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Abstract：
BACKGROUND: 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).
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.
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.
摘要：
背景：本分析的目的是评估ixekizumab对脊柱疼痛的改善，安慰剂,和阿达木单抗基于强直性脊柱炎（AS）患者炎症反应的客观指标。
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。
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。
