This accredited continuing education program is supported by an educational grant from Sanofi. Credit for the program can be obtained by visiting https://checkrare.com/learning/p-consider-rare-suspecting-and-diagnosing-cidp/ . 

This program, led by Jeffrey Allen, MD, Professor of Neurology at the University of Minnesota provides an overview on the diagnostic delays that often occur in patients with CIDP as well as best practices to suspect and diagnose this rare condition more efficiently. 

This activity has been designed to meet the educational needs of physicians specializing in family medicine, pediatrics, and neurology. Other members of the care team may also participate.

Learning Objectives
After participating in the activity, learners should be better able to:
Describe the early symptoms of CIDP.
List best practices which can be used to diagnose CIDP more efficiently.

Faculty 
Jeffrey Allen, MD
Professor of Neurology
Department of Neurology
Division of Neuromuscular Medicine
University of Minnesota
Minneapolis, MN

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. Scott discloses 
Consultant/Educational talks: Annexon, Alexion, Amgen, CSL Behring, Takeda,
BioCryst, Grifols, Argenx, Sanofi, Immunovant, ImmunoAbs, Octapharma, Alnylam, AstraZeneca, Dianthus, Johnson & Johnson, Laboratoire Français du Fractionnement et des Biotechnologies, Nuvig, Akcea Therapeutics, ImmunoPharma,
Pfizer.

Community Faculty/Patient (Christine Eleeson): No relevant financial relationships with any ineligible companies.

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.
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 0.5 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).

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Philip Molyneaux, MD, PhD, a Professor of Interstitial Lung Disease (ILD) at Imperial College London and the Asthma+Lung UK Chair of Respiratory Research at Royal Brompton Hospital, where is also the Director of the UK National Institute for Health and Care Research (NIHR) Clinical Research Facility, discusses the results of the CORAL study.

Dr. Molyneaux, chief investigator of the CORAL phase 2b study, presented the results at CHEST 2025, held October 18-21, 2025 in Phoenix. He reported that up to 80% of patients with ILD have frequent, chronic cough. In CORAL, a randomized, double-blind, parallel-group study of 165 patients with idiopathic pulmonary fibrosis (the most common form of ILD) and a history of chronic cough, nalbuphine extended-release tablets were tested against placebo in reducing 24-hour cough frequency. All patients had a cough severity score of ≥ 4 on the Cough Severity Numerical Rating Scale at baseline.

Patients were randomly assigned to receive placebo or nalbuphine in one of three doses: 27-mg, 54-mg, or 108-mg tablets bid. The primary endpoint of the study was reduction in cough frequency at 6 weeks, measured via a digital cough monitor. Secondary endpoints included safety, and changes in several patient-reported questionnaires and scoring indexes.

All doses produced statistically significant decreases in 24-hour cough frequency, but the higher doses produced greater reductions from baseline at 6 weeks compared with placebo (placebo, –17%; nalbuphine 27 mg, –48%, nalbuphine 54 mg, –53%; nalbuphine 108 mg, –60%). Furthermore, a reduction in cough was seen by week 2.

For patients receiving active therapy, the most common adverse events were nausea, vomiting, constipation, and dizziness. There was no difference in discontinuation rates in patients receiving placebo or any nalbuphine doses.

Dr. Molyneaux stated that not only did objectively measured cough frequency decrease, but patients also gained additional benefits within 2 weeks of taking nalbuphine, as determined by patient-reported outcomes data.

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Aman Chauhan, MD, Oncologist at the University of Miami, discusses details of a phase 3 study testing paltusotine in patients with carcinoid syndrome due to neuroendocrine tumors (NETs).

NETs are rare tumors that usually develop in the GI tract or lungs, but may develop in other parts of the body, such as the pancreas, testicle, or ovary. In later stages, symptoms may vary depending on where the tumor is located. The tumor may produce hormone-like substances that spread to the body and cause symptoms of carcinoid syndrome, such as flushing of the face and chest, diarrhea, and trouble breathing. The cause of neuroendocrine neoplasms is unknown.

Paltusotine is a selectively-targeted somatostatin receptor type 2(SST2) nonpeptide. The treatment is currently approved by the U.S. Food and Drug Administration (FDA) for patients with acromegaly.

