OP0263 FAVORABLE BALANCE OF BENEFIT AND HARM OF LONG-TERM, LOW-DOSE PREDNISOLONE ADDED TO STANDARD TREATMENT IN RHEUMATOID ARTHRITIS PATIENTS AGED 65+: THE PRAGMATIC, MULTICENTER, PLACEBO- CONTROLLED GLORIA TRIAL

Abstract

Background/Purpose: Low‐dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. We studied the effects of prednisolone (5 mg/day, 2 years) added to standard of care in patients aged≥65 with active RA (1988 or 2010 criteria). Methods: Pragmatic double‐blind placebo‐controlled randomized trial; all co‐treatments and changes therein were allowed during the trial except long‐term open label GC; Ca/D supplementation was advised in all patients. Minimal exclusion criteria were tailored to seniors. Benefit outcomes: disease activity (DAS28) and joint damage (Sharp/van der Heijde). Harm outcome: proportion of patients with ≥1 adverse event (AE) of special interest: includes serious events, GC‐specific events and those causing study discontinuation. Analysis: longitudinal models, one‐sided testing and 95% confidence limits (95%CL). Results: We randomized 451 patients with established, impactful RA and mean 2.1 comorbidities: mean age 72 (max 88) years, 70% female, RA duration 11 years; 67% were RF+, 56% ACPA+, 96% had joint damage on radiographs; mean DAS28 4.5. 79% were on disease‐modifying treatment, including 14% on biologics. 63% prednisolone vs 61% placebo patients completed the trial. Discontinuations were for AE (14%), active disease (4%), and for other (incl. COVID‐related) reasons (20%) in both groups; mean time in study 19 months. Prednisolone resulted in more benefit and harm than placebo. Disease activity rapidly declined in the first 3 months and stabilized after 1 year (Figure 1), and was lower in prednisolone patients (adjusted mean difference in DAS28 over 2 years: 0.37, 95%CL 0.23, p< 0.0001). In 331 patients adherent to protocol on stable treatment ('pure treatment comparison') the mean difference in DAS28 after 3 months was 0.62 (95%CL 0.44). Significant time‐treatment interaction in secondary analyses suggested a decrease in contrast after the first year; this was most likely caused by significantly more changes in DMARD treatment favoring the placebo group. Joint damage progression over 2 years was 1.7 point lower in the prednisolone group (95%CL 0.7, p=0.003). 60% prednisolone vs 49% placebo patients experienced the harm outcome: 60 vs 49%, adjusted RR 1.24, 95%CL 1.04, p=0.02; largest contrast in (mostly non‐severe) infections (Table 1). Other GC‐specific events were rare. In both groups, AE clustered in a subgroup of patients (Figure 2). Conclusion: Add‐on low dose prednisolone has powerful long‐term effects in established RA, with a tradeoff of 24% relative (11% absolute) increase in the number of patients with adverse events, mostly non‐severe; this suggests a favorable balance of benefit and harm.