Treatment of refractory myositis. A randomized crossover study of two 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 cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (IV MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Results. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with IV MTX during the crossover period. Of the 15 patients initially randomized to IV MTX therapy, 3 improved with the IV therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with IV therapy (P = 0.09). Conclusion. Combination oral MTX/AZA may benefit patients with treatment- resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. IV MTX with leucovorin rescue may also benefit some patients with refractory myositis.