Dimethyl Fumarate In Multiple Sclerosis Research Articles

Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study

BackgroundAdherence 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. MethodsThis 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. ResultsWe 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. ConclusionIn 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.

A cell-mimicking platelet-based drug delivery system as a potential carrier of dimethyl fumarate for multiple sclerosis

Dimethyl fumarate (DMF), is one of the lately approved therapeutic agents for the multiple sclerosis (MS) treatment. Despite the beneficial effects, DMF also suffers from low penetration into brain.In this study, we designed a precise drug delivery system of DMF to cross BBB for MS management. The novelty of this study is developing a cell based biomimetic vehicle for specific drug delivery to the inflamed area in peripheral and CNS. DMF-loaded platelet-based nanoparticle as a cell-based drug delivery system was developed and compared with chitosan nanogel and platelet membrane coated chitosan nanogel. Prepared nanoparticles were characterized for particle size, morphology, release characteristics, and drug loading parameters. In the optimum condition, all nanoparticles were prepared in desirable nano-size and showed appropriate loading parameters. The neuropharmacokinetic evaluation was performed by determining the brain uptake of DMF, and brain uptake clearance for passage from BBB. Results from in vivo study demonstrated that the brain concentration of nanoparticles was higher than the free drug solution. The brain uptake clearance and AUC (0-∞) brain of DMF-loaded platelet nanoparticle were higher than platelet membrane coated chitosan nanogel and chitosan nanogel. The results demonstrated that platelet nanoparticles can be proposed as a potential biomimetic carrier for MS management.

Thyroid Disorders in Patients Treated with Dimethyl Fumarate for Multiple Sclerosis: A Retrospective Observational Study.

Background: Dimethyl fumarate (DMF), a drug used for the treatment of multiple sclerosis (MS) and psoriasis, has been shown to activate the Keap1/Nrf2 antioxidant response. Nrf2 exerts pleiotropic roles in the thyroid gland; among others, single nucleotide polymorphisms (SNPs) in the gene encoding Nrf2 modulate the risk of Hashimoto’s thyroiditis (HT), suggesting that pharmacological activation of Nrf2 might also be protective. However, a patient with acute exacerbation of HT after starting DMF for MS was recently reported, raising questions about the thyroidal safety of Nrf2 activators. Methods: In a retrospective observational study, we investigated the prevalence and incidence of thyroid disorders (TD) among 163 patients with MS treated with DMF. Results: Only 7/163 patients (4.3%) were diagnosed with functional TD; most (5/163, 3.0%) were diagnosed before DMF treatment. Functional TD were diagnosed under or after DMF in only 2 patients (1.2%). Under DMF, one patient developed transient mild hypothyroidism with negative thyroid autoantibodies. After DMF discontinuation, another patient developed hyperthyroidism due to Graves’ disease. No patient developed thyroid structural disease under or after DMF. Conclusions: The very low incidence of functional TD indicates an overall very good thyroid tolerance of DMF, arguing against screening for TD in MS patients considered for or treated with DMF, and supporting the further study of Nrf2 activators for the prevention and treatment of TD.

Itaconate and fumarate derivatives inhibit priming and activation of the canonical NLRP3 inflammasome in macrophages.

