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

Nie Liu-Yan; Zhao Kun; Xu Cheng; Liu Ming-Hao; Jin Xue-Xiao; Han Yong-Mei

doi:10.1016/j.heliyon.2023.e17002

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

Heliyon. 2023 Jun 4;9(6):e17002. doi: 10.1016/j.heliyon.2023.e17002. eCollection 2023 Jun.

Authors

Nie Liu-Yan¹, Zhao Kun², Xu Cheng¹, Liu Ming-Hao¹, Jin Xue-Xiao^{1

3}, Han Yong-Mei¹

Affiliations

¹ Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
³ Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

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, I² = 0.00%); OR = 4.49, 95% CI 0.56 to 35.93, I² = 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.

Keywords: Gastrointestinal perforation; Hepatic disorder; Rheumatoid arthritis; Upadacitinib.