METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: NCT02696785.
方法:COAST-V52周,双盲,安慰剂对照,随机III期试验研究了ixekizumab在活动性AS患者中的疗效;阿达木单抗被用作主动参考组.通过控制和持续炎症的客观测量来评估疼痛减轻的治疗效果(由磁共振成像[MRI]定义,C反应蛋白[CRP],或MRI+CRP状态)。通路分析用于分析不归因于炎症生物标志物减少的治疗效果。
结果:在AS患者中,当通过MRI评估炎症得到控制时,用ixekizumab治疗的患者夜间脊柱疼痛减轻(SP-N,数字评级量表,在第16周,与安慰剂(平均值=-1.6)相比,ixekizumab平均值=-3.9,p<0.001,阿达木单抗平均值=-2.6,p<0.05)。当通过MRI+CRP评估炎症得到控制时,与安慰剂相比,在SP-N中,ixekizumab和阿达木单抗在第16周时的数量减少更大。所有ixekizumab组在第52周有进一步的改善。当通过MRI+CRP评估炎症持续存在时,ixekizumab治疗的患者与安慰剂(平均值=-1.7)相比,SP-N显着降低(平均值=-3.7,p<0.001),阿达木单抗的改善没有达到显著性(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对疼痛结果的影响更大。
结论:此事后分析支持以下假设:ixekizumab通过减轻可测量的炎症以外的其他机制减轻AS疼痛。
背景:NCT02696785。