Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis
Condition: Myasthenia Gravis
MeSH terms: Myasthenia Gravis; Muscle Weakness
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Prednisone - Azathioprine
Intervention type(s): Drug
Intervention description(s): 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.
Intervention MeSH terms: Prednisone; Azathioprine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Myasthenia gravis; Steroids side effects; Comparison of strategies for tapering steroids; Generalized MG corresponding to grade III, IV or V of MGFA