AUTHOR=Zhang Juqi , Li Wenhui , Gong Mingli , Gu Yanlun , Zhang Hanxu , Dong Bingqi , Guo Qi , Pang Xiaocong , Xiang Qian , He Xu , Cui Yimin 

TITLE=Risk of venous thromboembolism with janus kinase inhibitors in inflammatory immune diseases: a systematic review and meta-analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1189389

DOI=10.3389/fphar.2023.1189389

ISSN=1663-9812

ABSTRACT=<p><bold>Objectives:</bold> This study aimed to evaluate the risk of venous thrombosis (VTE) associated with Janus kinase (JAK) inhibitors in patients diagnosed with immune-mediated inflammatory diseases.</p><p><bold>Methods:</bold> We conducted a comprehensive search of PUBMED, Cochrane, and Embase databases for randomized controlled trials evaluating venous thromboembolic incidence after administering JAK inhibitors in patients with immune-mediated inflammatory diseases. The studies were screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and a meta-analysis was performed.</p><p><bold>Results:</bold> A total of 16 studies, enrolling 17,242 participants, were included in this review. Four approved doses of JAK inhibitors were administered in the included studies. The meta-analysis revealed no significant difference in the incidence of VTE between patients receiving JAK inhibitors, a placebo, or tumor necrosis factor (TNF) inhibitors (RR 0.72, 95% CI (0.33-1.55); RR 0.94, 95%CI (0.33-2.69)). Subgroup analysis showed a lower risk of VTE with lower doses of JAK inhibitors [RR 0.56, 95%CI (0.36-0.88)]. Compared with the higher dose of tofacitinib, the lower dose was associated with a lower risk of pulmonary embolism [RR 0.37, 95%CI (0.18-0.78)].</p><p><bold>Conclusion:</bold> Our meta-analysis of randomized controlled trials observed a potential increase in the risk of VTE in patients with immune-mediated inflammatory diseases treated with JAK inhibitors compared to placebo or tumor necrosis factor inhibitors, though statistical significance was not attained. Notably, a higher risk of pulmonary embolism was observed with high doses of tofacitinib. Our findings provide valuable insights for physicians when evaluating the use of JAK inhibitors for patients with immune-mediated inflammatory diseases.</p><p><bold>Systematic Review Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023382544" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023382544</ext-link>, identifier CRD42023382544</p>