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Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis.

BACKGROUND: Strategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation. OBJECTIVE: To provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patients. METHODS: We reanalyzed data from a retrospective, real-world cohort of MS patients to model disease activity for oral (dimethyl fumarate and fingolimod) and higher efficacy infusible (natalizumab and rituximab) DMTs by age. For patients with relapsing MS, we conducted a controlled, stratified a…

Economic evaluation of cladribine tablets in high disease activity (HDA) relapsing multiple sclerosis (RMS) patients in Lebanon.

BACKGROUND: Cladribine tablets are a newly launched short course oral treatment approved for high disease activity (HDA) relapsing multiple … were alemtuzumab, fingolimod, and natalizumab while budget impact analysis additionally considered dimethyl fumarate. A sensitivity analysis was also performed to assess the uncertainty in the analysis. RESULTS: The cost-utility results showed that cladribine tablets are an economically dominant therapeutic strategy (i.e., less costly and better quality-adjusted …

The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review.

In this narrative review, we analyze pre-registration and post-marketing data concerning hepatotoxicity of all disease-modifying therapies (DMTs) available for the treatment of relapsing-remitting multiple sclerosis, including beta interferon, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, cladribine, natalizumab, alemtuzumab, and ocrelizumab. We review the proposed causal mechanisms described in the literature and we also address issues like use of DMTs in patients with viral hepatitis or liver cirrhosis. Most data emerged in the post-marketing phase by reports to national …

Treatment patterns and comorbid burden of patients newly diagnosed with multiple sclerosis in the United States.

BackgroundThe treatment landscape for multiple sclerosis (MS) is quickly evolving. Understanding real-world treatment patterns of patients i … se of more than one DMT concomitantly occurred in just 1.8% of all treated patients. Glatiramer and dimethyl fumarate were by far the most common first-line treatments received accounting for nearly 62% of patients receiving a DMT.ConclusionApproximately two-thirds of patients newly diagnosed with MS did not receive a DMT and the disease is accompanied by a signifi …

Kappa Free Light Chains Reflect Treatment Response and Progression Independent of Focal Inflammation in Multiple Sclerosis.

BACKGROUND: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) is a sensitive marker of intrathecal immunoglobulin synthesis and is in … den). Paired CSF and serum samples were collected at baseline and after 12 months of treatment with dimethyl fumarate (DMF) or natalizumab (NTZ). KFLC index was calculated as [(CSF KFLC/serum KFLC)/(CSF albumin/serum albumin)]. Treatment response was assessed using no evidence of disease activity-3 (NEDA-3) and progression independent of relapse and MRI activity (P …

Субрегиональная атрофия мозга в релапирующих и излучающих множественных склерозах: фазовая динамика и фармакологическая модуляция.

Атрофия головного мозга все чаще признается в качестве важной патологической особенности множественного склероза (MS). Вместе с тем конкретные модели на различных этапах и их изменение с помощью методов коррекции заболеваний (ДМТ) не вполне понятны. ЦЕЛЬ: Данное исследование было направлено на изучение в зависимости от стадии церебрального субрегионального изменения объема выбросов MS (RRMS) и оценку воздействия различных классов DMT на атрофию мозжечного мозга и клинические результаты. В ходе этого исследования было принято на работу 181 пациент, имеющий RRMS, и 99 здоровых больных. Пациенты

Совпадение в аннотации оригинала
BACKGROUND: Cerebellar atrophy is increasingly recognized as an important pathological feature of multiple sclerosis (MS). However, the spec … o untreated, sphingosine-1-phosphate (S1P)_T (siponimod, fingolimod, and ozanimod) and not_S1P_DMT (dimethyl fumarate and teriflunomide). Cerebellar subregional volumes were quantified using the deep learning-based tool, CerebNet. Group comparisons were conducted, and interaction effects were examined. The correlations between the cerebellar subregions and cognitio …

Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy.

Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)assays, caspase activation, flowcyt

NF-κB Is a Potential Therapeutic Target for Histone Deacetylase Inhibitor-Resistant Cutaneous T-Cell Lymphoma.

Histone deacetylase inhibitors, such as vorinostat, show promise as treatment for T-cell lymphomas including cutaneous T-cell lymphoma. Howe … nt cell lines displayed heightened sensitivity to inhibition of the NF-κB pathway by bortezomib and dimethyl fumarate. These findings implicate aberrant NF-κB activation as a central driver of the emergence of histone deacetylase inhibitor resistance in cutaneous T-cell lymphoma. Ultimately, our results provide a strong rationale for exploring NF-κB inhibition as a …

Immunological changes following electroconvulsive therapy in multiple sclerosis.

INTRODUCTION: Electroconvulsive therapy (ECT) is a well-established treatment option in case of treatment-resistant depression (TRD). Only a few cases of ECT in depressed patients with multiple sclerosis (MS) were reported so far suggesting efficacy for the treatment of severe depression in MS, while data on possible neurological deterioration remained unclear. METHODS: In this case study we report on a case of a middle-aged man with MS. He was on dimethyl fumarate for relapse prevention since 2019 and without signs of active disease in a recent cerebral MRI. He suffered from treatment-resist…

Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall-King Hypothesis.

Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, jo … hritis should consider antifungals which are effective in psoriasis and multiple sclerosis, such as dimethyl fumarate and nystatin.

Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders.

OBJECTIVE: This article provides an overview of infections, their association with specific immunotherapies, preventive strategies, diagnost … ith similar infections; however, experience with them is also limited. Similarly, teriflunomide and dimethyl fumarate, previously considered relatively low risk, have now been associated with several infections. Evolving insights into vaccine responses in patients on immunotherapies have also helped inform discussions about their safety and utility. For example, al …

Варианты лечения соединения множественного склероза с другими хроническими воспламенительными заболеваниями.

В Германии около 280 000 человек страдают множественным склерозом (МС), аутоиммунным заболеванием центральной нервной системы. Из них около 5% страдают коморной хронической воспламенительной болезнью: наиболее распространенными из них являются псориаз, ревматоидный артрит (RA) и хронические подстрекательские кишечные заболевания (IDBs, основными видами которых являются язвительный колит и болезнь Крона). МЕТОДЫ: Настоящий описательный обзор основан на соответствующих публикациях, полученных в результате поиска литературы в Пубмеде, а также на соответствующих руководящих принципах. Все заявлени

Совпадение в аннотации оригинала
BACKGROUND: Approximately 280 000 people in Germany suffer from multiple sclerosis (MS), an autoimmune disease of the central nervous system … not be used in patients with MS, as they can worsen the disease. In patients with MS and psoriasis, dimethyl fumarate is a useful option for mild disease activity. In MS with comorbid RA, azathioprine and leflunomide/teriflunomide are suitable for mild disease activity. For more severe disease activity, anti-CD20 antibodies have been approved for both diseases and …

Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study.

BACKGROUND: The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs. METHODS: A multicentre dataset of 1200 patients who started three oral DMTs (fingolimod, teriflunomide and dimethyl fumarate) was collected within the MAGNIMS network. Disease activity after the first year was classified by the 'MAGNIMS' score based…

Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.

The nuclear factor erythroid derived 2-related factor 2 (Nrf2) and the antioxidant protein heme oxygenase-1 (HO-1) are crucial components of … 1 at the concentrations tested (5-20 μM) with carnosol, supercurcumin, cobalt protoporphyrin-IX and dimethyl fumarate exhibiting the best induction/low cytotoxicity profile. Up-regulation of HO-1 by some compounds resulted in increased cellular bilirubin levels but did not augment the expression of proteins involved in heme synthesis (ALAS 1) or biliverdin reductas …

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies.

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of se … OVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. CONCLUSIONS: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced …

β-Amyloid and glutathione dysregulation cooperatively drive lipid peroxidation and ferroptosis in neuron-like cells.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) accumulation and oxidative stress, with … ant were subjected to GSH depletion using complementary pharmacological (buthionine sulfoximine and dimethyl fumarate) and genetic (GCLC knockout) approaches. GSH depletion markedly sensitized APPSwe/Ind-expressing cells to ferroptotic cell death, characterized by increased lipid peroxidation, elevated malondialdehyde and 4-hydroxynonenal levels, enhanced lactate d …

Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments: A Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: JC virus (JCV) reactivation causing progressive multifocal leukoencephalopathy (PML) is a complication in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs). Although natalizumab (NTZ) is most frequently involved, PML also occurs less commonly with sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab. This study aimed to identify factors predicting worse outcomes, focusing on the influence of PML-immune reconstitution inflammatory syndrome (PML-IRIS), plasma exchange (PlEx), corticosteroids,…

Comparative effectiveness of disease-modifying therapies for highly active relapsing-remitting multiple sclerosis despite previous treatment - a systematic review and network meta-analysis.

BACKGROUND: Comparative assessments of all available disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting multiple sclerosis (RRMS) are lacking, even though some of these DMTs are restricted to this MS subpopulation. We therefore aimed to compare DMTs in patients with highly active RRMS using re-analyses of individual patient data (IPD) provided by study sponsors. METHODS: We searched for randomised controlled trials (RCTs) that included adult patients with RRMS and directly compared alemtuzumab, cladribine, dimethyl fumarate, fingolimod, natalizumab, ocrelizu…

Characterizing post-COVID-19 syndrome in multiple sclerosis: Vaccine status, infection burden, and therapy categories as predictors.

BACKGROUND: Post-COVID-19 syndrome (PCS) is a significant long-term complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co … : 71.4 % (5/7) of affected individuals were on category I therapies (Interferon/Glatiramer acetate, Dimethyl fumarate, Teriflunomide) compared to 17 % of pwMS without PCS (p < 0.001). No significant effect was observed for COVID-19 severity or vaccination status. CONCLUSIONS: PCS prevalence in this MS cohort was lower than in the general population, but category I …