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The effects of dimethyl fumarate and fingolimod on T-cell lymphocyte proliferation in patients with multiple sclerosis.

OBJECTIVE: The disease-modifying therapies (DMT), dimethyl fumarate (DMF) and fingolimod (FTY) improve the outcomes in multiple sclerosis (MS) by reducing relapses and numbers and volume of lesions. They mediate their effects through reduction of immune reactivation, which may potentially lead to lymphopaenia and increased risk of infections. Previous studies have examined the effects of these therapies on lymphocyte subsets; however, the in vivo effects on circulating lymphocyte proliferation require further elucidation. The aim of this study was to determine the effects of DMF and FTY on T-c…

The Role of Glutathione-S Transferase in Psoriasis and Associated Comorbidities and the Effect of Dimethyl Fumarate in This Pathway.

Psoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated scaly plaques. Oxidative stress plays a crucial role in the psoriasis pathogenesis and is associated with the disease severity. Dimethyl fumarate modulates the activity of the pro-inflammatory transcription factors. This is responsible for the downregulation of inflammatory cytokines and an overall shift from a pro-inflammatory to an anti-inflammatory/regulatory response. Both steps are necessary for the amelioration of psoriatic inflammation, although additional mechanisms have been proposed. Several st…

Comparison of Dimethyl Fumarate vs Fingolimod and Rituximab vs Natalizumab for Treatment of Multiple Sclerosis.

ImportanceAs disease-modifying treatment options for multiple sclerosis increase, comparisons of the options based on real-world evidence may guide clinical decision-making.ObjectiveTo compare the relapse outcomes between 2 pairs of disease-modifying treatments: dimethyl fumarate vs fingolimod and natalizumab vs rituximab.Design, setting, and participantsThis comparative effectiveness study integrated data from a clinic-based multiple sclerosis research registry and its linked electronic health records (EHR) system between January 1, 2006, and December 31, 2016, and built treatment groups for …

Interim Analysis of Pregnancy Outcomes After Exposure to Dimethyl Fumarate in a Prospective International Registry.

BACKGROUND AND OBJECTIVES: Oral delayed-release dimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies the potential fetal risk. Although DMF was well tolerated in clinical trials with consistent safety results in postmarketing surveillance, data are limited in pregnant women. The objective was to provide pregnancy outcomes and DMF exposure information from an interim analysis from a prospective, international registry (TecGistry; NCT01911767). METHODS: Women exposed to DMF from the first day of their last menstrual period before…

Combination treatment with secukinumab and dimethyl fumarate in a patient with psoriasis and recent diagnosis of multiple sclerosis.

The therapeutic approach to patients with psoriasis and concomitant multiple sclerosis is challenging. We report the clinical case of a 44-year-old man affected by psoriasis and psoriatic arthritis treated with secukinumab for 2 years, who received also dimethyl fumarate because of a recent diagnosis of relapsing remitting multiple sclerosis. Moreover, a mini-review of the available literature regarding the use of secukinumab in patients with psoriasis or ankylosing spondylitis and coexisting central nervous system demyelinating diseases was performed. To the best of our knowledge, this is the…

Risk factors for lymphopenia in patients with relapsing-remitting multiple sclerosis treated with dimethyl fumarate.

OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and characterize its impact on T lymphocyte subsets in MS patients. METHODS: We performed a retrospective analysis of 194 RRMS patients treated with DMF at the Beth Israel Deaconess Medical Center (BIDMC) over a median of 17 months. We reviewed demographics, ethnic background, prior medication history, complete blood counts and T lymphocyte subsets. Possible lymphopenia risk factors examined included age, prior natalizumab exposure, vitamin D levels, and concomitant exposure to carbamazepine, opiates, tobacco, or steroids. Lymph

[Dimethyl fumarate (tecfidera) is the first line treatment choice in patients with remitting multiple sclerosis].

Dimethyl fumarate (DMF) is a new oral option for disease-modifying therapy (DMT) in patients with remitting multiple sclerosis as a first line treatment. The results of international randomized studies comparing DMF with placebo and other DMTs are presented. DMF is a DMT with promised efficacy and favorable safety profile that could be a treatment option for patients with suboptimal response for other first line DMTs and used as initial therapy for treatment-naive patients with unfavorable prognostic factors.

