Gastrointestinal Symptoms in Early Dimethyl Fumarate Therapy

Background: Dimethyl fumarate (DMF) is an oral therapy approved for treatment of relapsing forms of multiple sclerosis (MS). Though DMF is generally well tolerated, gastrointestinal (GI) side effects are not uncommon, particularly during initiation of treatment.

Objectives: The aim of this study was to further characterize the prevalence, intensity and frequency of GI symptoms during initiation of therapy.

Methods: Twenty-four patients initiating DMF therapy for relapsing-remitting MS recorded their daily GI symptoms over the first 14 days of therapy, using the Modified Acute GI Symptom Scale- which evaluates 9 symptoms on a 10-point intensity scale.  Scores of 4-10 were considered moderate-to-severe intensity.

Results: Over the 14-day period, 1 patient discontinued treatment due to flushing, and another due to un-specified GI symptoms. Of the remaining 22 patients, 90% experienced at least 1 GI symptom of any intensity at any time, and 76% of patients experienced at least 1 symptom as moderate-to-severe intensity. Among these 22 patients, each symptom occurred as follows: lower abdominal pain (71%), upper abdominal pain (67%), flatulence (57%), bloating (55%), nausea (55%), diarrhea (55%), indigestion (55%), constipation (27%) and vomiting (5%).  Each of the 9 symptoms, except vomiting and constipation, were experienced as moderate-to-severe intensity at any time in about one-third of patients, but when averaging scores over the 14-day period, no symptom was considered moderate-to-severe in more than 10% of patients. Across all 22 patients, each of the 6 most prevalent symptoms occurred about 25-30% of the time, with intensity increasing in the last 4-5 days of the study period. Neither patient age nor weight was associated with symptom intensity; however, abdominal pains, bloating, flatulence and indigestion were rated higher in females. All 22 patients continued on therapy after study termination.

Conclusions: Over the first 2 weeks of DMF treatment, mild GI symptoms were wide-ranging and common.  Moderate-to-severe ratings occurred most with abdominal pain, nausea, bloating and flatulence, but were experienced for a sustained period in only a small minority of patients, and all patients chose to continue therapy after study termination. Many symptoms increased in intensity during the last 4-5 days. Symptom intensity was greater in females versus males for several symptoms. Strategies to mitigate GI symptoms will be discussed.