Anti-CD20 Therapy Reduces Microglial Activation and Lesion Volume in Focal Models of Pattern I and Pattern II Multiple Sclerosis (P02.085)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P02.085-P02.085 ◽  
Author(s):  
D. Leppert ◽  
S. Campbell ◽  
N. Seneca ◽  
E. Warren ◽  
M. Balazs ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Microglial Activation ◽  
Lesion Volume ◽  
Anti Cd20

scholarly journals A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis

2020 ◽  
pp. 135245852091837 ◽  
Author(s):  
Edward Fox ◽  
Amy E Lovett-Racke ◽  
Matthew Gormley ◽  
Yue Liu ◽  
Maria Petracca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
B Cell ◽  
Optimal Dose ◽  
Cell Depletion ◽  
Controlled Study ◽  
Lesion Volume ◽  
B Cell Depletion ◽  
Phase 2 ◽  
Anti Cd20

Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1–4 hours on day 1 and 450–600 mg over 1–3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts ( N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1–2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( p = 0.003) and a 10.6% decrease in T2 lesion volume ( p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

Anti-CD20 therapy down-regulates lesion formation and microglial activation in pattern I and pattern II rat models of multiple sclerosis

2014 ◽  
Vol 275 (1-2) ◽  
pp. 1-2
Author(s):  
Daniel C. Anthony ◽  
Alex M. Dickens ◽  
Nicholas Seneca ◽  
Yvonne Couch ◽  
Sandra Campbell ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Microglial Activation ◽  
Lesion Formation ◽  
Rat Models ◽  
Anti Cd20

scholarly journals Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey

2021 ◽  
pp. 135245852110053
Author(s):  
Emilio Portaccio ◽  
Mattia Fonderico ◽  
Bernhard Hemmer ◽  
Tobias Derfuss ◽  
Bruno Stankoff ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Access To Care ◽  
Online Survey ◽  
Dimethyl Fumarate ◽  
Standards Of Care ◽  
Treatment Practices ◽  
European Committee ◽  
Disease Modifying Therapy ◽  
Anti Cd20 ◽  
The Impact

Background: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS). Objectives: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices. Methods: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19. Results: Three-hundred and sixty neurologists from 52 countries (68% from Europe) completed the survey. 98% reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73%) or widely implemented (17%). 70% reported changes in DMT management. Interferons and glatiramer were considered safe. Dimethyl fumarate, teriflunomide and fingolimod were considered safe except for patients developing lymphopenia. No modifications were considered for natalizumab in 64%, cladribine in 24%, anti-CD20 in 22% and alemtuzumab in 17%; 18% (for alemtuzumab and cladribine) and 43% (for anti-CD20) considered postponing treatment. Conclusion: The ECTRIMS survey highlighted the challenges in keeping standards of care in clinical practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.

scholarly journals Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1712
Author(s):  
Roberta Magliozzi ◽  
Francesco Pezzini ◽  
Mairi Pucci ◽  
Stefania Rossi ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Protein Pattern ◽  
Fold Change ◽  
Cortical Lesion ◽  
Control Group ◽  
Lesion Volume ◽  
Mri Features ◽  
Csf Levels ◽  
Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

scholarly journals Multiple sclerosis risk gene Mertk is required for microglial activation and subsequent remyelination

Cell Reports ◽  
2021 ◽  
Vol 34 (10) ◽  
pp. 108835
Author(s):  
Kimberle Shen ◽  
Mike Reichelt ◽  
Roxanne V. Kyauk ◽  
Hai Ngu ◽  
Yun-An A. Shen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Microglial Activation ◽  
Risk Gene ◽  
Multiple Sclerosis Risk

Serum amyloid A level correlates with T2 lesion volume and cortical volume in patients with multiple sclerosis

2021 ◽  
Vol 351 ◽  
pp. 577466
Author(s):  
Hiroaki Yokote ◽  
Shuta Toru ◽  
Yoichiro Nishida ◽  
Takaaki Hattori ◽  
Nobuo Sanjo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Lesion Volume ◽  
Cortical Volume ◽  
Amyloid A

T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation

1998 ◽  
Vol 4 (5) ◽  
pp. 408-412 ◽  
Author(s):  
J I O'Riordan ◽  
M Gawne Cain ◽  
A Coles ◽  
L Wang ◽  
D AS Compston ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Strong Correlation ◽  
Measurement Techniques ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Mri Findings ◽  
Lesion Load ◽  
Post Contrast ◽  
Secondary Progressive

Magnetic resonance imaging (MRI) is increasingly being used as a monitoring tool for disease activity in therapeutic trials in multiple sclerosis. There is, however, only a limited relationship between MRI findings and clinical outcome measurements. It has been suggested that hypointense lesion load on T1 weighted imaging has a better correlation with disability than the more conventional T2 hyper intense lesion load. This study was undertaken to (i) evaluate different measurement techniques used to quantify T1 hypointense lesion load, and (ii) to compare lesion load as measured using different parameters and disability. Twenty-five patients with secondary progressive multiple sclerosis, mean age of 40 years (23-57), mean EDSS 5.7 (4-7) were analysed. T2 lesion load on FSE correlated well with both the hypointense lesion load on T1 pre-gadolinium (r=0.8, P50.0001) and T1 post-gadolinium (r=0.8, P50.0001) but less so with the enhancing lesion load (r=0.4, P50.05). There was a very strong correlation with T1 hypo-intense lesion volume pre and post gadolinium (r=0.96, P50.001). However, the EDSS was not correlated with the T2 lesion load (r=70.27, P=0.2), T1 pre-gadolinium load (r=70.3, P=0.1), T1 post gadolinium load (r=70.4, P=0.7) and enhancing lesion load (r=70.28, P=0.2), or with the degree of hypointensity of T1 weighted images determined using the threshold technique. There is a strong correlation between T1 hypointense lesion volume both pre and post gadolinium and also between T1 and T2 lesion volumes.

Extended dosing of monoclonal antibodies in multiple sclerosis

2021 ◽  
pp. 135245852110657
Author(s):  
Zoé LE van Kempen ◽  
Alyssa A Toorop ◽  
Finn Sellebjerg ◽  
Gavin Giovannoni ◽  
Joep Killestein
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Treatment Options ◽  
Future Research ◽  
Therapeutic Drug ◽  
Therapeutic Landscape ◽  
Anti Cd20 ◽  
Dosing Intervals ◽  
Care Costs ◽  
Review Current

Over the past two decades, treatment options for patients with multiple sclerosis (MS) have increased exponentially. In the current therapeutic landscape, “no evidence of MS disease activity” is within reach in many of our patients. Minimizing risks of complications, improving treatment convenience, and decreasing health care costs are goals that are yet to be reached. One way to optimize MS therapy is to implement personalized or extended interval dosing. Monoclonal antibodies are suitable candidates for personalized dosing (by therapeutic drug monitoring) or extended interval dosing. An increasing number of studies are performed and underway reporting on altered dosing intervals of anti-α4β1-integrin treatment (natalizumab) and anti-CD20 treatment (ocrelizumab, rituximab, and ofatumumab) in MS. In this review, current available evidence regarding personalized and extended interval dosing of monoclonal antibodies in MS is discussed with recommendations for future research and clinical practice.

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