For most people with myasthenia gravis (MG), the disease’s symptoms can be managed with the go-to medications that doctors typically prescribe first. These drugs, frequently referred to as first-line treatments, include pyridostigmine (Mestinon) and a corticosteroid such as prednisone (Deltasone).
But up to 1 in 5 MG patients don’t do well on these drugs. If you fall into that number, rest assured: Many other effective medications are available.
“The good news is we have more tools in our toolbox,” says John Morren, MD, a neurologist and neuromuscular medicine specialist at the Cleveland Clinic in Cleveland, Ohio. “Chances are you're going to do quite well if you get a diagnosis of myasthenia gravis.”
Signs That Your Initial Myasthenia Gravis Treatment Is No Longer Enough
Your body will begin to let you know if your first-line treatment becomes less effective.
“Patients will start to realize that they’re getting weaker,” says Morren.
As your current medication’s effectiveness decreases, activities that you could do with little or no difficulty will become fatiguing, such as getting out of a chair or putting dishes away, says Morren. Even light tasks such as brushing your teeth at night may become tiring. You also may notice that it’s harder to keep your eyelids from drooping.
“That’s not because you’re sleepy but because your eyelids are so fatigued, you can’t keep them up,” says Morren, who adds that this may begin to occur earlier in the day rather than later in the evening.
Another indicator: you require higher and higher doses of medication to maintain the same level of symptom control.
“That's a sign as well that they're becoming less effective,” says Morren, who adds that experts don't know exactly why this occurs. “And with higher doses of prednisone, your risk for adverse effects is going up exponentially.”
These side effects include:
- Insomnia
- Mood changes
- Irritability
- High blood pressure
- Bone weakening (osteoporosis)
- Weight gain
- Stomach problems like nausea, diarrhea, vomiting, and stomachache
Pyridostigmine, one of the most commonly used drugs to treat MG, also can be harmful at high doses. Morren says it can lead to a potentially life-threatening medical emergency called a cholinergic crisis. Symptoms include:
- Muscle weakness, paralysis, or involuntary contractions
- Breathing problems
- Sweating and salivating
- Blurred vision
- Excessive tear production
- Urinary frequency or incontinence
- Stomach problems, like vomiting, diarrhea, and cramps
What Your Doctor Will Prescribe Next
If your first-line treatment does not work or if the side effects have become too burdensome, a number of different types of effective medications are available to manage your symptoms.
Nonsteroidal immunosuppressants
Morren says that doctors typically prescribe nonsteroidal immunosuppressant medications next. These include:
- Azathioprine (Imura)
- Cyclosporine (Sandimmune)
- Methotrexate (Trexall)
- Mycophenolate mofetil (CellCept)
- Tacrolimus (Prograf)
How do these help? Your nervous system must be able to communicate with your muscles in order for your muscles to work properly. Myasthenia gravis causes your immune system to make abnormal antibodies that attack the means of that communication. These drugs suppress your immune system. This reduces the amount of these antibodies it produces. Fewer antibodies means less disruption of communication between your nerves and muscles. The result: you have fewer MG symptoms.
Morren says that these types of drugs are very effective for the majority of people who did not do well on first-line treatments like pyridostigmine and corticosteroids.
These drugs have fewer side effects than prednisone and other corticosteroids. However, Morren points out a significant drawback to this class of medication.
“They may take many months or even up to a year to take full effect,” he says. “For many patients, that is not feasible. You run the risk of a downward spiral that may turn into a myasthenic crisis.”
Such a life-threatening crisis occurs when MG weakens the muscles that control your breathing. This is a medical emergency that requires immediate treatment.
Many patients do well by taking a corticosteroid while waiting for their immunosuppressant drug to become fully effective. However, if a corticosteroid has proved ineffective for you, your doctor may recommend a newer targeted therapy during this period, says Morren.
Targeted therapies for MG
Targeted therapies are a recent addition to the treatment of MG. They fall into a class of drugs called biologics. They treat MG by targeting specific molecules or proteins involved in the disease.
“In the last few years, we’ve seen the approval of some novel agents that are very effective,” Morren says. “They kick in a lot earlier.”
Complement inhibitors
The complement system is a part of your immune system. It helps protect you against threats to your health such as bacterial infections. In MG, the complement system becomes overactive. This can damage the receptors that allow your nerves and muscles to communicate, causing MG symptoms. Complement inhibitors target certain parts of the complement system in order to prevent this damage from occurring.
Since 2017, the FDA has approved three complement inhibitors to treat MG. They are:
- Eculizumab (Soliris)
- Ravulizumab-cwvz (Ultomiris)
- Zilucoplan (Zilbrysq)
Neonatal Fc receptor inhibitors
Another new class of medications, these drugs target a protein called the neonatal Fc receptor (FcRn). FcRn helps maintain your immune system’s production of certain types of antibodies, including the abnormal antibodies responsible for MG’s symptoms. By blocking FcRn, your immune system produces fewer such antibodies and you experience fewer symptoms.
The FDA has approved three neonatal Fc receptor inhibitors for MG since 2021. They are:
- Efgartigimod alfa-fcab (Vyvgart) and efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo)
- Rozanolixizumab-noli (Rystiggo)
- Nipocalimab-aahu (Imaavy)
Both classes of drugs are extremely expensive. Morren says that targeted therapies can cost hundreds of thousands of dollars per year.
“Quite often, you’ll see them mentioned as a third-line treatment option, and one of the reasons why is because they’re so expensive,” says Morren.
However, there are circumstances in which they may be used sooner, he continues. For example, if you have severe MG but can’t take corticosteroids to quickly get your symptoms under control, you may benefit from a short course of one of these new drugs.
“You may jump to one of the targeted biologics because you can't wait for the traditional nonsteroidal immunosuppressive agents to kick in,” says Morren.
Show Sources
Photo Credit: iStock/Getty Images
SOURCES:
John Morren, MD, neurologist and neuromuscular medicine specialist, Cleveland Clinic, Cleveland, Ohio.
Muscular Dystrophy Association: “Myasthenia Gravis.”
Myasthenia Gravis Foundation of America: “Myasthenia Gravis Treatments.”
Mayo Clinic: “Myasthenia Gravis.”
Cleveland Clinic: “Complement System,” “Myasthenia Gravis.”
