Myasthenia Gravis

Nicholas J. Silvestri, MD, expresses gratitude for the impactful relationships and mentorship in the field of myasthenia gravis. Dr Chip Howard at the University of North Carolina is distinguished as a humble and inclusive mentor, considered influential in the field.

Dr Howard's influence goes beyond the efficacy of medications, emphasizing the importance of considering patient care comprehensively, including side effects and overall safety. This perspective has significantly shaped Dr Silvestri’s treatment approach, leading to a more holistic and patient-centered care paradigm for individuals with myasthenia gravis.

Nicholas J. Silvestri, MD, expresses gratitude for the impactful relationships and mentorship in the field of myasthenia gravis. Dr Chip Howard at the University of North Carolina is distinguished as a humble and inclusive mentor, considered influential in the field.

Dr Howard's influence goes beyond the efficacy of medications, emphasizing the importance of considering patient care comprehensively, including side effects and overall safety. This perspective has significantly shaped Dr Silvestri’s treatment approach, leading to a more holistic and patient-centered care paradigm for individuals with myasthenia gravis.

Nicholas J. Silvestri, MD, expresses gratitude for the impactful relationships and mentorship in the field of myasthenia gravis. Dr Chip Howard at the University of North Carolina is distinguished as a humble and inclusive mentor, considered influential in the field.

Dr Howard's influence goes beyond the efficacy of medications, emphasizing the importance of considering patient care comprehensively, including side effects and overall safety. This perspective has significantly shaped Dr Silvestri’s treatment approach, leading to a more holistic and patient-centered care paradigm for individuals with myasthenia gravis.

During her time in training at the University of Virginia, Kelly G. Gwathmey, MD, gained invaluable insights into myasthenia gravis (MG) care and research from the late Dr Ted Burns and Dr Larry Phillips. Dr Burns, a renowned leader in MG research, emphasized patient-centric approaches, fostering the development of crucial outcome measures like the MG composite scale and MG-QOL-15.

Burns' dedication to listening to patients' experiences shaped the development of health-related quality-of-life instruments used in MG clinical trials. For Dr Gwathmey, learning under Dr Burns underscored the significance of patient experiences in treatment decisions and highlighted the importance of incorporating patient perspectives in clinical care and research endeavors.

During her time in training at the University of Virginia, Kelly G. Gwathmey, MD, gained invaluable insights into myasthenia gravis (MG) care and research from the late Dr Ted Burns and Dr Larry Phillips. Dr Burns, a renowned leader in MG research, emphasized patient-centric approaches, fostering the development of crucial outcome measures like the MG composite scale and MG-QOL-15.

Burns' dedication to listening to patients' experiences shaped the development of health-related quality-of-life instruments used in MG clinical trials. For Dr Gwathmey, learning under Dr Burns underscored the significance of patient experiences in treatment decisions and highlighted the importance of incorporating patient perspectives in clinical care and research endeavors.

During her time in training at the University of Virginia, Kelly G. Gwathmey, MD, gained invaluable insights into myasthenia gravis (MG) care and research from the late Dr Ted Burns and Dr Larry Phillips. Dr Burns, a renowned leader in MG research, emphasized patient-centric approaches, fostering the development of crucial outcome measures like the MG composite scale and MG-QOL-15.

Burns' dedication to listening to patients' experiences shaped the development of health-related quality-of-life instruments used in MG clinical trials. For Dr Gwathmey, learning under Dr Burns underscored the significance of patient experiences in treatment decisions and highlighted the importance of incorporating patient perspectives in clinical care and research endeavors.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

PHOENIX – New treatments for myasthenia gravis are bringing new promise to patients, but their use must be balanced against short-term and long-term risks, according to Pushpa Narayanaswami, MD, who discussed the topic at the 2023 annual meeting of the American Association for Neuromuscular & Electrodiagnostic Medicine (AANEM).

The first Food and Drug Administration–approved drug was pyridostigmine in 1955, and it was more than 60 years before the second drug, eculizumab, gained FDA approval in 2017. Activity in more recent years has been much more brisk with the approvals of efgartigimod in 2021; ravulizumab in 2022; and efgartigimod SQ, rozanolixizumab, and zilucoplan (Japan) in 2023. Eculizumab, efgartigimod, efgartigimod SQ, ravulizumab, and rozanolixizumab are approved for patients who are anti–acetylcholine receptor (AchR) positive. Rozanolixizumab is also approved for patients who are anti–muscle-specific tyrosine kinase (MuSK) antibody positive.

The new drugs have novel mechanisms of action, giving physicians more tools to treat the condition. The mechanisms fall into two general groups: C5-complement inhibitors and neonatal Fc receptor (FcRn) agonists. Dr. Narayanaswami sought to provide guidance in thinking about how to prescribe the new drugs. “How do we really use these drugs? It’s sort of confusing in terms of where they fit in in the algorithm. I don’t pretend to have the answers, but I’m going to sort of give you a general overview of how I look at these based on the trial data and based on what we’ve done in the past,” she said during her talk.
 

Assessing the risk/benefit ratio

Myasthenia gravis treatment strategies should take into account both disease control and minimization of the adverse effects of treatment, which can include both short- and long-term concerns such as hematologic issues, changes in mood and sleep, diarrhea, infection risk, detriments to bone health, hypertension, diabetes mellitus, glaucoma, and cancer.

Disease control can be subjective. “Each patient may have a different approach to what their disease control means, so we don’t quite understand what the definition of disease control is,” said Dr. Narayanaswami. For example, “[a physician] may think of a sleep disturbance as mild, but [the patient] may not. They may not be able to function, so a lot of conversations [are needed] there,” she added.

The international consensus guidance for myasthenia gravis, first published in 2016 and updated a few years later, which Dr. Narayanaswami coauthored, suggested that minimal manifestation of disease is achievable and is relevant to patients. “These are patients who are doing well, they come to your office and say, ‘I’m doing well, I really don’t have any problem [though they may have some weakness],’ ” said Dr. Narayanaswami. In such patients, mild, grade 1 side effects from medications are acceptable.

Dr. Narayanaswami discussed the efficacy of older drugs, including evidence from a 2022 study of 367 patients, that found that 72% of patients achieved MGFA-PIS (postintervention status) of minimal manifestations within 2 years of treatment. That rose to 76% within 3 years and 84% within 5 years. “The incremental benefit [after the first 2] years was not huge, and I think that’s something to pay attention to,” said Dr. Narayanaswami. The study also found that disease duration at first visit was shorter among patients who achieved minimal manifestation at 12 months versus at 16 months. That finding follows a trend in current thinking about treatment of myasthenia gravis. “Chip (James) Howard [of Duke University], who’s my sort of guru, says you’ve got to address this like MS. You’ve got to hit them early and hit them hard. And I think we’re seeing more and more of this. If you think about it even in your clinical practice, patients who did well tended to do well early on,” said Dr. Narayanaswami. She noted an important limitation in that the study did not adjust for confounders or covariates.

In addition, the PROMISE-MG study, which Dr. Narayanaswami coauthored, found that 57%-89% of patients treated with azathioprine or mycophenolate achieved clinically meaningful improvement in a variety of different outcome measures. “More than half to two-thirds of patients do well in clinical practice with the older drugs,” said Dr. Narayanaswami. In terms of time to outcomes, the study found that it took 2-6 months of azathioprine treatment and 2-3 months of mycophenolate mofetil (MMF) treatment for 25% of patients to experience clinically meaningful improvements. It took 14-22 months and 13-18 months, respectively, for 75% of patients to achieve this benchmark.

Regarding when to consider switching to newer therapies, Dr. Narayanaswami pointed out that there is no FDA requirement that patients fail previous therapies, but insurance companies often require it before reimbursement.

Dr. Narayanaswami said that the benefits of these drugs are well known, so she focused instead on their safety profiles in clinical practice. C-5 complement inhibitors carry a risk of meningococcal infection, which has been addressed in various postmarketing studies. “I will say that data is difficult to interpret for various reasons … but the point is that there is a risk for meningococcal infections. The risk appears to be low, but it’s not zero, even if you immunize patients, and I think that’s the conversation we need to have [with patients],” she said. Other issues with C5-complement inhibitors can include headache, nasopharyngitis, diarrhea, abdominal pain, back pain, nausea, and other infections.

FcRn antagonists have a range of potential side effects, but Dr. Narayanaswami emphasized timing of vaccinations, since the drugs antagonize recycling of IgG. She said vaccines should be given before the first dose of the cycle. There are no data on their use in pregnancy, but the agents could potentially reduce the passive transfer of IgG antibodies to the fetus.
 

Treatment strategies

In clinical practice, Dr. Narayanaswami employs the newer drugs in patients who have failed older drugs, or who experience intolerable side effects. An important consideration is how long to wait before determining a failure on previous therapies. Her current inclination is to treat earlier, which leads her to consider newer drugs at 2 years after disease onset, or after 1 year if the patient has had no improvement at all. She would consider the therapies as first-line therapies in patients for whom she doesn’t feel comfortable prescribing older medications, often older or more frail patients, or patients at any age when comorbidities might contraindicate glucocorticoids.

