Time-varying risks of infection in patients as they proceed through the phases of ‘pre-RA’: results from the Scottish Early RA inception cohort

Rheumatoid arthritis (RA) develops after progressing through sequential ‘pre-RA’ phases. The mechanisms driving progression from one phase to the next remain poorly understood. This study examined the longitudinal rates of community and hospital infections in patients during sequential stages of pre-RA and early arthritis. METHODS: The Scottish Early RA inception cohort recruited patients with newly diagnosed RA. Incidences of infection were determined from community antibiotic prescriptions and serious infections were determined by hospital discharge coding. Dates of diagnosis and symptom onset allowed identification of asymptomatic/symptomatic pre-RA and early arthritis eras to analyse infection rates over time compared with age- and sex-matched controls. RESULTS: The incidence rate ratio (IRR) seen in the period 0–6 months prior to symptom onset was 1.28 (95% CI 1.15 to 1.42). In ‘symptomatic pre-RA’, the IRR was 1.33 (95% CI 1.18 to 1.49) which persisted into ‘early arthritis’. The rate of hospital admissions was numerically greater in ‘pre-RA’ and significantly greater in ‘early arthritis’ (IRR 1.82, 95% CI 1.32 to 2.46). CONCLUSION: Antibiotic risk is increased in patients with ‘pre-RA’ at least 6 months before symptoms develop, and this persists throughout the symptomatic pre-RA phase. Infections may be important in the mechanisms that drive progression to RA or be a manifestation of immune dysfunction (or both). These observations could inform safety and efficacy considerations for interventions in pre-RA to prevent progression. Patients with ‘pre-RA’ with recurrent antibiotic use may also be an identifiable ‘high risk’ group that could enrich the study population for intervention studies in pre-RA.