Complexity in Myasthenia Gravis: Bridging the Gaps in Diagnosis, Treatment, and Equitable Care

The therapeutic landscape for generalized myasthenia gravis (gMG) has shifted considerably in recent years, with 7 new medications approved in the past decade, 6 of which arrived within the last 4 years alone. Despite this, expanded treatment options have not totally resolved the field's most pressing clinical questions. Chief among them is how to select, sequence, and sustain therapies for patients whose disease defies simple categorization.

Against this backdrop, NeurologyLive convened a multidisciplinary global panel of neuromuscular specialists for a Bridging the Gaps consensus meeting. The group sought to examine persistent gaps in gMG diagnosis, treatment initiation, special populations, and equitable access to care. The meeting was chaired by James Howard, MD, of the University of North Carolina, Chapel Hill, and featured faculty from institutions across the United States, Italy, and Germany.

The Clinical and Societal Burden of Undertreated gMG

Ali Habib, MD, of the University of California, Irvine, opened the meeting by surveying gMG's clinical heterogeneity, noting that while most patients present in a relatively straightforward fashion, a meaningful subset poses diagnostic difficulty—including those with ICU-onset extubation failure, distal-predominant weakness, presymptomatic thymoma-associated disease, and misdiagnosed conditions such as oculopharyngeal muscular dystrophy or congenital myasthenic syndrome. The question of seronegative gMG was flagged as among the most consequential unresolved issues in the field, framing a thread that would run throughout the day.

Regional heterogeneity in care delivery was also addressed: the US market reflects an approximate 50/50 split between academic and community settings with payer-driven access variability; the UK relies on guideline-based models given extended wait times; and Germany benefits from immediate EMA-approved drug access provided clinicians document treatment response for health insurers.

Howard drew the discussion toward the full societal weight of inadequately controlled disease. "When you look at figures like employment rates—in Japan, nearly one-third of individuals with MG are unemployed, and another significant percent have reductions in work hours such that they can't care for their family. These are huge societal costs," he said. "Until we, as a group, can start to generate this kind of information, I think we're going to continue to fight with our payers trying to show that even though a drug is very expensive, the societal cost is very low if we can keep them employed."

The session on therapeutic pipeline and crisis management, led by Raffaele Iorio, MD, of Universita Cattolica del Sacro Cuore in Rome, underscored the absence of validated biomarkers to guide selection between complement inhibitors and FcRn antagonists. Patients presenting with impending myasthenic crisis were excluded from nearly all randomized controlled trials, leaving clinicians to rely on case series and retrospective data when considering these agents in the acute setting. Iorio noted that no consensus definition of nonresponse currently exists, with candidate criteria including persistent symptoms despite adequate immunotherapy, failure to achieve minimal symptom expression (MSE) within 6 to 12 months, recurrent exacerbation requiring rescue therapy, or inability to taper corticosteroids without relapse.

”In Japan, nearly one-third of individuals with MG are unemployed, and another significant percent have reductions in work hours such that they can't care for their family. These are huge societal costs.”
—James Howard, MD

Treating Early and Hard: The Case for Front-Loaded Disease Control

Pushpa Narayanaswami, MD, a neuromuscular neurologist in Boston, presented a pharmacoeconomic analysis underscoring the downstream costs of long-term oral corticosteroid (OCS) use. In a Markov microsimulation of 3000 patients receiving a mean maintenance prednisone dose of 16 mg daily, a 50% OCS dose reduction was associated with a 0.56 quality-adjusted life year (QALY) gain and approximately $24,000 in reduced adverse event management costs over a patient's lifetime. Complete OCS elimination yielded gains of 1.41 QALYs and $41,368 in cost savings, with larger gains observed in younger cohorts and those with baseline comorbidities.

The data reinforced a point Narayanaswami made directly: achieving disease control early is not simply a clinical preference but a time-sensitive imperative. "There's reasonably enough data to say, ‘Hit them fast and hit them hard,’ is a good idea," she said. "That dividing line appears to be to get them into control in the first 2 years, which gives us a small window—not 14 to 22 months."

For azathioprine and mycophenolate mofetil, participants acknowledged that 75% of patients will not reach a meaningful response until 13 to 22 months after initiation, a timeline that has increasingly shifted interest toward targeted agents as bridge or initial therapy.

Jan Luenemann, MD, of University Hospital Münster, outlined Germany's updated guidelines from the German Neurological Society, which reserve newer targeted therapies for patients meeting defined high-disease-activity criteria: myasthenic crisis or exacerbation within the first 2 years of disease or failure of at least 1 immunosuppressive agent after a minimum disease duration of 2 years. Clinical trial data referenced included an FcRn extension study showing MSE in approximately 60% of patients over 3 years and the CHAMPION MG trial, in which 88% achieved meaningful clinical improvement by ADL score criteria. The approval of inebilizumab in Germany prompted significant discussion about sequencing, with participants debating whether early B-cell depletion might alter disease natural history in ways that FcRn and complement inhibition, as downstream mechanisms, may not.