The phase 3 CAREFNDR (NCT07087054) clinical trial is a randomized, international, multicenter, placebo-controlled, double-blind study evaluating paltusotine in carcinoid syndrome due to NET. Patients will be treated for 16 weeks with a primary endpoint of change from baseline in flushing frequency at week 12. A second phase 3 trial is also in development, testing the nonpeptide drug candidate, CRN09682, in patients with somatostatin receptor 2-expressing tumors. The CAREFNDR study is currently enrolling patients. For more information, visit carefndr.com.

This study builds on a phase 2 study previously presented. Results from this study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency. A preliminary analysis of phase 2 data from the open-label trial of paltusotine in the treatment of patients with carcinoid syndrome due to NETs showed an overall investigator-assessed progression free survival rate of 74% following one year of treatment.

Chapters:
Introduction 00:00
Carcinoid Syndrome 00:58
Current Management 2:49
Ongoing Phase 3 Clinical Trials 4:52
Next Steps 7:57

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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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Naomi Patel, MD, MPH, Rheumatologist at Massachusetts General Hospital, discusses long-term data from the AQUARIUS study of avacopan in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

GPA is a type of vasculitis causing swelling of the blood vessels anywhere in the body. The condition mainly impacts the sinuses, nose, trachea, lungs, and kidneys. The swelling can limit the flow of blood to these body parts, causing damage. Symptoms of the disease can include sinus pain, recurrent respiratory infections, joint pain, fatigue, and skin lesions. The exact cause of GPA is unknown, but it is a type of autoimmune disease. MPA is also a type of vasculitis. The kidneys, lungs, nerves, skin, and joints are the most commonly affected areas of the body. The cause of this disorder is unknown.

Avacopan is a selective oral C5a receptor antagonist that was approved by the U.S. Food and Drug Administration (FDA) for the treatment of GPA/MPA in 2021. Data was recently presented at ACR and Kidney Week (ASN) from the AQUARIUS clinical trial of avacopan in patients with GPA/MPA.

Data From ACR Presentation (AQUARIUS Part 1) One-Year Real-World Effectiveness with Avacopan in GPA and MPA

This ongoing retrospective cohort study describes 12-month effectiveness and safety outcomes for avacopan in patients with GPA/MPA.

Among the 95 patients with available 12 month follow-up data, 64% were in remission at month 6, while at month 12, 95% had a BVAS v3 equal to zero, 87% were glucocorticoid-free, and 61% had sustained remission. The median discontinuation time was three months and the majority of patients experienced no worsening of glucocorticoid toxicity.

Sustained remission was similar in those with baseline kidney, lung, or ENT involvement. The most common GTI-MD domain with net worsening was blood pressure, followed by body mass index, lipid metabolism, and glucose tolerance. The majority had no net worsening of metabolic GC toxicity over 12 months, indicating either net improvement or no change.

Data From ASN Presentation of AQUARIUS Real-World Clinical Outcomes in a Large Health Care System After Avacopan Initiation for Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA) Involving the Kidneys

This is a retrospective cohort study of patients prescribed avacopan for GPA/MPA from December 1, 2021 to April 1, 2024, reporting 12-month outcomes in those with baseline kidney involvement.

Among 58 patients with kidney involvement treated with avacopan, 16% received dialysis less than or equal to 1 month following initiation. Of 54 patients with 12 month follow-up, 69% had sustained remission. Median estimated glomerular filtration rate (eGFR) among those not on dialysis at baseline and 12 months was 35 and 44, respectively. 4% of patients newly initiated dialysis greater than 1 month after avacopan initiation. Of 7 patients on dialysis at baseline with complete follow-up, 86% discontinued dialysis by 12 months. Among those with baseline urine protein:creatinine ratio (UPCR) greater than 2 g/g, median UPCR declined from 1.4 at baseline to 0.3 g/g at 12 months.

Chapters:
Introduction 00:00
GPA/MPA Overview 00:16
AQUARIUS Clinical Trial 1:01
Prior Treatment 2:54
Results of Trial 4:24
Take Home Message 9:00

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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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Joan Smith, patient with systemic mastocytosis, discusses her diagnostic journey with systemic mastocytosis (SM).

SM is a rare disease, usually caused by mutations in the KIT D816V gene. The disorder is characterized by uncontrolled mast cell proliferation and activation across multiple organ systems. Indolent systemic mastocytosis accounts for approximately 90% of SM. Common symptoms may include anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain. Most adults present with skin lesions, usually in the form of urticaria pigmentosa.

