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

Frank Buttgereit, Daksha Mehta, John Kirwan, Jacek Szechinski, Maarten Boers, Rieke E Alten, Jerzy Supronik, Istvan Szombati, Ulrike Romer, Stephan Witte, Kenneth G Saag, Frank Buttgereit, Daksha Mehta, John Kirwan, Jacek Szechinski, Maarten Boers, Rieke E Alten, Jerzy Supronik, Istvan Szombati, Ulrike Romer, Stephan Witte, Kenneth G Saag

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.

Conflict of interest statement

Competing interests: FB received consultancy fees, honoraria and travel expenses from Merck Serono, Horizon Pharma (formerly Nitec Pharma) Mundipharma Int Ltd and grant support from Merck Serono and Horizon Pharma. JK received honoraria, consultancy fees, grants and travel expenses paid to his institution from Horizon Pharma (formerly Nitec Pharma), AstraZeneca, CombinatoRx, GlaxoSmithKline, Merck and Wyeth. MB received consultancy fees from Augurex, Bristol-Myers Squibb, CombinatoRx, GlaxoSmithKline, Medimmune, Horizon Pharma (formerly Nitec Pharma), Mundipharma and Roche; honoraria from Genentech, Novartis and Sanofi; and payment for development of educational presentations from Schering-Plough and UCB. REA received consultancy fees and honoraria from Merck Serono and Horizon Pharma (formerly Nitec Pharma) and travel expenses and payment for development of educational presentations from Merck Serono. KGS received consultancy fees, honoraria and travel expenses from Merck Serono, Horizon Pharma (formerly Nitec Pharma), Novartis, Roche, Amgen, UCB, Genentech and Eli Lilly, and grant support from Merck Serono, Proctor & Gamble, Roche, GlaxoSmithKline, Amgen and Eli Lilly. SW and UR are employees of Horizon Pharma and have stock options. DM, JSz, JSu and IS reported no conflicts of interest.

Figures

Figure 1
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
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

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