SAVANNAH, Ga. — Patients myasthenia gravis (MG) continues to receive conventional treatment suppression of the immune system With medications such as corticosteroids and nonsteroidal agents? Or is it time to switch to new generation drugs?

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

On the one hand, Dr. of the Cleveland Clinic in Cleveland. Benjamin Claytor argued that “conventional treatment is very effective for the majority of myasthenia gravis patients” and said it should be considered as a first line.

But Amanda C. Guidon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, responded: “The immunosuppression of conventional treatments is too broad: The benefit period is too long, the burden of side effects is too high, and the risk of cancer is too high.” .”

Conventional Therapy: Affordable, Tolerable and Safe?

The ideal MG treatments are effective, tolerable and safe, Claytor said. They are also cost-effective, convenient (like a pill), lead to sustained improvement, and can be reduced in dosage.

Conventional treatments only – corticosteroids, azathioprine, mycophenolateAnd rituximab — meets the last three criteria, he said. Newer treatments don’t do this, he said.

Claytor emphasized: 2023 Duke University study A study that followed 367 MG patients treated with conventional therapies after 2000. Of these, 72% achieved the treatment goal of minimal symptoms in less than 2 years on average.

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

As for specific conventional treatments, Claytor corticosteroid prednisone It is “extremely affordable,” effective, and takes less than 2 weeks to work. All patients with MG can receive it, he said, and at least 75% of those with mild/moderate disease respond to lower doses.

Nonsteroidal Agents, Immune Globulin, Rituximab

He acknowledged the side effects of corticosteroids but said doses could be reduced when severity improves. Calcium and vitamin D He added that it may help support bone health.

As for nonsteroidal immunosuppressive treatments, he said they are easy to administer, increase the likelihood of achieving a minimal symptom state, can be effective at lower doses and allow patients to wean off steroids.

Two other conventional treatments, immune globulin and plasmapheresis, may be appropriate in cases of crisis or impending crisis or as adjunctive therapy if steroids and nonsteroidal immunosuppressive therapies do not work, he said.

How about Rituximab? “We are learning that patients with new onset disease and younger patients respond better,” Claytor said. While rituximab is expensive, it’s “not even in the same space” as newer agents when given only one or two doses, he said.

Are Steroids Ideal for MG? not so fast

In his response, Guidon stated that he was tasked with presenting an opposing viewpoint in his presentation and that “personal views are not fully represented here.” He then listed the weaknesses of conventional treatment in MG.

First of all, he said that the drugs did not work very well. emphasized a point 2019 registration work It revealed that “many myasthenia gravis patients continue to be negatively affected despite treatment.”

Additionally, “We cannot predict who will respond to which treatment… We start medications and we do not know if we will benefit from 6 months to 18 months. We also cannot determine the minimum effective dose in advance. “Some patients require higher doses, and some non-therapeutic doses are actually therapeutic for our patients.”

He added that widespread immunosuppression increases the risk of serious infections. “We’ve all heard from our patients that side effects can be worse than myasthenia, and now we’re going to talk about the role of corticosteroids in myasthenia.”

When it comes to corticosteroids in particular, “they really are the best treatment and they’re also the worst treatment.” Efficacy and side effects battle for the upper hand in patients, he said, “and you don’t know which one is going to win.”

Kicking Traditional Therapy to the Curb

He said steroids have many possible side effects; these include “profound” steroid-induced diabetes. Some patients never recover from it, he said.

In addition to all these risks, he said that 20-30 percent of patients are resistant to steroids.

As for other treatments, immune globulin and plasmapheresis “are actually not benign,” Guidon said. Like nonsteroidal immunosuppressive treatments, they come with their own set of potentially serious side effects, he said.

Better treatments are needed to minimize risks from traditional treatments, Guidon said. “We need targeted treatments that put the disease in remission, are taperable, administered orally or rarely by self-injection, and do not require frequent laboratory monitoring.”

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

Claytor had no explanation. Guidon disclosed consulting/medical advisory board (Alexion Pharmaceuticals, argenx, Regeneron, and UCB), publishing royalties (Oakstone), and other research support (Myasthenia Gravis Foundation of America, Myasthenia Gravis Rare Disease Network, National Institutes of Health, and National Institute of Neurological Disorders). and Stroke/BioSensics).