title: 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%).
  
  
  CONCLUSIONS
  Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms.   CLINICALTRIALS.GOV, NUMBER:  NCT00650078.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin 10117, Germany. frank.buttgereit@charite.de
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.forename: Daksha
authors.initials: D
authors.lastname: Mehta
authors.forename: John
authors.initials: J
authors.lastname: Kirwan
authors.forename: Jacek
authors.initials: J
authors.lastname: Szechinski
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.forename: Rieke E
authors.initials: RE
authors.lastname: Alten
authors.forename: Jerzy
authors.initials: J
authors.lastname: Supronik
authors.forename: Istvan
authors.initials: I
authors.lastname: Szombati
authors.forename: Ulrike
authors.initials: U
authors.lastname: Romer
authors.forename: Stephan
authors.initials: S
authors.lastname: Witte
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D055870:Drug Chronotherapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D011241:Prednisone