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Clinical and epidemiological research
Extended report
Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2)
  1. Frank Buttgereit1,
  2. Daksha Mehta2,
  3. John Kirwan3,
  4. Jacek Szechinski4,
  5. Maarten Boers5,
  6. Rieke E Alten6,
  7. Jerzy Supronik7,
  8. Istvan Szombati8,
  9. Ulrike Romer9,
  10. Stephan Witte9,
  11. Kenneth G Saag10
  1. 1Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany
  2. 2Center for Arthritis and Osteoporosis, Elizabethtown, Kentucky, USA
  3. 3University of Bristol, Bristol, UK
  4. 4Katedra I Klinika Reumatologii I Chorob Wewnetrznych AM, Wroclaw, Poland
  5. 5VU University Medical Center, Amsterdam, Netherlands
  6. 6Department of Internal Medicine, Rheumatology, Schlosspark-Klinik, Charité Teaching Hospital, Berlin, Germany
  7. 7NZOZ Centrum Medyczne, Bialystok, Poland
  8. 8OEC, Budapest, Hungary
  9. 9Horizon Pharma GmbH, Mannheim, Germany
  10. 10Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  1. Correspondence to Frank Buttgereit, Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin 10117, Germany; frank.buttgereit{at}charite.de

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

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode

http://dx.doi.org/10.1136/annrheumdis-2011-201067

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    Footnotes

    • Funding Horizon Pharma (formerly Nitec Pharma), Mannheim, Germany and Northbrook, Illinois, USA.

    • 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.

    • Provenance and peer review Not commissioned; externally peer reviewed.