During the Q&A session after the talk, an attendee asked Dr. Narayanaswami what she does when payers balk at paying for new drugs. She noted that payers don’t necessarily have a specific number of months in mind for patients who are quite sick. “They just want somebody to try something. That has been my experience,” she said. She also goes peer-to-peer when disputing coverage. “Sometimes you can convince them on a peer-to-peer [basis] because they don’t really know myasthenia gravis.”

Another questioner wondered if clinical trials have been done or are in progress to demonstrate that earlier treatment can lead to better results. Dr. Narayanaswami responded that several observational trials are looking at the question. “It’s challenging because sometimes we don’t know the time from diagnosis. We know the first time they came in, which is not necessarily the same as the time from diagnosis, and sometimes that can be hard to get. And, again, it’s observational data, which can be dirty,” she said.

Dr. Narayanaswami disclosed ties with Alexion, Argenx, Dianthus, GSK, Janssen, Patient Centered Outcomes Research Institute, Sanofi, and UCB.

PHOENIX – New treatments for myasthenia gravis are bringing new promise to patients, but their use must be balanced against short-term and long-term risks, according to Pushpa Narayanaswami, MD, who discussed the topic at the 2023 annual meeting of the American Association for Neuromuscular & Electrodiagnostic Medicine (AANEM).

The first Food and Drug Administration–approved drug was pyridostigmine in 1955, and it was more than 60 years before the second drug, eculizumab, gained FDA approval in 2017. Activity in more recent years has been much more brisk with the approvals of efgartigimod in 2021; ravulizumab in 2022; and efgartigimod SQ, rozanolixizumab, and zilucoplan (Japan) in 2023. Eculizumab, efgartigimod, efgartigimod SQ, ravulizumab, and rozanolixizumab are approved for patients who are anti–acetylcholine receptor (AchR) positive. Rozanolixizumab is also approved for patients who are anti–muscle-specific tyrosine kinase (MuSK) antibody positive.

The new drugs have novel mechanisms of action, giving physicians more tools to treat the condition. The mechanisms fall into two general groups: C5-complement inhibitors and neonatal Fc receptor (FcRn) agonists. Dr. Narayanaswami sought to provide guidance in thinking about how to prescribe the new drugs. “How do we really use these drugs? It’s sort of confusing in terms of where they fit in in the algorithm. I don’t pretend to have the answers, but I’m going to sort of give you a general overview of how I look at these based on the trial data and based on what we’ve done in the past,” she said during her talk.
 

Assessing the risk/benefit ratio

Myasthenia gravis treatment strategies should take into account both disease control and minimization of the adverse effects of treatment, which can include both short- and long-term concerns such as hematologic issues, changes in mood and sleep, diarrhea, infection risk, detriments to bone health, hypertension, diabetes mellitus, glaucoma, and cancer.

Disease control can be subjective. “Each patient may have a different approach to what their disease control means, so we don’t quite understand what the definition of disease control is,” said Dr. Narayanaswami. For example, “[a physician] may think of a sleep disturbance as mild, but [the patient] may not. They may not be able to function, so a lot of conversations [are needed] there,” she added.

The international consensus guidance for myasthenia gravis, first published in 2016 and updated a few years later, which Dr. Narayanaswami coauthored, suggested that minimal manifestation of disease is achievable and is relevant to patients. “These are patients who are doing well, they come to your office and say, ‘I’m doing well, I really don’t have any problem [though they may have some weakness],’ ” said Dr. Narayanaswami. In such patients, mild, grade 1 side effects from medications are acceptable.

Dr. Narayanaswami discussed the efficacy of older drugs, including evidence from a 2022 study of 367 patients, that found that 72% of patients achieved MGFA-PIS (postintervention status) of minimal manifestations within 2 years of treatment. That rose to 76% within 3 years and 84% within 5 years. “The incremental benefit [after the first 2] years was not huge, and I think that’s something to pay attention to,” said Dr. Narayanaswami. The study also found that disease duration at first visit was shorter among patients who achieved minimal manifestation at 12 months versus at 16 months. That finding follows a trend in current thinking about treatment of myasthenia gravis. “Chip (James) Howard [of Duke University], who’s my sort of guru, says you’ve got to address this like MS. You’ve got to hit them early and hit them hard. And I think we’re seeing more and more of this. If you think about it even in your clinical practice, patients who did well tended to do well early on,” said Dr. Narayanaswami. She noted an important limitation in that the study did not adjust for confounders or covariates.

In addition, the PROMISE-MG study, which Dr. Narayanaswami coauthored, found that 57%-89% of patients treated with azathioprine or mycophenolate achieved clinically meaningful improvement in a variety of different outcome measures. “More than half to two-thirds of patients do well in clinical practice with the older drugs,” said Dr. Narayanaswami. In terms of time to outcomes, the study found that it took 2-6 months of azathioprine treatment and 2-3 months of mycophenolate mofetil (MMF) treatment for 25% of patients to experience clinically meaningful improvements. It took 14-22 months and 13-18 months, respectively, for 75% of patients to achieve this benchmark.

Regarding when to consider switching to newer therapies, Dr. Narayanaswami pointed out that there is no FDA requirement that patients fail previous therapies, but insurance companies often require it before reimbursement.

Dr. Narayanaswami said that the benefits of these drugs are well known, so she focused instead on their safety profiles in clinical practice. C-5 complement inhibitors carry a risk of meningococcal infection, which has been addressed in various postmarketing studies. “I will say that data is difficult to interpret for various reasons … but the point is that there is a risk for meningococcal infections. The risk appears to be low, but it’s not zero, even if you immunize patients, and I think that’s the conversation we need to have [with patients],” she said. Other issues with C5-complement inhibitors can include headache, nasopharyngitis, diarrhea, abdominal pain, back pain, nausea, and other infections.

FcRn antagonists have a range of potential side effects, but Dr. Narayanaswami emphasized timing of vaccinations, since the drugs antagonize recycling of IgG. She said vaccines should be given before the first dose of the cycle. There are no data on their use in pregnancy, but the agents could potentially reduce the passive transfer of IgG antibodies to the fetus.
 

Treatment strategies

In clinical practice, Dr. Narayanaswami employs the newer drugs in patients who have failed older drugs, or who experience intolerable side effects. An important consideration is how long to wait before determining a failure on previous therapies. Her current inclination is to treat earlier, which leads her to consider newer drugs at 2 years after disease onset, or after 1 year if the patient has had no improvement at all. She would consider the therapies as first-line therapies in patients for whom she doesn’t feel comfortable prescribing older medications, often older or more frail patients, or patients at any age when comorbidities might contraindicate glucocorticoids.

During the Q&A session after the talk, an attendee asked Dr. Narayanaswami what she does when payers balk at paying for new drugs. She noted that payers don’t necessarily have a specific number of months in mind for patients who are quite sick. “They just want somebody to try something. That has been my experience,” she said. She also goes peer-to-peer when disputing coverage. “Sometimes you can convince them on a peer-to-peer [basis] because they don’t really know myasthenia gravis.”

Another questioner wondered if clinical trials have been done or are in progress to demonstrate that earlier treatment can lead to better results. Dr. Narayanaswami responded that several observational trials are looking at the question. “It’s challenging because sometimes we don’t know the time from diagnosis. We know the first time they came in, which is not necessarily the same as the time from diagnosis, and sometimes that can be hard to get. And, again, it’s observational data, which can be dirty,” she said.

Dr. Narayanaswami disclosed ties with Alexion, Argenx, Dianthus, GSK, Janssen, Patient Centered Outcomes Research Institute, Sanofi, and UCB.

PHOENIX – New treatments for myasthenia gravis are bringing new promise to patients, but their use must be balanced against short-term and long-term risks, according to Pushpa Narayanaswami, MD, who discussed the topic at the 2023 annual meeting of the American Association for Neuromuscular & Electrodiagnostic Medicine (AANEM).

The first Food and Drug Administration–approved drug was pyridostigmine in 1955, and it was more than 60 years before the second drug, eculizumab, gained FDA approval in 2017. Activity in more recent years has been much more brisk with the approvals of efgartigimod in 2021; ravulizumab in 2022; and efgartigimod SQ, rozanolixizumab, and zilucoplan (Japan) in 2023. Eculizumab, efgartigimod, efgartigimod SQ, ravulizumab, and rozanolixizumab are approved for patients who are anti–acetylcholine receptor (AchR) positive. Rozanolixizumab is also approved for patients who are anti–muscle-specific tyrosine kinase (MuSK) antibody positive.

The new drugs have novel mechanisms of action, giving physicians more tools to treat the condition. The mechanisms fall into two general groups: C5-complement inhibitors and neonatal Fc receptor (FcRn) agonists. Dr. Narayanaswami sought to provide guidance in thinking about how to prescribe the new drugs. “How do we really use these drugs? It’s sort of confusing in terms of where they fit in in the algorithm. I don’t pretend to have the answers, but I’m going to sort of give you a general overview of how I look at these based on the trial data and based on what we’ve done in the past,” she said during her talk.
 

