PharmD Candidate University of Houston College of Pharmacy, United States
Background: Janus Kinase inhibitors (JAKi) are a class of disease-modifying medications for rheumatoid arthritis (RA). Despite their positive therapeutic outcomes, studies have raised concerns regarding the risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE).
Objectives: This systemic review examined the risk of VTE with the use of JAKi versus Tumor Necrosis Factor inhibitors (TNFi) in patients with RA using real-world data.
Methods: This systematic review was conducted based on an a priori established protocol guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed/MEDLINE, EMBASE, and Cochrane/CENTRAL were utilized to extract relevant studies using the search terms: “RA”, “JAKi”, “TNFi” and “VTE”. Only English language observational or administrative claim studies comparing the risk of VTE with the use of JAKi or TNFi in RA were included. Two authors independently screened, retrieved full articles, and extracted data from observational studies that evaluated the VTE risk in patients using JAKi or TNFi for RA. Any conflict was resolved through discussion with the senior investigator. The risk of bias in the included studies was evaluated using the tool of the Quality in Prognosis Studies (QUIPS) tool.
Results: The systemic review identified 188 studies; seven observational studies met the inclusion criteria. These observational studies included a total of 234,854 patients; 40,829 were JAKi users and 140,577 were TNFi users. Four studies were conducted in the United States, and the other three were from France, Taiwan, Japan, and Sweden. Three studies used administrative claims datasets (Marketscan, Medicare), electronic medical records (EMR), and US registry, and the other four studies used non-US databases. Most studies were retrospective cohort studies, and all studies used a new user design. The average follow-up period of the studies was 32 months to 7 years. Of the three studies (N=3) that compared the risk of VTE between JAKi and TNF bDMARDs, two studies found an increased risk of VTE with JAKi use as compared to TNFi and one study reported no association between VTE risk with JAKi. Of the four drug-specific studies (N=4), three found no difference in VTE risk between tofacitinib vs TNFi; however, one found there was an increased risk of VTE with baricitinib vs TNFi.
Conclusions: The systemic review found mixed evidence regarding the risk of VTE with JAKi as compared to TNFi, and the JAKi class-specific VTE risk as compared to TNFi in RA was also unclear. However, there was variation in the risk of VTE with individual JAKi vs. TNFi. Future studies are needed to evaluate drug-specific VTE risk within the class of JAKi in RA.
