Alexandra C. Bayer Wildberger, PhD, Post-Doctoral Associate at Yale School of Medicine, discusses the shift to precision medicine in myasthenia gravis (MG).

MG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles, which in the majority of patients is due to the presence of antibodies against acetylcholine receptor (AChR). The exact reason this occurs is not known.

As Dr. Bayer explains, the therapeutic landscape for MG has greatly evolved past traditional immunosuppressants over the last few years. The advent of mechanism-based therapies, such as FcRn inhibitors, complement inhibitors, and the potential for isotype-specific proteases, are providing patients with more tailored treatment options.

Due to the heterogeneity of MG, the biggest challenge at present is identifying the most effective treatment for a patient’s specific underlying mechanism of disease. Dr. Bayer explains how this will help to optimize the usage of resources in disease treatment and reduce unnecessary side effects and exposure to treatments that are not beneficial to individual patients.

Current research is striving to better understand the complexities behind MG, such as the exact presence of immunoglobulin classes and the roles they play in the disease, to move towards a precision medicine approach. Recently, Yale has published work describing a previously unrecognized subset of patients with IgM-AChR specific autoantibodies. Next steps involve understanding the role of these autoantibodies in vivo.

Dr. Bayer notes the key role that the RDCRN’s MGNet has played in their research. Through scientific and clinical resources, such as clinical samples and data from the network’s biorepository and funding for further research, the consortium is helping to accelerate the understanding and more effective treatment of MG.

Chapters:
Introduction 00:00
AChR-Positive Myasthenia Gravis 00:26
Need for Tailored Therapeutics 1:37
Ongoing Research 3:23
RDCRN MG Consortium 4:38

0 0

Michael Weiss, MD, Neurologist at the University of Washington, discusses data on the RAISE and RAISE-XT clinical trials of zilucoplan for the treatment of generalized myasthenia gravis (gMG).

gMG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles, which is due to the presence of antibodies against acetylcholine. The exact reason this occurs is not known.

Zilucoplan and the RAISE Clinical Trial Program

Data on the RAISE and RAISE-XT clinical trials of zilucoplan for the treatment of generalized MG was recently presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting and Myasthenia Gravis Foundation of American (MDFA) Scientific Session.

Zilucoplan is a once-daily SC injection, self-administered peptide inhibitor of complement component 5 (C5 inhibitor). Zilucoplan may inhibit complement-mediated damage to the neuromuscular junction through its targeted mechanism of action. The treatment was approved by the U.S. Food and Drug Administration in October 2023 for the treatment of adult patients with AChR-positive gMG.

The RAISE clinical trial (NCT04115293) was a multicenter, randomized, double-blind, placebo-controlled, study evaluating the safety, efficacy, and tolerability of zilucoplan in patients with generalized MG. RAISE-XT (NCT04225871) is a phase 3, multicenter, open-label extension study of zilucoplan in patients with generalized MG.

Effect of Zilucoplan on Fatigue in Patients With gMG: RAISE-XT 120-Week Follow-Up

The RAISE clinical trial demonstrated that treatment with zilucoplan resulted in clinically meaningful and nominally significant improvement in fatigue versus placebo in patients with gMG. The objective of this post hoc analysis was to assess the long term effect of zilucoplan in the ongoing RAISE-XT extension study up to week 120.

At week 120, the mean change from baseline in the Neuro-QoL Short Form Fatigue T-score was 12.65. Of patients with available data at baseline and week 120, 77% showed clinicallt meaningful improvements in their T-score at week 120 compared to baseline. Additionally, 60.7% transitioned to a lower fatigue severity level. At week 120, 60.7% of patients had mild or no fatigue compared with 19.7% at baseline.

Long-Term Effectiveness of Zilucoplan in MG: Predictive Modeling in a United States Real-World Database

The objective of this study was to estimate the long-term effect of zilucoplan on the risk of severe exacerbations using predictive modeling based on clinical trial data and a U.S. real-world database. It assessed the medical benefit of zilucoplan on top of standard of care and its impact across different gMG therapy scenarios.

Step one included replication of most RAISE inclusion/exclusion criteria in the external control arm and weighting it with the zilucoplan arm. This resulted in a strong similarity in baseline patient characteristics. The adjusted hazard ratio of zilucoplan, compared to standard of care, on severe exacerbations over two years was 0.14.

