title: Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens.
abstract: 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 (I.V. 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 I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. 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 I.V. therapy (P = 0.09).
  
  
  CONCLUSIONS
  Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: L
authors.initials: L
authors.lastname: Villalba
authors.forename: J E
authors.initials: JE
authors.lastname: Hicks
authors.forename: E M
authors.initials: EM
authors.lastname: Adams
authors.forename: J B
authors.initials: JB
authors.lastname: Sherman
authors.forename: M F
authors.initials: MF
authors.lastname: Gourley
authors.forename: R L
authors.initials: RL
authors.lastname: Leff
authors.forename: B C
authors.initials: BC
authors.lastname: Thornton
authors.forename: S H
authors.initials: SH
authors.lastname: Burgess
authors.forename: P H
authors.initials: PH
authors.lastname: Plotz
authors.forename: F W
authors.initials: FW
authors.lastname: Miller
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009220:Myositis / Q000188:drug therapy*; D016879:Salvage Therapy
chemical_list: D000964:Antimetabolites, Antineoplastic; D018501:Antirheumatic Agents; D001379:Azathioprine; D002955:Leucovorin; D008727:Methotrexate