Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus)

Abstract

Efficacy and safety of long term use of FK506 (2-4.5 mg/ day) for a maximum of two years were evaluated in 12 patients with generalised myasthenia gravis (MG). At the end of the study, eight patients (67%) showed improvement in either MG score or Activities in Daily Living score, and prednisolone dosage could be reduced in seven patients (58%), with a mean reduction ratio of 37%. Long term use of FK506 for MG can be more effective than short term administration, with no serious side effects.

The emerging role of tacrolimus in myasthenia gravis

“…Various clinical situations have been studied, such as in patients refractory to, or intolerant of, corticosteroids or additional immunosuppression, presence of thymoma, and in patients with a relatively new diagnosis. The most common dosing strategies were: a fixed daily dose of 3 mg with or without assessment of trough drug concentrations; and a weight-based approach of 0.1 mg/kg/day in divided doses with dosage titrated to achieve a trough concentration of 7-8 ng/ml [Shimojima et al 2006;Nagaishi et al 2008;Tada et al 2006;Konishi et al 2003Konishi et al , 2005Zhao et al 2011;Yoshikawa et al 2011;Ponseti et al 2005aPonseti et al , 2005bPonseti et al , 2006Nagane et al 2005;Mitsui et al 2007]. While the weight-based regimen is within the manufacturer's dosing recommendations for prevention of transplant rejection, the 3 mg dose falls below the FDA-approved dosing range [Astellas Pharma, 2013].…”

“…The long-term effects of the use of tacrolimus for MG management were assessed in several trials [Shimojima et al 2006;Nagaishi et al 2008;Tada et al 2006;Konishi et al 2005;Ponseti et al 2005aPonseti et al , 2005bPonseti et al , 2006Nagane et al 2005]. These trials consistently showed positive effects on the QMGS or a reduction in adjunct therapies, and followed patients on tacrolimus for up to a period of 5 years.…”

“…Of the patients on prednisolone doses of 10 mg/day or more at study initiation, half were able to achieve a dose reduction after one year (mean dose 18.2 versus 10.4 mg/day) [Tada et al 2006]. A total of 12 patients from the above trial entered into a long-term follow-up study, which extended to 88-104 weeks [Konishi et al 2005]. Of note, two patients who did not respond in the original trial showed improvement in total MG score by 3 or more points at the end of the long-term followup evaluation, although one patient exhibited worsening symptoms.…”

“…Adverse effects occurred in eight patients, although most were noted to be mild in nature. One patient required tacrolimus administration be held due to headache and eye pain; however, the drug was later restarted [Konishi et al 2005]. …”

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

“…It is used to control rejection after kidney, liver, heart, and bone marrow transplantation, and is also used to control graftversus-host disease. In Japan, tacrolimus is additionally employed to treat myasthenia gravis [13,14], rheumatoid arthritis [15], and atopic dermatitis (as a topical preparation) [16]. Regarding the efficacy of tacrolimus for lupus nephritis, it has been shown to prolong survival and decrease proteinuria in murine models of SLE (MRL/lpr mice and NZB/NZWF1 mice) [17].…”