Prograf (tacrolimus) moderately improves myasthenia gravis (MG) in patients with inadequate response to glucocorticoids (GCs), a new study from China shows.
The study, “Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China,” appeared in the journal Therapeutic Advances in Neurological Disorders.
The research was led by Chongbo Zhao, MD, PhD, from the Department of Neurology, Huashan Hospital, Fudan University, in Shanghai, China.
MG is an autoimmune disease in which antibodies target the protein receptor of acetylcholine, the neurotransmitter that causes contraction of the muscles, or other related proteins at the neuromuscular junction. This junction is the connection between motor nerves and muscle fibers.
Long-term suppression of the immune system with glucocorticoids (GCs) is one treatment strategy for MG. This therapy can be effective, but some patients respond inadequately or show poor tolerance. It also has adverse effects including weight gain or osteoporosis, prompting the need for treatment regimens that lower or eliminate GC doses.
Prograf is an immunosuppressive medication used to prevent transplant rejection. Previous studies have shown that Prograf decreased the MG disease score and severity of symptoms in patients who were unresponsive or intolerant to GC. However, the only double-blind (in which neither the participant nor the researcher knows who receives which treatment), placebo-controlled study of Prograf benefits in MG patients with poor response to GC failed to detect significant improvements, although the quantitative myasthenia gravis (QMG) score could not be adequately assessed.
In this study, researchers assessed the effectiveness of low-dose, immediate-release, oral Prograf in MG patients with inadequate response to the GC Deltasone (prednisone), after at least six weeks of treatment at a dose not lower than 0.75 mg/kg/day or 60–100 mg/day.
Eighty-three patients were treated with a daily dose of either 3 mg of Prograf (45 patients) or a placebo (38 patients) for 24 weeks. Accompanying GCs and Mestinon (pyridostigmine) were allowed. Patients continued GC therapy from weeks one to four. The dose was reduced starting from week five at the discretion of the investigator. Scientists primarily analyzed whether Prograf reduced the QMG score.
The results revealed that treatment with Prograf was not statistically different from the placebo in a primary analysis of effectiveness over the 24-week period. A secondary assessment showed that Prograf significantly decreased the QMG score at week 24. Adverse effects were similar in both groups and generally mild.
Overall, the study shows that a dose of 3 mg of Prograf for MG patients with inadequate response to GCs improves the disease score.
However, unlike other studies, the results do not show that a dose reduction of concomitant GCs at week 24 with Prograf could alleviate GC-associated adverse effects. “It is possible that the duration of the current trial was too short to allow for a significant change in GC dose,” the authors wrote.
Also, “the research was limited by the low number of patients, the absence of testing for acetylcholine receptor antibody and the absence of stratification by disease duration.”
Another limitation was the difference in MG duration between study groups. MG duration for the Prograf group was 27.9 months, while for the placebo group it was 63.5 months. Future studies should control for the duration of MG to provide more consistency between groups and better interpretation of results, the authors suggested.