SAVANNAH, Ga. — Patients with myasthenia gravis (MG) continue to follow traditional therapy of immunosuppression with medications like corticosteroids and nonsteroidal agents? Or is it time for a new generation of drugs?

During a debate at American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) 2024two neurologists specializing in neuromuscular disorders presented opposing evidence for each approach.

On the one hand, Benjamin Claytor, MD, of the Cleveland Clinic in Cleveland, argued that “traditional treatment is very effective for the majority of patients with myasthenia gravis,” and he said it should be considered a first-line therapy.

But Amanda C. Guidon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, responded that “the immunosuppression of traditional therapies is too broad: the time to benefit is too long, the burden of effects secondary is too high, and the risk of cancer is too high.

Traditional therapy: affordable, tolerable and safe?

Claytor said ideal MG therapies are effective, tolerable and safe. They are also affordable, convenient (like a pill), lead to lasting remission, and can have reduced doses.

Only traditional therapies — corticosteroids, azathioprine, mycophenolateAnd rituximab – meet these last three criteria, he said. Newer therapies, he said, don’t do that.

Claytor pointed out a Study 2023 at Duke University which followed 367 patients with MG treated with traditional therapies after the year 2000. Among them, 72% achieved the goal of treating minimal manifestations within a median time of less than 2 years.

Additionally, Claytor noted that the percentage of MG patients who achieve minimal symptom expression ranges from 45% (6 months) to 60% or more (2 years), while studies suggest that newer treatments such that eculizumab (Soliris), efgartigimod (Vyvgart), rozanolixizumab (Rystiggo) and zilucoplan (Zilbrysq) did not reach these levels.

As for specific traditional therapies, Claytor said corticosteroids prednisone is “extremely affordable”, effective and takes less than 2 weeks to work. All patients with MG can take it, he said, and at least 75% of those with mild or moderate disease respond to low doses.

Nonsteroidal agents, immunoglobulin, rituximab

He acknowledged the side effects of corticosteroids, but said doses could be reduced once severity improved. Calcium and vitamin D can be helpful in supporting bone health, he added.

As for nonsteroidal immunosuppressive treatments, he said they are easy to administer, increase the likelihood of reaching a minimal manifestation state, may be effective at lower doses, and may allow patients to come off steroids.

Two other traditional therapies, immunoglobulins and plasmapheresis, may be appropriate in cases of seizure or impending seizure, he said, or as adjunctive therapy if steroids and nonsteroidal immunosuppressive therapies don’t work.

What about rituximab? “We’re learning that patients with new disease and younger patients seem to respond better,” Claytor said. Although rituximab is expensive, it is “not even in the same league” as newer agents if only a dose or two is given, he said.

Are steroids ideal for MG? Not so fast

In her response, Guidon noted that she had been tasked with offering a counterperspective in her presentation and that “personal opinions are not fully represented here.” She then listed the weaknesses of traditional therapy in MG.

On the one hand, she said the medications don’t work well. She highlighted a 2019 registry study which found that “many patients with myasthenia gravis remain negatively affected despite treatment.”

Additionally, “we can’t predict who will respond to which therapy… We start taking medications and we don’t know if we will benefit from them between 6 and 18 months. We also cannot determine a priori the minimum effective dose. Some patients require higher doses, and some subtherapeutic doses are actually therapeutic for our patients.

Widespread immunosuppression, she added, increases the risk of serious infections. “Our patients have all told us that the side effects can be worse than myasthenia gravis, and next we’re going to talk about the role of corticosteroids in myasthenia gravis.”

As for corticosteroids in particular, “it really is the best treatment but also the worst treatment”. Efficacy and side effects battle for supremacy among patients, she said, “and you don’t know which one is going to win.”

Scrapping traditional therapy

Steroids can cause many side effects, she said, including steroid-induced diabetes, which is “profound.” Some patients never recover, she said.

On top of all these risks, she says, 20 to 30 percent of patients are resistant to steroids.

As for other treatments, immunoglobulins and plasma exchange “are not really benign,” Guidon said. They carry their own potentially serious side effects, just like nonsteroidal immunosuppressive treatments, she said.

Guidon said better treatments are needed to minimize the risks associated with traditional therapies. “We need targeted therapies that result in disease remission, can be tapered, are administered orally or with infrequent self-injections, and do not require frequent laboratory monitoring. »

Additionally, ideal treatments should “have good safety data during pregnancy and breastfeeding and have a favorable side effect profile without significant long-term cancer risk.”

Claytor had no disclosures. Guidon has disclosed advisory/medical board (Alexion Pharmaceuticals, argenx, Regeneron, and UCB), publication royalties (Oakstone), and other research support (Myasthenia Gravis Foundation of America, Myasthenia Gravis Rare Disease Network, National Institutes of Health and National Institute). neurological disorders and stroke/BioSensics).