Infection risks associated with b/tsDMARDs in rheumatoid arthritis: a systematic review and network meta-analysis

To evaluate infection risks in rheumatoid arthritis (RA) patients with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) as monotherapy or combined with conventional synthetic DMARDs (csDMARDs).

A comprehensive literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from their inception to 31 October 2024 was conducted to identify randomized controlled trials (RCTs) assessing infection risks in RA patients receiving b/tsDMARDs. Primary outcome was serious infection incidence; secondary outcomes included any infection and specific events such as respiratory tract infections, gastroenteritis and herpes zoster. A frequentist network meta-analysis was performed to calculate odds ratios (ORs).

A total of 127 RCTs involving 55,749 patients were included. b/tsDMARD monotherapy showed a similar risk of serious infections versus csDMARDs. Combining csDMARDs with adalimumab, infliximab, tofacitinib, or upadacitinib (though not with other b/tsDMARDs) was associated with a significantly increased risk of serious infections (OR 1.51, 95% CI: 1.04-2.19; OR 1.75, 95% CI: 1.09-2.81; OR 2.52, 95% CI: 1.26-5.03; OR 2.31, 95% CI: 1.13-4.73). For any infection, b/tsDMARD monotherapy posed a similar risk to csDMARDs, except for etanercept. Certain tsDMARDs were associated with an increased incidence of herpes zoster versus csDMARDs, except for filgotinib and peficitinib.

Compared to csDMARDs, b/tsDMARD monotherapy showed no elevated serious infection risk, whereas specific combinations increased the risk of serious infections in RA patients. A clinical reference pathway was developed to inform drug selection optimization for RA patients receiving b/tsDMARDs.