Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study
Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study
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DOI：
10.1136/annrheumdis-2018-214943
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发表时间：
2019-08-01
影响因子：
27.4
通讯作者：
Shaw, Stevan
中科院分区：
文献类型：
--
作者：
Glatt, Sophie;Taylor, Peter C.;Shaw, Stevan
目的评价bimekizumab（一种单克隆IgG 1抗体）联合赛妥珠单抗（certolizumab pegol，CZP）双重中和白细胞介素（IL）-17 A和IL-17 F治疗赛妥珠单抗无效（IR）的类风湿关节炎（RA）患者的疗效和安全性。在NCT 02430909中，中重度RA患者在第0、2和4周接受开放标签CZP 400 mg，在第6周接受200 mg。在第8周具有IR的患者（疾病活动性评分28-关节计数C反应蛋白（DAS 28（CRP））> 3.2）以2：1随机分配至CZP（200 mg每2周（Q2 W））+bimekizumab（240 mg负荷剂量，然后120 mg Q2 W）或CZP+安慰剂。主要疗效和安全性变量为第8周和第20周之间DAS 28（CRP）的变化和治疗后出现的不良事件（TEAEs）的发生率。结果在159例入组患者中，79例在第8周出现IR，随机分配至CZP + bimekizumab组（n=52）或CZP+安慰剂组（n=27）。第20周时，CZP-IR + bimekizumab组的DAS 28（CRP）降幅大于CZP-IR+安慰剂组（后验概率为99.4%）。最常见的TEAE是感染和侵染（CZP + bimekizumab，50.0%（26/52）; CZP+安慰剂，22.2%（6/27））。在接受CZP伴随治疗的RA患者中，当中和IL-17 A和IL-17 F时，未发现非预期或新的安全性信号，但双重抑制的TEAE发生率较高。
Objective Evaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.Methods During this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))> 3.2) were randomised 2: 1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).Results Of 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).Conclusions PoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.