Abstract Background/Aims Non-melanoma skin cancer (NMSC) is the most common malignancy in rheumatoid arthritis (RA). Tofacitinib, a Janus kinase inhibitor (JAKi), has been associated with higher NMSC risk than tumour necrosis factor inhibitors (TNFi) in people with RA and cardiovascular risk in the ORAL Surveillance trial. It is uncertain whether that extends to other JAKi or the broader RA population, or if tofacitinib increased the risk or simply is less protective than TNFi. This analysis aims to assess NMSC risk with JAKi compared to interleukin-6 receptor inhibitors (IL-6Ri) in RA. Methods This study used data from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a national prospective RA cohort, linked to the National Cancer Registration and Analysis Service (NCRAS). People with RA initiating their first JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib) or first IL-6Ri (tocilizumab originator, tocilizumab biosimilar, or sarilumab) without prior exposure to the comparator class and history of skin cancer were included. The outcome, the first-ever NMSC, was identified from NCRAS. The primary analysis was an ever-exposed model and the secondary analysis was an on-treatment model (exposure time definitions in the Table). Cox proportional hazards models were used to estimate hazard ratios (HRs), using propensity score weighting to control for confounding. Missing data were addressed using multiple imputation. Results A total of 4,248 patients were included in the primary ever-exposed analysis. The IL-6Ri cohort (n = 2,945) had 91 NMSC events, and the JAKi cohort (n = 1,303) had 27 events. The propensity score weighted HR for JAKi vs IL-6Ri was 1.52 (95% CI: 0.82-2.85). In the secondary on-treatment analysis, 32 and 19 NMSC events occurred in IL-6Ri and JAKi cohorts. The crude HR was 1.91 (95% CI, 1.06-3.43). After propensity score weighting, the difference between JAKi and IL-6Ri was not statistically significant (HR, 1.69, 95% CI 0.78-3.65). Conclusion This cohort analysis did not identify a statistically significant difference in the risk of NMSC between JAKi and IL-6Ri, with a median follow-up of 3.3 years in the JAKi cohort in the primary analysis. Disclosure Z. Tian: None. L. Kearsley-Fleet: None. S. Zhao: Consultancies; Novartis, UCB, AlfaSigma, AbbVie, Jassen. Other; support for conference attendance from Novartis, UCB, AlfaSigma, Eli Lilly. J. Galloway: Honoraria; Abbvie, Alfasigma, Janssen, Lilly, Novartis, Pfizer, and UCB. Grants/research support; Abbvie, GSK, Janssen and Pfizer. M. Lunt: None. K. Watson: None. N. Azadbakht: None. K. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer and BMS. Other; NIHR Manchester Biomedical Research Centre (NIHR203308).
Tian et al. (Wed,) studied this question.