Very-low-dose glucocorticoid therapy in rheumatoid arthritis: impact of b/tsDMARDs initiation timing on glucocorticoid withdrawal

Objectives: We investigated the effectiveness and safety of very-low-dose (<5 mg/day) glucocorticoids (GCs) in patients with RA treated with biologic and targeted synthetic DMARDs (b/tsDMARDs). Methods: In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very-low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very-low-dose GCs on safety was also evaluated. Results: We enrolled 229 RA patients, of whom 68% were prescribed very-low-dose GCs and 32% received no GCs. After 3 years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off and 23% had permanently discontinued very-low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very-low-dose GC cessation [odds ratio 1.1 (95% CI 1.03, 1.14) for any 1-year decrease; P = 0.001]. A significant association existed between ongoing utilization of very-low-dose GCs and persistent moderate disease activity. Use of very-low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%). Conclusion: A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very-low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.