Very Low Dose Prednisolone on Newly Diagnosed Rheumatoid Arthritis

Objective To investigate the efficacy of prednisolone 4mg/day added to standard of care in newly diagnosed rheumatoid arthritis (RA) patients with active disease.

Hypothesis Add-on prednisolone 4mg/day is efficacious compared to placebo in newly diagnosed RA patients with active disease.

Design and subjects This is a 12-week, randomized, placebo-controlled, double-blind study. We plan to enroll 112 adult patients with newly diagnosed active RA (Disease Activity Score 28-C-Reactive Protein \[DAS28-CRP\] \> 3.2). They will be randomized 1:1 to receive prednisolone 4mg once daily for 5 weeks then tapering at 1mg/week each week till off or placebo. Conventional synthetic disease-modifying-anti-rheumatic-drugs (DMARDs) will be started and adjusted according to a standard protocol aiming to achieve low disease activity. Patients with contra-indications to prednisolone, or requiring biologic or targeted synthetic DMARDs will be excluded.

Study instruments Clinical response will be monitored using DAS28-CRP every 4 weeks. Adverse events (AE), severe AE (SAE) and AE of special interest (AESI) will be recorded at every visit.

Main outcome measures and analysis The primary outcome is the change of DAS28-CRP comparing the two groups at week-4 by student T test. Secondary outcomes include the changes of DAS28-CRP at week-8 and week-12 as well as proportion of patients with AE comparing the two groups. Independent factors predicting disease control will be analyzed by multivariate logistic regression.