Cancers and cardiovascular diseases in patients with seropositive rheumatoid arthritis treated with JAK inhibitors, biologics and conventional synthetic DMARDs

Abstract

Objectives: Janus kinase inhibitors and biologics (JAKi/biologics) are cornerstone treatments for rheumatoid arthritis (RA). We evaluated the risks of cancers and cardiovascular diseases (CVDs) in patients with seropositive RA (SPRA) treated with JAKi/biologics.

Methods: Patients with new-onset SPRA during 2010-2020 in the national healthcare database were identified. Events of overall and site-specific cancers, as well as CVD outcomes, including deep vein thrombosis, pulmonary embolism, and composite cardiovascular events, were investigated. The relative risk of cancers and CVDs compared to conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) users was compared by evaluating the incidence rate ratios (IRRs). Time-dependent Cox analyses were performed to evaluate the relationship between JAKi/biologics usage and patient outcomes.

Results: A total of 101,816 and 96,220 patients with SPRA were analysed for cancers and CVD outcomes, respectively. Compared with patients treated only with csDMARDs, the IRRs of overall cancers and CVDs in patients administered JAKi/biologics were 0.88 (95% confidence interval [CI] 0.86-0.89) and 0.91 (95% CI 0.90-0.92), respectively. Site-specific lung, liver, prostate, and skin cancers were more frequent in JAKi/biologics users; JAKi did not confer a greater risk of overall CVDs and cancers compared with other biologics and csDMARDs. JAKi/biologics usage was not accounted for overall cancers and CVDs in adjusted Cox analyses.

Conclusions: The incidence of overall cancer and CVD were not increased in patients with SPRA treated with JAKi/biologics and was relatively lower than csDMARD only users, underscoring optimal disease control for risk mitigation. The higher incidence of several site-specific cancers requires further investigation.