Assessing the risk/benefit ratio

Myasthenia gravis treatment strategies should take into account both disease control and minimization of the adverse effects of treatment, which can include both short- and long-term concerns such as hematologic issues, changes in mood and sleep, diarrhea, infection risk, detriments to bone health, hypertension, diabetes mellitus, glaucoma, and cancer.

Disease control can be subjective. “Each patient may have a different approach to what their disease control means, so we don’t quite understand what the definition of disease control is,” said Dr. Narayanaswami. For example, “[a physician] may think of a sleep disturbance as mild, but [the patient] may not. They may not be able to function, so a lot of conversations [are needed] there,” she added.

The international consensus guidance for myasthenia gravis, first published in 2016 and updated a few years later, which Dr. Narayanaswami coauthored, suggested that minimal manifestation of disease is achievable and is relevant to patients. “These are patients who are doing well, they come to your office and say, ‘I’m doing well, I really don’t have any problem [though they may have some weakness],’ ” said Dr. Narayanaswami. In such patients, mild, grade 1 side effects from medications are acceptable.

Dr. Narayanaswami discussed the efficacy of older drugs, including evidence from a 2022 study of 367 patients, that found that 72% of patients achieved MGFA-PIS (postintervention status) of minimal manifestations within 2 years of treatment. That rose to 76% within 3 years and 84% within 5 years. “The incremental benefit [after the first 2] years was not huge, and I think that’s something to pay attention to,” said Dr. Narayanaswami. The study also found that disease duration at first visit was shorter among patients who achieved minimal manifestation at 12 months versus at 16 months. That finding follows a trend in current thinking about treatment of myasthenia gravis. “Chip (James) Howard [of Duke University], who’s my sort of guru, says you’ve got to address this like MS. You’ve got to hit them early and hit them hard. And I think we’re seeing more and more of this. If you think about it even in your clinical practice, patients who did well tended to do well early on,” said Dr. Narayanaswami. She noted an important limitation in that the study did not adjust for confounders or covariates.

In addition, the PROMISE-MG study, which Dr. Narayanaswami coauthored, found that 57%-89% of patients treated with azathioprine or mycophenolate achieved clinically meaningful improvement in a variety of different outcome measures. “More than half to two-thirds of patients do well in clinical practice with the older drugs,” said Dr. Narayanaswami. In terms of time to outcomes, the study found that it took 2-6 months of azathioprine treatment and 2-3 months of mycophenolate mofetil (MMF) treatment for 25% of patients to experience clinically meaningful improvements. It took 14-22 months and 13-18 months, respectively, for 75% of patients to achieve this benchmark.

Regarding when to consider switching to newer therapies, Dr. Narayanaswami pointed out that there is no FDA requirement that patients fail previous therapies, but insurance companies often require it before reimbursement.

Dr. Narayanaswami said that the benefits of these drugs are well known, so she focused instead on their safety profiles in clinical practice. C-5 complement inhibitors carry a risk of meningococcal infection, which has been addressed in various postmarketing studies. “I will say that data is difficult to interpret for various reasons … but the point is that there is a risk for meningococcal infections. The risk appears to be low, but it’s not zero, even if you immunize patients, and I think that’s the conversation we need to have [with patients],” she said. Other issues with C5-complement inhibitors can include headache, nasopharyngitis, diarrhea, abdominal pain, back pain, nausea, and other infections.

FcRn antagonists have a range of potential side effects, but Dr. Narayanaswami emphasized timing of vaccinations, since the drugs antagonize recycling of IgG. She said vaccines should be given before the first dose of the cycle. There are no data on their use in pregnancy, but the agents could potentially reduce the passive transfer of IgG antibodies to the fetus.
 

Treatment strategies

In clinical practice, Dr. Narayanaswami employs the newer drugs in patients who have failed older drugs, or who experience intolerable side effects. An important consideration is how long to wait before determining a failure on previous therapies. Her current inclination is to treat earlier, which leads her to consider newer drugs at 2 years after disease onset, or after 1 year if the patient has had no improvement at all. She would consider the therapies as first-line therapies in patients for whom she doesn’t feel comfortable prescribing older medications, often older or more frail patients, or patients at any age when comorbidities might contraindicate glucocorticoids.

During the Q&A session after the talk, an attendee asked Dr. Narayanaswami what she does when payers balk at paying for new drugs. She noted that payers don’t necessarily have a specific number of months in mind for patients who are quite sick. “They just want somebody to try something. That has been my experience,” she said. She also goes peer-to-peer when disputing coverage. “Sometimes you can convince them on a peer-to-peer [basis] because they don’t really know myasthenia gravis.”

Another questioner wondered if clinical trials have been done or are in progress to demonstrate that earlier treatment can lead to better results. Dr. Narayanaswami responded that several observational trials are looking at the question. “It’s challenging because sometimes we don’t know the time from diagnosis. We know the first time they came in, which is not necessarily the same as the time from diagnosis, and sometimes that can be hard to get. And, again, it’s observational data, which can be dirty,” she said.

Dr. Narayanaswami disclosed ties with Alexion, Argenx, Dianthus, GSK, Janssen, Patient Centered Outcomes Research Institute, Sanofi, and UCB.

PHOENIX – Early responders to zilucoplan, the newly approved medication for myasthenia gravis, have sustained benefit for up to 60 weeks, a new analyses show.

“The information [in the studies] is valuable in making clinical decisions in managing myasthenia gravis, which is a chronic autoimmune condition that requires long-term use of immunosuppressives,” said Xinli Du, MD, PhD, an assistant professor in the department of neurology at Virginia Commonwealth University in Richmond, who was not involved in the research.

“Compared with conventional immunosuppressants, which take 3-9 months to know if the patient will respond, this is definitely a game-changer,” she said.

The research was presented at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).
 

FDA approval

Approved by the U.S. Food and Drug Administration in October, the targeted peptide inhibitor of complement component 5 represents the only once-daily self-administered subcutaneous injection for adult patients with acetylcholine receptor autoantibody–positive (AChR+) generalized myasthenia gravis.

The multicenter, phase 3, placebo-controlled RAISE trial demonstrated that zilucoplan was associated with significant improvement in myasthenia gravis–specific outcomes in adult patients with mild to severe AChR+ generalized myasthenia gravis.

Of note, approximately 40% of patients in the zilucoplan phase 2 and 3 clinical trials have a significant response as early as the first week of treatment. For the current post hoc analysis, first author Miriam Freimer, MD, and colleagues took a closer look at the longer-term outcomes in these patients in the ongoing RAISE-XT open-label extension study.

In these two double-blind studies, patients were randomly assigned to receive either daily subcutaneous injections of 0.3 mg/kg zilucoplan or placebo.

Among 93 patients receiving zilucoplan in the two studies, 40 (43%) were identified as early responders based on having at least a 3-point reduction from baseline on the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) within 1 week of treatment, and 31 (33%) qualified based on having at least 5-point reductions in Quantitative Myasthenia Gravis (QMG), at week 1.

Of these early responders, more than 80% meeting the MG-ADL and 85% meeting QMG criteria continued to show a treatment response at each assessment through week 60 in the open-label RAISE-XT trial.

Furthermore, week 1 responders maintained their response for 88.1% of their total treatment time in the MG-ADL group and 88.8% of their total treatment time on treatment in the QMG group, representing a median zilucoplan treatment duration of 450 days.

Of note, the week 1 early responders had no significant differences, compared with the study’s overall population. Participants had a mean age of 49.6 years versus 52.9 years in the overall population. Approximately 40% of patients in both studies were men, and 60%-64% were disease class III as assessed by the Myasthenia Gravis Foundation of America criteria.

“It is very exciting to see such a high response of rapid responders. This means that some patients may be able to avoid steroids or be able to taper them faster than with other accepted treatments for myasthenia gravis,” said Dr. Freimer, director of the division of neuromuscular disorders and the codirector of the Myasthenia Gravis Clinic at the Ohio State University in Columbus.
 

Impact on fatigue

In a separate post hoc analysis of patients who entered RAISE-XT, the researchers evaluated long-term effects of zilucoplan on fatigue.

Improvements in fatigue were already apparent at the end of the RAISE trial, with the least squares mean (LSM) change from baseline in fatigue assessed after 12 weeks with the Neuro-QOL T-score being –6.26 for zilucoplan (n = 86) compared with an increase of 2.65 for placebo (n = 88; LSM difference, –3.61; nominal P = .0060).

Patients who received placebo in the RAISE trial were able to switch to zilucoplan in the RAISE-XT open-label trail, and among those who did, fatigue, as measured in the T-scores, improved significantly within 1 week of switching.

Fatigue further improved out to week 16 in terms of T-scores for the placebo-switch as well as zilucoplan groups, and the improvements in the scores were sustained through week 60 (mean change from RAISE baseline, –10.71 [n = 42] and –9.15 [n = 42], respectively).

“Fatigue is a challenge for patients with [generalized myasthenia gravis]. Zilucoplan significantly and clinically meaningfully improved myasthenic fatigue versus placebo during RAISE,” the investigators report.

