Clinical effectiveness and safety of dimethyl fumarate for patients treated at least 5 years in the Swedish post-market surveillance study 'Immunomodulation and Multiple Sclerosis Epidemiology 5' (IMSE 5)

Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE). Objectives: To assess the effectiveness and safety of DMF with focus on patients treated at least 60 months. Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.Results: 2466 DMF-treated patients were included between March 2014 and April 2021 with an overall drug survival rate of 41.2% and a mean treatment duration of 34 months. The main reasons for discontinuation were AEs (49%) and lack of effect (30%). 198 AEs were reported of which 62 were serious. For both serious and non-serious AEs reported, gastrointestinal disorders were the most common (19% and 27%, respectively). 588 patients had continuous treatment for at least 60 months. This cohort had a mean age of 42.1 years and a mean treatment duration of 72.4 months. The majority (63%) had switched from interferon or glatiramer acetate and 22% were treatment naïve. Significant improvements in mean values at 60 months of treatment compared to baseline were noted for MSSS in the 60-month cohort (p<0.001). MSIS-29 Psychological showed a tendency for improvement while all other tests remained stable after 5 years of treatment. Number of relapses per 1000 patients years were improved from 198.9 before DMF treatment start to 27.9 during treatment with DMF. 69 patients (12%) have discontinued DMF treatment in the 60 month cohort with a mean treatment duration of 67