[CRP]或MRI + CRP状态定义）评估治疗对疼痛减轻的效果。采用通路分析来分析并非由炎症生物标志物降低所致的治疗效果。
在AS患者中，当通过MRI评估炎症得到控制时，与安慰剂组（均值 = -1.6）相比，接受ixekizumab治疗的患者在第16周时夜间脊柱疼痛（SP-N，数字评分量表，ixekizumab均值 = -3.9，p < 0.001，阿达木单抗均值 = -2.6，p < 0.05）有所减轻。当通过MRI + CRP评估炎症得到控制时，在第16周时ixekizumab和阿达木单抗治疗组的SP-N较安慰剂组在数值上有更大程度的降低。所有ixekizumab组在第52周时均有进一步改善。当通过MRI + CRP评估炎症持续存在时，与安慰剂组（均值 = -1.7）相比，接受ixekizumab治疗的患者SP-N显著降低（均值 = -3.7，p < 0.001），阿达木单抗治疗组的改善未达到显著水平（均值 = -2.6，p = 0.06）。在第16周的通路分析中，与阿达木单抗相比，ixekizumab对疼痛结局的影响更大。
这项事后分析支持以下假设：ixekizumab通过除降低可测量炎症之外的其他机制减轻AS患者的疼痛。
NCT02696785。
