Management of Reported Side Effects of Patients Initiating Therapy on Dimethyl Fumarate

Background: Dimethyl fumarate is an oral medication approved by the FDA in April 2013 for the treatment of relapsing-remitting Multiple Sclerosis (RRMS). Phase III pivotal clinical trials revealed common adverse events related to dimethyl fumarate (previously designated as BG-12), including flushing, diarrhea, nausea, abdominal pain, and itching. In an attempt to proactively manage these well-recognized, and not infrequently limiting side effects, providers recommended pre-treatment with a variety of medications including aspirin, anti-histamine agents, anti-cholinergic (e.g. glycopyrolate) agents, and bismuth salicylate.

Objectives: To characterize patient-reported side effects in patients with multiple sclerosis (MS) treated with dimethyl fumarate, and to ascertain whether pre-emptive symptom management strategies could impact side effect profiles and successfully lengthen duration of treatment.

Methods: The Clinical Center for MS at UT Southwestern Medical Center followed 66 MS patients treated with dimethyl fumarate. Patients were systematically evaluated for treatment-associated symptoms, subsequent symptom management, and duration of treatment. Patients were followed via telephone and secure EMR messages. Additionally, data were collected at a clinical follow-up visit 3 months after initiating treatment with the new disease modifying therapy.

Results: Regardless of the symptom being reported, patients most commonly reported side effects during titration from the initial dose of 120 mg twice daily to the maintenance dose of 240 mg twice daily. Similar to the Phase III clinical findings, patients most commonly reported flushing (35%), abdominal pain (12%), diarrhea (15%), nausea/vomiting (11%), and itching (9%). Low dose aspirin (81mg) was prescribed for flushing. Diphenhydramine or cetirizine was recommended for patients who experienced itching or rash. For diarrhea and abdominal discomfort, loperamide or bismuth salicylate was recommended. In rare instances, providers extended the length of time on 120 mg twice daily dosing before increasing to the 240 mg twice daily maintenance dose.

Conclusions: In a real-world environment, patients experience symptoms including flushing, abdominal pain, diarrhea, and itching. These common side effects can be managed in the majority of patients if pre-treated with aspirin, diphenhydramine, cetirizine, loperamide or bismuth salicylate.