“Further improvements were observed during RAISE-XT and were sustained up to 60 weeks of treatment,” they added.
 

Favorable safety profile

Zilucoplan continued to show a favorable safety profile in the RAISE-XT trial and was well tolerated in the long term.

The most common adverse reactions (10% or more) in patients with generalized myasthenia gravis were injection-site reactions, upper respiratory tract infection, and diarrhea.

Though additional therapies have also recently entered the market for generalized myasthenia gravis, they are either intravenous or subcutaneous infusions requiring a health care professional to administer them.

“This self-administered medication allows patients to be more independent and can even travel since it is not dependent on an infusion center,” Dr. Freimer noted.

However, similar to the other complement inhibitors, zilucoplan carries a risk for infection, particularly meningitis, Dr. Du noted. “Complement meningitis vaccination protocol and close monitoring for signs of infection are required,” she said.

However, she added, “the rapid action benefits shown as early as week 1 are impressive, and potentially open the door to use as adjunctive therapy in myasthenia gravis crisis.”

“I think zilucoplan definitely adds more excitement to the already active field of myasthenia gravis management,” she said.

The study was funded by UCB Pharma. Dr. Freimer has reports she has served as a paid consultant for argenx, UCB Pharma, and Alexion Pharmaceuticals and reports research support from the National Institutes of Health, UCB Pharma, Jansen Pharmaceuticals, Alnylam, Avidity, and Fulcrum. Dr. Du reports no disclosures.

A version of this article appeared on Medscape.com.

PHOENIX – Early responders to zilucoplan, the newly approved medication for myasthenia gravis, have sustained benefit for up to 60 weeks, a new analyses show.

“The information [in the studies] is valuable in making clinical decisions in managing myasthenia gravis, which is a chronic autoimmune condition that requires long-term use of immunosuppressives,” said Xinli Du, MD, PhD, an assistant professor in the department of neurology at Virginia Commonwealth University in Richmond, who was not involved in the research.

“Compared with conventional immunosuppressants, which take 3-9 months to know if the patient will respond, this is definitely a game-changer,” she said.

The research was presented at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).
 

FDA approval

Approved by the U.S. Food and Drug Administration in October, the targeted peptide inhibitor of complement component 5 represents the only once-daily self-administered subcutaneous injection for adult patients with acetylcholine receptor autoantibody–positive (AChR+) generalized myasthenia gravis.

The multicenter, phase 3, placebo-controlled RAISE trial demonstrated that zilucoplan was associated with significant improvement in myasthenia gravis–specific outcomes in adult patients with mild to severe AChR+ generalized myasthenia gravis.

Of note, approximately 40% of patients in the zilucoplan phase 2 and 3 clinical trials have a significant response as early as the first week of treatment. For the current post hoc analysis, first author Miriam Freimer, MD, and colleagues took a closer look at the longer-term outcomes in these patients in the ongoing RAISE-XT open-label extension study.

In these two double-blind studies, patients were randomly assigned to receive either daily subcutaneous injections of 0.3 mg/kg zilucoplan or placebo.

Among 93 patients receiving zilucoplan in the two studies, 40 (43%) were identified as early responders based on having at least a 3-point reduction from baseline on the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) within 1 week of treatment, and 31 (33%) qualified based on having at least 5-point reductions in Quantitative Myasthenia Gravis (QMG), at week 1.

Of these early responders, more than 80% meeting the MG-ADL and 85% meeting QMG criteria continued to show a treatment response at each assessment through week 60 in the open-label RAISE-XT trial.

Furthermore, week 1 responders maintained their response for 88.1% of their total treatment time in the MG-ADL group and 88.8% of their total treatment time on treatment in the QMG group, representing a median zilucoplan treatment duration of 450 days.

Of note, the week 1 early responders had no significant differences, compared with the study’s overall population. Participants had a mean age of 49.6 years versus 52.9 years in the overall population. Approximately 40% of patients in both studies were men, and 60%-64% were disease class III as assessed by the Myasthenia Gravis Foundation of America criteria.

“It is very exciting to see such a high response of rapid responders. This means that some patients may be able to avoid steroids or be able to taper them faster than with other accepted treatments for myasthenia gravis,” said Dr. Freimer, director of the division of neuromuscular disorders and the codirector of the Myasthenia Gravis Clinic at the Ohio State University in Columbus.
 

Impact on fatigue

In a separate post hoc analysis of patients who entered RAISE-XT, the researchers evaluated long-term effects of zilucoplan on fatigue.

Improvements in fatigue were already apparent at the end of the RAISE trial, with the least squares mean (LSM) change from baseline in fatigue assessed after 12 weeks with the Neuro-QOL T-score being –6.26 for zilucoplan (n = 86) compared with an increase of 2.65 for placebo (n = 88; LSM difference, –3.61; nominal P = .0060).

Patients who received placebo in the RAISE trial were able to switch to zilucoplan in the RAISE-XT open-label trail, and among those who did, fatigue, as measured in the T-scores, improved significantly within 1 week of switching.

Fatigue further improved out to week 16 in terms of T-scores for the placebo-switch as well as zilucoplan groups, and the improvements in the scores were sustained through week 60 (mean change from RAISE baseline, –10.71 [n = 42] and –9.15 [n = 42], respectively).

“Fatigue is a challenge for patients with [generalized myasthenia gravis]. Zilucoplan significantly and clinically meaningfully improved myasthenic fatigue versus placebo during RAISE,” the investigators report.

“Further improvements were observed during RAISE-XT and were sustained up to 60 weeks of treatment,” they added.
 

Favorable safety profile

Zilucoplan continued to show a favorable safety profile in the RAISE-XT trial and was well tolerated in the long term.

The most common adverse reactions (10% or more) in patients with generalized myasthenia gravis were injection-site reactions, upper respiratory tract infection, and diarrhea.

Though additional therapies have also recently entered the market for generalized myasthenia gravis, they are either intravenous or subcutaneous infusions requiring a health care professional to administer them.

“This self-administered medication allows patients to be more independent and can even travel since it is not dependent on an infusion center,” Dr. Freimer noted.

However, similar to the other complement inhibitors, zilucoplan carries a risk for infection, particularly meningitis, Dr. Du noted. “Complement meningitis vaccination protocol and close monitoring for signs of infection are required,” she said.

However, she added, “the rapid action benefits shown as early as week 1 are impressive, and potentially open the door to use as adjunctive therapy in myasthenia gravis crisis.”

“I think zilucoplan definitely adds more excitement to the already active field of myasthenia gravis management,” she said.

The study was funded by UCB Pharma. Dr. Freimer has reports she has served as a paid consultant for argenx, UCB Pharma, and Alexion Pharmaceuticals and reports research support from the National Institutes of Health, UCB Pharma, Jansen Pharmaceuticals, Alnylam, Avidity, and Fulcrum. Dr. Du reports no disclosures.

A version of this article appeared on Medscape.com.

PHOENIX – Early responders to zilucoplan, the newly approved medication for myasthenia gravis, have sustained benefit for up to 60 weeks, a new analyses show.

“The information [in the studies] is valuable in making clinical decisions in managing myasthenia gravis, which is a chronic autoimmune condition that requires long-term use of immunosuppressives,” said Xinli Du, MD, PhD, an assistant professor in the department of neurology at Virginia Commonwealth University in Richmond, who was not involved in the research.

“Compared with conventional immunosuppressants, which take 3-9 months to know if the patient will respond, this is definitely a game-changer,” she said.

The research was presented at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).
 

FDA approval

Approved by the U.S. Food and Drug Administration in October, the targeted peptide inhibitor of complement component 5 represents the only once-daily self-administered subcutaneous injection for adult patients with acetylcholine receptor autoantibody–positive (AChR+) generalized myasthenia gravis.

The multicenter, phase 3, placebo-controlled RAISE trial demonstrated that zilucoplan was associated with significant improvement in myasthenia gravis–specific outcomes in adult patients with mild to severe AChR+ generalized myasthenia gravis.

Of note, approximately 40% of patients in the zilucoplan phase 2 and 3 clinical trials have a significant response as early as the first week of treatment. For the current post hoc analysis, first author Miriam Freimer, MD, and colleagues took a closer look at the longer-term outcomes in these patients in the ongoing RAISE-XT open-label extension study.

In these two double-blind studies, patients were randomly assigned to receive either daily subcutaneous injections of 0.3 mg/kg zilucoplan or placebo.

Among 93 patients receiving zilucoplan in the two studies, 40 (43%) were identified as early responders based on having at least a 3-point reduction from baseline on the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) within 1 week of treatment, and 31 (33%) qualified based on having at least 5-point reductions in Quantitative Myasthenia Gravis (QMG), at week 1.

Of these early responders, more than 80% meeting the MG-ADL and 85% meeting QMG criteria continued to show a treatment response at each assessment through week 60 in the open-label RAISE-XT trial.

Furthermore, week 1 responders maintained their response for 88.1% of their total treatment time in the MG-ADL group and 88.8% of their total treatment time on treatment in the QMG group, representing a median zilucoplan treatment duration of 450 days.