The NLRP3 inflammasome is a multiprotein complex that regulates caspase‐1 activation and subsequent interleukin (IL)‐1β and IL‐18 release from innate immune cells in response to infection or injury. Derivatives of the metabolites itaconate and fumarate, dimethyl itaconate (DMI), 4‐octyl itaconate (4OI) and dimethyl fumarate (DMF) limit both expression and release of IL‐1β following NLRP3 inflammasome activation. However, the direct effects of these metabolite derivatives on NLRP3 inflammasome responses require further investigation. Using murine bone marrow‐derived macrophages, mixed glia and organotypic hippocampal slice cultures (OHSCs), we demonstrate that DMI, 4OI and DMF pretreatments inhibit pro‐inflammatory cytokine production in response to lipopolysaccharide (LPS), as well as inhibit subsequent NLRP3 inflammasome activation induced by nigericin. DMI, 4OI, DMF and monomethyl fumarate (MMF), another fumarate derivative, also directly inhibited biochemical markers of NLRP3 activation in LPS‐primed macrophages, mixed glia, OHSCs and human macrophages in response to nigericin and imiquimod, including ASC speck formation, caspase‐1 activation, gasdermin D cleavage and IL‐1β release. DMF, an approved treatment of multiple sclerosis, as well as DMI, 4OI and MMF, inhibited NLRP3 activation in macrophages in response to lysophosphatidylcholine, which is used to induce demyelination, suggesting a possible mechanism for DMF in multiple sclerosis through NLRP3 inhibition. The derivatives also reduced pro‐IL‐1α cleavage in response to the calcium ionophore ionomycin. Together, these findings reveal the immunometabolic regulation of both the priming and activation steps of NLRP3 activation in macrophages. Furthermore, we highlight itaconate and fumarate derivatives as potential therapeutic options in NLRP3‐ and IL‐1α‐driven diseases, including in the brain.

Comparative effectiveness of dimethyl fumarate in multiple sclerosis.

To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting. A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1-3.5years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively. Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61-0.86]) and TERI (0.81 [0.68-0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts. DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

Real-world discontinuation rate of teriflunomide and dimethyl fumarate in multiple sclerosis.

BackgroundFor patients with MS, medication switches increase the risk of disease reactivation.ObjectiveCompare discontinuation rates due to treatment failure or side effects between teriflunomide and dimethyl fumarate, and investigate clinical variables affecting discontinuation rates.MethodsAll patients who received teriflunomide or dimethyl fumarate at Haukeland University Hospital from 2013 until 2018 were identified. Clinical and demographic variables were extracted from the Norwegian MS Registry. Cause-specific Cox regression models estimated the rate of discontinuation due to treatment failure or side effects.ResultsWe included 354 patients treated with either dimethyl fumarate (n = 185) or teriflunomide (n = 169). We found 38% lower risk of discontinuation because of treatment failure for patients using dimethyl fumarate compared to teriflunomide (p < 0.05). In a treatment-naive subgroup (n = 183), we found a 38% reduced risk of discontinuation for any reason among patients using dimethyl fumarate (p < 0.05). There was no significant difference between treatment groups in discontinuation rate due to side effects, although more patients reported side effects when treated with dimethyl fumarate.ConclusionOur findings suggests that dimethyl fumarate has a lower risk of discontinuation because of treatment failure among both treatment-experienced and treatment-naive patients.

Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study.

Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baselineExpanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.

Hematological Alterations Related to Treatment with Teriflunomide and Dimethyl Fumarate in Multiple Sclerosis

The exact mechanism of action of different modifying treatments in the evolutionary course of multiple sclerosis (MS) remains unknown, but it is assumed that they act upon the cells involved in acquired immunity. One effect of these treatments is the development of lymphopenia, which carries inherent safety risks. This study was conducted to understand the alterations that teriflunomide (TERI) and dimethyl fumarate (DMF) exert upon white blood cells in a series of patients with MS. This study included a total of 99 patients; 44 treated with DMF and 55 patients treated with TERI. Blood counts were evaluated at baseline and every 6 months in order to track the absolute leukocyte, lymphocyte, and neutrophil counts. Twelve months after starting treatment, we observed a significant decrease in leukocytes (21.1%), lymphocytes (39.1%), and neutrophils (10%) in the DMF group. In the TERI group, leukocytes decreased by 11.1%, lymphocytes by 8.1%, and neutrophils by 15.7%. Both TERI and DMF produced a significant decrease in leukocytes during the first year of treatment and this was mainly related with a decrease in neutrophils in the TERI group and a decrease in lymphocytes in the DMF group.

