Infection Risk Profiles of Upadacitinib in Patient with Rheumatoid Arthritis: A Meta-Analysis of Randomized Clinical Trials

Abstract

Background There is a increasing suggestion that upadacitinib may elevate the risk of infections in patients with rheumatoid arthritis (RA). To better understand this potential infection risk, we conducted a meta-analysis using data from randomized clinical trials (RCTs) to evaluate the overall risk of infections in these patients. Methods We conducted a comprehensive systematic search in EMBASE, MEDLINE, and CENTRAL from their inception until 31st December 2023 to identify relevant RCTs reporting the occurrence of infections in patients with RA who were treated with monotherapy upadacitinib (15mg once daily orally) regardless of the background RA therapy used in these patients. The primary outcomes were the incidence of total infections, serious infections, non-serious infections, and opportunistic infections (including herpes zoster and tuberculosis). The secondary outcomes were the incidence of various sites of infections, including the upper respiratory tract, lower respiratory tract, gastrointestinal tract and others. In anticipation of study heterogeneity, the effect estimate was pooled with a random-effects model, to obtain the risk ratios (RR) and 95% confidence intervals (CI), using Mantel-Haenszel statistical method. Results Nine RCTs were included, involving a total of 4,575 RA patients. Compared to the control group (placebo and other active treatments), patients treated with upadacitinib exhibited a significant increase in the risk of total infections (RR, 1.18; 95% CI, 1.02-1.36; I2, 49%), and non-serious infections (RR, 1.16; 95% CI, 1.01-1.34; I2, 46%). Patients who were on upadacitinib were significantly at an increased risk of gastrointestinal infections (RR, 3.10; 95% CI, 1.47-6.56; I2, 0%) but not on other types of infections. Conclusion Compared with placebo and other active treatments, upadacitinib signi?cantly increased the overall risk of infections (total infections and non-serious infections), particularly gastrointestinal infections. These ?ndings may assist clinicians to weigh the benefit-risk balance of upadacitinib prior to their administration to patients with RA.