Abstract

Objective To identify risk of serious infections (SI) according to initial conventional synthetic DMARDs (csDMARD) and CS, in patients recruited to the National Early Inflammatory Arthritis Audit. Methods An observational cohort study was used, including adults in England and Wales with new diagnoses of RA between 2018 and 2023. The main outcome was SI events, defined as infections requiring hospitalization/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios (HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments. Results A total of 17 472 patients were included, of whom 10 997 were on MTX-based strategies, 4540 on other csDMARDs and 13 680 received CS. There were 1307 SI events, corresponding to incidence rates (IR) per 100 person-years of 3.02 (95% CI 2.86–3.19) and 311 cases of SI-related mortality (IR 0.69, 95% CI 0.61–0.77). MTX-based strategies were associated with reduced risk of SI events compared with other csDMARDs (adjusted HR 0.72, 95% CI 0.63–0.82). In unadjusted models, CS was associated with higher risk of SI events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI 0.87–1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive and having high DAS based on 28 joint count (DAS28) were all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI event by 10%. Conclusion MTX-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.