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 (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.
Villalba
L
L
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Hicks
J E
JE
Adams
E M
EM
Sherman
J B
JB
Gourley
M F
MF
Leff
R L
RL
Thornton
B C
BC
Burgess
S H
SH
Plotz
P H
PH
Miller
F W
FW
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
D000964:Antimetabolites, Antineoplastic; D018501:Antirheumatic Agents; D001379:Azathioprine; D002955:Leucovorin; D008727:Methotrexate