Early treatment with Prograf found safe, effective for juvenile MG
Patients on earlier treatment more likely to achieve complete stable remission
Treatment with the immunosuppressant Prograf (tacrolimus) within one year of the onset of juvenile myasthenia gravis (JMG) was found to be safe and effective in a study of pediatric patients in China.
Patients who were started on Prograf earlier after JMG onset were significantly more likely to achieve complete stable remission, pharmacological remission, or minimal manifestations. Side effects from the treatment were also found to be well tolerated.
“To our knowledge, this is the first large-sample study to evaluate the proper timing, efficacy and safety of [Prograf] in a pure JMG cohort,” researchers wrote in their study “Treatment of juvenile myasthenia gravis with tacrolimus: A cohort study,” which was published in the European Journal of Neurology.
Myasthenia gravis (MG) is an autoimmune disorder in which the immune system mistakenly attacks important proteins required for the communication between nerves and muscles, leading to symptoms such as muscle weakness and fatigue.
While it can occur at any age, approximately 10% of MG cases in the U.S affect children. When the rare disorder affects children and teens, it’s called juvenile myasthenia gravis or JMG.
Prograf helps to boost communication between nerve, muscle cells
Prograf is an approved immunosuppressant that improves communication between nerve and muscle cells by increasing the release of calcium ions in muscle cells. Calcium can then interact with two proteins within the muscle cell, known as actin and myosin, to improve muscle contraction.
Although there is some evidence that Prograf in conjunction with prednisolone is more beneficial for adult patients after thymus removal surgery than prednisolone alone, “there are limited studies for pure JMG,” the researchers wrote.
In this retrospective study, data from 43 patients treated with Prograf were analyzed, 39 of whom were positive for self-reactive antibodies, predominantly against the acetylcholine receptor. The JMG patient group included 22 cases of ocular myasthenia gravis and 21 cases of generalized myasthenia gravis (gMG), a more severe form of the disease.
Nearly half (48.83%) of all patients experienced the onset of JMG when they were 1 to 3 years old.
All children were treated for more than three months and followed for more than a year, with the mean interval of over two years from JMG onset to starting Prograf treatment.
However, there was a notable difference in the time from disease onset to treatment depending on whether patients had ocular MG or gMG. While gMG patients waited a mean of 16.27 months after disease onset to start treatment with Prograf, ocular MG patients waited nearly three years to start the treatment.
Prograf led to therapeutic benefits in 28 of 43 children in study
Treatment with Prograf led to complete stable remission, pharmacological remission, or minimal manifestations (the therapeutic goal) in 28 of the 43 enrolled children.
Given the negative impact of long-term treatment with glucocorticoids on overall health, the researchers also assessed whether Prograf treatment changed glucocorticoid usage. Twenty-eight children could reduce glucocorticoid dosages, and 15 were able to discontinue glucocorticoid use at the last follow-up.
The researchers compared the clinical features of those who were effectively treated with Prograf to those who did not achieve remission or minimal manifestations after treatment, and found gMG patients achieved the therapeutic goal more frequently than those with MG.
Those who achieved remission or minimal manifestations also received Prograf earlier than patients who did not respond as well to Prograf. For children who responded favorably, the mean time from JMG onset to Prograf treatment was 10.5 months versus three years for patients who did not achieve the therapeutic goal.
The researchers found 84.2% of patients who received Prograf within one year of disease onset were in remission or had minimal manifestations at follow-up, and they were also more likely to be diagnosed with gMG than ocular MG.
Overall, Prograf was well tolerated with no patients experiencing severe side effects that led to them stopping the therapy.
“This study provides additional evidence and guidance for clinicians regarding treatment of JMG,” the researchers wrote. “We propose the administration of low-dose [Prograf] at an early stage for both [ocular MG] and gMG patients (within 1 year of disease onset).”
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