Jonathan Strober, MD, pediatric neurologist and neuromuscular specialist at the University of California at San Francisco, discusses the use of nipocalimab in adolescent patients with 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.

Nipocalimab is a fully human IgG monoclonal antibody that binds to the neonatal Fc receptor (FcRn) with high specificity and affinity, blocking its interaction with IgG. The treatment is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of both adult and adolescent patients 12 years and older with gMG.

The objective of the study is to evaluate the safety and efficacy of nipocalimab in adolescents aged 12 to 18 years with gMG who exhibit an insufficient clinical response to standard-of-care therapy. Vibrance-mg (NCT05265273) is a phase 2/3 global, multicenter, open-label study evaluating nipocalimab plus standard of care in adolescents and children with gMG.

In adolescents with gMG, nipocalimab demonstrated a rapid, substantial and sustained reduction in total serum IgG levels over 24 weeks, with effects maintained through week 72 in the long term extension. Clinically meaningful improvements in MG Activities of Daily Living and Quantitative MG scores were achieved over 24 weeks and sustained in most participants through week 72. Treatment was well-tolerated in adolescents with gMG, with a favorable safety profile observed throughout the study.

Chapters:
Introduction 00:00
Myasthenia Gravis Overview 00:25
Data Presented at MGFA 2025 1:57
Next Steps 3:19

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Nolan Campbell, PhD, U.S. Medical Director at Johnson & Johnson, discusses the EPIC clinical trial design that will evaluate the efficacy of nipocalimab versus efgartigimod in patients with generalized myasthenia gravis (gMG).

gMG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles due to antibodies attacking the acetylcholine receptors in the neuromuscular junction. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. Weakness tends to increase during periods of activity and improve after periods of rest. 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. Some cases have been linked to tumors in the thymus gland. Some cases may go into remission temporarily, and muscle weakness may disappear so that medications can be discontinued.

Nipocalimab is a fully human neonatal FcRn inhibitor that enables the reduction of circulating IgG levels. It was approved earlier this year for the treatment of gMG following positive data from the Vibrance-MG clinical trial.

New data addressing unmet medical needs within the indication of nipocalimab was recently presented at the 2025 American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) meeting and the Myasthenia Gravis Foundation of America (MGFA) Scientific Session.

EPIC Clinical Trial Design

Efgartigimod is another FDA-approved FcRn-targeting treatment for gMG with differing molecular structures, binding affinities, and dosing to nipocalimab. EPIC (NCT07217587) is a phase 3b, multicenter, randomized, open-label, active-controlled interventional study with parallel-group design including treatment switching in adult participants with gMG.

The objective of EPIC aims to evaluate the efficacy of nipocalimab versus efgartigimod in participants initiating FcRn targeted therapy for gMG and to evaluate efficacy and safety of nipocalimab in participants switching from efgartigimod to nipocalimab. The study will consist of a screening phase of up to 32 days, a 12-week randomized open-label head-to-head phase (Arms 1 and 2) or an up to 12-week run-in phase and a 12-week open-label treatment switch phase (Arm 3), and an 8-week safety follow-up phase.

The study’s key primary and secondary endpoints are change from baseline in total immunoglobulin G (IgG) levels and sustained disease control measured by MG Activities of Daily Living and Quantitative MG scores 8-12 weeks post-initiation of treatment, respectively.

Insights and Challenges From Mapping Out the Patient Journey of gMG

Another study discussed at AANEM 2025 looked at the patient journey and further characterized the experience of living with gMG using key patient and caregiver insights from a pre-session survey and focus group discussions. There was a total of 16 participants, with 12 being patients and 4 caregivers.

Common challenges participants faced in the gMG patient journey included misdiagnosis or delayed diagnosis, insurance barriers, and the trial-and-error nature of finding effective treatments. Most participants described gMG as an emotionally challenging disease, due in part to self-doubt caused by HCPs not believing them, grief for lost abilities, and the emotional toll on caregivers of patients with gMG. Implementing self-care practices, finding support groups, and learning to identify limitations and triggers and express them to others were strategies participants utilized to improve their patient journey and protect their mental health. Leveraging these insights may help to improve gMG management and patient outcomes, as US patients with gMG continue to experience substantial disease instability despite currently available treatment options.

Chapters:
Introduction 00:00
Nipocalimab Overview 1:01
MGFA Poster Presentations 2:00
EPIC Clinical Trial 5:01
MG Patient Journey 7:00
Take Home Message 9:32

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Sindhu Ramchandren, MD, Executive Medical Director of Neuroscience at Johnson & Johnson, discusses long-term efficacy of nipocalimab in patients with 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.

Nipocalimab is a neonatal Fc receptor-binding monoclonal antibody that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of gMG in adult and pediatric patients 12 years of age and older who are anti-AChR or anti-MuSK antibody positive.

Analysis of Long-Term Efficacy of Nipocalimab in Myasthenia Gravis: Open-Label Extension of the Vivacity-MG3 Trial

The Vivacity-MG3 (NCT04951622) clinical trial was a phase 3 double-blind, 24-week study that demonstrated statistically significant and clinically meaningful improvements in MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores with nipocalimab plus standard of care. Patients on nipocalimab plus standard of care in the double-blind phase had the option of continuing treatment in the open-label extension phase assessing long-term efficacy.

A total of 98 patients rolled over into the extension phase where data was collected up to week 48. At Week 48, 84.6% of patients achieved minimal clinical improvement (MCI) in MG-ADL. Mean time to earliest MCI was 4.0 weeks and sustained MCI for 8 weeks or greater was observed in 77.6% of patients. The mean percentage of time with MCI up to Week 48 was 71.6% and 50% or greater study time with MCI was observed in 73.9% of patients. 75% or greater study time with MCI was observed in 67.0% of patients.

At Week 48, 26.9% of patients achieved minimal symptom expression (MSE) in MG-ADL. Mean time to earliest MSE was 14.5 weeks and sustained MSE for 8 weeks or greater was observed in 23.5% of patients. Mean percentage of time with MSE up to Week 48 was 30.21% and 50% or greater study time with MSE was observed in 17.0% of patients while 75% or greater study time with MSE was observed in 12.5% of patients.

Efficacy of Nipocalimab in Adult Patients with Moderate-to-Severe Ocular Manifestations of gMG in Phase 3 VIVACITY-MG3

In gMG, 15–50% of patients present with ocular manifestations such as ptosis or diplopia. The objective of this post-hoc analysis was to evaluate the efficacy of nipocalimab versus placebo in the subgroup of patients with moderate-to-severe ocular manifestations (MSOM).

At baseline, within the MSOM subgroup, nipocalimab and placebo arms were comparable in mean age, BMI and mean (SD) MG-ADL-ocular and MG-ADL-total scores. At week 24, the change from baseline LS mean difference in MG-ADL scores was significantly greater with nipocalimab than placebo. The mean difference MG-ADL-total for nipocalimab vs placebo was −1.35. Additionally, at week 24, the change from baseline LS mean difference in MG-ADL-ocular scores was greater with nipocalimab than placebo. 51% of participants achieved meaningful within-person improvement at week 24 on MG-ADL-ocular domain with nipocalimab, comnpared to 24% in the placebo group.

Chapters:
Introduction 00:00
Myasthenia Gravis Overview 00:57
AANEM Poster Presentations 2:03
Take Home Message 7:35

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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

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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

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James Howard, Jr., MD, Professor of Neurology at the University of North Carolina, discusses new data on the safety and efficacy of Vyvgart (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

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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

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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 any questions, please contact: [email protected]

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© 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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