title: Morning stiffness response with delayed-release prednisone after ineffective course of immediate-release prednisone.
abstract: OBJECTIVE
  To assess morning stiffness in rheumatoid arthritis (RA) patients switched from immediate-release (IR) to delayed-release (DR) prednisone.
  
  
  METHODS
  Circadian Administration of Prednisone in Rheumatoid Arthritis-1 (CAPRA-1) is a 12-week, randomized, multicentre, active-controlled study of morning stiffness that consisted of a double-blind phase and a 9-month open-label extension. Patients receiving IR prednisone with no significant improvement after the double-blind study were switched to DR prednisone. Morning stiffness duration and median absolute and relative changes in pain and global assessment were evaluated (3, 6, and 9 months).
  
  
  RESULTS
  In patients switched from IR to DR prednisone (n=110), statistically significant reductions in morning stiffness occurred over 3 months and were sustained for 9 months. Absolute reduction of morning stiffness was ~50 min with >40% relative reduction at each visit. Interleukin (IL)-6 levels were reduced by the same amount. Statistically significant and clinically meaningful mean reductions in morning stiffness were maintained at >67 min at each visit along with significant improvements in pain and patient global assessment. There was no evidence of tachyphylaxis seen over the 9-month study.
  
  
  CONCLUSIONS
  Patients receiving disease-modifying anti-rheumatic drugs (DMARDs) and IR prednisone who had not had significant reductions in morning stiffness demonstrated statistically significant and clinically meaningful improvements when switched to DR prednisone.
authors.affiliation: a Schlosspark-Klinik , Charité University Medicine , Berlin , Germany.
authors.forename: R
authors.initials: R
authors.lastname: Alten
authors.affiliation: b University of Illinois , Chicago , IL , USA.
authors.forename: R
authors.initials: R
authors.lastname: Holt
authors.affiliation: c Horizon Pharma , Deerfield , IL , USA.
authors.forename: A
authors.initials: A
authors.lastname: Grahn
authors.affiliation: d Premier Research , Naperville , IL , USA.
authors.forename: P
authors.initials: P
authors.lastname: Rice
authors.affiliation: c Horizon Pharma , Deerfield , IL , USA.
authors.forename: J
authors.initials: J
authors.lastname: Kent
authors.affiliation: e Charité University Medicine , Berlin , Germany.
authors.forename: F
authors.initials: F
authors.lastname: Buttgereit
authors.affiliation: f Hospital for Special Surgery , New York , NY , USA.
authors.forename: A
authors.initials: A
authors.lastname: Gibofsky
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002940:Circadian Rhythm / Q000502:physiology*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D010147:Pain Measurement; D011241:Prednisone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D016059:Range of Motion, Articular / Q000187:drug effects / Q000502:physiology*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003692:Delayed-Action Preparations; D015850:Interleukin-6; D011241:Prednisone