Scientific Perspectives on Fumarate Transitions in MS: A Clinical Review of MMF Data and Observations

Educational Webinar

Scientific Perspectives on Fumarate Transitions in MS: A Clinical Review of Monomethyl Fumarate (MMF) Data and Observations

Overview

The long-term management of relapsing-remitting multiple sclerosis (RRMS) necessitates a dual focus: maintaining sustained neuroprotection and mitigating treatment limiting side effects. While fumarate-based, disease-modifying therapies (DMTs) remain integral to the multiple sclerosis (MS) treatment landscape, clinicians frequently encounter practical barriers; specifically, lymphopenia and gastrointestinal (GI) distress which can undermine treatment adherence and patient quality of life.

Critical to therapeutic success is a nuanced understanding of how different fumarate formulations are associated with safety, tolerability, and monitoring considerations in clinical practice. This webinar will review real world evidence and case based clinical experience relating to fumarate based therapies, including discussion of lymphocyte monitoring, GI tolerability, and pharmacologic differences reported in routine care.

In this webinar

Clinicians from Vanderbilt University Neurology Clinic will present data from a retrospective review of lymphocyte changes in MS patients transitioning between fumarate formulations.
Dr. Berkovich, a leading expert with her own private practice will lead a case-based discussion examining clinical observations of lymphocyte monitoring and GI tolerability profiles during treatment transitions.

Meet the panelists

Dr. Harold Moses, MD

Dr. Harold Moses, MD, is an Associate Professor of Neurology at Vanderbilt University Medical Center and a clinician at the Vanderbilt Multiple Sclerosis Center. He specializes in neuroimmunology and MS, with clinical expertise spanning relapsing and progressive MS, neuromyelitis optica spectrum disorders, and related inflammatory neurologic conditions.

John Kramer, PA-C

John Kramer, PA‑C, is a certified physician assistant at the Vanderbilt Multiple Sclerosis Center with more than 20 years of experience in neuroimmunology. He is actively involved in the care of patients with neurological disorders and has contributed to numerous clinical research trials, peer‑reviewed publications, and national conference presentations.

Megan Schneider, PharmD

Megan Schneider, PharmD, is a clinical pharmacist at the Vanderbilt University Medical Center with expertise in the pharmacokinetics and clinical application of therapies for MS. She is the first author on research evaluating fumarate formulations and contributes to the interpretation of real‑world and clinical data to inform treatment optimization in MS.

Dr. Regina Berkovich, MD, PhD

Dr. Regina Berkovich, MD, PhD, is a leading neurologist and the founder of Dr. Regina Berkovich, MD, PhD, Private MS Center and Research Institute, which specializes in the care of patients with MS. She brings extensive clinical experience in MS diagnosis and long‑term disease management, with a focus on optimizing treatment strategies to improve patient outcomes.

Indication and Important Safety Information

Indications

BAFIERTAM^® is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Contraindications

BAFIERTAM is contraindicated in patients:

With known hypersensitivity to monomethyl fumarate, dimethyl fumarate, diroximel fumarate, or to any of the excipients of BAFIERTAM. Reactions may include anaphylaxis or angioedema.
Taking dimethyl fumarate or diroximel fumarate.

Important Safety Information

Warnings and Precautions

Anaphylaxis and Angioedema

BAFIERTAM can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in patients taking dimethyl fumarate (the prodrug of BAFIERTAM) have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue BAFIERTAM and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema.

Progressive Multifocal Leukoencephalopathy (PML)

PML has occurred in patients with MS treated with dimethyl fumarate (the prodrug of BAFIERTAM). PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received dimethyl fumarate (the prodrug of BAFIERTAM) for 4 years while enrolled in a clinical trial.
PML has also occurred in patients taking dimethyl fumarate in the postmarketing setting in the presence of lymphopenia (<0.9×109/L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8×109/L persisting for more than 6 months.
At the first sign or symptom suggestive of PML, withhold BAFIERTAM and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.
Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should prompt further investigation for early diagnosis, if present.

