Standards of Care for Myasthenia Gravis


A. Gordon Smith, MD, FAAN, discusses the role of acetylcholine esterase inhibitors, immunosuppressive agents, IV immunoglobulin, corticosteroids, as well as newer agents in the treatment of myasthenia gravis.

A. Gordon Smith, MD, FAAN: The care pathway or care standard for myasthenia gravis is in flux. What was the care pathway like or the care approach prior to the release of multiple new exciting disease-modifying therapies for myasthenia gravis? I can think of this as a sequence of treatment aggression. The first line of therapy, the lowest intensity therapy, would be acetylcholine esterase inhibitors, pyridostigmine being the most common one. These basically block the activity of acetylcholine esterase that sits in the neuromuscular junction, and it's responsible for breaking down acetylcholine. If you block these, you enhance acetylcholine signaling and that can help with muscle weakness and fatigue. There are some patients for whom this is adequate and controls their symptoms sufficiently, but most patients need additional therapy.

Traditional therapy is comprised of corticosteroids. These are started at a low dose and then gradually increased over a couple of week period of time because it's very common that patients started on high-dose steroids acutely and myasthenia gravis will have a period of transient worsening, which we want to avoid for obvious reasons. Patients will stay on a high dose, 60 to 80 milligrams of prednisone, for instance, for one to two months, and then a gradual taper. We know from experience and from clinical trial data that if you taper the steroids too quickly, particularly when you get into lower doses, or if you stop them prematurely, patients can relapse.

We also know that some patients do not have adequate response to doses of steroids that are tolerable. Therefore, it's very common that we use steroid-sparing agents or other immunosuppressant agents such as azathioprine, mycophenolate mofetil to try to more successfully taper steroids. Those treatments take a few months to work. Now, in the acute setting, we have for a long time, had access to therapeutic plasma exchange and intravenous immunoglobulin infusions, which are effective and it's easy to see that IVIG can be used in an outpatient chronic setting, either as a transition from an acute care setting to chronic setting, or in patients who aren't tolerant of or have contraindications to corticosteroids.

That's been the standard of care approach generally speaking, up until the last several years, during which time we've had an embarrassment of riches with multiple new drug approvals that fall into two categories, which are complement inhibitors and FCRN inhibitors, one on the market now and others in development. These have really proven a game changer. The most obvious situation where we use these treatments are in patients who aren't responding to traditional standard-of-care therapies or in patients who maybe have particularly severe disease or those who have contraindications to current standard-of-care therapies. These drugs are labeled specifically for acetylcholine receptor antibody disease. So for patients who have MuSK who are seronegative, we have to use other approaches. The last thing that's worth mentioning is thymectomy. Now, of course, patients with myasthenia gravis who have a thymoma need to have a thymectomy to get rid of the thymoma, but we now have good data for the MGTX trial that certain patients with myasthenia gravis, those that are 65 years or younger, acetylcholine receptor antibody positive with a recent diagnosis in the last several years on steroid monotherapy or not yet treated, do better when they are treated with or undergo a thymectomy. There are lots of nuances to how we use thymectomy, but this is now something that's very commonly used in that situation.

Transcript edited for clarity

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