scholarly journals FutureMS Cohort Profile: A Scottish Multi-Centre Inception Cohort Study of Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Author(s):  
P.K.A. Kearns ◽  
S.J. Martin ◽  
J. Chang ◽  
R. Meijboom ◽  
E.N. York ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cohort Study ◽  
Disease Activity ◽  
Treatment Decision ◽  
Response To Treatment ◽  
Disease Heterogeneity ◽  
Predictive Tools ◽  
Treatment Decision Making ◽  
Relapsing Remitting

ABSTRACTMultiple Sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries the most common cause of progressive neurological disability in working age persons. However, there is significant between-subject heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate, or aggressive disease course is very limited. There is therefore a need for integrated predictive tools to inform individualised treatment decision making. FutureMS is a nationally-representative, prospective observation cohort study comprising 440 participants with a new diagnosis of relapsing remitting MS living in Scotland between May 2016 and March 2019. Established with the aim of addressing this need for individualised predictive tools, the cohort is designed to combine detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow up at year one is complete and longer-term follow up is planned, beginning at five years after first visit. The study aims to address the biology and determinants of disease heterogeneity in MS. Here we describe the cohort design and present a profile of the participants at baseline and one year of follow up.

scholarly journals Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series

2021 ◽  
Vol 11 (10) ◽  
pp. 1341
Author(s):  
Marco Allinovi ◽  
Angelo Bellinvia ◽  
Francesco Pesce ◽  
Sabrina Milan Manani ◽  
Lorenzo Razzolini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Case Series ◽  
Multicentric Study ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Before And After ◽  
System Activation ◽  
Ms Pathogenesis

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Physician and patient treatment decision-making in relapsing-remitting multiple sclerosis in Europe and the USA

2019 ◽  
Author(s):  
Brown Hannah
Keyword(s):  
Multiple Sclerosis ◽  
Decision Making ◽  
Treatment Decision ◽  
Patient Treatment ◽  
Lead Author ◽  
Treatment Decision Making ◽  
Relapsing Remitting ◽  
The Usa ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

In this Publication Perspective, lead author Hannah Brown, Senior Research Executive at Ipsos Healthcare, London, UK, provides a summary of the recently published article 'Physician and patient treatment decision-making in relapsing-remitting multiple sclerosis in Europe and the USA', from Neurodegenerative Disease Management, that assessed factors used in treatment decision-making for relapsing-remitting multiple sclerosis in both the 5EU (UK/Germany/France/Italy/Spain) and the US.

Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012752
Author(s):  
Claire Bridel ◽  
Cyra E Leurs ◽  
Zoë YGJ van Lierop ◽  
Zoé LE van Kempen ◽  
Iris Dekker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Inflammatory Disease ◽  
Medical Center ◽  
Neurofilament Light ◽  
Longitudinal Dynamics ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveThe objective of this study was to investigate the potential of serum neurofilament light (NfL) to reflect or predict progression mostly independent of acute inflammatory disease activity in patients with relapsing remitting multiple sclerosis (RRMS) treated with natalizumab.MethodsPatients were selected from a prospective observational cohort study initiated in 2006 at the VU University Medical Center Amsterdam, The Netherlands, including patients with RRMS treated with natalizumab. Selection criteria included an age of 18 years or older and a minimum follow-up of 3 years from natalizumab initiation. Clinical and MRI assessments were performedon a yearly basis, and serum NfL was measured at 5 time-points during the follow-up, including on the day of natalizumab initiation (baseline), 3 months, 1 year and 2 years after natalizumab initiation, and on last follow-up visit. Using general linear regression models, we compared the longitudinal dynamics of NfL between patients with and without confirmed EDSS progression between year 1 visit and last follow-up, and between individuals with and without EDSS+ progression, a composite endpoint including the EDSS, 9 hole peg test and timed 25 foot-walk.ResultsEighty-nine natalizumab-treated patients with RRMS were included. Median follow-up time was 5.2 years (IQR 4.3-6.7, range 3.0-11.0) after natalizumab initiation, mean age at time of natalizumab initiation was 36.9 (SD: 8.5), and median disease duration was 7.4 years (IQR 3.8-12.1). Between year 1 and the last follow-up, 28/89 (31.5%) individuals showed confirmed EDSS progression. Data for the EDSS+ endpoint was available for 73 out of the 89 patients and 35/73 (47.9%) showed confirmed EDSS+ progression.We observed a significant reduction in NfL levels 3 months after natalizumab initiation, which reached its nadir of close to 50% of baseline levels 1 year after treatment initiation. We found no difference in the longitudinal dynamics of NfL in progressors versus non-progressors. NfL levels at baseline and 1 year after natalizumab initiation did not predict progression at last follow-up.DiscussionIn our cohort of natalizumab-treated patients with RRMS, NfL fails to capture or predict progression that occurs largely independently of clinical or radiological signs of acute focal inflammatory disease activity. Additional biomarkers may thus be needed to monitor progression in these patients.Classification of EvidenceThis study provides Class II evidence that serum NfL levels are not associated with disease progression in natalizumab-treated patients with RRMS.