"We think clinically: ‘The patient has no symptoms. The patient is on the drug.’ We don't think about whether they can come off the drug at some point, whether an upstream mechanism could give them a potential chance of getting off these lower downstream mechanisms. And that dialogue is lost."
—Suraj Muley, MD

Suraj Muley, MD, of the Bob Bove Neuroscience Institute at Arizona State University, pressed the field on whether the therapeutic success visible at the symptom level reflects actual immune control. "I don't know whether their immune attack against the muscle is gone," he said. "We think clinically: ‘The patient has no symptoms. The patient is on the drug.’ We don't think about whether they can come off the drug at some point, whether an upstream mechanism could give them a potential chance of getting off these lower downstream mechanisms. And that dialogue is lost."

Seronegative gMG, Special Populations, and the Limits of Current Evidence

Miriam Freimer, MD, of Ohio State University, and Beth Stein, MD, of St. Joseph's Health in New Jersey, covered special populations with particular urgency. In the pediatric setting, no validated disease-specific outcome measures exist for patients younger than 12 years; congenital myasthenic syndrome remains a critical and frequently missed mimic; and approved options are limited to nipocalimab for patients aged 12 and older and eculizumab for patients aged 6 and older. Participants noted that patients transitioning from pediatric to adult care often carry significant steroid- and immunosuppressant-related morbidity by their late teens.

In pregnant patients with gMG, Stein described a clinical reality that has yet to attract commensurate attention. "Nobody wants to deal with these patients," she said. "I think it's a really important time for these patients that nobody wants to put the time in to understand. And so, unfortunately, there are huge, important gaps that persist in the way we manage both pre- and post-conception."

Approximately 30% of patients experience exacerbation in the first trimester, and a similar proportion face postpartum vulnerability; mycophenolate mofetil and methotrexate are contraindicated, IVIG and plasma exchange are considered safe throughout pregnancy, and no standardized guidelines exist for preconception planning, intrapartum management, or postpartum reinitiation of therapy. A 30% higher cesarean delivery rate in patients with gMG was noted, with the drivers of that disparity unresolved.

"If you're entertaining autoimmune seronegative MG, there has to be a really extensive workup. Because if you're committing to immunosuppression of some sort, you need to make sure it's not genetic. I've just seen some—and I only have a few—but their lives were ruined by immunosuppression for no reason."
—Katherine Ruzhansky, MD

Muley's presentation on seronegative gMG laid out the competing risks of underdiagnosis and overdiagnosis with systematic clarity. Repetitive nerve stimulation carries approximately 65% sensitivity for gMG, and single-fiber EMG, while widely regarded as the gold standard, is subject to significant technical variability in pair selection, muscle choice, and interpreter expertise. Placebo response rates of 30% to 40% in gMG trials complicate the interpretation of treatment response as a diagnostic criterion.

Katherine Ruzhansky, MD, of the Medical University of South Carolina, raised the risk of immunosuppression-related harm in patients who may not have autoimmune gMG at all: "If you're entertaining autoimmune seronegative MG, there has to be a really extensive workup. Because if you're committing to immunosuppression of some sort, you need to make sure it's not genetic. I've just seen some—and I only have a few—but their lives were ruined by immunosuppression for no reason."

Equity, Access, and the Road to Consensus

Joshua Alpers, MD, of Erlanger Neuroscience Institute, spent the final session of the meeting mapping gMG care disparities onto the Healthy People 2030 social determinants of health framework. "Black patients in the US are nearly 30% less likely to see outpatient neurologists for chronic neurological conditions," he noted, "and Black patients are 3 times more likely to be hospitalized for crisis or exacerbation compared with White patients. There is a lower degree of access to care—whether it's outpatient care or inpatient emergent care."

Claims-based data showed that when controlling for insurance status, access disparities diminish substantially, identifying payer coverage as the primary structural driver. Participants discussed the MG Core Exam as a validated telemedicine tool for longitudinal follow-up, the potential of wearable devices for remote monitoring, and the neuromuscular fellowship pipeline as a workforce concern that will compound access challenges if not addressed.

Howard then closed the meeting with a call that extended beyond the day's discussions. "The MG field is 10 to 15 years behind our MS colleagues," he said. "We need a third party—with genuine interest in the disease but not with allegiance to any one particular asset—to bring patients, clinicians, research scientists, pharma, health ministries, and payers down at the table. And put forth a white paper. That's a desperate need."

The absence of a validated biomarker for gMG was identified as the field's most foundational unmet need, one that continues to impede rational therapy selection, equitable access, and meaningful outcome measurement across every domain discussed during the day.