Of note, the week 1 early responders had no significant differences, compared with the study’s overall population. Participants had a mean age of 49.6 years versus 52.9 years in the overall population. Approximately 40% of patients in both studies were men, and 60%-64% were disease class III as assessed by the Myasthenia Gravis Foundation of America criteria.

“It is very exciting to see such a high response of rapid responders. This means that some patients may be able to avoid steroids or be able to taper them faster than with other accepted treatments for myasthenia gravis,” said Dr. Freimer, director of the division of neuromuscular disorders and the codirector of the Myasthenia Gravis Clinic at the Ohio State University in Columbus.
 

Impact on fatigue

In a separate post hoc analysis of patients who entered RAISE-XT, the researchers evaluated long-term effects of zilucoplan on fatigue.

Improvements in fatigue were already apparent at the end of the RAISE trial, with the least squares mean (LSM) change from baseline in fatigue assessed after 12 weeks with the Neuro-QOL T-score being –6.26 for zilucoplan (n = 86) compared with an increase of 2.65 for placebo (n = 88; LSM difference, –3.61; nominal P = .0060).

Patients who received placebo in the RAISE trial were able to switch to zilucoplan in the RAISE-XT open-label trail, and among those who did, fatigue, as measured in the T-scores, improved significantly within 1 week of switching.

Fatigue further improved out to week 16 in terms of T-scores for the placebo-switch as well as zilucoplan groups, and the improvements in the scores were sustained through week 60 (mean change from RAISE baseline, –10.71 [n = 42] and –9.15 [n = 42], respectively).

“Fatigue is a challenge for patients with [generalized myasthenia gravis]. Zilucoplan significantly and clinically meaningfully improved myasthenic fatigue versus placebo during RAISE,” the investigators report.

“Further improvements were observed during RAISE-XT and were sustained up to 60 weeks of treatment,” they added.
 

Favorable safety profile

Zilucoplan continued to show a favorable safety profile in the RAISE-XT trial and was well tolerated in the long term.

The most common adverse reactions (10% or more) in patients with generalized myasthenia gravis were injection-site reactions, upper respiratory tract infection, and diarrhea.

Though additional therapies have also recently entered the market for generalized myasthenia gravis, they are either intravenous or subcutaneous infusions requiring a health care professional to administer them.

“This self-administered medication allows patients to be more independent and can even travel since it is not dependent on an infusion center,” Dr. Freimer noted.

However, similar to the other complement inhibitors, zilucoplan carries a risk for infection, particularly meningitis, Dr. Du noted. “Complement meningitis vaccination protocol and close monitoring for signs of infection are required,” she said.

However, she added, “the rapid action benefits shown as early as week 1 are impressive, and potentially open the door to use as adjunctive therapy in myasthenia gravis crisis.”

“I think zilucoplan definitely adds more excitement to the already active field of myasthenia gravis management,” she said.

The study was funded by UCB Pharma. Dr. Freimer has reports she has served as a paid consultant for argenx, UCB Pharma, and Alexion Pharmaceuticals and reports research support from the National Institutes of Health, UCB Pharma, Jansen Pharmaceuticals, Alnylam, Avidity, and Fulcrum. Dr. Du reports no disclosures.

A version of this article appeared on Medscape.com.

PHOENIX – The prevalence of myasthenia gravis is about 0.13% among U.S. adults, and the condition is more common in Whites than in African Americans, according to a new analysis of the National Institutes of Health All of Us database. The prevalence is higher than what has been seen in other studies, which could represent a true difference in prevalence, or reflect limitations of the database.

Worldwide estimates suggest that myasthenia gravis affects 700,000 people globally, with incidence rates ranging between 6.3 and 29 per 1,000,000 person-years in Europe and a prevalence between 111.7 and 361 per 1,000,000. Data from Australia, Taiwan, and South Korea also show evidence of increased prevalence in recent years.

However, there is little data about the prevalence of myasthenia gravis in the United States, or about differences between racial groups, according to Bhaskar Roy, MBBS, who presented the study at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). He noted that most studies are outdated, and the most recent study focused on ocular myasthenia gravis.
 

True incidence or artifact?

The finding is surprising and may be an artifact of the immature nature of the All of Us database, according to Srikanth Muppidi, MD, who asked about the limitation during the Q&A session following the talk. “The incidence of 0.13 is definitely higher than what we would think would be the true incidence of myasthenia gravis from [clinical experience]. It’s possible that our understanding of true incidence is wrong and this is the actual incidence. What I would like them to do, and I think they’re trying to do, is to look at this finding [and compare it with] other more mature databases and other regional databases. One of the current challenges of All of Us is that our patients are basically being recruited from some parts of the country, and the middle of the country has hardly any presence in the database, so it becomes really challenging to understand it,” Dr. Muppidi said in an interview.

However, Dr. Muppidi, who is a clinical professor of neurology at Stanford (Calif.) Medicine, noted that the All of Us database is still growing. When it has recruited more patients with a diverse population, “it [will be a] valuable source for rare diseases to try to understand true incidence of those diseases,” he said.
 

Understanding the true prevalence

Dr. Roy recognized the geographic limitations of the database. “Some states, particularly Massachusetts, New York, and California, had a lot of patients in the database, where there were no patients from many states,” said Dr. Roy, associate professor of neurology at Yale University, New Haven, Conn.

He said that the group is working with other databases, including UK Biobank. “The goal is to incorporate all of these databases together [to determine the true incidence],” said Dr. Roy.

It’s critical to understand the true prevalence of myasthenia gravis since new therapies are in development and coming to market. “I worry that myasthenia gravis might be considered less common than it truly is, and that will limit growth of the field if the feeling is that there are not that many [myasthenia gravis patients] in the country,” said Dr. Muppidi.

The study included data from 369,297 adult patients, using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases (ICD) codes to identify patients with myasthenia gravis. There were 479 cases of myasthenia gravis, for a prevalence of 0.13 (95% confidence interval [CI], 0.12-0.14). Of myasthenia gravis patients, 65% were female and the mean age was 64 years. The prevalence of myasthenia gravis in White individuals was 0.16 (95% CI, 0.15-0.18), of which 63% were female, and the mean age was 66 years. The prevalence among Black individuals was 0.078 (95% CI, 0.060-0.10), with 77% of the population female and a mean age of 58 years. The prevalence in Hispanics was 0.091 (95% CI, 0.070-0.12), with 80% female and a mean age of 58 years. Among Asians, the prevalence was 0.056 (95% CI, 0.025-0.12) and 57% were female, with a mean age of 58 years.

The researchers also looked at the EXPLORE-MG database drawn from Yale (n = 3,269,000), which showed a much lower overall myasthenia gravis prevalence of 0.019 (95% CI, 0.017-0.020), a female proportion of 46.8%, and a mean age of 56.6 years. Notably, EXPLORE-MG had a lower proportion of women and a younger population than All of Us.

The researchers compared data from All of Us with other databases for other conditions. The prevalence of ALS was the same as in other conditions, while diabetic neuropathy was significantly lower (2.7 versus 28.5-50 among diabetic patients) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was higher (0.084 versus 0.028).

Dr. Muppidi has been on advisory boards for Alexion, Argenx, UBC, and Immunovant. Dr. Roy has consulted for Alexion, Takeda Pharmaceuticals, and Argenx and owns stock in Cabaletta Bio. He has received research support from Takeda, Abcuro, and Argenx.

PHOENIX – The prevalence of myasthenia gravis is about 0.13% among U.S. adults, and the condition is more common in Whites than in African Americans, according to a new analysis of the National Institutes of Health All of Us database. The prevalence is higher than what has been seen in other studies, which could represent a true difference in prevalence, or reflect limitations of the database.

Worldwide estimates suggest that myasthenia gravis affects 700,000 people globally, with incidence rates ranging between 6.3 and 29 per 1,000,000 person-years in Europe and a prevalence between 111.7 and 361 per 1,000,000. Data from Australia, Taiwan, and South Korea also show evidence of increased prevalence in recent years.

However, there is little data about the prevalence of myasthenia gravis in the United States, or about differences between racial groups, according to Bhaskar Roy, MBBS, who presented the study at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). He noted that most studies are outdated, and the most recent study focused on ocular myasthenia gravis.
 

True incidence or artifact?

The finding is surprising and may be an artifact of the immature nature of the All of Us database, according to Srikanth Muppidi, MD, who asked about the limitation during the Q&A session following the talk. “The incidence of 0.13 is definitely higher than what we would think would be the true incidence of myasthenia gravis from [clinical experience]. It’s possible that our understanding of true incidence is wrong and this is the actual incidence. What I would like them to do, and I think they’re trying to do, is to look at this finding [and compare it with] other more mature databases and other regional databases. One of the current challenges of All of Us is that our patients are basically being recruited from some parts of the country, and the middle of the country has hardly any presence in the database, so it becomes really challenging to understand it,” Dr. Muppidi said in an interview.