Additionally, simulations showed 8.6%-15.1% reduction in severe exacerbations risk at two years when using zilucoplan in addition to standard of care versus standard of care alone in different scenarios. This suggests that zilucoplan significantly reduces the long-term risk of severe exacerbations with benefit across different gMG real-world standard of care therapy.

Interpreting Patient Quality of Life Experience With Zilucoplan in gMG in RAISE and RAISE-XT

In the RAISE clinical trial, treatment with zilucoplan resulted in statistically significant improvements in the Myasthenia Gravis Quality of Life 15-item revised (MG-QoL15r) versus placebo in patients with gMG. The objective of this study was to interpret the meaningfulness of MG-QoL15r improvements.

At Week 12, patients on zilucoplan were more likely than those on placebo to answer “not at all” for all items, including for the most severe symptoms (e.g., for “difficulty speaking”, placebo: 41.9%; zilucoplan: 63.9%). For the total population, this likelihood increased at Week 60.

Chapters:
Introduction 00:00
RAISE-XT Clinical Trial 00:12
Fatigue Versus Muscle Weakness 3:08
Patient Quality of Life Study 4:57

0 0

James Howard, Jr., MD, Professor of Neurology at the University of North Carolina, discusses new data on the safety and efficacy of Vygart (efgartigimod alfa) for patients with AChR-Ab seronegative generalized myasthenia gravis (gMG).

gMG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles, which is due to the presence of antibodies against acetylcholine. The exact reason this occurs is not known.

New data on the efficacy and safety of efgartigimod alfa was recently presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting and the Myasthenia Gravis Foundation of America (MGFA) Scientific Session.

Efgartigimod alfa is a first-in-class human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG autoantibodies. The ADAPT SERON clinical trial was a phase 3 randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of efgartigimod in adults with AChR-Ab seronegative gMG.

The study met its primary endpoint, demonstrating that AChR-Ab seronegative gMG patients treated with efgartigimod achieved a statistically significant improvement in MG Activities of Daily Living (MG-ADL) total score compared to placebo after four weeks.

In the overall population, mean change from baseline in patients treated with efgartigimod was a clinically meaningful 3.35 point improvement in MG-ADL total score at week four. These results illustrate significant improvements in one or a combination of their abilities in breathing, eating, eyesight, and motor functions. Improvements in MG-ADL and Quantitative MG (QMG) scores among patients treated with efgartigimod were increasingly pronounced across subsequent treatment cycles in the overall population and in all patient subgroups.

Efgartigimod was well tolerated across AChR-Ab seronegative subtypes and consistent with the established safety profile in patients with AChR-Ab seropositive gMG and other indications. No new safety concerns were identified.

Chapters:
Introduction 00:00
FcRn Inhibitors Versus Complement Inhibitors 00:12
ADAPT SERON Clinical Trial 4:29
Patients Without a Specific Antibody 8:31
Take Home Message 9:26

0 0

Philip J. Ferrone, MD, Vitreoretinal Consultants of New York, discusses results from the TEASE-2 clinical trial of gildeuretinol in patients with Stargardt disease.


Stargardt disease is a genetic eye disorder that causes progressive vision loss. It affects the macula, an area of the retina responsible for sharp, central vision. Vision loss is due to abnormal accumulation of lipofuscin in the cells within the macula. Patients with Stargardt disease also have problems with night vision, and some have problems with color vision. It is most commonly caused by genetic changes in the ABCA4 gene. There are currently no available treatments for this condition.

Gildeuretinol is an investigational compound designed to reduce the dimerization of vitamin A without modulating the visual cycle. TEASE-2 was a randomized, double-masked, placebo-controlled study in 79 patients with moderate Stargardt disease. Results from the TEASE-2 clinical trial (NCT02402660) of gildeuretinol for the treatment of moderate Stargardt disease were recently presented at the 2025 American Academy of Ophthalmology (AAO) meeting.

