TREATMENT OF REFRACTORY MYOSITIS - A RANDOMIZED CROSSOVER STUDY OF 2 NEW CYTOTOXIC REGIMENS

Objective. To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Methods. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cyt otoxic therapy? were randomized to begin either a combination of weekl y oral methotrexate and daily azathioprine (MTX/AZA) or intravenous me thotrexate with leucovorin rescue (IV MTX) every 2 weeks for 6 months, Crossover to the alternate therapy occurred according to defined rule s; evaluations of muscle strength and functional abilities were perfor med at the beginning, and after 3 and 6 months, of each treatment. Res ults. Of the 15 patients initially randomized to oral MTX/AZA, 8 impro ved with oral therapy and 1 improved with TV MTX during the crossover period, Of the 15 patients initially randomized to IV MTX therapy, 3 i mproved with the IV therapy and 4 with the oral combination during the crossover period, Although the study lacked the power to directly com pare both treatments, intention-to-treat analysis showed a trend in fa vor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral co mbination therapy and 0.16 per patient-month with IV therapy (P = 0.09 ). Conclusion. Combination oral MTX/AZA may benefit patients with trea tment-resistant myositis, including those who previously had inadequat e responses to either MTX or AZA alone. IV MTX with leucovorin rescue may also benefit some patients with refractory myositis.