title: Modified-release prednisone for polymyalgia rheumatica: a multicentre, randomised, active-controlled, double-blind, parallel-group study.
abstract: OBJECTIVE
  To assess the efficacy and safety of modified-release (MR) versus immediate-release (IR) prednisone in newly diagnosed glucocorticoid (GC)-naïve patients with polymyalgia rheumatica (PMR).
  
  
  METHODS
  Patients were randomised to double-blind MR prednisone (taken at approximately 22:00) or IR prednisone (taken in the morning), 15 mg/day for 4 weeks. The primary end point was complete response rate (≥70% reduction in PMR visual analogue scale, duration of morning stiffness and C reactive protein (CRP) (or CRP <2× upper limit of normal (ULN))) at week 4. Non-inferiority was decided if the lower 95% confidence limit (MR vs IR prednisone) was above -15%. 400 patients were planned but only 62 were enrolled due to difficulties in recruiting GC-naïve patients with PMR with CRP ≥2×ULN.
  
  
  RESULTS
  The percentage of complete responders at week 4 was numerically greater for MR prednisone (53.8%) than for IR prednisone (40.9%). Non-inferiority of MR versus IR prednisone was not proven in the primary analysis on the per protocol population (N=48; treatment difference: 12.22%; 95% CI -15.82% to 40.25%). However, sensitivity analysis on the full analysis population showed an evident trend favouring MR prednisone (N=62; treatment difference: 15.56%; 95% CI -9.16% to 40.28%). Adverse events were generally mild and transient with no unexpected safety observations.
  
  
  CONCLUSIONS
  The study showed a clear trend for favourable short-term efficacy of MR prednisone versus IR prednisone in early treatment of PMR. Further studies are warranted.
  
  
  BACKGROUND
  EudraCT number 2011-002353-57; Results.
authors.affiliation: Research Laboratories and Academic Division of Clinical Rheumatology , University of Genova , Genova , Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Mundipharma Research GmbH & Co. KG , Limburg, Hessen , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hopp
authors.affiliation: Mundipharma Research GmbH & Co. KG , Limburg, Hessen , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebscher
authors.affiliation: Department of Rheumatology , Southend University Hospital , Westcliff-on-Sea , UK.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Dasgupta
authors.affiliation: Department of Rheumatology and Clinical Immunology , Charité University Medicine , Berlin , Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
keywords: Autoimmune Diseases; Corticosteroids; Inflammation; Polymyalgia Rheumatica; Treatment