How methotrexate works
The immune system produces antibodies that help fight infections and other threats. In autoimmune diseases such as myasthenia gravis, the antibodies mistakenly attack healthy cells and tissues — so scientists call them autoantibodies.
In the case of myasthenia gravis, the autoantibodies are directed against the acetylcholine receptors found on muscle cells. Signaling molecules released from nerve endings are supposed to bind to these receptors.
But when the immune system destroys acetylcholine receptors, there is no place to acetylcholine to bind to, so it is also destroyed. The result is lack of communication between nerve and muscle cells, which causes muscle weakness and fatigue.
Methotrexate is an immunomodulator, or molecule that regulates immune system activity. It helps reduce or suppress the production of antibodies. The idea is to allow some acetylcholine receptors to be spared. The hope is this will facilitate the transmission of messages from nerves to muscles, improving muscle strength and reducing the weakness and fatigue seen in myasthenia gravis patients.
Methotrexate in clinical trials for myasthenia gravis
Researchers evaluated methotrexate’s ability to treat myasthenia gravis in a placebo-controlled, randomized Phase 2 clinical trial (NCT00814138) between April 2009 and August 2014.
Fifty patients who were on the corticosteroid medicine prednisone were given either 20 mg of methotrexate or a placebo every week. The trial’s primary goal was to see if methotrexate could reduce the amount of prednisone patients required.
Secondary goals were to see if methotrexate could improve patients’ quantitative myasthenia gravis score, myasthenia gravis composite score, manual muscle testing score, myasthenia gravis quality of life score, and myasthenia gravis activities of daily living score.
Methotrexate was unable to reduce the amount of prednisone patients required or improve their disease, muscle function, quality of life, and daily activity scores over 12 months, the results showed. But a commentary accompanying the article noted that most patients were already on low-dose prednisone, so the goal of cutting the dose further might have been unrealistic.
Further studies are needed to determine whether methotrexate can keep patients’ levels of corticosteroids to a minimum, scientists said.
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