Effectiveness of Dimethyl Fumarate in Real-World Clinical Practice and Strategy to Minimize Adverse Effects and Use of Healthcare Resources

Abstract

Background Dimethyl fumarate (DMF) has shown efficacy in reducing relapse rates in patients with multiple sclerosis (MS). However, associated adverse effects (AE) such as gastrointestinal (GI) AE, flushing and lymphopenia are the main cause of treatment discontinuation. The aim of this study was to evaluate the effectiveness of DMF, and to assess strategies to reduce treatment discontinuation rates in routine clinical practice. Patients and Methods Ninety patients started DMF treatment between August 2015 and February 2020. Prior to DMF therapy, patients received written information regarding treatment and the management of AE, along with medical prescriptions. Clinical and analytical data were collected at clinical visits performed at least 6-monthly, and disease progression was evaluated by brain magnetic resonance imaging (MRI). Results Prior to DMF, 78.7% of patients had an annualized relapse rate (ARR) of 1.07 (range: 1–3) and median Expanded Disability Status Scale (EDSS) score of 1.0 (range: 0–2). At final follow-up, ARR and median EDSS scores were significantly reduced to 0.09 (range: 0–2; p< 0.001) and 0 (range: 0–1.625; p< 0.001), respectively. Just over one quarter of patients with brain MRI (26.8% of 71 patients) showed improvement in disease activity based on MRI evaluation. Lymphopenia was associated with previous treatment lines (p=0.042) and longer disease duration (p=0.032). A total of twelve patients abandoned DMF treatment, mainly due to lymphopenia (7.9%), but none did it because of GI AE or flushing. Conclusion In our series, DMF showed high clinical and radiological efficacy. Providing patients with complete information prior to treatment on the management of associated AE helps them to better understand what to expect, improves tolerance and reduces clinical and telephone consultations, which may help to reduce the use and cost of healthcare resources.

Safety and Discontinuation Rate of Dimethyl Fumarate (Zadiva®) in Patients with Multiple Sclerosis: An Observational Retrospective Study

“…Furthermore, our study found a lower incidence of flushing compared to previous observational studies by Rodríguez-Regal et al and Conde et al, where flushing was reported in 43.3% and 48% of patients, respectively [16,17]. Administering the medication with food may reduce the incidence of flushing, as reported in a study by Kappos et al [18].…”

“…Of these, 8 out of 142 patients (5.63%) discontinued due to adverse events and 5 out of 142 patients (3.52%) discontinued due to lack of efficacy. In comparison, a study conducted by Rodríguez-Regal et al on 90 patients reported that 12 patients (13.5%) discontinued treatment, with 3 patients (3.4%) discontinuing due to therapeutic failure and 8 patients (8.9%) discontinuing due to adverse events [16].…”

How to choose initial treatment in multiple sclerosis patients: a case-based approach

“…Very commonly reported adverse effects include flushing (up to 35% of patients) and Gastrointestinal (GI) disorders (up 44%), both presented mainly in the first month of use and constituting the main reasons for treatment discontinuation 36 , 38 Strategies to minimize adverse effects include: nutritional counseling, use of proton-pump inhibitors and symptomatic drugs for dyspepsia, and use of aspirin 30 minutes before taking the drug, to avoid flushing 39 . Recently, a new once-a-day fumarate formulation (viroximel fumarate) reduces the risk of GI symptoms and provides similar therapeutic benefits of DMF.…”