Long-term therapeutic efficacy and safety of low-dose tacrolimus (FK506) for myasthenia gravis.
OBJECTIVE
To elucidate the long-term therapeutic efficacy and safety of low-dose FK506 (tacrolimus) in patients with myasthenia gravis (MG).


METHODS
We treated nine patients with MG (all women: age range: 35-83 years (mean: 51.1 years); MGFA classification: 4 type IIa, 4 type IIb, and 1 type IVb patients) with FK506 for more than 24 months (observation period: 24-46 months). All the patients had undergone extended thymectomy before FK506 treatment; two patients (22.2%) had noninvasive thymoma and six (66.7%) had thymic hyperplasia. We evaluated total Quantitative MG (Q-MG) score, anti-acetylcholine receptor (AChR) antibody titer in the blood, interleukin 2 (IL-2) production in peripheral blood mononuclear cells (PBMCs), administration dosage of prednisolone (PSL), and adverse effects of FK506.


RESULTS
A reduction in steroid dosage of 50% without worsening of the symptoms was observed 1 year after FK506 administration in three out of six steroid-dependent MG patients (50.0%). The total Q-MG scores (range: 0-39 points) at 6 months and 1 year after FK506 administration improved by 3 points or more in six (66.7%) and seven (77.8%) out of nine patients, respectively. The efficacy of FK506 was maintained for more than 2 years. Although adverse effects were observed in three patients (33.3%), these were not serious.


CONCLUSIONS
Our study indicates that low-dose FK506 treatment may be efficacious not only in controlling intractable myasthenic symptoms, but also in reducing steroid dosage, and that FK506 is safe as an adjunctive drug to PSL for MG treatment for a maximum of 3 years.
Tada
Masayoshi
M
Department of Neurology, Resource Branch for Brain Disease Research, Brain Research Institute, Niigata University, 1-757 Asahi-machi-dori Niigata, Niigata, Japan.
Shimohata
Takayoshi
T
Tada
Mari
M
Oyake
Mutsuo
M
Igarashi
Shuichi
S
Onodera
Osamu
O
Naruse
Satoshi
S
Tanaka
Keiko
K
Tsuji
Shoji
S
Nishizawa
Masatoyo
M
D000328:Adult; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D007166:Immunosuppressive Agents; D011239:Prednisolone; D016559:Tacrolimus