OBJECTIVES: In rheumatoid arthritis (RA), low-dose glucocorticoids (GCs) demonstrate disease-modifying potential when added to DMARDs. Modified-release (MR) prednisone taken at bedtime (released 2am) is more effective than immediate-release (IR) GC taken in the morning. METHODS: In an open-label observational study, 950 RA outpatients (mean age 57 ± 13 years; 75% females) treated with GCs and DMARDs (83.7% methotrexate, 10.5% leflunomide; 15.8% biologics) were switched from IR-prednisone or 6-methyl (6M)-prednisolone to low-dose MR-prednisone and followed for 4 months. Morning stiffness duration (MS), pain intensity (numerical rating scale [NRS], 0-10), patient and physician global assessment (GA, 0-10 scale) and disease activity score (DAS28) were assessed at baseline, 2 and 4 months. RESULTS: 513 patients were switched to MR-prednisone from IR-prednisone (9.4±5.4 mg) and 437 from 6M-prednisolone (6.7±3.7 mg). Among 920 patients (96.8%) completing 4-months' MR-prednisone treatment, MS decreased from 58±37 min at T1 to 32±24 min at endpoint (p<0.001); NRS pain intensity reduced from 5.4±1.8 to 3.5±1.4 (p<0.001), and patient and physician GA scores improved from 5.4±1.7 to 3.5±1.4 and 5.1±1.7 to 3.3±1.4, respectively (p<0.001). DAS28 score decreased from 4.2±1.4 to 3.3±1.2 (p<0.001). Mean daily MR-prednisone dosage decreased from 8.2mg to 6.7mg between baseline and endpoint and significantly higher improvements in MS, NRS pain and GA scores were seen in patients switched from 6M-prednisolone versus IR-prednisone. MR-prednisone was well tolerated. CONCLUSIONS: Switching GC-treated RA patients to low-dose MR-prednisone significantly improved outcomes over 4 months