Effectiveness and side effects of dimethyl fumarate in multiple sclerosis after 12 months of follow up: An Iranian clinical trial

Background: Multiple sclerosis (MS) is a neurologic disorder with a considerable global burden. During the last decades, some pharmaceutical treatments have been approved for patients with MS. Dimethyl fumarate (DMF) is one of these drugs which has been reported to have early promising results in recent studies, but the efficacy of this drug in patients with MS is still being studied in different parts of the world. In the present study, we evaluated the effectiveness of DMF therapy on reducing relapses, lesions, and disability in Iranian patients with MS. Methods: The present single-arm before-after study was approved by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran [Iranian Registry of Clinical Trial (IRCT) code: IRCT20190121042439N1]. Every patient who was diagnosed with relapsing MS was considered eligible to enroll in the present clinical trial. Before receiving DMF therapy, the baseline liver function tests and complete blood count were obtained from all individuals. Also, a baseline brain magnetic resonance imaging (MRI) was obtained and Expanded Disability Status Scale (EDSS) was documented from all patients. After receiving 240 mg DMF twice daily for 12 months, the laboratory and imaging measurements as well as EDSS were repeated. Furthermore, the total number of relapses within the study period was recorded. Satisfaction with DMF treatment was determined by answering a yes-no question. Results: A total number of 50 patients enrolled in the study and most of them were female (80%). There was a significant decrease in EDSS score and gadolinium (GD)-enhancing lesions after the study period (P < 0.001 for each). Moreover, the attacks significantly dropped after the study period (P < 0.001) and 86% of patients were satisfied with their treatment. Conclusion: The findings of this study showed that 240 mg DMF administered twice daily can effectively reduce disability and provide satisfaction within the first year of therapy in patients with MS.

Assessing Barriers to Adherence with the Use of Dimethyl Fumarate in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory, central nervous system demyelinating disease that requires long-term use of disease-modifying therapies (DMT). Patient adherence to DMT is key in reducing the inflammation that leads to relapses and neurodegeneration. Dimethyl fumarate (DMF) poses unique challenges to adherence including being the only twice-daily dosing DMT. Previous research suggests there are direct roles that providers play on improving their patients' adherence rates, such as focusing on the patient-provider relationship, helping put the patient at ease so that they feel understood and respected. Also, route of administration affects adherence in other chronic healthcare conditions. However, the issue of adherence to DMT in MS is more complex than just route of administration, with adverse effects being the main predictor of adherence. (1) To define various patient specific factors (e.g. fatigue and mood disorders) that affect adherence with DMF and (2) to understand how patients' perceptions of treatment satisfaction (such as effectiveness, convenience, side effects and global satisfaction) and DMFs impact on quality of life (such as social support, activities of daily living, coping) influence adherence. Our study was a prospective, observational measurement of adherence to treatment with DMF in MS patients over 52weeks. Twenty-five out of thirty-five patients enrolled completed the study. Adverse event (AE) data was reviewed on all participants. Adherence rates correlated with patient's perceived effectiveness (0.25, p < 0.023) and the level of bothersome symptoms the patient experienced (0.45, p < 0.0001). The majority of new AE onset was reported within 12weeks of DMF initiation. This is consistent with previously published data with DMF use. Adherence rates are an important factor to be considered when starting patients on DMT. DMF creates its own barriers to adherence with our study highlighting some, including twice-daily dosing and AEs experienced following treatment initiation. Healthcare providers should be aware of these barriers prior to treatment initiation and counsel patients appropriately.

Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

IntroductionPatients with multiple sclerosis may have a distinct gut microbiota profile. Delayed-release dimethyl fumarate is an orally administered drug for relapsing–remitting multiple sclerosis, which has been associated with gastrointestinal side-effects in some patients.ObjectivesThe purpose of this study was to determine if dimethyl fumarate alters the abundance and diversity of commensal gut bacteria, and if these changes are associated with gastrointestinal side-effects.MethodsThirty-six patients with relapsing–remitting multiple sclerosis received either dimethyl fumarate (n = 27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons, n = 9) for 12 weeks. Stool samples were collected at baseline, two and 12 weeks. We included 165 healthy individuals as controls.ResultsAt baseline, 16 microbial genera were altered in multiple sclerosis patients compared with healthy controls. In the dimethyl fumarate-treated patients (n = 21) we observed a trend of reduced Actinobacteria (p = 0.03, QFDR = 0.24) at two weeks, mainly driven by Bifidobacterium (p = 0.06, QFDR = 0.69). At 12 weeks, we observed an increased abundance of Firmicutes (p = 0.02, QFDR = 0.09), mostly driven by Faecalibacterium (p = 0.01, QFDR = 0.48).ConclusionsThis pilot study did not detect a major effect of dimethyl fumarate on the gut microbiota composition, but we observed a trend towards normalization of the low abundance of butyrate-producing Faecalibacterium after 12 weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.

