Phase II trial of methotrexate in myasthenia gravis.
Author(s): Pasnoor M, He J, Herbelin L, Dimachkie M, Barohn RJ; Muscle Study Group.
Collaborators: Nations S, Jackson C, Burns T, Benatar M, Elsheikh B, Jackson C,
Burns T, Benatar M, Elsheikh B, Howard J, Walk D, Katz J, Swenson A, Shaibani A,
Simpson E, Wicklund M, Saperstein D, Pulley M, Bril V, Genge A, Becker M, Wang A,
Latinis K, Amato A, Ensrud E, Goldstein J.
Affiliation(s): University of Kansas Medical Center, Kansas City, Kansas, USA. mpasnoor@kumc.edu
Publication date & source: 2012, Ann N Y Acad Sci. , 1275:23-8
Prednisone is a frequently used treatment for myasthenia gravis (MG) but it has
numerous side effects. Methotrexate is a selective inhibitor of dihydrofolate
reductase and lymphocyte proliferation and is an effective immuosuppressive
medication for autoimmune diseases. Given the negative results of the
mycophenolate mofetil study, search for an effective immunosuppressant drug
therapy is ongoing. The objective is to determine if oral methotrexate is safe
and effective for MG patients who take prednisone. We have initiated a
randomized, double-blind, placebo-controlled multicenter trial of methotrexate
versus placebo in patients taking at least 10 mg/day of prednisone at enrollment.
The methotrexate dose is increased to 20 mg and the prednisone dose is adjusted
per protocol during the study. Clinical and laboratory evaluations are performed
monthly for 12 months, with the primary efficacy measure being the nine-month
prednisone area under the curve (AUC) from months 3 to 12. Secondary outcome
measures include MG outcomes, quality of life measures, and a polyglutamation
biomarker assay. A total of 18 U.S. sites and 2 Canadian sites are participating,
with 48 screened cases, 42 enrolled, with 19 still active in the study.
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