King's College London, London, UK.
Arthritis Rheumatol. 2021 May;73(5):779-788. doi: 10.1002/art.41580. Epub 2021 Mar 25.
JAK inhibitor therapies are effective treatment options for immune-mediated inflammatory diseases (IMIDs), but their use has been limited by venous thromboembolism (VTE) risk warnings from licensing authorities. We undertook this study to evaluate the VTE risk of JAK inhibitors in patients with IMIDs.
Systematic searches of Medline and Embase databases from inception to September 30, 2020 were conducted. Phase II and phase III double-blind, randomized controlled trials (RCTs) of JAK inhibitors at licensed doses were included in our analyses. RCTs with no placebo arm, long-term extension studies, post hoc analyses, and pooled analyses were excluded. Three researchers independently extracted data on exposure to JAK inhibitors or placebo and VTE events (e.g., pulmonary embolism [PE] and deep vein thrombosis [DVT]) and assessed study quality.
A total of 42 studies were included, from an initial search that yielded 619. There were 6,542 JAK inhibitor patient exposure years (PEYs) compared to 1,578 placebo PEYs. There were 15 VTE events in the JAK inhibitor group and 4 in the placebo group. The pooled incidence rate ratios (IRRs) of VTE, PE, and DVT in patients receiving JAK inhibitors were 0.68 (95% confidence interval [95% CI] 0.36-1.29), 0.44 (95% CI 0.28-0.70), and 0.59 (95% CI 0.31-1.15), respectively.
This meta-analysis of RCT data defines the VTE risk with JAK inhibitors as a class in IMID patients. The pooled IRRs do not provide evidence that support the current warnings of VTE risk for JAK inhibitors. These findings will aid continued development of clinical guidelines for the use of JAK inhibitors in IMIDs.
JAK 抑制剂疗法是治疗免疫介导的炎症性疾病（IMIDs）的有效治疗选择，但由于许可机构对静脉血栓栓塞（VTE）风险的警告，其应用受到限制。我们进行这项研究是为了评估 JAK 抑制剂在 IMIDs 患者中的 VTE 风险。
系统检索了 Medline 和 Embase 数据库，检索时间从建库至 2020 年 9 月 30 日。我们的分析纳入了 JAK 抑制剂在许可剂量下的 II 期和 III 期双盲、随机对照试验（RCTs）。不包括无安慰剂组、长期扩展研究、事后分析和汇总分析的 RCTs。三位研究人员独立提取 JAK 抑制剂或安慰剂暴露和 VTE 事件（如肺栓塞[PE]和深静脉血栓形成[DVT]）的数据，并评估了研究质量。
共纳入 42 项研究，最初检索到 619 项研究。JAK 抑制剂组有 6542 例患者暴露年（PEY），安慰剂组有 1578 例 PEY。JAK 抑制剂组有 15 例 VTE 事件，安慰剂组有 4 例。接受 JAK 抑制剂治疗的患者 VTE、PE 和 DVT 的汇总发生率比（IRR）分别为 0.68（95%置信区间[95%CI] 0.36-1.29）、0.44（95%CI 0.28-0.70）和 0.59（95%CI 0.31-1.15）。
这项对 RCT 数据的荟萃分析定义了 JAK 抑制剂类药物在 IMID 患者中的 VTE 风险。汇总 IRR 并未提供支持 JAK 抑制剂 VTE 风险当前警告的证据。这些发现将有助于继续制定 JAK 抑制剂在 IMIDs 中的使用临床指南。
