Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis
Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis
复制标题
DOI：
10.1056/nejmoa2027892
复制
发表时间：
2021-01-07
影响因子：
158.5
通讯作者：
Paolini, John F.
中科院分区：
文献类型：
--
作者：
Klein, Allan L.;Imazio, Massimo;Paolini, John F.
背景：白细胞介素-1被认为是复发性心包炎的中介。rilonacept是一种白细胞介素-1 α和白细胞介素-1 β细胞因子诱捕剂，此前在一项涉及复发性心包炎患者的2期试验中研究了rilonacept的有效性和安全性。方法：我们对复发性心包炎急性症状（以患者报告的量表评估）和全身炎症（以c反应蛋白（CRP）水平升高为表现）的患者进行了一项多中心、双盲、事件驱动、随机停药的3期临床试验。在接受标准治疗时出现心包炎复发的患者被纳入了一个12周的磨合期，在此期间开始使用rilonacept，并停止使用背景药物。有临床反应（即满足预先规定的反应标准）的患者按1:1的比例随机分配接受持续的rilonacept单药治疗或安慰剂，每周皮下给药一次。用Cox比例风险模型评估的主要疗效终点是第一次心包炎复发的时间。安全性也进行了评估。结果磨合期共纳入86例心包炎疼痛伴CRP水平升高的患者。在磨合期，疼痛缓解或接近缓解的中位时间为5天，CRP水平正常化的中位时间为7天。共有61名患者接受了随机分组。在随机停药期间，利洛那接受组的复发事件太少，无法计算到第一次确诊复发的中位时间；安慰剂组首次确诊复发的中位时间为8.6周(95%可信区间[CI]， 4.0 ~ 11.7； Cox比例风险模型的风险比为0.04;95% CI, 0.01 ~ 0.18
BACKGROUNDInterleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1 alpha and interleukin-1 beta cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis.METHODSWe conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed.RESULTSA total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P