Although the prevalence of myasthenia gravis (MG) has increased over the past century, the associated mortality has decreased with the development of effective treatments. The treatment landscape for MG began in the 1930s, with the first 2 treatments – physostigmine and neostigmine – followed by the first thymectomy for MG in 1936. Over the years, corticosteroids and plasma exchange were introduced, and other options including cyclophosphamide, azathioprine, and IVIG followed later.
Over the past two decades, several newer, highly effective options have been approved by the FDA, including mycophenolate mofetil in 2008, rituximab (Rituxan; Genentech) in 2012, eculizumab (Soliris; Alexion) in 2017, l efgartigimod (Vyvgart; Argenx) in 2021 and ravulizumab (Ultomiris; AstraZeneca) in 2022. George Small, MD, adult neurologist at the Allegheny Health Network, believes there has never been a better time to treat patients with of MG.
In a new iteration of NeuroVoices, Small provided commentary on the current state of care for the disease, including the significance of recent therapeutic expansion. He explained how clinicians like him get used to new therapies and if there have been any challenges using them in the clinical setting. Additionally, he provided an insider’s perspective on how clinicians improve quality of life for GPs, including non-pharmacological options and a focus on healthy lifestyle choices.
NeurologyLive®: With the new therapies, what challenges have you encountered from a clinical point of view?
George Small, MD: Dosage really isn’t a problem. It is prohibited, it is a standard dosage. For Solaris and Ultomiris, a person should be vaccinated as they are important immunosuppressants before full treatment begins, which requires patient counseling. For Vyvgart, this is not necessary. Intravenous dosing is very simple, both for Vyvgart and Ultomiris. The real problem is getting the home care companies to talk to the insurance companies and have the manpower to administer these drugs and, frankly, to get them approved. It may take several phone calls for this to happen. As it is very difficult to enter doctors’ offices at present, partly because of COVID, partly because support staff – providers, nurses, physician assistants, etc. – many of them go into other areas of health care and do not work in offices. It may be the challenge, not the dosage. The fact that for Vyvgart, which is a longer-acting version given once every several months, and for Ultomiris dosing, which is already every 8 weeks, this challenge was avoided because at some point during next year, there should be at least 2 medications that do not require you to have 2 visits per month.
Are there non-pharmacological options or ways to improve quality of life outside of these typical prescribed treatments?
Absolutely. There are supplements that I will cover in a minute. I know dr. [Nicholas] Silvestri, MD, personally, we use first names. I was at the same meeting (AANEM) that you attended. I had the great pleasure of meeting him about a year ago regarding his discussion of one of these therapies. Much of the research conducted in the myasthenia gravis portion of the AANEM meeting was aimed not only at saving people’s lives and preventing them from needing ventilators, but also at improving quality of life. It’s not just octogenarians who can have strokes and whose lives can be saved with these drugs, but it’s someone your age, or even mine, who is very active. If I couldn’t speak, if I wasn’t able to get up in the morning, get out of bed, and eat quickly, I couldn’t do my job. You get depressed, then it hits a vicious circle.
Apart from psychological counseling, the Internet has provided a very good source of information. If people are properly directed there by their suppliers – by someone like Silvestri, or I hope, myself – to get correct information and not wrong information about drugs. Suggestions like just staying out of the heat can be helpful and point out that even though people have summer homes in Florida or they want to go to Hawaii there are certain suggestions or warnings or provide information that we should give people to minimize some risk of feeling lousy. One of them is to stay away from significant heat. Another may be eating certain foods that will not contribute to significant weight gain. Significant weight gain—I’m sure there is documentation on this—can increase the risk of exacerbation of myasthenia gravis.
Additionally, and regardless of how personal this is, I hope to give a great talk in neurology here at Allegheny regarding the cost savings of properly treating people with myasthenia gravis. Some drugs will still cost quite a bit of money. The question is whether they allow a person to work and function and contribute to the [gross domestic product] of the country, then, in a sense, the cost is avoided by the fact that the person is a useful member of society. There’s going to be more and more pressure, frankly, pharmaceutical companies – which have absolutely verified treatments for patients – can suggest or use because they save money in the long run. It’s much better to have someone who has myasthenia gravis which is very severe at 30 and treat it, maybe with a drug that’s maybe in the 5 or 6 digit range a year , but get them to work as an executive, get them to work as an inventor, get them to work as ideas for computing, and keep them active and not make them a burden on society.
While it’s not really a personal item per se, I think the country and the state of Pennsylvania has an interest in studying these [drugs] After. You only take out what you put into things. It’s been true for a long time. Steroids are cheap in the short term. In the long run, if you put 70 pounds on someone, they have a heart attack, they may have a stroke, and their brain is damaged. They are going to be a burden on society because they are disabled. I’m not an actuary, I’m a doctor. I am not an economist. But there is no doubt that this research exists now, and even more research will prove it. Basically, to keep people happy in their lives where they can deal with moderately severe myasthenia gravis, [you have to ensure] that they are getting the right information and maintaining an appropriate weight. It is true that you can exercise with myasthenia gravis. You have to keep an eye on it, and there are physiotherapists who are specialists in providing suggestions for these types of exercises for MG, and also for avoiding certain things. Maybe not eating big meals in the middle of the day so that you are, in a sense, useless the rest of the day, not moving. Eating very small meals can be a very simple thing to suggest, but it can be helpful. Trying to avoid large amounts of carbs because if you’re overweight it can just exacerbate myasthenia gravis, cause a vicious cycle, and a doctor may want to give you more steroids because they make you feel better short term, but in the long term, it’s a bad thing for you.
The idea is that if the government can see that people with MG can return to work and contribute more to society, they are more willing to give back to that community?
I don’t see that now. It may exist, but I don’t see it. Even when we have authorization denials for these new drugs and even some of the older drugs that have come out. Some of the oldest drugs are proven to be unsafe long term. Several abridged versions of the research that was part of this meeting (AANEM), where people lectured, also addressed these questions. I hope to address these questions more in my research in the future and make them part of a teaching mechanism that my fellows and our residents can participate in. I think most residents and fellows are, of course, interested in treating patients and making people feel better, but aren’t really trained in the economics of medicine, nor in wellness long-term psychology of their patients. And I know that Dr. [Sandeep] Rana, MD, the residency program director, tries to emphasize that, and it’s also an impetus from the American College of Graduate Medical Education to do that as well. Not just for doctors to give medicine.
Transcript edited for clarity. Click here for more NeuroVoices.