Impact of upadacitinib on the risk of digestive events in patients with rheumatoid arthritis: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, is an effective treatment option for rheumatoid arthritis (RA), but its use has been associated with an increased risk of digestive events. This systematic review aimed to investigate the risk of digestive events in RA patients treated with UPA. METHODS: Systematic searches of electronic databases (PubMed, Cochrane Library, and EMBASE) from inception to September 2022 were conducted to locate randomized controlled trials (RCTs) that compared UPA with control treatment and reported digestive events in RA patients. We pooled data using the random-effects model and meta-analysis was conducted by Stata software. RESULTS: Ten RCTs met the inclusion criteria and were analyzed, with a total of 6103 patients. Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), pooled analysis of 8 trials revealed no statistical difference in hepatic disorder (HD) risk and gastrointestinal (GI) perforation (GIP) risk ((OR = 1.16, 95% CI 0.86 to 1.56, I(2) = 0.00%); OR = 4.49, 95% CI 0.56 to 35.93, I(2) = 0.00%)). When we considered the influence of UPA on the grade of liver enzymes, the data indicated that grade 3 and 4 elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were infrequent. Additionally, a dose-dependent impact of UPA on the risks of HD was not observed. The results suggested no interaction by dose of drug, or indication for treatment of GIP risk. CONCLUSION: Our results showed that RA patients receiving UPA compared with csDMARDs had no significant increased risk associated with digestive events. Further long-term research of emerging data is urgently needed to gain a better understanding of the association between UPA and digestive events in the RA population.