Efficacy of rituximab in refractory RRMS

2018 ◽  
Vol 25 (6) ◽  
pp. 828-836 ◽  
Author(s):  
Pierre Durozard ◽  
Adil Maarouf ◽  
Clémence Boutiere ◽  
Aurelie Ruet ◽  
Bruno Brochet ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Rescue Therapy ◽  
Outcome Data ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Retrospective Multicenter Study

Objective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5–6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4–18.4) months after rituximab ( p < 0.0001). Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

scholarly journals The Neutrophil-to-Lymphocyte Ratio is Related to Disease Activity in Relapsing Remitting Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1114 ◽  
Author(s):  
D’Amico ◽  
Zanghì ◽  
Romano ◽  
Sciandra ◽  
Palumbo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Large Scale ◽  
Total Sample ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

: Background: The role of the neutrophil-to-lymphocyte ratio (NLR) of peripheral blood has been investigated in relation to several autoimmune diseases. Limited studies have addressed the significance of the NLR in terms of being a marker of disease activity in multiple sclerosis (MS). Methods: This is a retrospective study in relapsing–remitting MS patients (RRMS) admitted to the tertiary MS center of Catania, Italy during the period of 1 January to 31 December 2018. The aim of the present study was to investigate the significance of the NLR in reflecting the disease activity in a cohort of early diagnosed RRMS patients. Results: Among a total sample of 132 patients diagnosed with RRMS, 84 were enrolled in the present study. In the association analysis, a relation between the NLR value and disease activity at onset was found (V-Cramer 0.271, p = 0.013). In the logistic regression model, the variable NLR (p = 0.03 ExpB 3.5, CI 95% 1.089–11.4) was related to disease activity at onset. Conclusion: An elevated NLR is associated with disease activity at onset in RRMS patients. More large-scale studies with a longer follow-up are needed.

scholarly journals Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1264
Author(s):  
Margarete M. Voortman ◽  
Anna Damulina ◽  
Lukas Pirpamer ◽  
Daniela Pinter ◽  
Alexander Pichler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Neuronal Damage ◽  
Brain Mri ◽  
Time Interval ◽  
Antioxidative Capacity ◽  
Subclinical Disease ◽  
Relapsing Remitting

Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = −0.365, p = 0.004) and risk for future relapses (exp(β) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS.

scholarly journals Evidence of disease control: a realistic concept beyond NEDA in the treatment of multiple sclerosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 566 ◽  
Author(s):  
Ana C. Londoño ◽  
Carlos A. Mora
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Disease Control ◽  
Tissue Damage ◽  
Early Stage ◽  
Response To Treatment ◽  
Stage Of Disease

Although no evidence of disease activity (NEDA) permits evaluation of response to treatment in the systematic follow-up of patients with multiple sclerosis (MS), its ability to accomplish detection of surreptitious activity of disease is limited, thus being unable to prevent patients from falling into a non-reversible progressive phase of disease. A protocol of evaluation based on the use of validated biomarkers that is conducted at an early stage of disease would permit the capture of abnormal neuroimmunological phenomena and lead towards intervention with modifying therapy before tissue damage has been reached.

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