scholarly journals Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab

2021 ◽  
Vol 11 (12) ◽  
pp. 1347
Author(s):  
Júlia Granell-Geli ◽  
Cristina Izquierdo-Gracia ◽  
Ares Sellés-Rius ◽  
Aina Teniente-Serra ◽  
Silvia Presas-Rodríguez ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Serum Levels ◽  
Therapeutic Window ◽  
Dosing Regimen ◽  
Dosing Schedule ◽  
Blood Samples ◽  
Standard Interval ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Relapsing Remitting Multiple Sclerosis

Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4wks or extended interval dose (EID) of 300 mg/6wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual’s dosing schedule.

scholarly journals Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients

2017 ◽  
Vol 24 (11) ◽  
pp. 1453-1460 ◽  
Author(s):  
Cyra E Leurs ◽  
Zoé LE van Kempen ◽  
Iris Dekker ◽  
Lisanne J Balk ◽  
Mike P Wattjes ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lymphocyte Count ◽  
Odds Ratio ◽  
Jc Virus ◽  
Observational Cohort Study ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Observational Cohort ◽  
Carry Over ◽  
Relapsing Remitting Multiple Sclerosis

Background: Natalizumab is an effective treatment in relapsing-remitting multiple sclerosis (MS). Mainly because of the risk of progressive multifocal leukoencephalopathy (PML), a substantial proportion of John Cunningham (JC) virus–positive patients switch to fingolimod. Previous reports show a clear benefit when the duration of a washout (WO) period of natalizumab is 0–3 months in comparison to longer WO periods. However, there is no consensus regarding the optimal duration of a WO period under 3 months. Objective: We compared MS disease activity after different WO periods. In addition, we investigated several factors that possibly influence recurrence of disease activity, including serum natalizumab concentration and lymphocyte counts. Methods: From a prospective observational cohort study of natalizumab-treated patients, we selected 52 patients who switched to fingolimod. We divided the patients in three groups (<6 weeks, 6–8 weeks, >8 weeks WO). Serum natalizumab concentration and lymphocyte count were assessed during and after natalizumab treatment. Results: Patients with a WO period of >8 weeks had a significant higher recurrence of disease activity (odds ratio, 6.8; 95% confidence interval, 1.4–32.8) compared to patients with a WO period of <6 weeks. Serum natalizumab concentration and lymphocyte count did not predict recurrence of disease activity. Interpretation: A short WO period decreases the risk of recurrence of disease activity. The possible impact of a short WO period on the risk of carry-over PML in JC virus–positive patients remains uncertain.

Natalizumab Treatment for Relapsing-Remitting Multiple Sclerosis

2018 ◽  
Vol 41 (6) ◽  
pp. 199-201 ◽  
Author(s):  
Hussein Algahtani ◽  
Bader Shirah ◽  
Hind Abobaker ◽  
Nebras Alghanaim ◽  
Fatemah Kamel
Keyword(s):  
Multiple Sclerosis ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Natalizumab restores evoked potential abnormalities in patients with relapsing–remitting multiple sclerosis

2010 ◽  
Vol 17 (2) ◽  
pp. 198-203 ◽  
Author(s):  
Sven G Meuth ◽  
Stefan Bittner ◽  
Carola Seiler ◽  
Kerstin Göbel ◽  
Heinz Wiendl
Keyword(s):  
Multiple Sclerosis ◽  
Evoked Potentials ◽  
Motor Evoked Potentials ◽  
Sum Score ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Remitting Multiple Sclerosis ◽  
Sum Scores ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background and Objective: The objective of this study was to examine the effects of natalizumab on functional parameters assessed by evoked potentials (visual [VEP], somatosensory [SEP] and motor evoked potentials [MEP]) in a cohort study in relapsing–remitting multiple sclerosis patients. Methods: EP data of 44 patients examined 12 months prior to natalizumab treatment, at the timepoint of treatment initiation and 1 year later were compared. Sum scores (VEP, MEP, SEP) were evaluated and correlated with the Expanded Disability Status Scale. Results: Improvement of the VEP sum score was found in 33% of natalizumab-treated patients but only in 9% of the same patients prior to treatment ( p = 0.041). A comparable situation was found for SEP (improvement: 32% versus 5%; worsening: 11% versus 37%; p = 0.027). For MEP no significant differences were seen (improvement: 10% versus 18%; worsening: 5% versus 29%; p = 0.60). EP recordings (VEP = SEP > MEP) have the capacity to demonstrate treatment effects of natalizumab on a functional level. Conclusions: Natalizumab therapy increases the percentage of patients showing stable or even ameliorated electrophysiological parameters in the investigated functional systems.

scholarly journals B cell depletion can be effective in multiple sclerosis but failed in a patient with advanced childhood cerebral X-linked adrenoleukodystrophy

2019 ◽  
Vol 12 ◽  
pp. 175628641986813
Author(s):  
Hendrik Rosewich ◽  
Stefan Nessler ◽  
Wolfgang Brück ◽  
Jutta Gärtner
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
B Lymphocytes ◽  
Specific Pattern ◽  
B Cell Depletion ◽  
Compassionate Use ◽  
Clinical Imaging ◽  
Relapsing Remitting ◽  
Advanced Stages ◽  
Relapsing Remitting Multiple Sclerosis

Rituximab exerts its clinical efficacy by its specific pattern of depletion of CD20+ B lymphocytes and it has been demonstrated that rituximab is an effective treatment for relapsing remitting multiple sclerosis. X-linked adrenoleukodystrophy (X-ALD), the most common monogenetic neuroinflammatory disorder, shares substantial overlap with multiple sclerosis in the neuropathological changes found in brain tissues in advanced stages of the disease. While there is no effective therapy for these patients, we hypothesized that rituximab might be effective in arresting the neuroinflammatory process. Our detailed clinical, imaging and immunological data revealed that rituximab is not effective in advanced stages of X-ALD and consequently should not be applied for compassionate use in these patients.

Persistence of neutralizing antibodies after discontinuation of IFNβ therapy in patients with relapsing-remitting multiple sclerosis

2006 ◽  
Vol 12 (3) ◽  
pp. 247-252 ◽  
Author(s):  
Bodil Petersen ◽  
Klaus Bendtzen ◽  
Nils Koch-Henriksen ◽  
Mads Ravnborg ◽  
Christian Ross ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Cytopathic Effect ◽  
Serum Levels ◽  
Neutralizing Capacity ◽  
Relapsing Remitting ◽  
Long Time ◽  
Relapsing Remitting Multiple Sclerosis

Objective The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNβ) after discontinuation of IFNβ therapy. Background A large proportion of patients treated with recombinant IFNβ for multiple sclerosis (MS) develop therapy-induced NABs. Knowledge of persistence of NABs after discontinuation of therapy is limited. Design/patients: A retrospective follow-up study of patients treated in Denmark for relapsing-remitting (RR) MS with IFNβ for at least 12 months. NAB-positive patients, who discontinued therapy, were followed up with measurements of NABs. Methods We measured NAB-neutralizing capacity and NAB titres a.m. Kawade using a clinically validated cytopathic effect assay. Results Thirty-seven patients were included. Mean follow-up time was 22 months. Of the 29 patients with a NAB titre at or above 25 prior to termination of therapy, only three patients reverted to a titre below 25. Of these, two had a titre below 200 and one patient a titre of 600 at the last examination before treatment stop. The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months. Conclusion NABs against IFNβ, especially with high titres, tend to persist for a long time after discontinuation of IFNβ therapy. NABs should always be measured before reinstitution of IFNβ treatment in NAB-positive patients.

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