Malignancy risk in patients with rheumatoid arthritis initiating biological or targeted synthetic disease-modifying antirheumatic drugs: a 5-year population-based cohort study

Background: Data regarding malignancy risk amongst rheumatoid arthritis (RA) patients using biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) was conflicting, and real-world Taiwanese data was lacking. Objectives: To compare the malignancy risk and to investigate factors associated with malignancies amongst RA patients initiating b/tsDMARDs. Design: Nationwide, population-based, retrospective cohort study. Methods: We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database from 2001 to 2020. Adult patients with newly diagnosed, biologic-naïve RA were included if they initiated b/tsDMARDs, and those with prior malignancies were excluded. The primary outcome was the first diagnosis of malignancies after b/tsDMARD initiation. Time-dependent Cox proportional hazards models were performed to evaluate malignancy risk across different b/tsDMARDs and to identify independent risk factors. Results: A total of 8732 adult RA patients were included. Over both 5-year and extended 18-year follow-up periods, there was no statistically significant difference in malignancy risk amongst the four treatment groups (tumour necrosis factor inhibitors (TNFis), tocilizumab, abatacept and tsDMARDs). Independent associated factors included male gender, older age at b/tsDMARD initiation, chronic lung diseases including chronic obstructive pulmonary disease and higher-dose corticosteroid prescription. Use of conventional DMARDs and more frequent ambulatory follow-up were associated with a lower risk. Conclusion: In this Taiwanese nationwide RA cohort, b/tsDMARD class demonstrated no difference in malignancy risk within 5 years after their initiation. Clinicians should instead focus on individual associated factors, particularly male gender, older age at b/tsDMARD initiation, chronic lung diseases and higher-dose corticosteroid exposure, while optimising the protective role of conventional DMARDs and regular follow-up for better disease control.