Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA, USA.
Division of Cardiology, Department of Internal Medicine, Lahey Hospital Medical Center, Burlington, MA, 01805, USA.
Am J Cardiovasc Drugs. 2024 Nov;24(6):791-799. doi: 10.1007/s40256-024-00672-2. Epub 2024 Aug 21.
Mavacamten is a first-in-class cardiac myosin inhibitor approved by the US Food and Drug Administration (FDA) for symptomatic obstructive hypertrophic cardiomyopathy (HCM). This pharmacovigilance study aimed to assess mavacamten-related adverse drug reactions (ADRs) in the real world as reported in the FDA Adverse Event Reporting System (FAERS).
We conducted disproportionality analyses with four signal detection algorithms-reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and the multi-item gamma Poisson shrinker to identify mavacamten-related ADRs.
Out of 4,500,131 reports from the FAERS database, 1004 mavacamten-related ADRs were identified from 1 January 2022 to 30 September 2023. A total of 26 significant disproportionality preferred terms (PTs) conforming to the four signal detection algorithms were noted. Some of the statistically significant cardiac ADRs at PT level include decreased ejection fraction (EF) [ROR 33.60 (95% confidence interval, CI 21.79-51.82), PRR 32.86 (χ 615.96), information component (IC) 5.03, IC025 4.61, empirical Bayesian geometric mean (EBGM) 32.77, EBGM05 21.25], cardiac failure [ROR 9.39 (95% CI 6.49-13.60), PRR 9.13 (χ 202.42), IC 3.19, IC025 2.83, EBGM 9.12, EBGM05 6.30], and atrial fibrillation [ROR 16.63 (95% CI 12.72-21.75), PRR 15.66 (χ 769.93), IC 3.97, IC025 3.71, EBGM 15.64, EBGM05 11.96].
The results of our study were consistent with the safety data of clinical trials, including reduced ejection fraction, atrial fibrillation, dyspnea, and syncope. We also found potential new and unexpected ADR signals, such as urinary tract infection, gout, and peripheral edema.
Mavacamten 是一种首创的心肌肌球蛋白抑制剂，已被美国食品和药物管理局 (FDA) 批准用于治疗有症状的梗阻性肥厚型心肌病 (HCM)。本项药物警戒研究旨在通过 FDA 不良事件报告系统 (FAERS) 评估现实世界中报告的 Mavacamten 相关药物不良反应 (ADR)。
我们使用四种信号检测算法——报告比值比 (ROR)、比例报告比 (PRR)、贝叶斯置信传播神经网络和多项伽马泊松收缩器进行了不成比例性分析，以识别与 Mavacamten 相关的 ADR。
在 FAERS 数据库的 4500131 份报告中，我们于 2022 年 1 月 1 日至 2023 年 9 月 30 日期间确定了 1004 份与 Mavacamten 相关的 ADR。共有 26 个符合四种信号检测算法的显著不成比例性首选术语 (PT) 被注意到。在 PT 水平上，一些具有统计学意义的心脏 ADR 包括射血分数降低 [ROR 33.60 (95%置信区间，CI 21.79-51.82)，PRR 32.86 (χ 615.96)，信息成分 (IC) 5.03，IC025 4.61，经验贝叶斯几何平均值 (EBGM) 32.77，EBGM05 21.25]、心力衰竭 [ROR 9.39 (95% CI 6.49-13.60)，PRR 9.13 (χ 202.42)，IC 3.19，IC025 2.83，EBGM 9.12，EBGM05 6.30] 和心房颤动 [ROR 16.63 (95% CI 12.72-21.75)，PRR 15.66 (χ 769.93)，IC 3.97，IC025 3.71，EBGM 15.64，EBGM05 11.96]。
我们的研究结果与临床试验的安全性数据一致，包括射血分数降低、心房颤动、呼吸困难和晕厥。我们还发现了一些潜在的新的和意外的 ADR 信号，如尿路感染、痛风和外周水肿。
