Efficacy of Methotrexate in Myasthenia Gravis
Efficacy of Methotrexate in Myasthenia Gravis
Myasthenia gravis is a rare neuromuscular disorder characterized by weakness and fatigability
 of ocular, bulbar, and extremity musculature. The specific aim of this study is to determine
 if oral methotrexate is an effective therapy for myasthenia gravis (MG) patients who are
 prednisone dependent. Patients will be randomized to receive either methotrexate or placebo
 and those who are entered onto this trial will have symptoms and signs of the disease while
 on prednisone therapy. The hypothesis is that adding methotrexate therapy in these patients
 will improve the MG manifestations so that the prednisone dose can be reduced and clinical
 measures of MG severity will improve.

 Funding Source - FDA OOPD
Inclusion Criteria:

 -  Patients must have MGFA MG grades 2, 3, or 4 generalized myasthenia gravis, according
 to the MGFA classification system

 -  Elevated acetylcholine receptor antibody (AChR-Ab) titer.

 -  Patient's signs and symptoms should not be better explained by another disease
 process.

 -  Prednisone dose of at least 10 mg/day (or the equivalent in alternate days) and the
 subject must be on a stable dose of prednisone for 30 days prior to the screening
 visit.

 Exclusion Criteria:

 -  A history of chronic degenerative, psychiatric, or neurologic disorder other than MG
 that can produce weakness or fatigue.

 -  Other major chronic or debilitating illnesses within six months prior to study entry.

 -  Female patients who are premenopausal and are: (a) pregnant on the basis of a serum
 pregnancy test, (b) breast-feeding, or (c) not using an effective method of double
 barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth
 control (birth control pills, male condom, female condom, intrauterine device,
 Norplant, tubal ligation, or other sterilization procedures).

 -  Altered levels of consciousness, dementia, or abnormal mental status.

 -  Evidence of thymoma on chest CT or MRI. Such a finding could require immediate
 thymectomy and would preclude entry into the study.

 -  Thymectomy in the previous three months.

 -  Patients who have been medicated with azathioprine, cyclosporine, cyclophosphamide,
 mycophenolate mofetil, IVIg, or other immunosuppressive drugs within the last 60 days.

 -  Chest X-ray with evidence of tumor, infection, or interstitial lung disease.

 -  Clinical history of chronic or recurrent infections.

 -  Daily use of non-steroidal anti-inflammatory drugs (NSAIDs).

 -  History of renal or hepatic insufficiency or liver enzymes greater than the upper
 limit of normal.

 -  History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia,
 clinical or laboratory evidence of immunodeficiency syndromes.

 -  Forced Vital Capacity (FVC) <50% of predicted.

 -  MG Grade 1 (ocular only) or 5 (crisis, requiring ventilator).

 -  Prior use of methotrexate for any condition.