By Xinli Du, MD, PhD, as told to Kathryn Whitbourne
I started my residency about 15 years ago. Back then, we didn't have many treatment options for myasthenia gravis. We normally started with a cholinesterase inhibitor (pyridostigmine), a drug that helps communication between the nerves and muscles to lessen muscle weakness. This action is very short-lived, and it lasts for 4 hours. It doesn't treat the underlying disease itself. Instead, it just gives a temporary boost.
We started with that treatment because it's quick and has few side effects. Very often, we needed to move on to the drug that targets the underlying autoimmune process.
Back then, mainstream medications to suppress the immune system included oral corticosteroids, followed by steroid-sparing immunosuppressants such as azathioprine, cyclosporine, mycophenolate mofetil, and tacrolimus.
Azathioprine and mycophenolate were the two most often used immunosuppressants because of their benefits and fewer side effects. Most neurologists and neuromuscular specialists preferred them to manage myasthenia gravis.
With all these available immunosuppressants, there were 20% to 30% of patients who were not responding to treatment or only partially responding.
(I do want to mention that the steroid prednisone works faster compared to the other immunosuppressants. So, I still use it even though it has horrible long-term side effects. I think it still has value as a short-term treatment, so I talk to my patients about trying it to see whether it helps.)
Some people also have what we call myasthenia crisis. That's where the patient has serious muscle weakness affecting their breathing and swallowing muscles. They have trouble breathing and they cannot swallow safely. They may aspirate, causing aspirationpneumonia.
When a person has an MG crisis, we give them immunoglobulin through their vein (an infusion of blood antibodies) or plasmapheresis (plasma exchange where the abnormal antibodies in blood are circulated and filtered out by a machine), so they can get better, faster.
Some immunosuppressive drugs can harm fetuses, so we offered thymectomy – removal of the thymus gland – to young women, especially those of childbearing age. We didn't have the control trial data to support it, but some case reports suggested that removing the thymus gland (part of the immune system and a major source of the autoimmunity that causes myasthenia gravis) can help cause clinical remission or reduce the need to take many immunosuppressants.
Myasthenia Gravis Treatment Now
Our toolbox has greatly expanded in the last few years. Since 2017, five new medications have gained FDA approval for generalized myasthenia gravis. We also have new data on the effects of thymectomy and the drug rituximab.
In 2016, The New England Journal of Medicine published the results of a thymectomy trial. The group treated through thymectomy did very well in the clinical assessment, required a lower dose of steroids, and had fewer hospital admissions than the untreated group.
That trial clearly showed a benefit for thymectomy in a particular group: Younger than 50 years old, with generalized myasthenia gravis and the acetylcholine receptor antibody.
Since that trial, there's been a surge in patients with that profile getting thymectomies. Even though it's not a new treatment, we have this new data that can affect our clinical practice.
The majority of myasthenia gravis patients have the acetylcholine receptor antibody, but there's a small group of patients that has the antibody MuSK, or muscle specific tyrosine kinase.
Studies have shown that people who have the MuSK antibody respond much better to the drug rituximab. If someone has MuSK, we don't need to try conventional immunosuppressants. We want to move up to rituximab as early as possible. That can be considered another development, even though rituximab has been around and used by rheumatologists for autoimmune rheumatological diseases.
The FcRn Protein
A protein called the neonatal FC receptor (FcRn) helps maintain the amount of immunoglobulin G (IgG) antibodies present in your body. It's very closely involved in regulating the IgGs in our body. IgG antibodies connect to FcRns and get recycled back into the bloodstream. This recycling plays a major role in many autoimmune diseases.
There are two new medications that target that pathway and block IgG recycling. They will eliminate the antibody, almost like plasmapheresis.
One of these medications, efgartigimod, was approved in 2021. The second one, rozanolixizumab, was approved in 2023.
Efgartigimod is available as an intravenous (vein) injection or in a subcutaneous (under the skin) infusion. Rozanolixizumab is available in subcutaneous form. You can get them at a hospital or infusion center.
The infusion schedule for efgartigimod can be troublesome for some people. It’s done weekly for 4 weeks, followed by a 4-week break before the cycle restarts. You have to take a day or half-day off for the infusions.
Success of the FcRn Inhibitors
Clinical trials have shown that FcRn inhibitors work effectively and quickly to reduce symptoms of myasthenia gravis, with few side effects.
These medications are a very unique way to get rid of antibodies, not just for patients with myasthenia gravis, but also for those with other autoimmune neurological diseases.
Other New MG Treatments
Complement inhibitors work by blocking activation of the complement system, which is part of the body's immune system. The class of medications that block the activation of the complement system has been a very hot target.
Three medications targeting this pathway have come out just in the past 5 years or so with FDA approval. The first one, eculizumab, was approved in 2017. The second one, ravulizumab, was engineered on the backbone of eculizumab, but has a much longer half-life. Instead of using it every 2 weeks, now you can get the same benefit by getting an infusion every 8 weeks. That gives you a much better quality of life.
In late 2023, the third, called zilucoplan, came out. This medication has an advantage for patients because you can inject it subcutaneously yourself at home. That's very appealing because you don't need to take time off to get an infusion.
Advice for MG Patients About Treatments
These new medications give us a lot more power to control myasthenia gravis, and much more information to share with patients. We have this information because the trials for these new treatments were done on patients who had already been treated with other immunosuppressants.
We currently use these newer treatments more as an adjunct therapy when someone has myasthenia gravis that we can’t manage with our conventional drugs. Also, since these treatments are very expensive, it can be a battle to get approved by insurance.
Just to give you an example, I think the price tag for eculizumab is over $700,000 a year. Remember, this is not a one-time deal. Myasthenia gravis is a chronic disease and likely requires long-term immunotherapy. We really think about benefits, risks, and the cost-health benefits for patients.
I still talk to patients about the older medications, because we know the long-term benefits and risks very well. They can take these older medications orally at home. It's a lot easier in terms of administration – and a lot cheaper.
The downside of these standard immunosuppressants is that it takes several months to show a benefit. So, I might use some of the newer medications for quicker response if someone can’t tolerate oral corticosteroids (which work faster, compared to other immunosuppressants). Many of them show benefits in 1 or 2 weeks.
I let patients know that we can consider those new medications to get them relief faster, and eventually taper down the expensive treatment once the other immunosuppressant kicks in.
Show Sources
Photo Credit: E+/Getty Images
SOURCES:
Xinli Du, MD, PhD, clinical associate professor, Department of Neurology, Virginia Commonwealth University.
Cleveland Clinic: " Myasthenia Gravis (MG)."
British Medical Journal: "New and emerging treatments for myasthenia gravis."
