Long-term use of tacrolimus found safe, effective in MG in study
Immunosuppressant eased symptoms in patients with anti-MuSK antibodies
Long-term use of the immunosuppressant tacrolimus was found to be safe and effective in myasthenia gravis (MG) patients with self-reactive antibodies targeting muscle-specific kinase, or MuSK — a protein important in nerve-muscle communication — according to the findings of a new study by researchers in China.
Treatment with tacrolimus significantly lowered the levels of anti-MuSK antibodies in the bloodstream, the data showed. Its use also eased symptom severity and enabled patients to decrease their steroid doses.
Overall, nearly 90% of tacrolimus-treated patients reported experiencing no symptoms at their last visit.
“Our results suggest that tacrolimus may be an effective and safe steroid-sparing treatment for patients with MuSK-MG,” the researchers wrote.
The study, “Long-term efficacy and safety of tacrolimus in anti-MuSK antibody-positive myasthenia gravis: a retrospective single-center cohort study,” was published earlier this month in the journal Neurological Sciences.
Scant data on tacrolimus use in patients with anti-MuSK antibodies
MG is an autoimmune disorder in which the immune system attacks proteins important for the function of the neuromuscular junction, where nerve and muscle cells communicate to coordinate voluntary movements. For most patients, MG is caused by self-reactive antibodies that target the acetylcholine receptor, or AChR. However, in about 5% to 8% of patients, self-reactive antibodies target MuSK, another protein involved in nerve-muscle communication.
Compared with patients harboring anti-AChR antibodies, those with anti-MuSK antibodies are more likely to experience symptoms of muscle weakness in the head and neck, as well as myasthenic crises, or episodes of symptom worsening marked by serious issues with breathing, in the early stages of the disease.
Tacrolimus, marketed as Prograf and others, is an immunosuppressant that can be used to reduce the activity of the immune system and ease MG symptoms. While the benefits of tacrolimus are well-established in MG patients with anti-AChR antibodies, the efficacy and safety of long-term treatment in patients with anti-MuSK antibodies are less well-understood.
“The long-term outcome of tacrolimus in the treatment of patients with MuSK-MG has been rarely reported,” the researchers wrote.
To learn more, researchers from Tongji Medical College at Huazhong University of Science and Technology examined the medical records of 18 Chinese MG patients with anti-MuSK antibodies who were treated with tacrolimus for more than a year.
Two-thirds of these patients — 12 in total — were women. At the time the patients began taking tacrolimus, approximately 66% were experiencing a moderate level of generalized muscle weakness, which affected the limbs and muscles controlling the head and neck, as measured by the Osserman scale.
The median duration of treatment with tacrolimus was 2.5 years. After 32 weeks, or nearly eight months, of treatment, all patients achieved minimal manifestation status, a classification indicating that patients had no symptoms of functional limitations from MG, but still experienced some degree of muscle weakness.
Nearly 90% of patients asymptomatic at last study visit
After an average of 1.4 years on tacrolimus, more than half of the patients (about 56%) were able to discontinue steroid treatment with prednisone.
Beginning at four weeks following the start of treatment, patients experienced a significant reduction in symptom severity, as measured by a significant drop in the scores of several standardized measures of MG severity.
At their last visit, all patients showed improvements on the Osserman scale. A total of 16 were symptom-free and the remaining two were graded as class 1, meaning muscle weakness was restricted to eye muscles.
Altogether, the team noted, “88.9% … were asymptomatic at the last visit.”
Researchers also were able to examine whether long-term use of tacrolimus affected the levels of anti-MuSK antibodies in the blood of nine study participants. Those results showed that, after an average of 1.4 years of treatment, the mean levels of anti-MuSK antibodies in the bloodstream decreased significantly from 0.777 to 0.283 nanomoles per liter.
Based on our data, we conclude that tacrolimus is relatively safe for MuSK-MG patients.
Seven patients (about 39%) slowly reduced their dosage of tacrolimus and stopped treatment over a median follow-up of 4.4 years. Within 28 weeks of dose reduction, four patients experienced exacerbations, or episodes of MG symptom worsening, including problems swallowing and speaking.
However, two of the patients who stopped taking tacrolimus achieved complete stable remission without experiencing symptom worsening for more than two years after stopping tacrolimus.
These findings led the researchers to note that “there may be large individual differences in the safety of tacrolimus reduction in well-controlled patients with MuSK-MG.”
Overall, tacrolimus was well tolerated. However, one patient stopped treatment after 5.8 years due to mildly abnormal levels of blood sugar, or glucose, and creatinine, a marker of kidney dysfunction. However, these abnormal lab parameters resolved within two weeks of stopping treatment.
“Based on our data, we conclude that tacrolimus is relatively safe for MuSK-MG patients,” the researchers wrote.
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