Evaluation of serious infections, including Mycobacterium tuberculosis, during treatment with biologic disease-modifying anti-rheumatic drugs: does line of therapy matter?

Objectives: This study aimed to evaluate if and how the incidence of serious infection (SI) and active tuberculosis (TB) differ among seven biologic DMARDs (bDMARDs) in patients with RA considering the line of therapy.

Methods: Patients with RA from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) cohort who initiated etanercept, certolizumab, infliximab, adalimumab, abatacept, rituximab or tocilizumab from the first to fifth line of therapy were included. Follow-up extended up to 3 years. The primary outcome was SI and the secondary outcome was TB. Event rates were calculated and compared using Cox proportional hazards models, controlling for confounding with inverse probability of treatment weights. Comparisons were made overall and stratified by line of therapy. Sensitivity analysis was restricted to all treatment courses from 2009 (tocilizumab availability) until the end of the study (2018).

Results: Among 33 897 treatment courses (62 513 patient-years) the incidence of SI was 4.4/100 patient-years (95% CI 4.2, 4.5). After adjustment, hazards ratios (HRs) of SI were slightly higher with adalimumab and infliximab compared with etanercept. However, no clear pattern was observed when stratifying by line of therapy in terms of incidence rate or HR. Sensitivity analyses showed similar HRs among these treatments. Regarding TB, all 49 cases occurred during the first three lines of treatment and rarely since 2009.

Conclusion: The risk of serious infections does not appear to be influenced by the line of therapy in patients with RA. However, the risk of TB seems to be more frequent during the initial lines of treatment or prior to 2009.