However, Dr. Muppidi, who is a clinical professor of neurology at Stanford (Calif.) Medicine, noted that the All of Us database is still growing. When it has recruited more patients with a diverse population, “it [will be a] valuable source for rare diseases to try to understand true incidence of those diseases,” he said.
 

Understanding the true prevalence

Dr. Roy recognized the geographic limitations of the database. “Some states, particularly Massachusetts, New York, and California, had a lot of patients in the database, where there were no patients from many states,” said Dr. Roy, associate professor of neurology at Yale University, New Haven, Conn.

He said that the group is working with other databases, including UK Biobank. “The goal is to incorporate all of these databases together [to determine the true incidence],” said Dr. Roy.

It’s critical to understand the true prevalence of myasthenia gravis since new therapies are in development and coming to market. “I worry that myasthenia gravis might be considered less common than it truly is, and that will limit growth of the field if the feeling is that there are not that many [myasthenia gravis patients] in the country,” said Dr. Muppidi.

The study included data from 369,297 adult patients, using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases (ICD) codes to identify patients with myasthenia gravis. There were 479 cases of myasthenia gravis, for a prevalence of 0.13 (95% confidence interval [CI], 0.12-0.14). Of myasthenia gravis patients, 65% were female and the mean age was 64 years. The prevalence of myasthenia gravis in White individuals was 0.16 (95% CI, 0.15-0.18), of which 63% were female, and the mean age was 66 years. The prevalence among Black individuals was 0.078 (95% CI, 0.060-0.10), with 77% of the population female and a mean age of 58 years. The prevalence in Hispanics was 0.091 (95% CI, 0.070-0.12), with 80% female and a mean age of 58 years. Among Asians, the prevalence was 0.056 (95% CI, 0.025-0.12) and 57% were female, with a mean age of 58 years.

The researchers also looked at the EXPLORE-MG database drawn from Yale (n = 3,269,000), which showed a much lower overall myasthenia gravis prevalence of 0.019 (95% CI, 0.017-0.020), a female proportion of 46.8%, and a mean age of 56.6 years. Notably, EXPLORE-MG had a lower proportion of women and a younger population than All of Us.

The researchers compared data from All of Us with other databases for other conditions. The prevalence of ALS was the same as in other conditions, while diabetic neuropathy was significantly lower (2.7 versus 28.5-50 among diabetic patients) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was higher (0.084 versus 0.028).

Dr. Muppidi has been on advisory boards for Alexion, Argenx, UBC, and Immunovant. Dr. Roy has consulted for Alexion, Takeda Pharmaceuticals, and Argenx and owns stock in Cabaletta Bio. He has received research support from Takeda, Abcuro, and Argenx.

PHOENIX – The prevalence of myasthenia gravis is about 0.13% among U.S. adults, and the condition is more common in Whites than in African Americans, according to a new analysis of the National Institutes of Health All of Us database. The prevalence is higher than what has been seen in other studies, which could represent a true difference in prevalence, or reflect limitations of the database.

Worldwide estimates suggest that myasthenia gravis affects 700,000 people globally, with incidence rates ranging between 6.3 and 29 per 1,000,000 person-years in Europe and a prevalence between 111.7 and 361 per 1,000,000. Data from Australia, Taiwan, and South Korea also show evidence of increased prevalence in recent years.

However, there is little data about the prevalence of myasthenia gravis in the United States, or about differences between racial groups, according to Bhaskar Roy, MBBS, who presented the study at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). He noted that most studies are outdated, and the most recent study focused on ocular myasthenia gravis.
 

True incidence or artifact?

The finding is surprising and may be an artifact of the immature nature of the All of Us database, according to Srikanth Muppidi, MD, who asked about the limitation during the Q&A session following the talk. “The incidence of 0.13 is definitely higher than what we would think would be the true incidence of myasthenia gravis from [clinical experience]. It’s possible that our understanding of true incidence is wrong and this is the actual incidence. What I would like them to do, and I think they’re trying to do, is to look at this finding [and compare it with] other more mature databases and other regional databases. One of the current challenges of All of Us is that our patients are basically being recruited from some parts of the country, and the middle of the country has hardly any presence in the database, so it becomes really challenging to understand it,” Dr. Muppidi said in an interview.

However, Dr. Muppidi, who is a clinical professor of neurology at Stanford (Calif.) Medicine, noted that the All of Us database is still growing. When it has recruited more patients with a diverse population, “it [will be a] valuable source for rare diseases to try to understand true incidence of those diseases,” he said.
 

Understanding the true prevalence

Dr. Roy recognized the geographic limitations of the database. “Some states, particularly Massachusetts, New York, and California, had a lot of patients in the database, where there were no patients from many states,” said Dr. Roy, associate professor of neurology at Yale University, New Haven, Conn.

He said that the group is working with other databases, including UK Biobank. “The goal is to incorporate all of these databases together [to determine the true incidence],” said Dr. Roy.

It’s critical to understand the true prevalence of myasthenia gravis since new therapies are in development and coming to market. “I worry that myasthenia gravis might be considered less common than it truly is, and that will limit growth of the field if the feeling is that there are not that many [myasthenia gravis patients] in the country,” said Dr. Muppidi.

The study included data from 369,297 adult patients, using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases (ICD) codes to identify patients with myasthenia gravis. There were 479 cases of myasthenia gravis, for a prevalence of 0.13 (95% confidence interval [CI], 0.12-0.14). Of myasthenia gravis patients, 65% were female and the mean age was 64 years. The prevalence of myasthenia gravis in White individuals was 0.16 (95% CI, 0.15-0.18), of which 63% were female, and the mean age was 66 years. The prevalence among Black individuals was 0.078 (95% CI, 0.060-0.10), with 77% of the population female and a mean age of 58 years. The prevalence in Hispanics was 0.091 (95% CI, 0.070-0.12), with 80% female and a mean age of 58 years. Among Asians, the prevalence was 0.056 (95% CI, 0.025-0.12) and 57% were female, with a mean age of 58 years.

The researchers also looked at the EXPLORE-MG database drawn from Yale (n = 3,269,000), which showed a much lower overall myasthenia gravis prevalence of 0.019 (95% CI, 0.017-0.020), a female proportion of 46.8%, and a mean age of 56.6 years. Notably, EXPLORE-MG had a lower proportion of women and a younger population than All of Us.

The researchers compared data from All of Us with other databases for other conditions. The prevalence of ALS was the same as in other conditions, while diabetic neuropathy was significantly lower (2.7 versus 28.5-50 among diabetic patients) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was higher (0.084 versus 0.028).

Dr. Muppidi has been on advisory boards for Alexion, Argenx, UBC, and Immunovant. Dr. Roy has consulted for Alexion, Takeda Pharmaceuticals, and Argenx and owns stock in Cabaletta Bio. He has received research support from Takeda, Abcuro, and Argenx.

PHOENIX – Open-label extension studies of two neonatal Fc receptor–blocking antibodies showed good safety and efficacy in patients with myasthenia gravis (MG). The two drugs, rozanolixizumab (Rystiggo, UCB) and efgartigimod PH20 (Vyvgart, Argenx SE), received Food and Drug Administration approval in June 2023 and December 2021, respectively, for the treatment of MG.

The neonatal Fc receptor binds to IgG within cells and recycles it back into the blood, leading to increased serum levels. The antibodies bind to the neonatal Fc receptor and promote its degradation, therefore preventing IgG recycling without interfering with its production. They do not affect the levels of other immunoglobulin isotypes.

At the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM), researchers presented data from an open-label extension study following the phase 3 MycarinG trial of rozanolixizumab and the ADAPT-SC+ study of efgartigimod.

In the MycarinG study, rozanolixizumab “showed both statistically significant and clinically meaningful improvements in multiple endpoints,” said Vera Bril, MD, during a presentation of the results.

Rozanolixizumab is approved for MG patients who are anti–acetylcholine receptor (AchR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive. Efgartigimod is approved for MG patients who are AChR positive.

After completing MycarinG, patients were eligible to enroll in one of two open-label studies, one of each dose.

The new efficacy analysis focused on 110 patients who underwent two or more consecutive symptom-driven treatment cycles. A safety analysis focused on 188 patients who received at least one cycle of treatment.

“The post hoc analysis showed that the clinically meaningful improvements in the generalized myasthenia gravis symptoms were maintained over time for the cohort across rozanolixizumab cycles, while individual patients move through the consecutive treatment cycles, rozanolixizumab had an acceptable safety profile that was maintained across repeated treatments cycles. This is consistent with previous results of rozanolixizumab,” said Dr. Bril, who is a clinical investigator at University of Toronto
 

A reduction in steroid use?

During the Q&A session, George Small, MD, asked if the study had shown a reduction in steroid use among patients with MG.

As clinical associate director of neurology at Allegheny Medical Center, Pittsburgh, he has overseen the care of several hundred patients with generalized MG, as well as participated in clinical trials. “Many physicians use steroids for very quick responses in their patients. I love steroids and I hate steroids. I’ve helped save people’s lives with them, but I’ve also probably hastened their demise, unfortunately, because of the long-term side effects of the medications. Many neurologists in the community will over-utilize steroids because they don’t have access to these more expensive therapies. I look forward to both using these medications more as they become FDA approved and being an advocate for them, because it is my belief that they help decrease the use of steroids,” said Dr. Small in an interview.