Ms. Smith believes she’s had SM her entire life, citing symptoms sporadically appearing throughout childhood and early adulthood. However, it was not til her late 30s and early 40s that symptoms began to warrant her attention. That started when she awoke to an episode of gastrointestinal symptoms, flushing, rash, and tachycardia. That began a 16 year diagnostic journey.

SM can be difficult to diagnose due to the heterogeneity of symptoms that mimic many other conditions. After that first episode, Ms. Smith thought that she just had an allergic reaction. Following a second episode three weeks later, she went to her primary care physician where bloodwork came back normal and she was referred to a psychiatrist. Determined to figure out what was actually causing her symptoms, Ms. Smith went to St. Louis to see an endocrinologist and allergist, who tested her tryptase levels (a biomarker of SM). However, her levels came back as a false negative for SM and she tested positive for a variety of allergens.

For a period of time, Ms. Smith was placed on some medications for allergies that helped relieve some of her symptoms before beginning to worsen. Following a move to Colorado to see if an environment change would help, new symptoms began to appear and she again seeked out the guidance of an allergist/immunologist where she finally got a positive tryptase test and SM diagnosis. Ms. Smith was started on additional medications and higher doses of her previous medications and found a doctor who specializes in SM.

Eventually, these medications also began to stop working and her symptoms progressed, greatly impacting her quality of life. It was then that Ms. Smith was able to enroll in a clinical trial for, then investigational, Ayvakit (avapritinib). Following treatment with avapritinib, her symptoms greatly improved and she continued to use the medications to this day.

Ms. Smith notes the lasting mental burden of disease; overcoming the fear of having a severe reaction and not having medicine available and grieving the time that was lost due to undiagnosed disease and symptom burden.

Her advice for diagnosed patients is to find specialists in the disease to help with management and treatment plans, finding community and support groups, and becoming aware of personal triggers and doing your best to avoid them. For those who do not currently have a diagnosis, she stresses the importance of taking a break from the exhaustion and frustration of having an undiagnosed condition, but not to give up on finding a solution.

Ms. Smith wants doctors to know that it is important to listen to their patients and that just because they may not be able to figure out a diagnosis right away, they should not jump to the conclusion that someone is suffering from a mental or psychological disorder.

Chapters:
Introduction 00:00
Systemic Mastocytosis Overview 1:17
Diagnostic Journey 2:30
Signs and Symptoms 6:40
Treatment and Clinical Trial Involvement 8:38
Advice for Patients 13:13
Advice for Physicians 16:12

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Bernd Kasper, MD, PhD, University of Heidelberg Cancer Center, discusses results from the DeFi clinical trial of nirogacestat in patients with desmoid tumors.

Desmoid tumors are abnormal growths that arise from connective tissue. The tumors can occur anywhere in the body and are fibrous, much like scar tissue. They are generally not considered malignant because they do not metastasize, however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically. These tumors often recur, even after apparently complete removal. The most common symptom of desmoid tumors is pain. Other signs and symptoms, depending on the size and location of the tumor, may include constipation, limping, or difficulty moving the arms or legs.

The DeFi clinical trial (NCT03785964) is a phase 3 global, randomized, multicenter, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of nirogacestat in adult patients with progressing desmoid tumors. Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor approved by the U.S. Food and Drug Adminsitration (FDA) as monotherapy for the treatment of adults with progressing desmoid tumors. Long-term safety and efficacy data from the DeFi clinical trial was recently published in the Journal of Clinical Oncology.

With a data cutoff date of December 2024, new results showed that median best percent reduction from baseline in target tumor size with continuous nirogacestat treatment was -32.3% at year 1 and -75.8% for patients completing at least 4 years of treatment. Objective response rate increased from 34.3% in year 1 to 45.7% in patients who received nirogacestat for up to 4 years. There were also three additional partial responses since the primary analysis, yielding 24 partial responses and 8 complete responses in total.

Improvements in patient-reported outcomes of pain, desmoid tumor-specific symptom severity and physical functioning, and global health status/quality of life and role functioning occurred early and were sustained up to 45 months of treatment. Overall, the incidence and severity of frequently reported treatment-emergent adverse events decreased through years two, three, and four of treatment. The most common adverse events were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.

Chapters:
Introduction 00:00
Current Management 00:35
DeFi Clinical Trial 1:41
Next Steps 2:42
Take Home Message 4:15

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