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

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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.

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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).

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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:

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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:

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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

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Jack Johnson, Co-Founder and Executive Director of FSIG, discusses symptom and treatment burden in Fabry disease.

Fabry disease is a rare lysosomal storage disease characterized by a deficiency in the enzyme alpha-galactosidase (alpha-GAL). Alpha-GAL helps break down a fatty acid called globotriaosylceramide (GL3). Symptoms of Fabry disease may include episodes of pain, especially in the hands and feet, clusters of small angiokeratomas, hypohidrosis, corneal opacity, and hearing loss. Internal organs, such as the kidney, heart or brain, may also be affected, leading to progressive kidney damage, heart attacks, and strokes. Fabry disease is caused by changes in the GLA gene.

Mr. Johnson explains that the most burdensome symptoms for patients with Fabry disease are typically those that are difficult to measure, and therefore manage. This most notably includes pain, fatigue, inadequate temperature regulation, and gastrointestinal issues. While these symptoms cannot be measured through medical tests, they are often measured via patient reported outcome surveys.

Alternatively, health care practitioners tend to focus on symptoms that can be measured through imaging or blood and urine testing. The focus on these components of Fabry disease can be frustrating to patients who may not experience effect on daily life due to these symptoms. However, Mr. Johnson notes the importance of these tests in addressing issues early on before they become bigger problems that do affect a patient’s daily life.

An additional burden for patients with Fabry disease is the burden of treatment with enzyme replacement therapy. Many patients with Fabry disease receive transfusions once every two weeks, greatly impacting daily activities such as school and work. This can also make travel difficult as patients have to plan around their transfusion appointments, with some patients noticing changes in symptoms if an appointment is off by even just one day. Initiation of therapy can also pose challenges such as not noticing any effects up to 6 months to one year after. This causes many patients to discontinue treatment and only return when medically necessary.

Because of such great burdens of symptoms and treatment in Fabry disease, patients are hopeful for advancements that address these unmet needs. Mr. Johnson discusses the hopes of patients for a new therapy that would reduce the number of infusions per year or even for a one-time gene therapy.

Chapters:
Introduction 00:00
Fabry Disease Overview 00:22
Most Burdensome Symptoms 00:51
Symptoms That Physicians Focus On 4:10
Tracking Patient Reported Outcomes 5:38
Treatment Burden 6:07
Emerging Clinical Trials and Treatment 9:04
FSIG Meetings 10:23

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