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AANEM Annual Meeting

Access daily, concise peer-reviewed reports from the AANEM Annual Meeting selected by the Neurology Today editors.

Sunday, October 24, 2021

​More patients diagnosed with myasthenia gravis had minimal symptom expression if treated with efgartigimod than with placebo, researchers reported at the 2021 American Association for Neuromuscular and Electrodiagnostic Medicine annual meeting.

Of 44 patients with acetylcholinesterase antibody-positive myasthenia gravis who were treated with efgartigimod, 59.1 percent (26 of 44) had minimal symptom expression, compared with 36.8 percent (seven of 19) of patients treated on placebo during the first cycle of treatment, reported James F. Howard Jr., MD, FAAN, professor of neurology, medicine and allied health and director of the Myasthenia Gravis Clinical Trials and Translational Research Program at the University of North Carolina at Chapel Hill.

In the second cycle of therapy, 44.4 percent of patient on efgartigimod remained with minimal symptom expression compared with none of the patients in the placebo arm, Dr. Howard reported in his poster presentation. 

“Efgartigimod blocks the body's neonatal Fc receptor, which is now recognized as a recycling or salvage pathway for immunoglobulin G," Dr. Howard explained. “By blocking this pathway, one has a safe and efficacious way to remove the pathogenic antibody, which is causal in autoimmune disease, thereby improving the disease state.

“In myasthenia gravis, antibodies to acetylcholine receptor are effectively cleared in a rapid fashion," Dr. Howard continued. “Preliminary data suggests that it is also beneficial in those patients who do not have an identifiable antibody as well."

“These results are compelling and have the potential to provide a rapid, safe, and endurable treatment to a broad range of patients with myasthenia gravis," he said. “My prediction is that anti-neonatal Fc receptor therapy has the potential to replace the current treatment of plasma exchange and immunoglobulin therapy because of its apparent nominal side effect profile."

Dr. Howard noted that adverse events, serious adverse events, and discontinuations were similar between efgartigimod-treated patients and those on placebo.

“Current trials are underway to look at a self-injectable subcutaneous formation of the product and determine whether its efficacy is as good as the intravenous form," Dr. Howard said. “If such is the case, this will offer new options to patients who desire 'independence' in their treatment and will not be burdened by the logistics of intravenous therapy. A pediatric program is also in development."

Commenting on the study, Sami Saba, MD, assistant professor of neurology at Lenox Hill Hospital and the Zucker School of Medicine at Hofstra/Northwell, said, “These results are promising because a majority of subjects who received efgartigimod achieved substantial improvement in their daily functioning, and a significant percentage reached minimal symptom expression during the first cycle."

“However, it remains to be seen if this improvement can be maintained over a longer period of time," Dr. Saba told Neurology Today At the Meetings. “Minimal symptom expression is a great marker for the efficacy of the medication, since it signifies that the disease is no longer significantly affecting that person's daily life."

Dr. Howard disclosed relationships with Alexion Pharmaceuticals, argenx, Millennium Pharmaceuticals, Ra Pharmaceuticals, Immunovant, Regeneron, Sanofi, Toleranzia, Viela Bio, Johnson & Johnson, Pfizer, and Bio SmithKline. Dr. Saba disclosed relationships with Olson Research.

AANEM Abstract 4: Howard J, Bril V, Vu T, et al. Minimal symptom expression in patients with generalized myasthenia gravis from treatment with efgartigimod.

Monday, October 18, 2021

Reports of myopathy after influenza vaccination are extremely rare, and when myopathy is reported, it is typically within two weeks after the shot, according to a study presented at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine.

“The message is that there is no association between myopathy and influenza vaccination," said Nizar Souaya, MD, professor of neurology at Rutgers and the senior author on the study. 

Researchers examined data from the national Vaccine Adverse Event Reporting System database, looking for cases of myopathy, myositis, and rhabdomyolysis reported soon after vaccination for the flu, from 1990 to 2018.

Almost all of the 224 cases—97.8 percent—were reported within six weeks, the period that researchers considered to be the risk period for an association with the vaccine. And the overwhelming number of cases, 93.2 percent were reported within two weeks. The average age of those reported was 41.9 years.

The reported rate of myopathy post-vaccination was just 0.861 cases per 10 million vaccinations—even below the occurrence rate seen in the general population.

Sixty-two of those patients reported muscle weakness, 112 reported muscle pain, 98 visited the emergency room or the doctor, 66 were hospitalized, and 18 reported disability. There were no deaths among the patients, according to the findings, presented by Parison Thepmankorn, a medical student at Rutgers University.

