Myasthenia gravis (MG) is caused by antibodies produced by the immune system that impair the transmission of nerve impulses to muscles. This results in muscle weakness that characteristically fluctuates. About one person in every 10 000 - 50 000 develops MG each year. The natural history of the disorder is typically a series of exacerbations and remissions. Severe attacks can be life-threatening because of weakness of muscles involved in swallowing causing choking, and chest muscles causing difficulty with breathing. In MG, immunosuppressant drugs act mainly by reducing the production of antibodies.
There were seven randomised controlled trials to include in this review. Each trial compared different interventions in generalised MG: (1) azathioprine plus initial prednisolone versus prednisolone - 41 participants; (2) azathioprine plus prednisolone versus prednisolone plus placebo (dummy treatment) - 34 participants; (3) ciclosporin monotherapy versus placebo - 20 participants; (4) ciclosporin plus prednisolone versus prednisolone plus placebo - 39 participants; (5) cyclophosphamide plus prednisolone versus prednisolone plus placebo - 23 participants; (6) mycophenolate mofetil plus either ciclosporin or prednisolone or no immunosuppressants versus placebo plus either ciclosporin or prednisolone or no immunosuppressants trial - 14 participants; (7) tacrolimus plus corticosteroids with or without plasma exchange versus no tacrolimus plus corticosteroids with or without plasma exchange trial - 34 participants.
It is difficult to draw useful clinical conclusions from this small number of often short-term, randomised controlled trials. Each trial had relatively few participants and different trials used different study designs. The limited evidence available found that MG improved significantly with either ciclosporin (alone or in combination with corticosteroids) or cyclophosphamide (in combination with corticosteroids) compared with placebo. There is no clear evidence from randomised controlled trials of benefit for any of the immunosuppressant drugs used more commonly in MG - azathioprine (alone or in combination with corticosteroids), mycophenolate mofetil (as monotherapy or in combination with either corticosteroids or ciclosporin) or tacrolimus (in combination with corticosteroids or plasma exchange or both). There is no randomised controlled trial of methotrexate in MG. Long-term studies of the potentially formidable toxic effects of all of these drugs are lacking in MG.