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Ann. N.Y. Acad. Sci., Annals PrePrint, published online ahead of print December 20, 2007
doi: 10.1196/annals.1405.000
Copyright © 2007 by the New York Academy of Sciences
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Articles by Ponseti, J. M
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Articles by Ponseti, J. M
Articles by Armengol, M.
Tacrolimus for Myasthenia Gravis: A Clinical Study of 212 Patients

Jose M Ponseti 1*, Josep Gamez 2, Jamal Azem 3, López-Cano Manuel 3, Ramón Vilallonga 3, Manuel Armengol 3

1 Surgery, Hospital General Universitari Vall d'Hebron, P. Vall d'Hebron, 119-129, Barcelona, 08035, Spain
2 Neurology, Hospital General Universitari Vall d'Hebron, Barcelona, Barcelona, Spain
3 Surgery, Hospital General Universitari Vall d'Hebron, Barcelona, Barcelona, Spain

* To whom correspondence should be addressed. E-mail: jmponseti{at}vhebron.net.

PrePrint Abstract

Tacrolimus is a macrolide T-cell immunomodulator the use of which in patients myasthenia gravis (MG) is supported by its effect on muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing in muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking its export mechanism), and also increasing apoptosis of T cells. We here report the results of low dose tacrolimus (0.1 mg/kg/day) in 212 MG patients. There were 110 thymectomyzed, cyclosporine- and prednisone-dependent patients, 68 thymectomyzed starting tacrolimus early postoperatively (24 h after operation), and 34 patients with non-thymomatous generalized MG over 60 years or in whom thymectomy was contraindicated. The mean follow-up was 49.3 ± 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. AChR antibodies decreased significantly from a mean of 33.5 nmol/L at baseline to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn due to major adverse effects. Our results suggest than low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable.

Key Words: Immunosuppressive agents, myasthenia gravis, muscle weakness, prednisone, postoperative period, tacrolimus, neuromuscular junction






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