Lasa Juan S, Olivera Pablo A, Bonovas Stefanos, Danese Silvio, Peyrin-Biroulet Laurent
IBD Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigación Clínica (CEMIC), Buenos Aires, Argentina.
Gastroenterology Department, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.
Drug Saf. 2021 Jun;44(6):645-660. doi: 10.1007/s40264-021-01057-z. Epub 2021 Mar 5.
Sphingosine-1-phosphate modulators are approved for the treatment of multiple sclerosis and are under development for other immune-mediated conditions; however, safety concerns have arisen.
The objective of this systematic review was to investigate the safety profile of S1P modulators in patients with multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and systemic lupus erythematosus.
We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1 January, 1990 through 1 April, 2020. We also performed a manual review of conference databases from 2017 through 2020. The primary outcome was the occurrence of adverse events and serious adverse events. We also estimated the occurrence of serious infections, herpes zoster infection, malignancy, bradycardia, atrio-ventricular block, and macular edema. We performed a meta-analysis of controlled studies to assess the risks of such events.
We identified 3843 citations; of these, 26 studies were finally included, comprising 9604 patients who were exposed to a sphingosine-1-phosphate modulator. A meta-analysis of randomized controlled trials showed an increased risk in herpes zoster infection [risk ratio, 1.75 (95% confidence interval 1.09-2.80)], bradycardia [2.64 (1.77-3.96)], and atrio-ventricular block [1.73 (1.03-2.91)] among subjects exposed to sphingosine-1-phosphate modulators as compared with a placebo or an active comparator.
We found an increased risk of herpes zoster infection, and transient cardiovascular events among patients treated with sphingosine-1-phosphate modulators.
PROSPERO CRD42020172575.
鞘氨醇-1-磷酸调节剂已被批准用于治疗多发性硬化症，并且正在针对其他免疫介导疾病进行研发；然而，安全性问题已经出现。
本系统评价的目的是调查鞘氨醇-1-磷酸调节剂在多发性硬化症、溃疡性结肠炎、克罗恩病、银屑病和系统性红斑狼疮患者中的安全性。
我们检索了1990年1月1日至2020年4月1日期间的MEDLINE、EMBASE和Cochrane对照试验中央注册库。我们还对2017年至2020年的会议数据库进行了人工检索。主要结局是不良事件和严重不良事件的发生情况。我们还估计了严重感染、带状疱疹感染、恶性肿瘤、心动过缓、房室传导阻滞和黄斑水肿的发生情况。我们对对照研究进行了荟萃分析，以评估这些事件的风险。
我们识别出3843条引文；其中，最终纳入26项研究，包括9604例暴露于鞘氨醇-1-磷酸调节剂的患者。对随机对照试验的荟萃分析显示，与安慰剂或活性对照相比，暴露于鞘氨醇-1-磷酸调节剂的受试者发生带状疱疹感染[风险比，1.75（95%置信区间1.09 - 2.80）]、心动过缓[2.64（1.77 - 3.96）]和房室传导阻滞[1.73（1.03 - 2.91）]的风险增加。
我们发现接受鞘氨醇-1-磷酸调节剂治疗的患者发生带状疱疹感染和短暂性心血管事件的风险增加。
PROSPERO CRD42020172575。
