Objective: A randomized double-blind placebo-controlled withdrawal clinical trial of prednisone versus placebo in patients with rheumatoid arthritis (RA), treated in usual clinical care with 1–4 mg prednisone per day, withdrawn to the same dose of 1 mg prednisone or identical placebo tablets.
Methods: All patients were from one academic setting; all trial visits were conducted in usual clinical care. Patients were taking stable doses of 1-4 mg prednisone, with stable clinical status, documented quantitatively by patient questionnaire scores. The protocol included three phases: “equivalence” – 1–4 study prednisone 1-mg tablets taken for 12 weeks, to ascertain their efficacy versus the patient’s usual tablets prior to randomization; “transfer” – substitution of a 1-mg prednisone or identical placebo tablet every 4 weeks (over 0-12 weeks) to the same number as baseline prednisone; “comparison” – observation over 24 subsequent weeks taking the same number of either placebo or prednisone tablets as at baseline. The primary outcome was withdrawal due to patient-reported lack of efficacy versus continuation in the trial for 24 weeks.
Results: Thirty-one patients were randomized, 15 to prednisone and 16 to placebo, with 3 administrative discontinuations. In “intent-to-treat” analyses, 3/15 prednisone and 11/16 placebo participants withdrew (p=0.03). Among participants eligible for the primary outcome, 3/13 prednisone versus 11/15 placebo participants withdrew for lack of efficacy (p=0.02). No meaningful adverse events were reported, as anticipated.
Conclusion: Efficacy of 1-4 mg prednisone was documented. Evidence of statistically significant differences with only 31 patients may suggest a robust treatment effect.