Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis
Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis
Pathology - Generalized myasthenia gravis (MG) is cause of muscle weakness that can have a
 significant impact on daily life activity but can also be, when respiratory or bulbar muscles
 are involved, life-threatening.

 Rationale - Additionally to thymectomy, which indication of is still debated in absence of
 thymoma, the long-term treatment of generalized myasthenia gravis includes usually prednisone
 and azathioprine. However, the most used scheme for prescribing and tapering corticosteroid
 in MG resulted in a very important cumulative dose of prednisone. Indeed, at twelve month,
 more than 50 percent of patients are still daily treated with at least 18 mg of prednisone
 and the proportion of patients who are in remission and no longer taking prednisone is very
 low (Palace and NEWSOM Davis, Neurology 1998). Prolonged corticosteroid therapy is
 accompanied with various and major side effects, hypertension, osteoporosis, weight gain,
 glaucoma. Therefore, tapering, eventually discontinuing, prednisone earlier is a relevant
 therapeutic goal.

 For this reason, the investigators will compare to the standard one, a strategy consisting of
 a rapid decrease in corticosteroid.

 Objective - To assess whether, in patients with generalized MG requiring a long-term
 treatment with corticosteroids and azathioprine, that the strategy of rapid tapering allows
 discontinuing more rapidly the prednisone for equivalent efficacy than the classical
 strategy.
Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the
 patient fulfils the criteria for improvement or minimal manifestation state, in order to
 discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.

 Classical strategy consists of decreasing the prednisone dose if at each monthly consultation
 the patient fulfils the criteria for minimal manifestation state, in order to discontinue it
 before twelve months. The starting dose is 1.5 mg/kg/2days.

 Duration of follow-up is 15 months.

 In both arms, Myasthenia Muscular Score (MMS), activities of Daily Living Scale (ADLS), MGFA
 Clinical Classification and MGFA Post-Intervention Status as well as prednisone and
 azathioprine side effects will be monthly assessed by a senior neurologist who will be blind
 for treatment group. A second physician, who is aware of the patient's therapeutic group,
 will then prescribe prednisone dose and tapering for a month, according to MGFA
 Post-Intervention Status.

 In case of worsening, prednisone dose will be increased. In case of exacerbation, the
 patients will be hospitalised for eventually IvIg infusion or plasma exchange. In case of a
 severe side effect, prednisone will be reduced irrespectively of MGFA Post-Intervention
 Status. In case of side effect, azathioprine will be replaced by mycophenolate mofetil.
Inclusion Criteria:

 -  Written consent of the patient, after informing

 -  Generalized MG of grade III, IV or V - Classification MGFA

 -  Follow-up on 15 months possible and accepted by patients

 Exclusion Criteria:

 -  Age<18 or >80 years

 -  Pregnancy

 -  Myasthenia of grade I or II of MGFA

 -  Patients already treated with prednisone or azathioprine

 -  Contraindication for prednisone or azathioprine

 -  Other associated disease requiring a treatment with prednisone or azathioprine

 -  Weight >100kg

 -  Invasive thymoma