When you live with myasthenia gravis (MG), a chronic autoimmune disorder where your immune system attacks the connection between your nerves and muscle, understanding your treatment options is likely to be at the top of your mind.
During a recent WebMD Reddit AMA with Ryan Donaghy, MD, a neuromuscular medicine specialist at Northwestern Medicine in Chicago, questions focused on treatment options: What's available now? What's to come? What can you expect out of MG treatment?
Donaghy dives deeper into these topics below.
Targeted Therapies
For many years, treatment for MG centered on medications such as corticosteroids, intravenous immunoglobulin (IVIG), and immunosuppressants like mycophenolate mofetil (CellCept) and azathioprine. These were "broad treatments that suppressed the immune system as a whole," Donaghy says.
Today, doctors can often target specific parts of the immune system that drive the disease. This means treatment plans can be more tailored to your symptoms, specific antibodies in your system, and overall health.
Traditional treatments are still an important tool in MG management, Donaghy says. For example, doctors often prescribe steroids when symptoms first start because they can help reduce your immune activity and improve muscle weakness. But steroids can also cause significant side effects, including weight gain, skin changes, cataracts, and diabetes.
Other older immunosuppressants that don't use steroids such as methotrexate or cyclosporine may help control MG, but they can take months to work at full strength, which means living longer with symptoms that are impacting your daily life. Researchers are focused on targeted treatments as a way to address these concerns and offer more effective options.
Precision Medicine
Targeted biologic therapies work by getting in the way of the immune processes in your body that cause MG symptoms. One of the biggest factors guiding treatment decisions is antibody status.
Most people with MG have antibodies that attack the acetylcholine receptor, a protein that helps nerves send signals to muscles. Others have antibodies that attack a different protein called MuSK, which also helps nerves and muscles communicate. Some people have seronegative MG, which means blood tests don't find any of the known MG antibodies, but their symptoms and other tests still show they have the disease. Because these types of MG affect the body in different ways, they may respond differently to treatment.
One newer group of medications called FcRn inhibitors targets a protein called the neonatal Fc receptor (FcRn). These drugs, which include efgartigimod (Vyvgart), nipocalimab (Imaavy), and rozanolixizumab (Rystiggo), help lower the levels of harmful antibodies that attack communication points between nerves and muscles.
Another class of drugs targets B cells, the immune cells responsible for producing those antibodies. These include inebilizumab (Uplizna), which is FDA-approved for generalized MG, as well as rituximab (Rituxan) and ofatumumab (Kesimpta), which doctors sometimes use off-label based on emerging evidence.
A third class, called complement inhibitors, blocks part of the immune response that damages the neuromuscular junction, the area that connects nerves to muscles.
Doctors also look at whether symptoms are limited to the eyes or affect other muscle groups throughout the body.
"The beauty of how you treat myasthenia now is we can think about each person and their specific comorbidities," says Donaghy. "And then we can use these medicines in a very selective way to target the underlying disease and improve their symptom burden."
If you have ocular MG, which can cause drooping eyelids and double vision, your doctor may opt for a less aggressive treatment at first. You may start on pyridostigmine (Mestinon), which helps improve communication between nerves and muscles but does not directly alter your immune system. Your doctor may also add a low-dose steroid. Researchers are now studying whether some of the newer targeted therapies could benefit people with ocular MG as well.
If you have generalized MG, your treatment may start with steroids, and then your doctor may add in newer biologic therapies. Some of the FcRn-targeting treatments work fairly quickly, while B-cell therapies may take longer to show benefits. Your doctor may only choose a complement inhibitor if you have more moderate to severe disease.
What to Expect From Your MG Treatment
As you treat your MG, your doctor will use tools to measure your progress. One common test is the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, which tracks how your symptoms are affecting everyday tasks such as speaking, swallowing, breathing, and physical activity.
Donaghy says even a small improvement on this scale can mean a big change in quality of life.
"One of my goals in treating patients is to try to get them to what's known as minimal symptom expression," he says. "That means that although I might be able to detect some MG clinically if I do a very deep, detailed examination maneuver, you might not be feeling any symptoms."
With the growing number of treatment options, doctors now have more ways to adjust your therapy when one approach isn't giving you enough relief.
Looking Ahead
For Donaghy, one of the most exciting areas of research is expanding treatment options for ocular MG, a form of the disease that has so far had fewer studies and fewer targeted therapies. Several clinical trials are testing new treatments for this MG subtype.
"Ocular MG has a similar disease process, but the symptoms are milder and not as dangerous, so it hasn't been as aggressively studied" says Donaghy. "But they're still very bothersome, so I'm excited that some of the FcRn medications are being looked into for this population."
Recent studies on biological medications suggest they continue to work well years after treatment starts, without the degree of treatment "wear-off" that doctors once worried about.
Another area of interest is using targeted therapies earlier during severe MG flares that require hospitalization. Researchers are exploring whether FcRn inhibitors, B-cell therapies, or complement inhibitors can reduce the number of hospitalizations and the need for long-term steroid use.
"We have a lot of clinical trial evidence now behind all of these medicines to support us doing that more than we ever did from older medicines."
Show Sources
Photo Credit: iStock/Getty Images
SOURCES:
Ryan Donaghy, MD, neuromuscular medicine specialist, Northwestern Medicine, Chicago.
Myasthenia Gravis Foundation of America: "Myasthenia Gravis Treatments."
Mayo Clinic: "New frontiers in myasthenia gravis therapy: FcRN inhibitors, complement inhibitors and anti-CD-19 therapy."
Journal of Clinical Medicine: "New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies."
