Phase II trial of methotrexate in myasthenia gravis

Ann N Y Acad Sci. 2012 Dec;1275(1):23-8. doi: 10.1111/j.1749-6632.2012.06804.x.


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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Double-Blind Method
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Methotrexate / therapeutic use*
  • Myasthenia Gravis / drug therapy*
  • Myasthenia Gravis / physiopathology
  • Placebos
  • Quality of Life


  • Immunosuppressive Agents
  • Placebos
  • Methotrexate