Gastrointestinal Symptoms in Early Dimethyl Fumarate Therapy
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.