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白介素-1诱捕剂rilonacept治疗复发性心包炎的3期试验
Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis


Allan L. Klein ... 心脑血管疾病 • 2021.01.07

摘要


背景

白介素-1被认为是复发性心包炎的介质。之前一项2期试验研究了rilonacept(白介素-1α和白介素-1β细胞因子诱捕剂)对复发性心包炎患者的疗效和安全性。

 

方法

我们在有复发性心包炎急性症状(根据患者报告的量表评分进行评估)和全身炎症(如C反应蛋白[CRP]水平升高所示)的患者中对rilonacept开展了一项3期、多中心、双盲、事件驱动、随机停药试验。在接受标准治疗期间心包炎复发的患者被纳入为期12周的导入期,在此期间开始使用rilonacept,并停用背景药物。我们以1∶1的比例将有临床缓解(即符合预设的缓解标准)的患者随机分组,两组分别继续接受每周一次皮下给药的rilonacept单药治疗或安慰剂。应用Cox比例风险模型判定的主要疗效终点是至心包炎首次复发的时间。本试验还评估了安全性。

 

结果

共计86例心包炎疼痛合并CRP水平升高的患者被纳入导入期。在导入期,至疼痛消退或接近消退的中位时间为5日,至CRP水平恢复正常的中位时间为7日。共计61例患者接受了随机分组。在随机停药期间,rilonacept组的复发事件太少,无法计算至首次裁定复发的中位时间;安慰剂组至首次裁定复发的中位时间为8.6周(95%置信区间[CI],4.0~11.7;Cox比例风险模型中的风险比,0.04;95% CI,0.01~0.18;时序检验的P<0.001)。在此期间,rilonacept组30例患者中有2例(7%)出现了心包炎复发,而安慰剂组31例患者中有23例(74%)。在导入期,4例患者发生了导致停止rilonacept治疗的不良事件,rilonacept最常见的不良事件是注射部位反应和上呼吸道感染。

 

结论

在复发性心包炎患者中,rilonacept使复发性心包炎发作快速消退,并且与安慰剂相比显著降低了心包炎复发风险(由Kiniksa Pharmaceuticals资助,RHAPSODY在ClinicalTrials.gov注册号为NCT03737110)。





作者信息

Allan L. Klein, M.D., Massimo Imazio, M.D., Paul Cremer, M.D., Antonio Brucato, M.D., Antonio Abbate, M.D., Ph.D., Fang Fang, Ph.D., Antonella Insalaco, M.D., Martin LeWinter, M.D., Basil S. Lewis, M.D., David Lin, M.D., Sushil A. Luis, M.B., B.S., Stephen J. Nicholls, M.B., B.S., Ph.D., Arian Pano, M.D., Alistair Wheeler, M.D., and John F. Paolini, M.D., Ph.D. for the RHAPSODY Investigators*
From the Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland (A.L.K., P.C.); University Cardiology, Cardiovascular, and Thoracic Department, Azienda Ospedaliero–Universitaria (AOU) Città della Salute e della Scienza di Torino and University of Turin, Turin (M.I.), the Department of Biomedical and Clinical Science, University of Milan, Fatebenefratelli Hospital, Milan (A.B.), and the Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome (A.I.) — all in Italy; Pauley Heart Center, Virginia Commonwealth University, Richmond (A.A.); Kiniksa Pharmaceuticals, Lexington, MA (F.F., A.P., J.F.P.); the Cardiology Unit, University of Vermont Medical Center, Burlington (M.L.); the Cardiovascular Clinical Research Institute, Lady Davis Carmel Medical Center and the Technion–Israel Institute of Technology, Haifa, Israel (B.S.L.); the Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis (D.L.), and the Division of Cardiovascular Ultrasound, Department of Cardiovascular Medicine, Mayo Clinic, Rochester (S.A.L.) — both in Minnesota; the Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Clayton, VIC, Australia (S.J.N.); and Kiniksa Pharmaceuticals, Hamilton, Bermuda (A.W.). Address reprint requests to Dr. Klein at the Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, 9500 Euclid Ave., Desk J1-5, Cleveland, OH 44195, or at kleina@ccf.org; or to Dr. Imazio at University Cardiology, Cardiovascular, and Thoracic Department, AOU Città della Salute e della Scienza di Torino, Corso Bramante, 88, 10126 Turin, Italy, or at massimo_imazio@yahoo.it. *A complete list of the RHAPSODY investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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