Abstract: Seven trials are included but few reported the outcomes selected for this review. A meta-analysis of ciclosporin versus placebo from two trials (59 participants) - one as monotherapy (20 participants) and the other with corticosteroids (39 participants) - showed that it resulted in improvement of participants in the ciclosporin group compared with those in the placebo group, with a relative rate of improvement of 2.44 (95% confidence interval (CI) 1.13 to 5.27). In addition the weighted mean difference in QMG score between the ciclosporin and placebo groups was -0.34 (95% CI -0.52 to -0.17). Azathioprine (plus prednisolone for first month) had no significant benefit over prednisolone alone (41 participants). The effects of azathioprine plus prednisolone versus prednisolone plus placebo were similar (34 participants). Cyclophosphamide was reported to be statistically more efficacious than placebo at 12 months in corticosteroid-dependent participants (23 participants), but no raw data were available. Trials of mycophenolate mofetil and tacrolimus did not provide relevant endpoint data for this review. All trials had low numbers of participants. Adverse event reporting was variable. Trial protocol heterogeneity prevented comparison of the different immunosuppressants. In generalised MG, limited evidence from small RCTs suggests that ciclosporin, as monotherapy or with corticosteroids, or cyclophosphamide with corticosteroids, significantly improve MG.  Limited evidence from RCTs shows no significant benefit from azathioprine (as monotherapy or with steroids), mycophenolate mofetil (as monotherapy or with either corticosteroids or ciclosporin) or tacrolimus (with corticosteroids or plasma exchange). Bigger, better-designed, longer trials are needed.

Plain-language summary: 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.