AIV INITIALLY DOUBLE-BLIND CONTROLLED 96 WEEK TRIAL OF DEPOT METHYLPREDNISOLONE AGAINST ORAL PREDNISOLONE IN THE TREATMENT OF POLYMYALGIA-RHEUMATICA

The objective was to compare the efficacy and safety of intramuscular methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in th e treatment of polymyalgia rheumatica (FMR), a common steroid-treated illness where prolonged therapy can lead to steroid side-effects. The cumulative dose with i.m. MP injections given every 3-4 weeks is consi derably smaller than that with conventional OP, and may therefore be a ssociated with fewer long-term side-effects. A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks. The study was mu lticentre hospital out-patient based and included 60 patients with unt reated PMR. In the double-blind phase, either 120 mg 3-weekly i.m. MP or gradually tapering daily OP (initial dose 15 mg) were administered. In the open phase, subjects continued their active treatment with gra dual tapering of the steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of disease activity, i.e. sedimentation r ate, pain and morning stiffness, and percentage of adverse reactions a nd serious complications such as fractures, were the main outcome meas ures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25 OP:24 i.m. MP) completed the study. There were similar remission rates after the double-blind phase (60.6% OP and 66.6% i.m. MP, respectively) and simi lar disease control in the succeeding open phase. With steroid taperin g, the mean erythrocyte sedimentation rate for the entire cohort regis tered a significant increase in the absence of an increase in symptoms . At 96 weeks, the cumulative mean steroid dose in subjects treated wi th i.m. MP was equivalent to 56% that of subjects treated with OP. The re were eight fractures with OP compared to one on i.m. MP. Mean weigh t gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg , P < 0.005). Minor adverse reactions were similar in both groups apar t from slightly increased bruising with i.m. MP. Only patients on OP r eported moon face, hypertension, cataracts, back pain and depression, but the numbers were small. It is possible to achieve equivalent long- term disease control in PMR with i.m. MP compared to OP. I.m. MP was a ssociated with far fewer fractures and lesser weight gain, presumably related to lower cumulative dose. These findings may have implications in the steroid treatment of PMR, and other rheumatic and nonrheumatic diseases.