Of those treated with gildeuretinol, there was a 28% reduction in progression of disease. However, due to the heterogeneity of the patient population enrolled, the p-value was not statistically significant. As Dr. Ferrone notes, these results still show great promise in the potential of this treatment in Stargardt disease. Additionally, the safety profile of gildeuretinol is favorable with limited side effects and adverse events.

Next steps include further analysis of the TEASE-2 population and ongoing TEASE-3 and TEASE-4 studies hope to bring data to the U.S. Food and Drug Administration.

Chapters:
Introduction 00:00
Diagnostic Journey 1:46
Red Flag Symptoms 2:59
Current Management 3:24
Gildeuretinol Overview 3:36
TEASE-2 Clinical Trial 4:56
Next Steps 8:57

0 0

Phioanh Leia Nghiemphu, MD, Professor of Clinical Neurology at University of California Los Angeles, discusses the use of mirdametinib for neurofibromatosis type 1 with symptomatic plexiform neurofibromas (NF1-PN).


NF1 is a genetic condition that affects the skin, skeleton, and peripheral nervous system. The main signs and symptoms of NF1 include dark colored spots on the skin, neurofibromas, and freckles in the underarm and groin. Other symptoms may include colored spots in the eye, curvature of the spine, learning disabilities, and an increased risk for cancer. Plexiform neurofibromas are benign tumors that develop on or around neurons. The number of neurofibromas typically increases over time, and some can get large or turn cancerous and need to be removed. This condition is caused by genetic changes in the NF1 gene.

Earlier this year, the U.S. Food and Drug Administration (FDA) approved mirdametinib for the treatment of adult and pediatric patients ages 2 years and older with NF1 who have symptomatic plexiform neurofibromas (PN). Mirdametinib is an oral, small molecule, MEK inhibitor. It is the first and only FDA-approved therapy for this indication. Miradametinib received an accelerated approval based on results from the phase 2b ReNeu trial.

The study enrolled 114 patients with NF1-PN two years of age and older. Dr. Nghiemphu explains that the primary endpoint of the study, confirmed objective response rate (ORR), was met with a 41% ORR in adults and 52% in children. Tumor volume reductions were also significant and durable. Additionally, patients experienced reductions from baseline in pain and quality of life.

The safety and tolerability profile of mirdametinib was favorable with the most common adverse events in adults including rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common adverse events in pediatric patients included rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.

Chapters:
Introduction 00:00
NF1-PN Overview 00:31
Presentation and Diagnosis 3:04
Mirdametinib Overview 4:04
Similarity to RASopathies 4:59
ReNeu Clinical Trial 5:24
Specialty Clinics 7:50
What Physicians Should Know 10:06

0 0

This program is supported by an educational grant from UCB, Inc. 

This accredited CME program highlights the latest clinical research about myasthenia gravis, a rare, autoimmune disease that targets the neuromuscular junction.  This program, led by Dr. James Howard Jr, provides a summary of clinically relevant data presented at the American Academy of Neurology Annual Meeting (AAN 2025) held in San Diego, CA that can enhance the care of patients with myasthenia gravis.  

To obtain CME credit for this program, visit https://checkrare.com/learning/p-myasthenia-gravis-clinical-research-highlights-aan-2025/

Target Audience
This activity has been designed to meet the educational needs of physicians specializing in neurology, ophthalmology, rheumatology, and family practice. Other members of the care team may also participate.

Learning Objectives
After participating in the activity, learners should be better able to:
Describe the latest research being presented to better manage individuals with myasthenia gravis and its clinical relevance.

FACULTY 
James F. Howard Jr, MD, FAAN
Professor of Neurology
University of North Carolina at Chapel Hill

Disclosure Statement
According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.

Disclosure of relevant financial relationships are as follows:

Faculty Educator/Planner

Dr. Howard discloses the following relevant financial relationships with ineligible companies:

Advisory Board/Consultant: Alexion AstraZeneca Rare Disease, Amgen, argenx, Biohaven Ltd, Cartesian Therapeutics, CoreEvitas, Curie.bio, Hansa Biopharma, H. Lundbeck A/S, Merck EMD Serono, NMD Pharma, Novartis Pharma, Regeneron Pharmaceuticals, Sanofi US, Seismic Therapeutics, TG Therapeutics, Toleranzia AB, and UCB Pharma
Grant/Research Support: Ad Scientiam, Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, NMD Pharma, and UCB Pharma
Other Relationships: non-financial support (eg travel) Alexion AstraZeneca Rare Disease, argenx, Biohaven Ltd, Cartesian Therapeutics, Toleranzia AB, and UCB Pharma.

