Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2)

Abstract

Objective: To assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release (MR) formulation for the treatment of rheumatoid arthritis (RA).

Methods: In this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12. Changes in morning pain, duration of morning stiffness, 28-joint Disease Activity Score and health-related quality of life were also assessed.

Results: MR prednisone plus DMARD treatment produced higher response rates for ACR20 (48% vs 29%, p<0.001) and ACR50 (22% vs 10%, p<0.006) and a greater median relative reduction from baseline in morning stiffness (55% vs 35%, p<0.002) at week 12 than placebo plus DMARD treatment. Significantly greater reductions in severity of RA (Disease Activity Score 28) (p<0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score) (p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p<0.001) were seen at week 12 for MR prednisone versus placebo. The incidence of adverse events was similar for MR prednisone (43%) and placebo (49%).

Conclusion: Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms. CLINICALTRIALS.GOV, NUMBER: NCT00650078.

Figure 1

Patient disposition. A total of 350 patients were enrolled from 50 centres in six countries: Germany (3 centres, 3 patients), UK (3 centres, 12 patients), Poland (10 centres, 145 patients), Hungary (9 centres, 102 patients), Canada (2 centres, 13 patients) and USA (23 centres, 75 patients). AE, adverse event; MR, modified release.

Figure 2

Improvements in rheumatoid arthritis symptoms. (A) Percentage of patients achieving a 20% improvement in rheumatoid arthritis signs and symptoms according to American College of Rheumatology criteria (ACR20) (primary end point). p<0.003 for the between-group difference at weeks 2, 6 and 12. (n Values for weeks 2, 6 and 12 were 231, 229 and 229, respectively, for the modified-release (MR) prednisone group and 119, 119 and 119, respectively, for the placebo group.) (B) Change in duration of morning stiffness from baseline. p<0.004 for the between-group difference at weeks 2, 6 and 12. (n Values for weeks 2, 6 and 12 were 228, 220 and 216, respectively, for the MR prednisone group and 119, 112 and 107 for the placebo group.)