Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study.

BACKGROUND: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark. METHODS: This was a nationwide, registry and population study of patients treated with DMF. We calculated standard residuals (SR) demonstrate differences between clinics. For survival analysis regarding discontinuation rates and discontinuation due to specific AEs we used log-rank test Cox-proportional hazards and plotted Kaplan-Meier graphics. RESULTS: We included 2,448 people with MS, treated with DMF from 2013 to 2020. Average treatment duration was 26 months (5,382 treatment years). 49.2 % of patients who initiated treatment with DMF (n = 1205) were continuously treated. Reasons for discontinuation were adverse events (54.5 %, n = 656), active disease (26.1 %, n = 315), pregnancy (9.4 %, n = 113) or other reasons (13.2 %, n = 159). We compared SR to the mean regarding reasons for discontinuation and found significant differences between sites regarding gastrointestinal adverse events, flushing and lymphopenia. Discontinuation due to all adverse events, flushing and lymphopenia were more frequent in female than male patients. CONCLUSION: In this population-based study, we found major differences between the MS clinics in rates and reason for discontinuation of DMF. Our results suggest that management strategies during DMF treatment can reduce discontinuation rates.

Long-term structural retinal changes in patients with optic neuritis related to multiple sclerosis.

PURPOSE: To evaluate the long-term structural and functional outcome in patients with multiple sclerosis (MS) with and without a history of optic neuritis (ON). METHODS: This was a cross-sectional study of 82 patients diagnosed with MS between 2000 and 2006 from a tertiary hospital center in Denmark. Patients gave a self-reported history of ON, and functional (visual acuity and color vision) and structural (spectra domain optical coherence tomography) markers of vision were tested. RESULTS: Median age and MS duration at the time of the clinical examination were 49.9 years (range 30.7-72.6 years) and 13 years (range 9-15 years), respectively. ON was not associated with impairment of visual acuity or color vision. Twenty-three patients had a history of ON in at least one eye. Compared to non-affected patients, these had a lower inferior (109 vs 113 µm, P=0.04) and temporal retinal nerve fiber layer (RNFL) thickness (56 vs 67 µm, P=0.01). In an age- and sex-adjusted logistic regression model, lower inferior and temporal RNFL were associated with a higher risk of ON (odds ratio [OR] 1.56 [95% confidence interval {CI} 1.01-2.41] and OR 1.74 [95% CI 1.10-2.77] per 10 µm decrement in RNFL thickness, respectively). Twenty patients had a history of ON in one eye. Compared to the non-affected eye, this eye had a lower RNFL (109 vs 115 µm, P=0.04) and a higher central retinal thickness/mean RNFL ratio (2.7 vs 2.4, P=0.04). CONCLUSION: Although patients with long-term MS and a previous history of ON did not have any functional loss of vision, structural neurodegeneration could be demonstrated in the affected eye.

Practice effect in Symbol Digit Modalities Test in multiple sclerosis patients treated with natalizumab.

OBJECTIVES: How practice effect influences cognitive testing measured by monthly Symbol Digit Modalities Test (SDMT) during natalizumab treatment, and what factors confound such effect. METHODS: Eighty patients were examined monthly with SDMT for 26.2±8.4 months. After 26.0±8.1 months, SDMT was also performed with a rearranged key in 59 cases. Results of SDMTs with the rearranged and previous regular key were compared. We examined if gender, age, Extended Disability Status Scale (EDSS), relapses, and disability progression/improvement influence SDMT performed with the regular and the rearranged key, respectively. We also explored if natalizumab applied before regular monthly SDMT may influence practice effect and cognition. RESULTS: SDMT performance improved by 1.2 points/test during the first six months and by 0.4 points/test thereafter. Rearranging the symbols of the key after 26.0±8.1 months returned SDMT scores to baseline indicating a practice effect. Such practice effect was more significant after longer testing period, but was not influenced by gender, age, relapses, disability progression and prior natalizumab treatment. Although the change from baseline to 2.5 years was significant in subgroups with EDSS 0-3, 3.5-5.5 and 6-7.5, this was higher in patients with EDSS 0-3 compared to 6-7.5. CONCLUSIONS: Practice effect significantly contributes to continuous improvement in SDMT performance during natalizumab treatment: to test cognition, a change in key is required. Practice effect is less pronounced in patients with advanced disease. Cognition remains stable even in patients with progressive disease during more than 2 years of natalizumab treatment indicated by scores corresponding to baseline after changing the key.