Experience with starting tacrolimus postoperatively after transsternal extended thymectomy in patients with myasthenia gravis

Abstract

ABSTRACTBackground: Thymectomy is a standard treatment of myasthenia gravis (MG). Immunomodulating agents are frequently given during the postthymectomy latency period until complete remission is fully consolidated, but serious side effects is a relevant clinical problem for patients on long-term immunomodulating treatment.Objective: To assess the effectiveness of starting tacrolimus in the immediate postoperative period in MG patients undergoing transsternal extended thymectomy, with complete stable remission (CSR) as the primary outcome of the study.Methods: Forty-eight MG patients received tacrolimus, 0.1 mg/kg per day b.i.d. (started 24 h after thymectomy) and prednisone 1.5 mg/kg/day. Histologically, 34 patients had hyperplasia, 20 thymic involution, and 14 thymoma. Of the 48 patients, 40 completed 1 year of tacrolimus therapy, 38 completed 2 years, 27 completed 3 years, 21 completed 4 years, and 9 more than 5 years. Mean dose of tacrolimus was 4.9 mg/day (range 2–8 mg/day) with a mean plasma drug concentration of 7.6 ng/mL (range 7–9 ng/mL). Prednisone could be withdrawn after the first year in 93.7% of patients and at 2 years in 100%.Results: The mean follow-up was 24.4 months, SD 17.3 (range 6–60 months). Improvement of muscular strength and decrease of anti-AChR antibodies were statistically significant ( p < 0.001) shortly after operation. CSR was obtained in 33.4% of patients, pharmacological remission in 62.6%; 4% of patients had minimal symptoms. None of the patients with thymoma achieved CSR. The estimated median follow-up to obtain a CSR was 37.9 months (95% confidence interval [CI] 26.4–49.5 months). The overall crude CSR rate was 33.4%, with 47% for non-thymoma patients. The probability to achieve CSR at 3 years was 67% for the non-thymomatous group.Conclusions: Long-term immune-directed treatment with tacrolimus to improve the effectiveness of thymectomy in MG is feasible and was associated with a high rate of CSR in patients without thymoma.