Lymphopenia and DMTs for relapsing forms of MS

Fox, Edward J.; Buckle, Guy J.; B, Singer; Singh, Vibhuti; Boster, Aaron

doi:10.1212/cpj.0000000000000567

Cited by 35 publications

(24 citation statements)

References 67 publications

(77 reference statements)

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“…The treatments available for MS are all variants of immunomodulatory therapies, most of which produce their primary effect via induction of lymphopaenia or a shift to a more TH2-driven phenotype [155]. Many of them are also used in cancer therapy and common side effects include an increased incidence of opportunistic infections or reactivation of latent infections.…”

Section: Antiviral Effects Of Ms Treatmentmentioning

confidence: 99%

“…Interestingly, the first drug successfully used in MS is IFNβ, which is also one of the principal antiviral cytokines produced by virus-infected fibroblasts [156]. It may seem a counterintuitive use of an antiviral cytokine to treat an inflammatory disorder but the feedback loops induced by IFNβ inhibit many T cell functions [155].…”

Section: Antiviral Effects Of Ms Treatmentmentioning

confidence: 99%

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Role of Viruses in the Pathogenesis of Multiple Sclerosis

Tarlinton

Martynova

Rizvanov

et al. 2020

Viruses

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Multiple sclerosis (MS) is an immune inflammatory disease, where the underlying etiological cause remains elusive. Multiple triggering factors have been suggested, including environmental, genetic and gender components. However, underlying infectious triggers to the disease are also suspected. There is an increasing abundance of evidence supporting a viral etiology to MS, including the efficacy of interferon therapy and over-detection of viral antibodies and nucleic acids when compared with healthy patients. Several viruses have been proposed as potential triggering agents, including Epstein–Barr virus, human herpesvirus 6, varicella–zoster virus, cytomegalovirus, John Cunningham virus and human endogenous retroviruses. These viruses are all near ubiquitous and have a high prevalence in adult populations (or in the case of the retroviruses are actually part of the genome). They can establish lifelong infections with periods of reactivation, which may be linked to the relapsing nature of MS. In this review, the evidence for a role for viral infection in MS will be discussed with an emphasis on immune system activation related to MS disease pathogenesis.

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Section: Antiviral Effects Of Ms Treatmentmentioning

confidence: 99%

Section: Antiviral Effects Of Ms Treatmentmentioning

confidence: 99%

Role of Viruses in the Pathogenesis of Multiple Sclerosis

Tarlinton

Martynova

Rizvanov

et al. 2020

Viruses

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“…T-cell monitoring: During alemtuzumab treatment, absolute lymphocyte counts (ALC) decreases rapidly after the first infusion. B cells return to pre-treatment levels within 3 to 8 months, CD8 + T within 30 months, whereas CD4 + T cell can require 2 to 3 years to normalize [ 236 , 237 , 238 , 239 , 240 ]. This lymphocytes reconstitution process is the primary mechanism of treatment effect but is also associated with long-term safety [ 241 ].…”

Section: Monitoring Of Adverse Eventsmentioning

confidence: 99%

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis

et al. 2020

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In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.

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“…Every treatment used to modify the evolutionary course of MS affects adaptive immunity, that is, B and T lymphocytes, among others. Specifically, teriflunomide (TERI) inhibits the production of T and B cells, resulting in a 15% decrease in the white blood cell count (especially lymphocytes and neutrophils), which usually occurs in the third month of treatment but subsequently remains stable [4,5]. Dimethyl fumarate (DMF) reduces the percentage of T cells and of every B cell population type present in peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

“…Dimethyl fumarate (DMF) reduces the percentage of T cells and of every B cell population type present in peripheral blood. Regarding the effects of DMF on T lymphocytes, it disproportionately decreases CD8+ lymphocytes compared to CD4+ lymphocytes, which translates into an increase in the CD4/CD8 ratio [4,5].…”

Section: Introductionmentioning

confidence: 99%

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

García-Estévez¹

2020

NeuroSci

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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.

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Lymphopenia and DMTs for relapsing forms of MS

Cited by 35 publications

References 67 publications

Role of Viruses in the Pathogenesis of Multiple Sclerosis

Role of Viruses in the Pathogenesis of Multiple Sclerosis

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis

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

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