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

Camille Roubille (1, 2) , Amandine Coffy (3, 4) , Nathalie Rincheval (3, 4, 5) , Maxime Dougados (6, 7) , René-Marc Flipo (8) , Jean-Pierre Daurès (3, 4) , Bernard Combe (5, 9)

1 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 AIDMP - Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415
4 Clinique Médicale Beausoleil
5 Département de Rhumatologie[Montpellier]
6 EA 4058 - Groupe de recherche sur les maladies systémiques
7 Service de rhumatologie [CHU Cochin]
8 Service de rhumatologie[Lille]
9 IGMM - Institut de Génétique Moléculaire de Montpellier

Objectives: To explore the 10-year tolerability profile of glucocorticoids (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 ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (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: (ClinicalTrials.gov Identifier: NCT03666091).

Mots clés: Rheumatoid arthritis; early arthritis; glucocorticoids; safety outcomes

Domaines: Rhumatologie et système ostéo-articulaire; Pharmacologie

Camille Roubille, Amandine Coffy, Nathalie Rincheval, Maxime Dougados, René-Marc Flipo, et al.. Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early Rheumatoid Arthritis. Rheumatology, In press, ⟨10.1093/rheumatology/keaa850⟩. ⟨hal-03079489⟩