OP0116 TEN-YEAR ANALYSIS OF VERY LOW-DOSE GLUCOCORTICOIDS IN EARLY RA (ESPOIR COHORT) SUPPORTS A TIME-DEPENDENT RISK OF SEVERE OUTCOMES
Authors: C. Roubille, A. Coffy, N. Rincheval, M. Dougados, R. M. Flipo, J. P. Daures, B. Combe
Journal: Annals of the Rheumatic Diseases (2020)

Background: We previously failed to find any significant difference with regard to severe outcomes (death, severe infections, fractures, cardiovascular diseases [CVD]) between recent-onset RA patients taking or not low-dose GC treatment in a 7-year analysis of the ESPOIR cohort (1). Objectives: To explore the 10-year tolerability profile of GC use in patients with early RA. Methods: We analysed data from the early arthritis (less than 6 months disease duration) ESPOIR cohort. Patients were stratified in two groups, with or without GC treatment at least once during their follow-up (median 10 years IQR [9-10]). The primary outcome was a composite of death, CVD (including myocardial ischemia, cerebrovascular accident and heart failure), severe infection and fracture. In order to reduce the impact of treatment selection bias and potential confounding factors, the weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. Results: Among the 608 RA patients (480 women, mean age of 47.5 ± 12.1 years), 397 patients (65%) received low-dose prednisone (median 1.9 mg/day [IQR 0.6-4.2], mainly during the first 6 months (70%). The mean duration of GC treatment was 44.6 months ± 40.1. Overall, 95 events were identified during follow-up: 10 deaths, 18 CVD, 32 fractures and 35 severe infections. Based on univariate analysis at 10 years, patients taking GC experienced significantly more events (n=71) than those without GC (n=24) (p=0.035), especially severe infections (n=30 with GC versus 5 without GC, p=0.009) (table 1), with a cumulative dose effect (p=0.007). On weighted Cox time-dependent analysis, using the IPTW propensity score method, the risk of events over time was significantly associated with GC treatment (p &lt;0.001), age, history of hypertension and erythrocyte sedimentation rate. The risk associated with GC treatment, estimated by the hazard ratio (HR), increased between the first follow-up visit (HR at 6 months = 0.39, 95% CI 0.19-0.82) and 10 years (HR=6.83, 95% CI 2.29-20.35 ) (figure 1 and table 2). Table 1. Primary outcome and events at 10 years: univariate analysis Total study population (n=608) Without GC With CG P Value Primary outcome 95 (15.6%) 24 (11.4%) 71 (17.9%) 0.035 Death 10 (1.6%) 1 (0.5%) 9 (2.3%) 0.103 Cardiovascular diseases 18 (3%) 3 (1.4%) 15 (3.8%) 0.177 Severe infections 35 (5.8%) 5 (2.4%) 30 (7.6%) 0.009 Fractures 32 (5.3%) 15 (7.1%) 17 (4.3%) 0.137 Table 2. Time-dependent relationship between glucocorticoids treatment and risk of events estimated by hazard ratio Time (Months) Hazard Ratio (95% CI) 12 0.46 (0.23 - 0.90) 24 0.62 (0.36 - 1.08) 36 0.83 (0.52 - 1.33) 48 1.12 (0.73 - 1.72) 60 1.52 (0.96 - 2.40) 72 2.05 (1.19 - 3.52) 84 2.77 (1.44 - 5.34) 96 3.74 (1.69 - 8.26) 108 5.05 (1.98 - 12.91) 120 6.83 (2.29 - 20.35) Figure 1. Time-dependent relationship between glucocorticoids treatment and risk of events estimated by hazard ratio (HR ) Conclusion: This 10-year analysis of the ESPOIR cohort supports a dose and time-dependent impact of very low-dose GC treatment in early RA, with a long-term high risk of severe outcomes. Disclosure of Interests: Camille Roubille Consultant of: Servier, Pfizer, Novartis, Amandine Coffy: None declared, Nathalie Rincheval: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Jean-Pierre Daures: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp &amp; Dohme; Pfizer; Roche-Chugai; UCB