Li H Henry, Mycroft Sarah, Christiansen Sandra, Wood Daniel N, Feuersenger Henrike, Pawaskar Dipti, Jacobs Iris
From the Institute for Asthma and Allergy, P.C., Chevy Chase, Maryl.
CSL Behring, King of Prussia, Pennsylvania.
Allergy Asthma Proc. 2018 Sep 14;39(5):365-370. doi: 10.2500/aap.2018.39.4164. Epub 2018 Aug 14.
The first subcutaneous (SC) C1-esterase inhibitor concentrate (C1-INH) was approved by the U.S. Food and Drug Administration in June 2017 as routine prophylaxis to prevent hereditary angioedema attacks in adolescents and adults at a dose of 60 IU/kg twice weekly based on the phase III Clinical Study for Optimal Management of Preventing Angioedema With Low-volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT) trial.
This article aimed to evaluate the relationship of the C1-INH (SC) dose regimens tested in the COMPACT trial (40 IU/kg and 60 IU/kg twice weekly) and the occurrence of adverse events (AEs).
Patients were instructed to record any AEs in their e-diary daily. Safety and tolerability were assessed based on reported AEs, including injection-site reactions (ISRs); unsolicited AEs (AEs other than ISRs); serious AEs; thrombotic, thromboembolic, anaphylactic, hypersensitivity, sepsis, and bacteremia events; inhibitory antibodies to C1-INH; and clinically significant abnormalities in laboratory assessments. Information on ISRs was specifically solicited.
No relationship between the dose of C1-INH (SC) and the incidence of ISRs or unsolicited AEs was observed. The proportion of injections followed by at least one ISR was 12% with C1-INH (SC) 40 IU/kg versus 5% with 60 IU/kg and 6% with placebo. No ISRs were serious or led to treatment discontinuation, and all resolved. There were no anaphylaxis, thromboembolic, sepsis, or bacteremia events reported during treatment with C1-INH (SC). All hypersensitivity AEs were nonserious, and the majority were assessed as being unrelated to treatment. No inhibitory antibodies to C1-INH were observed.
C1-INH (SC) is safe and well tolerated with no dose-dependent safety concerns, as demonstrated in the COMPACT trial.Clinical trial NCT01912456,
2017年6月，美国食品药品监督管理局批准首款皮下注射C1酯酶抑制剂浓缩物（C1-INH），根据预防血管性水肿的皮下C1抑制剂低容量替代疗法最佳管理的III期临床研究（COMPACT）试验，其作为常规预防措施，用于预防青少年和成人遗传性血管性水肿发作，剂量为60 IU/kg，每周两次。
本文旨在评估COMPACT试验中测试的C1-INH（皮下注射）剂量方案（40 IU/kg和60 IU/kg，每周两次）与不良事件（AE）发生情况之间的关系。
指导患者每天在电子日记中记录任何不良事件。根据报告的不良事件评估安全性和耐受性，包括注射部位反应（ISR）；自发不良事件（非ISR的不良事件）；严重不良事件；血栓形成、血栓栓塞、过敏、超敏反应、败血症和菌血症事件；针对C1-INH的抑制性抗体；以及实验室评估中的临床显著异常。特别询问了有关ISR的信息。
未观察到C1-INH（皮下注射）剂量与ISR或自发不良事件发生率之间的关系。C1-INH（皮下注射）40 IU/kg时，至少发生一次ISR的注射比例为12%，而60 IU/kg时为5%，安慰剂组为6%。没有ISR是严重的或导致治疗中断，所有ISR均已缓解。在C1-INH（皮下注射）治疗期间，未报告过敏、血栓栓塞、败血症或菌血症事件。所有超敏反应不良事件均不严重，大多数被评估为与治疗无关。未观察到针对C1-INH的抑制性抗体。
如COMPACT试验所示，C1-INH（皮下注射）安全且耐受性良好，不存在剂量依赖性安全问题。临床试验NCT01912456，<网址 xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</网址> 。