Dr. Souaya said it's important to note that the number doesn't represent incidence, only the reported rate, and the reported cases don't represent causation. Also important, he said, is that that these are reports from patients, physicians, and non-physicians, and don't necessarily represent underlying disease.

“It's very good to detect some rare side effect, but it should be followed by controlled studies, or retrospective studies, looking at the charts of the patient to confirm that," he said. “We use this data with a lot of caution…. We have to be careful with this type of surveillance."

Anthony Amato, MD, FAAN, professor of neurology and chief of the neuromuscular division at Harvard Medical School, pointed out several potential pitfalls in interpreting the data.

“These databases are often biased," he said. “They can be self-reported or reported by a clinician who may not be an expert in muscle diseases."

He also pointed out that myopathy wasn't defined in the study's methods, and that no muscle enzyme measurements were included.

“Myalgias—muscle pain—are non-specific symptoms and don't imply an underlying myopathy," he said. “Patients may have had subjective weakness, but there was no documentation of (whether) there was objective weakness."

Still, the study's overall point is positive, he said.

“That all said, there really was no evidence of increased myopathy amongst patients vaccinated by flu vaccine," he said. “If anything, the annual rate was decreased, possibly because they had reduced risk of getting the flu, which itself is a rare case of myositis. So, overall, this is encouraging and patients should not fear that the flu vaccine may cause myositis."

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AANEM Abstract 18: Thepmankorn P, Jedid N, Souaya S, et al. Myopathy after influenza vaccination: Reports to the Vaccine Adverse Event Reporting System.​

Monday, October 18, 2021

Patients with myasthenia gravis (MG) who are triple seronegative for antibodies appear to have a milder course of the disease, but frequently have ocular manifestations of the autoimmune disorder, researchers said at the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting.

Jonathan Morena, DO, a neurology resident at the Ohio State University Wexner Medical Center in Columbus, retrospectively reviewed charts of 255 patients with myasthenia gravis, including 21 with triple negative pathology.

“Triple seronegative patients required significantly fewer immunosuppressive agents compared with patients who are acetylcholine receptor antibody-positive (p=0.0001), and they trended towards having a less frequent history of hospitalizations, myasthenic crises, and intubations compared to all antibody positive groups," Dr. Morena reported in his presentation.

The researchers reviewed the records at Ohio State University from 2009 to 2019. Triple seronegative MG was defined by a history and examination consistent with myasthenia gravis and positive single fiber electromyography, repetitive nerve stimulation or edrophonium testing, but negative serology for acetylcholine receptor antibody, anti-muscle-specific tyrosine kinase, and lipoprotein-related protein 4 antibodies.

They identified 210 patients who were acetylcholine receptor antibody-positive, nine patients who were muscle-specific tyrosine kinase-positive; six patients who exhibited lipoprotein-related protein 4 antibodies; nine patients had double seronegative MG, and 21 patients were triple seronegative patients.,

Dr. Moreno and his colleagues found that 33 percent of the patients who had triple seronegative myasthenia gravis had ocular disease, which was significantly higher compared with 13 percent of those who were acetylcholine receptor antibody-positive (p=0.0250). One triple and one double seronegative myasthenia gravis patient had thymic hyperplasia and improved after thymectomy. Eleven triple seronegative myasthenia gravis patients had negative genetic testing for congenital myasthenic syndrome.

“Although likely rare, investigation for thymic pathology should be a consideration even in seronegative myasthenia gravis, and thymectomy should be considered when there are thymic abnormalities on imaging," Dr. Morena said. “We did not find alternate diagnoses in seronegative myasthenia gravis patients. Thus ancillary testing should be considered in carefully selected patients for cost-effective care."

Commenting on the study, Robert  Lisak, MD, FAAN, the Parker Webber Chair in Neurology, and professor of neurology, and professor of biochemistry, microbiology and immunology, at Wayne State University in Detroit, explained, “In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction, which prevents the muscle from contracting. This is most often caused by antibodies to the acetylcholine receptor itself, but antibodies to other proteins, such as muscle-specific kinase protein, also can impair transmission at the neuromuscular junction.

“The findings of a recent multicenter study that a small percentage of those who are double seronegative have antibodies to lipoprotein-related protein 4 and seem not to differ from acetylcholine receptor antibody-positive patients, although still not completely worked out, is helpful, Dr. Lisak told Neurology Today At the Meetings.The current study suggests triple negative patients have mild disease and often ocular, although 50 percent or so of ocular are acetylcholine receptor antibody-positive, so there is overlap." 

