Modified-release prednisone for polymyalgia rheumatica: a multicentre, randomised, active-controlled, double-blind, parallel-group study

Objective: To assess the efficacy and safety of modified-release (MR) versus immediate-release (IR) prednisone in newly diagnosed glucocorticoid (GC)naive 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 <2x 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-naive patients with PMR with CRP =2xULN. 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. Trial registration number: EudraCT number 2011-002353-57; Results.