Utilization of Dimethyl Fumarate and Related Molecules for Treatment of Multiple Sclerosis, Cancer, and Other Diseases.

Several drugs have been approved for treatment of multiple sclerosis (MS). Dimethyl fumarate (DMF) is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF), a related compound, has not been examined in greater details although it has the potential as a therapeutic drug for MS and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species. However, other mechanisms have also been descri…

FDA-approved dimethyl fumarate targets thioredoxin reductase to induce apoptosis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by poor prognosis, which is closely linked to significant tumor heterogeneity and the absence of effective targeted treatments beyond conventional chemotherapy, thereby necessitating the discovery of novel therapeutic options. Altered thioredoxin reductase (TrxR) activity is tightly associated with tumorigenesis and cancer progression, positioning TrxR as a promising target for anticancer intervention. Dimethyl fumarate (DMF), an FDA-approved drug for treatment of psoriasis and multiple sclerosis, has also demonstrated direct antitumor acti…

Dimethyl Fumarate Ameliorates Collagen-Induced Arthritis in Lewis Rats by Modulation of Th17/Treg Balance.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects approximately 1% of the world's population. Due to its anti-inflammatory effects, Dimethyl fumarate (DMF) can be used to treat RA. However, its molecular mechanisms have not yet been fully elucidated. In this study, an animal model of collagen-induced arthritis (CIA) was used to investigate DMF's In Vivo effects and probable mechanism of action on arthritis. Twenty-five rats were divided into five groups: healthy control group (normal), CIA rats without any treatment (CIA control), CIA rats treated with vehicle…

ДиметилФумарат Аттенуаты циклофосфамидозные повреждения мочевого пузыря и усиление цитотоксичной активности против клеток SH-SY5Y.

Острый кистит, вызванный циститом цилофосфамида (КХ), является изнурительной дисфункцией мочевого пузыря, которая, как правило, наблюдается у больных раком, главным образом в результате окислительных повреждений и воспаления тканей мочевого пузыря. Диметилфумарат (DMF) — эстер фумарной кислоты, утвержденный для лечения множественных склерозов в силу его антиоксидантов и противовоспалительных свойств. Таким образом, мы намеревались изучить многообразное воздействие ДМФ, включая как его потенциальное синергетическое воздействие с ХП на клетки SH-SY5Y, так и его незащищенное воздействие на острый

Совпадение в аннотации оригинала
Cylophosphamide (CP)-induced acute cystitis is a debilitating bladder dysfunction commonly observed in cancer patients, primarily resulting from oxidative damage and inflammation in the bladder tissue. Dimethyl fumarate (DMF) is a fumaric acid ester approved for the treatment of multiple sclerosis due to its antioxidant and anti-inflammatory properties. Thus…

Dimethyl Fumarate Reduces Methylglyoxal-derived Carbonyl Stress Through Nrf2/GSH Activation in SH-SY5Y Cells.

Carbonyl stress refers to the excessive accumulation of advanced glycation end products (AGEs) in mammalian tissues. This phenomenon plays a significant role in the pathogenesis of various diseases, including diabetes, chronic renal failure, arteriosclerosis, and central nervous system (CNS) disorders. We have previously demonstrated that an increase in glutathione concentration, dependent on the nuclear factor erythroid 2-related factor 2 (Nrf2) system, provides a potent cytoprotective effect against Methylglyoxal (MGO)-induced carbonyl stress. Meanwhile, dimethyl fumarate (DMF), known for it…

Dimethyl Fumarate Ameliorated Cardiorenal Anemia Syndrome and Improved Overall Survival in Dahl/Salt-Sensitive Rats.

Cardiovascular disease, chronic kidney disease, and anemia are known to adversely affect each other. Inflammation is commonly involved in these diseases. Cardiorenal anemia syndrome (CRAS) is the name given to this mutually harmful condition. Dimethyl fumarate (DMF) is a Food and Drug Administration-approved antioxidant and anti-inflammatory agent. The purpose of this study was to investigate the effects of DMF on Dahl/salt-sensitive (DS) rats as a CRAS model. Six-week-old DS rats were divided into three groups: the control group, the high-salt (HS) group, and the HS+DMF group. The HS and HS+D…

Neuroprotective Properties of Dimethyl Fumarate Measured by Optical Coherence Tomography in Non-inflammatory Animal Models.

