Efficacy of Methotrexate in Myasthenia Gravis

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.