背景:囊性纤维化跨膜调节因子(CFTR)通道调节剂(ivacaftor,lumacaftor,tezacaftor和elexacaftor)代表了囊性纤维化治疗的重大进展。然而,关于这些药物的真实安全性的数据很少,特别是可能导致其停药的不良事件。这项研究的目的是描述导致停药的tezacaftor/ivacaftor/elexacaftor组合的不良反应的特征和演变,并报告给雷恩(法国)的药物警戒中心(CRPV)。
方法:从2021年12月至2023年5月进行了一项回顾性研究,重点研究了由于发生一种或多种不良反应而停用tezacaftor/ivacaftor/elexacaftor组合的病例,并向雷恩的CRPV报告,法国。
结果:向RennesCRPV报告了10例停药(6名女性/4名男性)。不良反应主要涉及神经精神疾病(n=6),其次是肝脏疾病(n=2),耳朵,鼻子和喉咙疾病(n=1),和消化系统疾病(n=1)。停药时的平均治疗持续时间为339.8[39-668]天。7名患者在停药后平均48.7[7-123]天重新使用该药物,剂量调整(n=4)包括给药时间的变化或每日剂量的减少,根据具体情况,在缓解不良症状方面取得了不同的成功。
结论:这个小病例系列表明,在开始使用tezacaftor/ivacaftor/elexacaftor后,神经精神不良反应可能比最初描述的更频繁。并应仔细筛选和监测。对于经历这些不良反应的患者,可以考虑剂量或给药方案修改。需要进一步的药物警戒研究,以更好地了解“自助餐厅”的不良反应概况,他们可能的风险因素,以及调整给药方式的影响。
BACKGROUND: Cystic fibrosis transmembrane regulator (CFTR) channel modulators (ivacaftor, lumacaftor, tezacaftor and elexacaftor) represent a major advance in the management of cystic fibrosis. However, few data are available on the real-life safety profile of these medications, in particular on adverse events that may lead to their discontinuation. The aim of this study is to describe the characteristics and evolution of adverse reactions to the tezacaftor/ivacaftor/elexacaftor combination that led to discontinuation and were reported to the Centre régional de pharmacovigilance (CRPV) in Rennes (France).
METHODS: A retrospective study was conducted from December 2021 to May 2023, focusing on cases of discontinuation of the tezacaftor/ivacaftor/elexacaftor combination due to the occurrence of one or more adverse effects, and reported to the CRPV of Rennes, France.
RESULTS: Ten cases of drug discontinuation were reported to the Rennes CRPV (6 women/4 men). Adverse effects mainly involved neuropsychiatric disorders (n=6), followed by liver disorders (n=2), ear, nose and throat disorders (n=1), and digestive disorders (n=1). The average duration of treatment at discontinuation was 339.8 [39-668] days. The drug was reintroduced in 7 patients on average 48.7 [7-123] days after discontinuation, with a dosage adjustments (n=4) consisting of changes in dosing times or a reduction in daily doses, with varying success in alleviating adverse symptoms depending on the case.
CONCLUSIONS: This small case series suggests that neuropsychiatric adverse effects may occur more frequently than initially described after initiation of tezacaftor/ivacaftor/elexacaftor, and should be carefully screened and monitored. Dosage or administration schedule modifications may be considered for patients experiencing these adverse effects. Further pharmacovigilance studies are needed to better understand the adverse effect profiles of \"caftors\", their possible risk factors, and the impact of adjusting dosing modalities.