While great advances have been made in the immunomodulatory treatment of multiple sclerosis (MS), there is still an unmet need for drugs with neuroprotective potential. Dimethyl fumarate (DMF) has been suggested to exert both immunomodulatory and neuroprotective effects in MS. To investigate if DMF has neuroprotective effects independent of immunomodulation we evaluated its effects in the non-inflammatory animal models of light-induced photoreceptor loss and optic nerve crush. This might also reveal applications for DMF besides MS, such as age related macular degeneration. Retinal neurodegener…

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

BACKGROUND: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. OBJECTIVE: 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. METHODS: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, swi…

Прогрессивная многофукальная лейкоэнцефалопатия на диметилфумарате с сохраняющимся количеством лимфоцитов, но глубоким истощением Т-клеток.

: Прогрессивная многофукальная лейкоэнцефалопатия (ПМЛ) у многочисленных склерозов (МС) пациентов, получающих диметилфумарат (ДМФ), связана с иатрогенной лимфопенией, преобладающей на CD8+T-клетках. ЦЕЛИ И МЕТОДЫ: Мы сообщаем о необычайном случае ДМВ в 66-летнем пациенте MS с сохраненным количеством лимфоцитов (nadir: 810/мм3) и нормальным количеством CD8+T-клеток. Результаты: Было обнаружено массированное перевыражение ингибиторного рецептора Программируемой Клеточной Смерти 1 (PD-1) на CD8+ и эффектом памяти Т-клеток вместе с поврежденным антиJC вирусом (JCV) специфической реакцией Т-клеток,

Совпадение в аннотации оригинала
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) among multiple sclerosis (MS) patients receiving dimethyl fumarate (DMF) is associated with iatrogenic lymphopenia, predominating on CD8+ T-cells. OBJECTIVES AND METHODS: We report an unusual case of DMF-related PML in a 66-year-old MS patient with preserved lymphocyte count (nadir: 810/mm3) and n…

Диметил Фумарат смягчает синовиальное воспаление, уменьшает нозицепцию и препятствует развитию посттравматического остеоартрита.

В настоящее время не существует лечения посттравматического остеоартрита (ПТОА) или лечения от болезней. Цель этого исследования заключается в оценке эффективности диметилфумарата (ДМФ), который является утвержденным в США лекарством против множественных склерозов в качестве средства лечения ПТОА. PTOA была вызвана крысами-мужчинами из Льюиса медиальной менезальной трансекции (MMT), а DMF был введён в действие один раз, через неделю после операции. Прогресс PTOA оценивался с помощью гистологического, молекулярного и радиографического анализа, в то время как вторичная аллодиния измерялась в про

Совпадение в аннотации оригинала
There is currently no cure or disease-modifying treatment for post-traumatic osteoarthritis (PTOA). This study aims to assess the efficacy of dimethyl fumarate (DMF), a US-FDA approved drug for multiple sclerosis, as a treatment for PTOA. PTOA was induced in male Lewis rats by medial meniscal transection (MMT) surgery, and DMF was intra-articularly administe…

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis.

Background: Pediatric multiple sclerosis (MS) is rare: only 1.5-5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS. Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13-17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DM…

A case of progressive multifocal leukoencephalopathy under dimethyl fumarate treatment without severe lymphopenia or immunosenescence.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is the main safety concern for dimethyl fumarate (DMF) treatment in persons with multiple sclerosis (pwMS). Risk stratification under DMF is currently based on age above 50 years and prolonged lymphopenia below 500 cells/μL. OBJECTIVE: To report a case of PML under DMF without severe lymphopenia or immunosenescence. METHODS: Case report. RESULTS: A 39-year-old female pwMS developed DMF-associated oligosymptomatic PML. The patient had not experienced any repeated lymphocyte counts below 800 cells/μL and was 15 years younger than pr…

Catastrophic relapses following initiation of dimethyl fumarate in two patients with neuromyelitis optica spectrum disorder.

We report two cases of neuromyelitis optica spectrum disorder (NMOSD) who were misdiagnosed as multiple sclerosis (MS) and developed catastrophic relapses following initiation of dimethyl fumarate. Both patients developed a severe myelitis extending from the cervical cord to the medulla with significant cord swelling, resulting in complete quadriplegia and respiratory difficulties, in addition to severe bilateral visual loss in one patient. It is of note that both catastrophic relapses occurred 2 and 3 months following initiation of dimethyl fumarate.