Even if new medications do reduce steroid use, there remains a hurdle with insurance companies. “I’ve felt I’ve been forced to use treatments that I know may not be efficacious in the short term in order to get authorization for more expensive therapies that I use now. I’ve had patients admitted to the hospital as I’ve tried to jump through hoops that the insurance companies demanded,” said Dr. Small.
 

Clinical improvements seen

In the MycarinG study, patients received weekly injections of 7 mg/kg, 10 mg/kg rozanolixizumab, or placebo over a 6-week period. Both treatment groups had reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.

MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were consistent across treatment cycles. The mean MG-ADL score dropped by about 4 points at week 6. At around week 10, the mean improvement declined to 2 points, and then by week 14 it increased to 3 points, where it remained consistent out to 50 weeks. A similar pattern was seen in QMG scores, with an approximate 5-point drop at 6 weeks, then about a 1.5-point improvement at 10 weeks, then a mean decrease of around 4 points that stayed stable out to 50 weeks.

Over all cycles of treatment, 89.9% of patients experienced a treatment-emergent adverse event, including 22.3% who had a serious TEAE; the study dropout rate because of TEAEs was 15.4%.

In the ADAPT-SC study, 110 patients were randomized to 10 mg/kg intravenous efgartigimod or 1,000 mg efgartigimod PH20, which is formulated with recombinant human hyaluronidase to allow for rapid administration of larger volumes. After completion of ADAPT-SC, 105 patients from both groups and an additional 79 patients entered the open-label extension study with 1,000 mg efgartigimod PH20.

The study included 141 patients who were AChR-Ab positive and 38 who were AChR-Ab negative. In the first cycle, 34.6% experienced an injection-site reaction, which steadily dropped to 11.5% by the sixth cycle. After each cycle of treatment, the mean change in MG-ADL from study baseline at week 4 was between 4.1 and 4.7 points. The mean change in Myasthenia Gravis Quality of Life 15-Item Questionnaire revisited from study baseline at week 4 was between 5.1 and 6.5 points. The mean change in EuroQoL 5-dimension, 5-level visual analog scale was between 12.3 and 16.0 points at week 4.

MyCarinG was funded by UCB Pharma. ADAPT-SC was funded by Argenx SE. Dr. Bril has financial relationships with Behring, Argenyx, Alexion, Immunovant, Alnylam, Akcea, Takeda, Sanofi, Ionis, Roche, Novo Nordisk, Octapharma, Momenta, Pfizer, CSL Behring, Grifols, Powell Mansfield, UCB, and Viela Bio. Dr. Small is on the speaker’s bureau for Alexion.

PHOENIX – Open-label extension studies of two neonatal Fc receptor–blocking antibodies showed good safety and efficacy in patients with myasthenia gravis (MG). The two drugs, rozanolixizumab (Rystiggo, UCB) and efgartigimod PH20 (Vyvgart, Argenx SE), received Food and Drug Administration approval in June 2023 and December 2021, respectively, for the treatment of MG.

The neonatal Fc receptor binds to IgG within cells and recycles it back into the blood, leading to increased serum levels. The antibodies bind to the neonatal Fc receptor and promote its degradation, therefore preventing IgG recycling without interfering with its production. They do not affect the levels of other immunoglobulin isotypes.

At the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM), researchers presented data from an open-label extension study following the phase 3 MycarinG trial of rozanolixizumab and the ADAPT-SC+ study of efgartigimod.

In the MycarinG study, rozanolixizumab “showed both statistically significant and clinically meaningful improvements in multiple endpoints,” said Vera Bril, MD, during a presentation of the results.

Rozanolixizumab is approved for MG patients who are anti–acetylcholine receptor (AchR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive. Efgartigimod is approved for MG patients who are AChR positive.

After completing MycarinG, patients were eligible to enroll in one of two open-label studies, one of each dose.

The new efficacy analysis focused on 110 patients who underwent two or more consecutive symptom-driven treatment cycles. A safety analysis focused on 188 patients who received at least one cycle of treatment.

“The post hoc analysis showed that the clinically meaningful improvements in the generalized myasthenia gravis symptoms were maintained over time for the cohort across rozanolixizumab cycles, while individual patients move through the consecutive treatment cycles, rozanolixizumab had an acceptable safety profile that was maintained across repeated treatments cycles. This is consistent with previous results of rozanolixizumab,” said Dr. Bril, who is a clinical investigator at University of Toronto
 

A reduction in steroid use?

During the Q&A session, George Small, MD, asked if the study had shown a reduction in steroid use among patients with MG.

As clinical associate director of neurology at Allegheny Medical Center, Pittsburgh, he has overseen the care of several hundred patients with generalized MG, as well as participated in clinical trials. “Many physicians use steroids for very quick responses in their patients. I love steroids and I hate steroids. I’ve helped save people’s lives with them, but I’ve also probably hastened their demise, unfortunately, because of the long-term side effects of the medications. Many neurologists in the community will over-utilize steroids because they don’t have access to these more expensive therapies. I look forward to both using these medications more as they become FDA approved and being an advocate for them, because it is my belief that they help decrease the use of steroids,” said Dr. Small in an interview.

Even if new medications do reduce steroid use, there remains a hurdle with insurance companies. “I’ve felt I’ve been forced to use treatments that I know may not be efficacious in the short term in order to get authorization for more expensive therapies that I use now. I’ve had patients admitted to the hospital as I’ve tried to jump through hoops that the insurance companies demanded,” said Dr. Small.
 

Clinical improvements seen

In the MycarinG study, patients received weekly injections of 7 mg/kg, 10 mg/kg rozanolixizumab, or placebo over a 6-week period. Both treatment groups had reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.

MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were consistent across treatment cycles. The mean MG-ADL score dropped by about 4 points at week 6. At around week 10, the mean improvement declined to 2 points, and then by week 14 it increased to 3 points, where it remained consistent out to 50 weeks. A similar pattern was seen in QMG scores, with an approximate 5-point drop at 6 weeks, then about a 1.5-point improvement at 10 weeks, then a mean decrease of around 4 points that stayed stable out to 50 weeks.

Over all cycles of treatment, 89.9% of patients experienced a treatment-emergent adverse event, including 22.3% who had a serious TEAE; the study dropout rate because of TEAEs was 15.4%.

In the ADAPT-SC study, 110 patients were randomized to 10 mg/kg intravenous efgartigimod or 1,000 mg efgartigimod PH20, which is formulated with recombinant human hyaluronidase to allow for rapid administration of larger volumes. After completion of ADAPT-SC, 105 patients from both groups and an additional 79 patients entered the open-label extension study with 1,000 mg efgartigimod PH20.

The study included 141 patients who were AChR-Ab positive and 38 who were AChR-Ab negative. In the first cycle, 34.6% experienced an injection-site reaction, which steadily dropped to 11.5% by the sixth cycle. After each cycle of treatment, the mean change in MG-ADL from study baseline at week 4 was between 4.1 and 4.7 points. The mean change in Myasthenia Gravis Quality of Life 15-Item Questionnaire revisited from study baseline at week 4 was between 5.1 and 6.5 points. The mean change in EuroQoL 5-dimension, 5-level visual analog scale was between 12.3 and 16.0 points at week 4.

MyCarinG was funded by UCB Pharma. ADAPT-SC was funded by Argenx SE. Dr. Bril has financial relationships with Behring, Argenyx, Alexion, Immunovant, Alnylam, Akcea, Takeda, Sanofi, Ionis, Roche, Novo Nordisk, Octapharma, Momenta, Pfizer, CSL Behring, Grifols, Powell Mansfield, UCB, and Viela Bio. Dr. Small is on the speaker’s bureau for Alexion.

PHOENIX – Open-label extension studies of two neonatal Fc receptor–blocking antibodies showed good safety and efficacy in patients with myasthenia gravis (MG). The two drugs, rozanolixizumab (Rystiggo, UCB) and efgartigimod PH20 (Vyvgart, Argenx SE), received Food and Drug Administration approval in June 2023 and December 2021, respectively, for the treatment of MG.

The neonatal Fc receptor binds to IgG within cells and recycles it back into the blood, leading to increased serum levels. The antibodies bind to the neonatal Fc receptor and promote its degradation, therefore preventing IgG recycling without interfering with its production. They do not affect the levels of other immunoglobulin isotypes.

At the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM), researchers presented data from an open-label extension study following the phase 3 MycarinG trial of rozanolixizumab and the ADAPT-SC+ study of efgartigimod.

In the MycarinG study, rozanolixizumab “showed both statistically significant and clinically meaningful improvements in multiple endpoints,” said Vera Bril, MD, during a presentation of the results.

Rozanolixizumab is approved for MG patients who are anti–acetylcholine receptor (AchR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive. Efgartigimod is approved for MG patients who are AChR positive.

