Refractory Generalized Myasthenia Gravis (gMG)

What is refractory generalized myasthenia gravis (gMG)?

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fatigable muscle weakness. MG is specifically thought to be an antibody-mediated disease. MG can be treated, but a subset of patients remains refractory to conventional therapies, leading to refractory generalized myasthenia gravis (gMG). These patients experience frequent clinical relapse upon tapering their immunotherapy, are not clinically stable on their immunotherapy regimen, or develop severe side effects from immunosuppressive therapy. The antibodies in patients with gMG attack the neuromuscular junction where the nerves trigger the muscles to work and interrupt the signals between nerves and muscles, which causes muscle weakness.

What are the symptoms of refractory generalized myasthenia gravis (gMG)?

The symptoms of gMG are similar to those of MG. They include:

• Slurred speech
• Difficulty chewing and swallowing food
• Drooping of one or both eyelids
• Double vision or blurred vision
• Upper and lower extremity weakness
• Disabling fatigue
• Shortness of breath due to respiratory muscle weakness
• Episodes of respiratory failure

Up to 20 percent of patients will experience a myasthenic crisis, defined as severe weakness requiring respiratory support.

What causes of refractory generalized myasthenia gravis (gMG)?

In patients with MG, the immune system mistakenly produces antibodies that block, alter, or destroy receptors at the neuromuscular junction, the area where nerve cells connect with the muscles they control. The disruption of communication between the nerve and muscle prevents normal muscle contraction from occurring, resulting in debilitating muscle weakness.

How is refractory generalized myasthenia gravis (gMG) diagnosed?

gMG is typically diagnosed with a physical examination to evaluate distinct symptoms. Other exams to confirm diagnosis include:

• Blood tests
• Nerve and muscle stimulation
• Body imaging studies

What are the available treatments for refractory generalized myasthenia gravis (gMG)?

Many patients with gMG manage symptoms with conventional therapy, including acetylcholinesterase inhibitors and immunosuppressive therapies such as corticosteroids. Short-term “rescue therapy” with plasma exchange and intravenous immunoglobulin (IVIG) may also be used to treat acute, severe disease exacerbations. However, a subset of gMG patients remains refractory to conventional therapies, characterized by continued suffering from severe symptoms despite otherwise adequate doses and duration of treatment, poor tolerability of conventional therapy, or repeated rescue treatments. To date, there are no therapies that are effective for this ultra-rare segment of patients with refractory gMG.

Where can I find out more about refractory generalized myasthenia gravis (gMG)?

• NIH
• Alexion Pharmaceuticals Fact Sheet