Randomised, double-blind, placebo-controlled study of tacrolimus in myasthenia gravis

Abstract

Objectives To evaluate the ability of tacrolimus to reduce the corticosteroid dose in patients with myasthenia gravis (MG) and the drug's safety in a double-blind, placebo-controlled, parallel group study. Methods Patients being treated with oral prednisolone at doses equivalent to 10e20 mg/day, and with stable symptoms, were randomised to tacrolimus or placebo in a 28-week double-blind study. The dose of corticosteroid was tapered with the procedures specified in the protocol. The primary efficacy endpoint was the mean daily prednisolone dose given in the last 12 weeks of the study.Results Eighty patients received the study drug (40 patients in each group) and were included in the full analysis set. In the full analysis set, there was no significant difference in the primary efficacy endpoint between the two groups (p¼0.078). However, some secondary analyses suggested the steroid-sparing effect of tacrolimus. Tacrolimus was well tolerated, and no safety concerns were noted. Conclusions This study suggests that tacrolimus has a potential advantage as a steroid-sparing agent in the treatment of MG patients. Clinical trial registration number NCT00309088. Name of the trial registry: FK506 Phase 3 Study: A Study for Steroid Non-Resistant MG Patients.

The emerging role of tacrolimus in myasthenia gravis

“…Citations of retrieved articles were also examined for relevance and included if applicable. A total of 12 studies met inclusion criteria [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]. Table 2 provides a summary of the pertinent findings from each trial.…”

“…Yoshikawa and colleagues conducted a 28 week randomized, double blind, placebo-controlled trial to assess the steroid-sparing effect of tacrolimus in patients with MG class I-V [Yoshikawa et al 2011]. Patients were included if they were on a stable dose of prednisolone 10-20 mg/day in the month preceding enrollment and had MM of the disease as per the PSC-MGFA.…”

“…Adverse effects were experienced by 87.5% and 80% of subjects in the tacrolimus and placebo groups, respectively. Tacrolimus was discontinued in one patient after development of appendicitis and in another patient due to insomnia [Yoshikawa et al 2011].…”

“…The review covered seven articles which evaluated the use of tacrolimus in steroid-dependent patients [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]. …”

Precision medicine in myasthenia graves: begin from the data precision

“…This phenomenon was found in other autoimmune disease, for example, in a proportion of multiple sclerosis patients, oligoclonal bands could become positive in repeated testing several months after the first negative testing (25); (III) effects of treatment on antibody levels. In MG, once the antibodies appear, they tend to be positive consistently even their level decrease after effective treatment with potent immunosuppressive agents or thymectomy (26)(27)(28)(29)(30). This may be related to persistence of long-lived plasma cell (31).…”