Mycophenolate Mofetil in Myasthenia Gravis
Mycophenolate Mofetil in Myasthenia Gravis
This is a prospective, multi-center, double-blind, placebo-controlled trial to determine the
 efficacy and safety of mycophenolate mofetil (MM) in combination with prednisone as the
 initial form of immunosuppression in patients with acquired myasthenia gravis (MG).
80 patients with seropositive MG at 18 academic centers will be randomized to 3 months of
 treatment with 2.5 gm MM/day (1,250 mg q 12 hours, +/- 2 hours) plus 20 mg prednisone/day
 versus placebo plus 20 mg/day prednisone. The primary measure of efficacy will be the change
 from baseline in Quantitative MG (QMG) score at the end of 3 months. Secondary outcome
 measures include survival analysis for treatment failure, MG-related impairment of daily
 activities, functional assessment, manual muscle testing, SF-36 Health Status, and serum
 concentration of antibodies to the acetylcholine receptor. Study completers will have the
 option of taking open-label MM for an additional 6 months, during which prednisone will be
 reduced to the lowest dose necessary to maintain the optimum clinical response.
Inclusion criteria

 1. Acquired generalized MG diagnosed by one of the Principal Investigators based on:

 -  Examination by site PI showing myasthenic weakness that is not limited to the
 ocular or peri-ocular muscles.

 -  Elevated acetylcholine receptor antibodies.

 -  Positive edrophonium chloride test or abnormal neuromuscular transmission
 demonstrated by single fiber EMG or repetitive nerve stimulation.

 2. Aged at least 18.

 3. Able to give informed consent.

 4. Taking a constant dose of Mestinon for at least 2 weeks.

 5. Symptom severity that would, in the judgment of the site investigator, justify
 initiation of immunosuppressive treatment.

 6. Able and willing to comply with study requirements.

 Exclusion criteria

 1. Thymoma now or in the past.

 2. Plasma exchange or IVIG treatment within 90 days of randomization.

 3. Treatment with azathioprine, cyclosporine, mycophenolate mofetil, or other
 immunosuppressive medication since onset of MG. Treatment with prednisone or other
 corticosteroids within the previous 90 days.

 • Exception: patients may have taken doses of these immunosuppressant medications that
 are judged by the Principal Investigator to have been clinically insignificant, i.e.
 unlikely to produce improvement in MG.

 4. Women of childbearing potential who are pregnant, breast-feeding or not practicing
 effective contraception.

 5. Renal failure, active thyroid or hepatocellular disease, chronic infection, poorly
 controlled cardiac disease, or any other illness, including psychiatric disease, that
 would, in the opinion of the treating physician, make it unsafe for the patient to
 participate or would interfere with the interpretation of study results.

 6. Weakness affecting only ocular or peri-ocular muscles (Myasthenia Gravis Foundation of
 America Class I).

 7. Severe weakness predominantly affecting oropharyngeal, respiratory muscles or both
 (MGFA Class IVB).

 8. Crisis or impending crisis (defined as FVC <10ml/Kg or bulbar weakness severe enough
 to compromise airway protection.)

 9. Hemoglobin <10mg/dl; WBC <3,500.

 10. History of non-compliance with treatment and office visits.

 11. Thymectomy within 12 months before randomization.

 12. Concurrent medical condition that would pose an unacceptable risk from
 immunosuppression, including a positive skin test for tuberculosis (PPD), unless the
 patient has previously received appropriate treatment.