“We should realize the triple negatives might have different antibodies among them, still to be discovered," he said.

“As of now," he said, “differences in response to some therapies are most notable between acetylcholine receptor antibody-positive patients and muscle-specific tyrosine kinase-positive patients. Therapies aimed at inhibiting complement activation wouldn't be expected to work in muscle-specific tyrosine kinase-positive myasthenia gravis since the antibodies are predominately IgG4 and don't fix or activate complement.

“Muscle-specific tyrosine kinase-positive patients often fail to respond to acetylcholine esterase inhibitors and sometime worsen. IVIG seems more effective in were acetylcholine receptor antibody-positive patients than muscle-specific tyrosine kinase-positive myasthenia gravis and rituximab is more effective in muscle-specific tyrosine kinase-positive patients."

Dr. Morena did not disclose any relationships with industry.
Dr. Lisak disclosed relationships with Argenx, Guidepoint, Clearview, Clarivate, and Guidepointe.

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AANEM Abstract 1: Morena J, Jiang B, Freimer M, et al. Characteristics of triple seronegative myasthenia gravis. A single center experience.

Monday, October 18, 2021

Treating patients who have treatment-refractory myasthenia gravis (MG) with the monoclonal antibody eculizumab can result in real-world improvements in their ability to work, according to findings from a short case series presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.

Raghav Govindarajan, MD, associate medical director of the neurology outpatient clinic at the University of Missouri Medicine, said he and his colleagues looked at those patients for whom they had data on hours worked. So the study did not involve consecutive patients or randomized patients, but does offer a portrait of what is possible in the real world for patients for whom previous treatments have been unsuccessful and who then try eculizumab, Dr. Govindarajan said.

Clinical parameters, such as scores on the MG Activities of Daily Living Scale, are only so useful, Dr. Govindarajan said.

“If we say there is 2-point improvement on MG-ADL, it's clinically meaningful—what do I mean by that? It's hard to explain that to a patient…. I really wanted to figure out what is the real-life impact of treatment."

Before their MG diagnosis, all of the patients were employed. After the diagnosis, three patients reduced their hours worked, and three stopped working altogether. A year after they started treatment with eculizumab, which blocks complement C5, the people who had reduced their work hours had gone back to working the same number of hours in the same occupation. Those who had stopped working completely were able to resume working in some capacity.

Overall, the people had meaningful reductions in MG-ADL scores three months after they started treatment. They also had an average drop of 2.3 acute exacerbations per patient in the 12 months after treatment began, compared to the previous 12 months (p < 0.05).

One patient was a customer service advisor who had been working six days a week but reduced their work week to three days when first diagnosed with MG, according to findings presented by Seung Ah Kang, a third-year medical student at the University of Missouri School of Medicine. A year after treatment began, the patient was again working six days a week. Another was a high school teacher who had been working five days a week but stopped working after diagnosis, then was back to working as a teacher three days a week a year after treatment started.

Dr. Govindarajan said that employment is a particularly trying challenge when it comes to MG because its effects might not be clear to observers.

“Unlike ALS or muscular dystrophies where patients become paralyzed, and you can see it obviously, sometimes the impact of myasthenia you cannot see obviously. But it causes profound functional weakness in patients, sometimes double vision, sometimes blurry vision, and that really affects their employment status," he said.

One of his patients, not included in this study, was a phone operator and was fired because her employer thought she was coming to work drunk, he said.

Not all patients respond to the medication; in his experience, about 20 percent of patients do not respond to eculizumab, Dr. Govindarajan said. But those who do often have significant life benefits, he said.

“It's a new way to think about treatment impact."

Dianna Quan, MD, FAAN, professor of neurology at the University of Colorado School of Medicine, said these are welcome findings.

“Getting back to work is an important real-life metric of improvement, arguably as important or more important than some of our functional scales used in clinical trials," she said.

She said more follow-up is needed to see whether the effects on employment prove to be durable. And she cautioned that the study is small and retrospective and included no controls, limitations that the authors acknowledged.

She said the ability to work generally deserves more attention in the assessment of drugs' efficacy, especially when it comes to treatments that have a high price tag.

“Employment outcomes should be looked at in more detail going forward in this and other expensive therapies," she said.

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AANEM Abstract 10: Ah Kang S, Sweeney M, Govindarajan R. Real life impact of eculizumab in treatment-refractory acetylcholine receptor antibody-positive generalized myasthenia gravis.​