levoleucovorin and Myositis

To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis.. 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.. 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).. 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.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antirheumatic Agents; Azathioprine; Cross-Over Studies; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Myositis; Salvage Therapy

We have sought to examine the response to immunosuppressive therapeutic intervention in inclusion body myositis (IBM) in a retrospective review of prior responses to therapy and in an open, randomized crossover trial. We collected information on the response to prior therapy on 25 patients, and for prospective therapy on 11 of these patients. All met criteria for a definite idiopathic inflammatory myopathy and had biopsy-proven IBM. Clinical and laboratory results were assessed by interviews of patients and by chart review in the retrospective trial. Manual muscle strength was assessed by a single trained observer; the patients' activities of daily living were assessed by questionnaire; and serum tests of muscle-associated enzymes were measured in the prospective trial. In the retrospective review, prednisone appeared to have been of some, albeit modest, clinical benefit in 10 of 25 (40%) patients. Other therapies, primarily azathioprine and methotrexate, also appeared to have halted the progression of weakness in 8 of 35 trials (23%). In the prospective study, combination therapy of oral azathioprine and methotrexate and a biweekly infusion of high-dose intravenous methotrexate with leucovorin rescue were given for 3 to 6 months in an open, crossover design. Both the oral and the intravenous regimens were clinically effective in some patients. There was clinical improvement in 3 trials, stabilization in 11 trials, and worsening in 5 trials, out of a total of 19 completed (22 intended) trials. The presence of active inflammation at entry into the prospective therapeutic protocol, either directly observed on muscle biopsy or indirectly indicated by serum creatine kinase level, may have been associated with clinical improvement. A complete laboratory response with normalization of creatine kinase and other muscle-associated enzymes did not, however, significantly predict clinical responsiveness in the prospective trial. In this first report, to our knowledge, of a prospective trial of immunosuppressive therapy for this disease, stabilization and even slight improvement of strength and functional abilities appeared to be achieved in some patients. We believe that prednisone and other immunosuppressive therapies were of modest benefit in about half of patients with inclusion body myositis, especially those with some evidence of active inflammation. Stabilization of an otherwise inexorably deteriorating course appears, therefore, to be an attainable goal in so

Topics: Adult; Aged; Autoantibodies; Azathioprine; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Inclusion Bodies; Leucovorin; Male; Methotrexate; Middle Aged; Muscles; Myositis; Prednisone; Prospective Studies; Retrospective Studies

A patient with toxoplasmosis had cerebellar, spinal cord, nerve root, and skeletal muscle symptoms. Toxoplasma gondii was isolated from skeletal muscle, and toxoplasma antibody titers were persistently elevated. The disease has been recurrent during a 3-year period with only temporary response to specific antimicrobial therapy.

Topics: Antigens; Biopsy; Cerebellar Ataxia; Complement Fixation Tests; Creatine Kinase; Gold Colloid, Radioactive; Humans; Leucovorin; Lymphocyte Activation; Lymphocytes; Male; Methylene Blue; Middle Aged; Mitogens; Muscles; Myositis; Pyrimethamine; Recurrence; Serologic Tests; Sulfadiazine; Toxoplasmosis