[Treatment of severe myasthenia gravis with cyclosporin. A 12-month open trial]

Cyclosporine A, an immunosuppressor and immunomodulator, has been proposed as an alternative in patients with autoimmune disease not responding to the usual immunosuppressants. We treated with cyclosporine 19 patients with severe myasthenia gravis in a 12-month open uncontrolled trial. There were 14 women and 5 men aged 51.5 +/- 18.5 years (range 20 to 81 years) who had had the disease for 50.8 +/- 43.6 months. Myasthenia gravis was generalized in 18 and ocular in 1. Previously, 4 patients had been unsuccessfully treated with azathioprine, 1 with cyclophosphamide, 12 with steroids; 5 had undergone thymomectomy and 5 thymectomy. Anti-acetylcholine receptor antibodies (AChR-ab) were detected in the sera of 15. The severity of the disease was assessed by a myasthenic muscle score (MMS) ranging from 0 to 100 and a 5-grade functional scale (FS) from 1 = severe disability to 5 = complete remission. Depending on changes in MMS and FS, the effectiveness of cyclosporine was deemed very good, good or nil. Cyclosporine was administered orally 3 times daily in doses of 5.6 +/- 1.6 mg/kg/day over 11.6 +/- 1.6 months. The final dosage was targeted to achieve a peak serum level and a trough level respectively below 200 and 100 mg/ml, and was adapted if side effects occurred. No other cytotoxic drug was allowed. Seventeen patients completed the treatment (M12); 1 died of uterine cancer at M6 and 1 was lost to follow-up at M5. At M12 clinical results were considered very good in 6 patients, good in 8, nil in 3. The MMS increased significantly from 56.1 +/- 17.2 (n = 19) at D0 to 83 +/- 15 (n = 17) (P less than 0.0005), as did the FS, from 2 +/- 1 to 3.7 +/- 0.85 (P less than 0.0005). Subsequently, cyclosporine was discontinued in 7 of the 14 patients who responded well and maintained in 7 at a reduced dosage (3.4 +/- 0.8 mg/kg/day). In the former group 3 patients relapsed 1, 1 and 5 months respectively after the drug was withdrawn; the remainder had, at the last follow-up (29.6 +/- 8.5 months from D0), MMS 62.9 +/- 34.1 and FS 3 +/- 2. In the latter group, at the last follow-up (17.6 +/- 3.6 months), MMS was 86.7 +/- 16.6 and FS 4.2 +/- 0.8, differing significantly from D0 values. AChR-ab titers and CD4/CD8 were unaltered at M12.(ABSTRACT TRUNCATED AT 250 WORDS)