Other Planners for this activity have no relevant financial relationships with any ineligible companies.

This activity will review off-label or investigational information.

The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.

CREDIT 
Accreditation and Credit Designation
In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physicians
American Academy of CME, Inc., designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. 

Other HCPs
Other members of the care team will receive a certificate of participation.

There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days.

Privacy
For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare’s privacy policy, please access https://checkrare.com/privacy/

Contact
For any questions, please contact: [email protected]

Copyright
© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

0 0

Shaishav Dhage, MD, Endocrinologist at The Christie Hospital, discusses a case report on a patient with alemtuzumab-induced thyroid eye disease (TED).

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

Alemtuzumab is a humanized monoclonal antibody that targets CD52 glycoprotein found on most mature leukocytes. The treatment is used in patients with relapsing/remitting multiple sclerosis. Due to its immunomodulatory effects, however, it is commonly associated with secondary autoimmunity. Although not frequently observed, alemtuzumab-induced TED (AI-TED) is a possible secondary autoimmunity. It is caused by antibody-mediated activation of the thyroid-stimulating hormone receptor in orbital tissues.

Two patients were reviewed who developed AI-TED between one to three years after treatment. The average clinical activity score on presentation was 3/7, which was also the peak score during the active phase of disease. Both patients were treated with lubricant eye drops, selenium, and intravenous methylprednisolone. One patient also required mycophenolate mofetil and azathioprine as second-line therapy before remission was achieved.

The review highlights that as the use of alemtuzumab increases in the management of MS, the incidence of AI-TED is likely to also increase. AI-TED can develop several years following treatment, requiring careful attention for timely diagnosis, especially in mild cases. The potential for significant morbidity in moderate to severe TED emphasizes the importance of early recognition, diagnosis, and appropriate treatment.

Chapters:

1 0

Jui-En Lo, MD, Resident of Internal Medicine at MetroHealth, discusses trends and social determinants of teprotumumab in thyroid eye disease (TED).

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

Teprotumumab is a monoclonal antibody that targets the insulin-like growth factor-1 receptor (IGF-1R), inhibiting orbital fibroblast activation. It was approved for treatment of TED by the U.S. Food and Drug Administration (FDA) in 2020. A study presented at the ENDO 2025 meeting examined treatment trends for TED and explored clinical and demographic factors of prescribing teprotumumab. The study was retrospective and observational and included 100,000 patients with hyperthyroidism between 2018 and 2024.

Of these 100,000 patients, over 200 received teprotumumab annually, with a peak in 2021 following the FDA approval. Additionally, the number of patients undergoing orbital decompression significantly dropped after 2020. Glucocorticoid use remained relatively stable compared to the number of patients with hyperthyroidism.

Multivariable Cox regression showed that White patients were significantly more likely to receive teprotumumab than non-White patients. Specifically, Black and Asian patients were significantly less likely to receive the treatment compared to White patients but Hispanic or Latino ethnicity was not significantly associated with use of teprotumumab. Additionally, patients with low socioeconomic status were significantly less likely to receive teprotumumab.

Chapters:

0 0

Margarita Ochoa-Maya, MD, Medical Director of the Rare Disease Business Unit at Amgen, discusses the TEDucation campaign for thyroid eye disease (TED).

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

The Amgen TEDucation campaign is an educational initiative for endocrinologists to learn more about TED so that it can be better identified, diagnosed, and treated proactively. The campaign utilizes games and guest speakers to engage endocrinologists while identifying gaps in care and giving physicians the tools they need to open up conversation with their patients.

Dr. Ochoa-Maya explains how the recent meeting identified the need for educating endocrinologists in their understanding of the American Thyroid Association and European Thyroid Association consensus of their role in identifying TED.

Chapters:
Introduction 00:00
Thyroid Eye Disease Overview 00:23
Diagnosis 1:04
Amgen Campaign Overview 2:08
Red Flags of Thyroid Eye Disease 4:05

0 0