Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1.
Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1.
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ixekizumab，一种白介素17a特异性单克隆抗体，用于治疗活性银屑病性关节炎的生物学患者：由24周的随机，双盲，安慰剂对照和活性（Adalimumab）的24周随机，III阶段（Adalimumab）的结果。试验精神-P1。
DOI：
10.1136/annrheumdis-2016-209709
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发表时间：
2017-01
影响因子：
27.4
通讯作者：
SPIRIT-P1 Study Group
中科院分区：
文献类型：
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作者：
Mease PJ;van der Heijde D;Ritchlin CT;Okada M;Cuchacovich RS;Shuler CL;Lin CY;Braun DK;Lee CH;Gladman DD;SPIRIT-P1 Study Group
在一项双盲III期试验中评估ixekizumab（一种抑制白细胞介素-17A的单克隆抗体）的安全性和疗效，该试验招募了活动性银屑病关节炎（PsA）患者。未接受过活性PsA生物制剂治疗的患者随机接受安慰剂（N=106）、阿达木单抗40 mg每2周一次（活性对照; N=101）、ixekizumab 80 mg每2周一次（IXEQ 2 W）（N=103）或ixekizumab 80 mg每4周一次（IXEQ 4 W）（N=107）皮下注射。 两种ixekizumab方案均包括160 mg起始剂量。主要目的是评估IXEQ 2 W或IXEQ 4 W相对于安慰剂的优效性，通过在第24周达到美国流变学会20（ACR 20）应答的患者比例进行测量。与安慰剂组（30.2%）相比，ixekizumab组（62.1%）或ixekizumab组（57.9%）达到ACR 20应答的患者显著更多（p≤0.001;非应答者插补方法）。在第12周和第24周，两种ixekizumab剂量组与安慰剂组相比，疾病活动性和功能障碍均显著改善，第24周时结构损伤进展显著减少（p≤0.01）。ixekizumab对斑块状银屑病的清除率高于安慰剂（p≤0.001）。阿达木单抗（活性对照组）的疗效结果显示，与安慰剂相比，疗效显著改善。ixekizumab（65.7-66.4%）和阿达木单抗（64.4%）治疗后出现的不良事件比安慰剂（47.2%）更频繁（p<0.05）。在未接受过生物制剂治疗的活动性PsA患者中，ixekizumab治疗可改善疾病活动性和身体功能，并抑制结构损伤进展。总体而言，与安慰剂组相比，所有活性药物组的不良事件更频繁。NCT 01695239; EudraCT 2011 -002326-49;结果。
To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA). Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24. Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7–66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05). In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo. NCT01695239; EudraCT2011-002326-49; Results.