Clinical and Serological Biomarkers of Treatment’s Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade

Bărcuțean, Laura; Romaniuc, Anatole; Maier, Smaranda; Bajko, Zoltan; Moţăţăianu, Anca; Adina, Hutanu; Simu, Iunius; Andone, Sebastian; Bălaşa, Rodica

doi:10.2174/1871527317666180917095256

Cited by 16 publications

(8 citation statements)

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“…This suggests that the nature of immune system repopulation is more important than the number of lymphocytes itself, in particular T and B cell subsets [ 37 ]. Several studies, especially phase II and III trials, have addressed how repopulation of CD4 + , CD8 + T and CD19 + B cells occurred in alemtuzumab treated MS patients [ 38 , 39 ], but only a few focused on the evaluation of their subsets and cytokines produced as their level has been shown to be related to therapy response [ 40 , 41 , 42 , 43 , 44 , 45 ], thus contributing to clarifying the long-lasting efficacy of alemtuzumab. Here we will review the current knowledge on immune reconstitution after alemtuzumab analyzing together the various studies and trying to outline a common mechanism (summarized in Table 1 ).…”

Section: Immune System Reconstitution After Alemtuzumab Treatmentmentioning

confidence: 99%

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Rolla

Maglione

Mercanti

et al. 2020

Cells

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Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing–remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period. After the robust T and B cell depletion induced by alemtuzumab, the immune system undergoes radical changes during its reconstitution. In this review, we will discuss the current knowledge on the reconstitution of the lymphocyte repertoire after alemtuzumab treatment and how it could affect the development of side effects, which led to its temporary suspension by the European Medical Agency.

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Section: Immune System Reconstitution After Alemtuzumab Treatmentmentioning

confidence: 99%

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Rolla

Maglione

Mercanti

et al. 2020

Cells

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“…It also blocks the class II major histocompatibility complex (MHC) and reduces the subsequent expression of the antigen presentation, blocking the activity of the adhesion molecules, reducing thus the inflammation in the CNS [17]. At a umoral level, the agents act upon reduction of the pro-inflammatory cytokines and augment the expression of anti-inflammatory agents [18].…”

Section: Discussionmentioning

confidence: 99%

Interferon Beta-1b for the Treatment of Multiple Sclerosis – More than 10 Years of Experience

Bărcuțean

Maier

Bajkó

et al. 2019

Acta Medica Marisiensis

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Objective: Interferon beta-1b (IFNβ-1b) was the first disease-modifying agent (DMT) used for the treatment of multiple sclerosis (MS). We aimed to evaluate the first patients with MS that started treatment in our clinic.Methods: An observational, retrospective study was performed on 78 patients that had continuous treatment with IFNβ-1b for more than 10 years. The collection of the demographical data and periodical clinical evaluation was performed on all patients. The disability was quantified using the Expanded Disability Status Scale (EDSS), creating two groups of patients, G1: EDSS < 4.0 and G2: EDSS ≥ 4.0. The hallmarks of the disability evolution were gathered by direct patient interview, such as the symptoms at onset and relapse frequency.Results: After more than 17 years of disease evolution, more than half (65.38%) of the patients present a mild disability score. The majority (54.90%) started treatment in the first three years after the onset, while the patients in G2 started treatment after more than 3 years from the onset. The initiation of IFNβ-1b lead to a significant reduction of the relapse rates. A reduced number of patients (<25%) transitioned from RRMS to SPMS.Discussion: Continuous evaluation of MS patients allows us to assess the possibility of prolonged treatment with IFNβ-1b and to differentiate the responders from non-responders. The clear reduction in relapse rates and disability progression, notably in patients that started treatment early ensure us into continuing administering this medication. Compared to historical cohorts, our lot had a slower disability evolution and a significant proportion hadn’t reach an important disability score.

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“…Interferon-beta (IFN-β) therapy has been used for RRMS treatment for almost three decades (since 1993). IFN-β was the first DMT approved; its main effect was the immunomodulation of the peripheral proinflammatory cells and the resultant downregulation of the inflammatory cytokines [66,67]. There are two types of IFN-β: IFN-β-1a and IFN-β-1b used in RRMS, with the latter having been approved for secondary progressive MS [68].…”

Section: Chronic Ms Dmts With Central Effect Beyond the Bbbmentioning

confidence: 99%

Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

Bălaşa

Barcutean

Mosora

et al. 2021

IJMS

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The disruption of blood–brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained ‘inside-out’ demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB’s endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS might be produced per se by the NVU malfunction or secondary to mitochondria dysfunction. We present three different but related terms that denominate the ongoing neurodegenerative process in progressive forms of MS that are indirectly related to BBB disruption: progression independent of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effective in treating MS. Detailed mechanisms of action of these DMTs are described and also illustrated in dedicated images. With increasing knowledge about the involvement of BBB in MS pathology, BBB might become a therapeutic target in MS not only to make it impenetrable against activated immune cells but also to allow molecules that have a neuroprotective effect in reaching the cell target inside the CNS.

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Clinical and Serological Biomarkers of Treatment’s Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade

Cited by 16 publications

References 0 publications

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Interferon Beta-1b for the Treatment of Multiple Sclerosis – More than 10 Years of Experience

Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

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