Non-melanoma skin cancer risk with Janus kinase inhibitors compared to interleukin-6 receptor inhibitors in rheumatoid arthritis: results from a national cohort study.

Abstract

Non-melanoma skin cancer (NMSC) is one of the most common malignancies in rheumatoid arthritis (RA). This analysis assessed NMSC risk with Janus kinase inhibitors (JAKi) compared to interleukin-6 receptor inhibitors (IL-6Ri). This study used data from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA) linked to National Cancer Registration and Analysis Service (NCRAS). People with RA initiating first JAKi or IL-6Ri without prior exposure to the comparator class were included. The primary analysis was ever-exposed model with first 90 days after treatment initiation excluded. Cox proportional hazards models estimated hazard ratios (HRs) with inverse probability of treatment weighting (IPTW) to adjust for confounding. Secondary analysis was on-treatment analysis. A total of 3,985 people with RA were included in primary analysis, with 116 first-ever NMSC recoded. The IPTW HR for JAKi vs IL-6Ri was 1.64 (95% CI: 0.85, 3.17). The IPTW-weighted absolute rate difference was 3.3 events per 1,000 person-years with JAKi versus IL-6Ri, which is around one additional NMSC event for every 307 patients who initiated JAKi rather than IL-6Ri and followed for 1 year. In on-treatment analysis, 32 and 19 NMSC events occurred among patients actively receiving IL-6Ri and JAKi, with IPTW HR of 1.82 (95% CI: 0.84, 3.96). Initiation of JAKi was associated with a clinically small, plausibly higher NMSC risk than IL-6Ri, although not statistically significant over 3.3 years. Rheumatologists and patients should weigh the potential risk of NMSC against the benefits of disease control when considering treatment choices.