After completing MycarinG, patients were eligible to enroll in one of two open-label studies, one of each dose.

The new efficacy analysis focused on 110 patients who underwent two or more consecutive symptom-driven treatment cycles. A safety analysis focused on 188 patients who received at least one cycle of treatment.

“The post hoc analysis showed that the clinically meaningful improvements in the generalized myasthenia gravis symptoms were maintained over time for the cohort across rozanolixizumab cycles, while individual patients move through the consecutive treatment cycles, rozanolixizumab had an acceptable safety profile that was maintained across repeated treatments cycles. This is consistent with previous results of rozanolixizumab,” said Dr. Bril, who is a clinical investigator at University of Toronto
 

A reduction in steroid use?

During the Q&A session, George Small, MD, asked if the study had shown a reduction in steroid use among patients with MG.

As clinical associate director of neurology at Allegheny Medical Center, Pittsburgh, he has overseen the care of several hundred patients with generalized MG, as well as participated in clinical trials. “Many physicians use steroids for very quick responses in their patients. I love steroids and I hate steroids. I’ve helped save people’s lives with them, but I’ve also probably hastened their demise, unfortunately, because of the long-term side effects of the medications. Many neurologists in the community will over-utilize steroids because they don’t have access to these more expensive therapies. I look forward to both using these medications more as they become FDA approved and being an advocate for them, because it is my belief that they help decrease the use of steroids,” said Dr. Small in an interview.

Even if new medications do reduce steroid use, there remains a hurdle with insurance companies. “I’ve felt I’ve been forced to use treatments that I know may not be efficacious in the short term in order to get authorization for more expensive therapies that I use now. I’ve had patients admitted to the hospital as I’ve tried to jump through hoops that the insurance companies demanded,” said Dr. Small.
 

Clinical improvements seen

In the MycarinG study, patients received weekly injections of 7 mg/kg, 10 mg/kg rozanolixizumab, or placebo over a 6-week period. Both treatment groups had reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.

MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were consistent across treatment cycles. The mean MG-ADL score dropped by about 4 points at week 6. At around week 10, the mean improvement declined to 2 points, and then by week 14 it increased to 3 points, where it remained consistent out to 50 weeks. A similar pattern was seen in QMG scores, with an approximate 5-point drop at 6 weeks, then about a 1.5-point improvement at 10 weeks, then a mean decrease of around 4 points that stayed stable out to 50 weeks.

Over all cycles of treatment, 89.9% of patients experienced a treatment-emergent adverse event, including 22.3% who had a serious TEAE; the study dropout rate because of TEAEs was 15.4%.

In the ADAPT-SC study, 110 patients were randomized to 10 mg/kg intravenous efgartigimod or 1,000 mg efgartigimod PH20, which is formulated with recombinant human hyaluronidase to allow for rapid administration of larger volumes. After completion of ADAPT-SC, 105 patients from both groups and an additional 79 patients entered the open-label extension study with 1,000 mg efgartigimod PH20.

The study included 141 patients who were AChR-Ab positive and 38 who were AChR-Ab negative. In the first cycle, 34.6% experienced an injection-site reaction, which steadily dropped to 11.5% by the sixth cycle. After each cycle of treatment, the mean change in MG-ADL from study baseline at week 4 was between 4.1 and 4.7 points. The mean change in Myasthenia Gravis Quality of Life 15-Item Questionnaire revisited from study baseline at week 4 was between 5.1 and 6.5 points. The mean change in EuroQoL 5-dimension, 5-level visual analog scale was between 12.3 and 16.0 points at week 4.

MyCarinG was funded by UCB Pharma. ADAPT-SC was funded by Argenx SE. Dr. Bril has financial relationships with Behring, Argenyx, Alexion, Immunovant, Alnylam, Akcea, Takeda, Sanofi, Ionis, Roche, Novo Nordisk, Octapharma, Momenta, Pfizer, CSL Behring, Grifols, Powell Mansfield, UCB, and Viela Bio. Dr. Small is on the speaker’s bureau for Alexion.

The U.S. Food and Drug Administration has approved rozanolixizumab (Rystiggo) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.

Olivier Le Moal/Getty Images

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rozanolixizumab (Rystiggo) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.

Olivier Le Moal/Getty Images

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved rozanolixizumab (Rystiggo) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.

Olivier Le Moal/Getty Images

A version of this article first appeared on Medscape.com.

Clinical advances in myasthenia gravis from the 2023 American Academy of Neurology (AAN) Annual Meeting include the association between fatigue and disease severity and promising results from three ongoing trials of novel therapies, as reported by Dr Nicholas Silvestri, from the University at Buffalo, Buffalo, New York. 

Dr Silvestri begins by discussing a study of autoantibodies in patients with seronegative disease, which highlighted the potential for impaired B-cell tolerance, and goes on to examine research underscoring the association between fatigue and disease severity, as well as anxiety and depression. 

Moving on to novel therapies, Dr Silvestri reviews a combined analysis of three trials of rozanolixizumab, which demonstrated the drug's encouraging efficacy and favorable safety profile. 

Next, he turns to the ADAPT+ trial, which showed that efgartigimod continued to have an improved clinical response after patients rolled over from the initial ADAPT trial to ADAPT+, with no new safety signals apparent. 

Finally, Dr Silvestri looks at data from the postmarketing registry of eculizumab, which revealed how a significant proportion of patients were able discontinue or reduce their other medications once they started the drug. 

--

Nicholas J. Silvestri, MD, Associate Professor, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 

Nicholas J. Silvestri, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: argenx; Alexion; Immunovant; UCB 

Serve(d) as a speaker or a member of a speakers bureau for: argenx; Alexion 

Clinical advances in myasthenia gravis from the 2023 American Academy of Neurology (AAN) Annual Meeting include the association between fatigue and disease severity and promising results from three ongoing trials of novel therapies, as reported by Dr Nicholas Silvestri, from the University at Buffalo, Buffalo, New York. 

Dr Silvestri begins by discussing a study of autoantibodies in patients with seronegative disease, which highlighted the potential for impaired B-cell tolerance, and goes on to examine research underscoring the association between fatigue and disease severity, as well as anxiety and depression. 

Moving on to novel therapies, Dr Silvestri reviews a combined analysis of three trials of rozanolixizumab, which demonstrated the drug's encouraging efficacy and favorable safety profile. 

Next, he turns to the ADAPT+ trial, which showed that efgartigimod continued to have an improved clinical response after patients rolled over from the initial ADAPT trial to ADAPT+, with no new safety signals apparent. 

Finally, Dr Silvestri looks at data from the postmarketing registry of eculizumab, which revealed how a significant proportion of patients were able discontinue or reduce their other medications once they started the drug. 

--

Nicholas J. Silvestri, MD, Associate Professor, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 

Nicholas J. Silvestri, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: argenx; Alexion; Immunovant; UCB 

Serve(d) as a speaker or a member of a speakers bureau for: argenx; Alexion 

Clinical advances in myasthenia gravis from the 2023 American Academy of Neurology (AAN) Annual Meeting include the association between fatigue and disease severity and promising results from three ongoing trials of novel therapies, as reported by Dr Nicholas Silvestri, from the University at Buffalo, Buffalo, New York. 

Dr Silvestri begins by discussing a study of autoantibodies in patients with seronegative disease, which highlighted the potential for impaired B-cell tolerance, and goes on to examine research underscoring the association between fatigue and disease severity, as well as anxiety and depression. 

Moving on to novel therapies, Dr Silvestri reviews a combined analysis of three trials of rozanolixizumab, which demonstrated the drug's encouraging efficacy and favorable safety profile. 

Next, he turns to the ADAPT+ trial, which showed that efgartigimod continued to have an improved clinical response after patients rolled over from the initial ADAPT trial to ADAPT+, with no new safety signals apparent. 

Finally, Dr Silvestri looks at data from the postmarketing registry of eculizumab, which revealed how a significant proportion of patients were able discontinue or reduce their other medications once they started the drug. 

--

Nicholas J. Silvestri, MD, Associate Professor, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 

Nicholas J. Silvestri, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: argenx; Alexion; Immunovant; UCB 

Serve(d) as a speaker or a member of a speakers bureau for: argenx; Alexion 

There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.

Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.

Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.

In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained. 
 

Claims-based analysis

To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.

They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.

Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.

Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.

For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.

When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.

In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).

Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.

The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.

These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.

A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
 

Underestimated burden

Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”

“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”

“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.

“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added. 

Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.

A version of this article originally appeared on Medscape.com.

There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.

Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.

Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.

In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained. 
 

Claims-based analysis

To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.

They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.

Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.

Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.

For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.

When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.

In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).

Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.

The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.

These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.

A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
 

Underestimated burden

Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”

“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”

“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.

“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added. 

Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.

A version of this article originally appeared on Medscape.com.

There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.

Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.

Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.

In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained. 
 

Claims-based analysis

To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.

They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.

Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.

Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.

For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.

When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.

In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).

Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.

The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.

These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.

A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
 

Underestimated burden

Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”

“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”

“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.

“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added. 

Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.

A version of this article originally appeared on Medscape.com.