Herpes Zoster and Other Serious Opportunistic Infections

Serious cases of herpes zoster have occurred with dimethyl fumarate (the prodrug of BAFIERTAM), including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Monitor patients on BAFIERTAM for signs and symptoms of herpes zoster. If herpes zoster occurs, appropriate treatment for herpes zoster should be administered.
Other serious opportunistic infections have occurred with dimethyl fumarate (the prodrug of BAFIERTAM), including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment.
Consider withholding BAFIERTAM treatment in patients with herpes zoster or other serious infections until the infection has resolved.

Lymphopenia

BAFIERTAM may decrease lymphocyte counts. Prolonged, severe lymphopenia (lymphocyte counts <0.5 × 10⁹/L for ≥6 months) has been reported with dimethyl fumarate (the prodrug of BAFIERTAM), and recovery after discontinuation may be delayed.
Obtain a complete blood count (CBC), including lymphocyte count, before initiating treatment with BAFIERTAM, at 6 months after initiation, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of BAFIERTAM in patients with lymphocyte counts <0.5 × 10⁹/L persisting for more than 6 months. Continue to monitor lymphocyte counts until recovery if BAFIERTAM is discontinued or interrupted because of lymphopenia. Consider withholding treatment in patients with serious infections until resolution. Decisions to restart BAFIERTAM should be individualized.

Liver Injury

Clinically significant cases of liver injury have been reported in the postmarketing setting with dimethyl fumarate (the prodrug of BAFIERTAM), with onset ranging from a few days to several months after treatment initiation. Findings have included elevations of serum aminotransferases (>5× ULN) and total bilirubin (>2× ULN). Some cases required hospitalization, and abnormalities resolved following treatment discontinuation. The combination of new aminotransferase elevations with increased bilirubin levels is an important predictor of serious drug‑induced liver injury.
Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating BAFIERTAM and during treatment, as clinically indicated. Discontinue BAFIERTAM if clinically significant liver injury induced by BAFIERTAM is suspected.

Flushing

BAFIERTAM may cause flushing (e.g., warmth, redness, itching, and/or burning sensation). In clinical trials of dimethyl fumarate (the prodrug of BAFIERTAM), flushing was reported in approximately 40% of patients, generally occurring soon after treatment initiation and typically improving or resolving over time. In most patients, flushing was mild to moderate in severity. Administration of non-enteric coated aspirin (up to 325 mg) approximately 30 minutes prior to dosing may reduce the incidence or severity of flushing.

Serious Gastrointestinal Reactions

Serious gastrointestinal reactions, including perforation, ulceration, hemorrhage, and obstruction, some with fatal outcomes, have been reported in the postmarketing setting with the use of fumaric acid esters, including dimethyl fumarate, with or without concomitant aspirin use. The majority of these events have occurred within 6 months of fumaric acid ester treatment initiation. In controlled clinical trials, the incidence of serious gastrointestinal adverse events was 1% in patients treated with dimethyl fumarate; these events, none of which were fatal, included vomiting (0.3%) and abdominal pain (0.3%).
Monitor patients, promptly evaluate, and discontinue BAFIERTAM for new or worsening severe gastrointestinal signs and symptoms.

Adverse Reactions

The most common adverse reactions reported with dimethyl fumarate (the prodrug of BAFIERTAM) were flushing and gastrointestinal-related events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). Gastrointestinal events generally occurred early in treatment and often decreased over time.
A transient increase in mean eosinophil counts was observed during the first 2 months of treatment.

For more detailed information, please refer to the full Prescribing Information here.

To report SUSPECTED ADVERSE REACTIONS, contact Banner Life Sciences at toll free phone: 1-866-MMF-95MG or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch.

Disclaimer: This discussion will reflect the clinical experience of Vanderbilt University and a private MS practice. Due to the specific patient cohorts observed, the results regarding the impact of switching between fumarates are not fully generalizable to all MS patient populations or diverse clinical settings. In determining the propriety of any treatment plan, clinicians should consider their professional judgment and the needs, preferences, and specific clinical circumstances of the individual patient. Further research with clinical trials is required to investigate these outcomes.

This webinar is intended for healthcare professionals (HCPs) involved in the management and treatment of patients with multiple sclerosis.

This educational webinar is sponsored and hosted by Cycle Pharmaceuticals, and the speakers have been compensated for their time.

This is a non‑promotional webinar.

BAFIERTAM^® is a registered trademark of Banner Life Sciences, LLC, a Cycle Pharmaceuticals company.