番茄社区

Management of generalized myasthenia gravis (gMG) is beginning to address aspects of the autoimmune condition patients care about, including treatment tolerability and fatigue.

Conventional treatments -- corticosteroids, non-steroidal immunosuppressive drugs, plasma exchange, IV immunoglobulin, and such -- have fallen short in controlling symptom burden, noted James Howard Jr., MD, of the University of North Carolina at Chapel Hill.

Some 10% to 20% of patients with gMG are deemed refractory to those treatments. "Though virtually every single patient has some improvement, it's just inadequate improvement," Howard noted.

The traditional measures used to capture improvement have left important gaps for patient-centered care, added Carolina Barnett-Tapia, MD, PhD, of the University of Toronto Prosserman Centre for Neuromuscular Diseases.

"So, for instance, sometimes we ask patients in a clinical trial to hold their arms out for 3 minutes, and that works fairly well, but it doesn't reflect ... real-life difficulties and how those translate to real life. And we don't do such a good job at capturing sometimes the arms and the legs, how that affects mobility," she said.

Measures that ask about fluctuation of symptoms are very helpful, Barnett-Tapia said. Technologies for symptom logging daily or once a week and tracking devices are being explored to help capture some of those fluctuations.

Newer measures are starting to be used to assess fatigue, which isn't included in the Myasthenia Gravis-Activities of Daily Living () score.

"Most patients with myasthenia will tell you [fatigue] is a big problem," Barnett-Tapia observed. "Clinicians often dismiss fatigue because it's kind of a little bit of a gray area. And we feel sometimes that it's hard to know."

Trials with newer drugs for gMG have used fatigue scales and shown not only improvements in gMG-specific symptoms but also .

The field has borrowed extensively from measurement science in rheumatology, noted Barnett-Tapia, who has been involved in developing a novel symptom measure in gMG. For example, whereas most myasthenia measures have focused on change in symptoms, she said, the latest trials and some registries are starting to use the concept of a patient-acceptable symptom state, tracking whether patients are overall satisfied with their current symptoms.

In a 2021 nationwide , almost half of the some 1,077 patients surveyed reported an unsatisfactory level of current disease symptoms, which was defined as an MG-ADL score of 3 or greater.

"The truth is you can get better and still be disabled," Barnett-Tapia pointed out. "We should be aiming not just to get patients better, but get patients to a state where they have minimal symptoms, where they're really able to do all their daily life activities as they want. ... We're moving to a more patient-centered landscape."

Medication side effects are the number one thing patients will say bothers them about treatment, Howard said.

"Everyone talks about prednisone, a phenomenal drug to treat MG, but the most hated drug on the landscape of the earth because of its side effects," he told 番茄社区, which include weight gain, acne, diabetes, hypertension, and osteoporosis. "And that's never factored into our conscious decisions in treating patients, except in extreme cases, in part because we don't have ways to measure it; in part because they don't come on until after a period of time of therapy."

It's now recognized that these effects start within 3 months then continue to smolder, he noted.

The next most bothersome issue for patients is how long immunosuppressant medications take to work -- 4 to 6 months to start and up to 3 years for full effect, Howard said. "That's a huge time loss for the patient."

New complement inhibition and neonatal Fc receptor agents work quickly, within weeks, and have narrower adverse event profiles, although "cost is the elephant in the room," he said.

"In the past, that's all we've really cared about: 'I can make you stronger. Your quality of life, therefore, has to be better, and so be it,'" he said. "The past is no longer acceptable to the patient and to the clinician. Our expectation is to make you normal with as little side effects as possible and keep you there."

No real-world data are available yet to make comparisons among the newer agents, but that information will help patient-centered care identify which patients might benefit most, Howard suggested.

Unlike MRI lesion burden in multiple sclerosis, no biomarker can predict response to treatment, he noted. "Myasthenia is about 10 to 15 years behind MS."

Global registries to track responses are needed, as right now each drug company has siloed the data for each treatment in gMG, Howard noted. He's involved with an initiative to build an adverse event database that would cover patients across treatments. Although not gathering efficacy data, "that's a start," he said.

Comment