Acute exacerbation of Hashimoto's thyroiditis in a patient treated with dimethyl fumarate for multiple sclerosis: A case report: Erratum.

Acute exacerbation of Hashimoto's thyroiditis in a patient treated with dimethyl fumarate for multiple sclerosis: A case report: Erratum.

Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis.

Dimethyl fumarate (DMF) is an oral, disease-modifying agent for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, details regarding its mode of action are still emerging. It is believed that the mode of action of DMF involves both nuclear factor erythroid-derived 2-related factor (Nrf2)-dependent and independent pathways, which lead to an anti-inflammatory immune response due to type II myeloid cell and Th2 cell differentiation and neuroprotection. In this review, we will focus on the molecular and signaling effects of DMF that lead to changes in peripheral immune cell composition and function, alteration in CNS cell-specific functions, and effect on the blood-brain barrier.

Safety and Efficacy of Dimethyl Fumarate in Multiple Sclerosis: An Italian, Multicenter, Real-World Study.

Two phase III trials have demonstrated the clinical and radiological efficacy of delayed-release dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). However, data on its safety and effectiveness in real-world practice are still limited. The aim of our study was to explore the safety and tolerability profile of DMF in RRMS. We also tried to identify individual variables associated with better clinical and radiological outcomes. We collected the clinical and magnetic resonance imaging (MRI) data of patients with RRMS who started DMF between 2012 and 2017 in seven MS clinics in central Italy. We first evaluated DMF discontinuation rates and the incidence of adverse events and side effects. We then assessed the annualized relapse rate (ARR), the number of patients with clinical relapses or disability worsening and the presence of radiological activity. Third, we investigated which baseline variables were associated with clinical and radiological outcomes. We collected data for 1089 patients with a mean on-treatment follow-up of 17 ± 8months; 331 (30.4%) of these patients were treatment naïve. In total, 210 (19.5%) patients discontinued DMF mainly because of poor tolerability (n = 103) and disease activity (n = 63), and 166 (16.5%) patients presented with lymphopenia. The ARR reduced from 0.55 to 0.13. Mean change in Expanded Disability Status Scale (EDSS) score was 0.08 ± 0.44 per year. The occurrence of clinical and/or radiological activity during follow-up was associated with younger age [hazard ratio (HR) 0.97; p < 0.001], higher EDSS score (HR 1.18; p < 0.001), greater number of Gd-enhancing lesions at baseline scan (HR 1.14; p = 0.003) and prior exposure to MS treatments (HR 1.43; p = 0.02). This post-marketing data confirms the short-term safety, tolerability and effectiveness of DMF, supporting its use as an early treatment in MS.

Dimethyl Fumarate in Multiple Sclerosis

At the end of 2016, dimethyl fumarate (DMF) was approved as the sixth disease-modifying drug for multiple sclerosis by the Pharmaceuticals and Medical Devices Agency of Japan. Two randomized, placebo-controlled, phase III studies (DEFINE and CONFIRM) showed beneficial effects in patients in Western countries, with relapsing-remitting multiple sclerosis (RRMS). Some of the benefits included a decreased annual relapse rate, inhibition of disease activity (shown using brain magnetic resonance imaging), and a decreased proportion of patients with confirmed disease progression. The APEX study, which included Japanese patients with RRMS, also showed similar results, but reported some adverse effects. Flushing and gastrointestinal events (e.g., nausea, vomiting, abdominal pain, and diarrhea) occurring within 1 month of the initiation of DMF treatment are major causes of discontinuation of the drug. The most serious adverse event is progressive multifocal leukoencephalopathy (PML), which was reported in four patients with MS treated with DMF, worldwide. Grade 3 lymphopenia (less than 500/mm³) due to apoptosis occurs in some DMF-treated patients with MS and is more prevalent among older patients. A reduction in CD8⁺ T cells is more pronounced than that in CD4⁺ T cells. Patients with grade 3 lymphopenia, aged more than 50 years, are at a risk for PML development. Further studies are needed to determine the appropriate final dose and an acceptable dose-escalation method for DMF treatment, to prevent or decrease adverse effects in Japanese patients with MS.

Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case–control study protocol for dimethyl fumarate-induced lymphopenia

IntroductionAdverse drug reactions (ADRs) are a global public health issue. The potential for pharmacogenomic biomarkers has been demonstrated in several therapeutical areas, including HIV infection and oncology. Dimethyl fumarate (DMF)...

Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study

Background: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit–risk profile for patients with relapsing–remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. Objective: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). Methods: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. Results: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1–5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. Conclusion: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.

Dimethyl fumarate in multiple sclerosis: latest developments, evidence and place in therapy

Dimethyl fumarate (DMF) is one of the newer additions to the armamentarium of potent immunomodulators for the treatment of relapsing-remitting multiple sclerosis (RRMS). After more than 2 years of real-world experience and more than 190,000 patients currently treated with DMF worldwide, it is a good timepoint to review the experience gathered so far and to re-evaluate the potential of this first-line oral multiple sclerosis (MS) drug. Post-hoc analyses of clinical and magnetic resonance imaging (MRI) data, some comprising more than 6 years of drug exposure including patients from the clinical trials, and the overall notion in clinical practice widely confirm the good efficacy of DMF in RRMS. Despite an overall good safety profile, it became also clear that the necessary clinical vigilance while using DMF may not be neglected. So far, four reported cases of progressive multifocal leukoencephalopathy (PML), a towering shadow over many MS therapies, warrant proper attention in newly-updated risk management plans. This review recapitulates efficacy and safety aspects of DMF therapy in relation to reported data from the pivotal clinical trials. In addition, we summarize recent insights into DMF mechanisms of action drawn from the field of basic research which may have important implications for clinical practice.

Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study.

Dimethyl fumarate (DMF) was recently approved for treating patients with relapsing-remitting multiple sclerosis (RRMS) based on two phase III clinical trials demonstrating its efficacy. This prompts the need for demonstrating the clinical efficacy and safety of DMF in the real world. By retrospective analysis of medical records at two German MS centers, 644 MS patients treated with DMF were identified. All were included in a safety analysis, and a subgroup of patients with available efficacy data during previous MS therapies (n=352) was further analyzed for annualized relapse rate and disability progression assessed by the EDSS. In the overall DMF population studied, the annualized relapse rate decreased from 0.52 at baseline to 0.35, and the annualized disability progression from 0.15 to 0.10. Patients who were switched from interferons or glatiramer acetate to DMF revealed a greater benefit, whereas patients pretreated with more potent immunotherapies did not respond that well. Interestingly, patients with a lymphocyte count ≥2000/µl after 0.52years (mean, SD 0.2) of DMF treatment did not benefit compared to those with lower lymphocyte counts. In total, 22.2% of the patients withdrew from DMF due to side effects, with gastrointestinal discomfort (12.7%) and lymphopenia (5.3%) as most frequently reported reasons. Our study corroborates that DMF is an overall safe and effective drug that reduces relapse rate as well as disability progression in MS patients. Further prospective studies are warranted to establish the additional parameters predicting DMF response, especially in patients switching from other first-line immunotherapies.

Treatment Satisfaction and Side Effect Experience with Fingolimod and Dimethyl Fumarate for Multiple Sclerosis: Findings from an Online Patient Cohort (P3.119)

Treatment Satisfaction and Side Effect Experience with Fingolimod and Dimethyl Fumarate for Multiple Sclerosis: Findings from an Online Patient Cohort (P3.119)