Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early Rheumatoid Arthritis

Objectives To explore the 10-year tolerability profile of GC use in patients with early RA. Methods Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. Results Among the 608 patients (480 women, mean age of 47.5 ± 12.1 years), 397 (65%) received low-dose GC (median 1.9 mg/day [IQR 0.6-4.2], mean cumulative prednisone dose 8468 mg ±8376, mean duration 44.6 months ± 40.1). In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (p= 0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, p= 0.007), CVDs (7.9%, p= 0.001) and severe infections (9.9%, p= 0.024). The risk of events over time was significantly associated with GC, age, hypertension and erythrocyte sedimentation rate. The risk associated with GC treatment increased between the first follow-up visit (HR at 1 year = 0.46, 95% CI 0.23 - 0.90) and 10 years (HR = 6.83, 95% CI 2.29-20.35). Conclusion The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. Trial registration (NCT03666091).