Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs

Abstract

Introduction: Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce.

Methods: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years.

Results: In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups.

Conclusion: In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.