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Age-related adverse events of disease-modifying treatments for multiple sclerosis: A meta-regression
Multiple Sclerosis Journal ( IF 5.8 ) Pub Date : 2020-10-26 , DOI: 10.1177/1352458520964778
Luca Prosperini 1 , Shalom Haggiag 1 , Carla Tortorella 1 , Simonetta Galgani 1 , Claudio Gasperini 1
Affiliation  

OBJECTIVE To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action. METHODS We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms. RESULTS A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51, p < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52, p = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms (p = 0.017), especially above 45 years of age. DISCUSSION Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.

中文翻译:

多发性硬化症改善治疗的年龄相关不良事件:元回归

目的 验证在具有不同作用机制的疾病缓解治疗 (DMT) 下,多发性硬化 (MS) 患者感染和肿瘤随年龄增加而增加的假设。方法 我们从 45 项关于目前获得许可的 DMT 的随机临床试验 (RCT) 中提取相关数据。我们将逆方差加权元回归与随机效应模型拟合,以估计当前获得许可的 DMT 的年龄和/或作用机制(免疫调节、隔离和消耗)是否影响了实验组和对照组之间特定疾病发生率的差异。不良事件,即总体感染、机会性感染和肿瘤。结果 在具有消耗性 DMT 的 RCT 中观察到更高的总体感染发生率(事件率比 = 1.25,p < 0.001)。在 RCT 中更频繁地观察到疱疹感染,其中既有消耗性(事件率比 = 3.51,p < 0.001),也有在较小程度上隔离 DMT(事件率比 = 1.52,p = 0.078)。年龄与消耗性 DMT 的相互作用与更高的肿瘤发生率(p = 0.017)相关,尤其是在 45 岁以上。讨论 我们的研究支持年龄对消耗性 DMT 安全性的不利影响,尤其是 45 岁以上的肿瘤发病率增加。我们未能证明与年龄相关的感染发生率增加,可能是由于其发生的潜伏期。年龄与消耗性 DMT 的相互作用与较高的肿瘤发病率相关(p = 0.017),尤其是在 45 岁以上。讨论 我们的研究支持年龄对消耗性 DMT 安全性的不利影响,尤其是 45 岁以上的肿瘤发病率增加。我们未能证明与年龄相关的感染发生率增加,可能是由于其发生的潜伏期。年龄与消耗性 DMT 的相互作用与更高的肿瘤发生率(p = 0.017)相关,尤其是在 45 岁以上。讨论 我们的研究支持年龄对消耗性 DMT 安全性的不利影响,尤其是 45 岁以上的肿瘤发病率增加。我们未能证明与年龄相关的感染发生率增加,可能是由于其发生的潜伏期。
更新日期:2020-10-26
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