THUR 198 Safe monitoring of natalizumab therapy in multiple sclerosis

2018 ◽  
Vol 89 (10) ◽  
pp. A29.1-A29
Author(s):  
Hosty J ◽  
Kass-Iliyya L ◽  
Bell S ◽  
Barker L ◽  
Packwood S ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Safety Monitoring ◽  
Brain Infection ◽  
Audit Data ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Specialist Nurses ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Natalizumab is one of the most effective therapies for relapsing-remitting Multiple Sclerosis. One complication is Progressive Multifocal Leucoencephalopathy (PML), a viral brain infection in patients already infected with JC virus. Monitoring of neurological symptoms, JC virus serology and regular brain imaging are required to ensure safe use of this therapy. Local audit data from 2015 indicated poor compliance with safety monitoring, with less than 25% of patients undergoing required investigations within the recommended time intervals. Subsequently a protocol was implemented to improve monitoring, with specialist nurses coordinating the requests for MRI scans and arranging JC virus serology, the frequency of which was determined according to the JC virus index. The records of all patients receiving Natalizumab at the centre were audited to assess the impact of this protocol (n=155). 99.2% of patients were appropriately tested for JC virus and 95.3% were imaged within the recommended interval. Additional work with the informatics and virology team ensured serology results became more easily accessible. The use of a standardised nurse-led operating procedure has resulted in marked improvement in the safety monitoring of Natalizumab.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

scholarly journals Balancing the Demands of Two Tasks: An Investigation of Cognitive–Motor Dual-Tasking in Relapsing Remitting Multiple Sclerosis

2017 ◽  
Vol 24 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Emma Butchard-MacDonald ◽  
Lorna Paul ◽  
Jonathan J. Evans
Keyword(s):  
Multiple Sclerosis ◽  
Dual Task ◽  
Postural Stability ◽  
Digit Span ◽  
Dual Tasking ◽  
Stable Surface ◽  
Relapsing Remitting ◽  
Task Conditions ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

AbstractBackground:People with relapsing remitting multiple sclerosis (PwRRMS) suffer disproportionate decrements in gait under dual-task conditions, when walking and a cognitive task are combined. There has been much less investigation of the impact of cognitive demands on balance.Objectives:This study investigated whether: (1) PwRRMS show disproportionate decrements in postural stability under dual-task conditions compared to healthy controls, and (2) dual-task decrements are associated with everyday dual-tasking difficulties. The impact of mood, fatigue, and disease severity on dual-tasking was also examined.Methods:A total of 34 PwRRMS and 34 matched controls completed cognitive (digit span) and balance (movement of center of pressure on Biosway on stable and unstable surfaces) tasks under single- and dual-task conditions. Everyday dual-tasking was measured using the Dual-Tasking Questionnaire. Mood was measured by the Hospital Anxiety & Depression Scale. Fatigue was measuredviathe Modified Fatigue Index Scale.Results:No differences in age, gender, years of education, estimated pre-morbid IQ, or baseline digit span between groups. Compared with controls, PwRRMS showed significantly greater decrement in postural stability under dual-task conditions on an unstable surface (p=.007), but not a stable surface (p=.679). Balance decrement scores were not correlated with everyday dual-tasking difficulties or fatigue. Stable surface balance decrement scores were significantly associated with levels of anxiety (rho=0.527;p=.001) and depression (rho=0.451;p=.007).Conclusions:RRMS causes dual-tasking difficulties, impacting balance under challenging conditions, which may contribute to increased risk of gait difficulties and falls. The relationship between anxiety/depression and dual-task decrement suggests that emotional factors may be contributing to dual-task difficulties. (JINS, 2018,24, 247–258)

scholarly journals Subcutaneous interferon β-1a three times weekly and the natural evolution of gadolinium-enhancing lesions into chronic black holes in relapsing and progressive multiple sclerosis: Analysis of PRISMS and SPECTRIMS trials

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774534
Author(s):  
A Traboulsee ◽  
DKB Li ◽  
R Tam ◽  
G Zhao ◽  
A Riddehough ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Holes ◽  
Progressive Multiple Sclerosis ◽  
Repair Capacity ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
History Of ◽  
Lesion Level ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background Evolution of gadolinium-enhancing lesions into chronic black holes (CBH) may be reduced by interferon (IFN) therapy. Objective The objective of this paper is to assess the effect of IFN β-1a and placebo on CBH evolution and disability in patients with relapsing–remitting multiple sclerosis (RRMS), as well as CBH evolution in patients with secondary progressive multiple sclerosis (SPMS). Methods A post hoc, exploratory analysis of patients with RRMS and SPMS with monthly MRI scans (months –1 to 9) from two separate placebo-controlled clinical trials of IFN β-1a was conducted. Results In RRMS patients, the risk of ≥1 evolved CBH was lower for IFN β-1a versus placebo (odds ratio 0.42; p = 0.024); volume of newly evolved CBH was numerically reduced. A numerically higher proportion of patients with ≥1 evolving CBH vs no evolving CBH had confirmed three-month disability progression (four-year rate 55.8% vs 43.1%, respectively). Proportion of lesions evolving into CBH (patient level: 34.7% vs 12.6%, p < 0.0001; lesion level: 28.8% vs 11.0%, p < 0.0001) and evolved CBH volume (median 33.5 mm3 (Quartile 1, 0.0; Quartile 3, 173.4) vs 0.0 mm3 (0.0; 52.4); p = 0.0008) was higher for SPMS than RRMS patients treated with IFN β-1a. Conclusion In RRMS, IFN β-1a significantly decreased the proportion of new T1 Gd+ lesions evolving into CBH and the risk of developing a CBH. In patients with SPMS, more lesions develop to CBH, indicating reduced repair capacity, and the natural history of lesion development appears to be unaffected by IFN β-1a treatment.

The contribution of depressive symptoms to slowness of information processing in relapsing remitting multiple sclerosis

2016 ◽  
Vol 22 (12) ◽  
pp. 1607-1615 ◽  
Author(s):  
Genny Lubrini ◽  
Marcos Ríos Lago ◽  
Jose A Periañez ◽  
Antonio Tallón Barranco ◽  
Consuelo De Dios ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Information Processing ◽  
Depressive Symptoms ◽  
General Population ◽  
Cognitive Demands ◽  
Fundamental Factor ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Background: Slowness of information processing has been suggested as a fundamental factor modulating cognitive impairment in multiple sclerosis (MS). However, the contribution of depressive symptoms (DS) to slowness remains unclear. One of the most accepted hypotheses on the impact of depression on the general population suggests that depression interferes only with tasks requiring high cognitive demands. However, no studies have investigated if the same pattern occurs in MS. Objective: The aim of this study was to determine the profile of the contribution of DS to slowness. Methods: Four Reaction Time (RT) tasks requiring an increasing level of cognitive demands were administered to 35 relapsing remitting MS patients with DS, 33 MS patients without DS, 17 depressed non-MS patients and 27 controls. Results: MS patients without DS obtained longer RTs than controls in all the tasks. On the contrary, depressed non-MS patients were slower than controls only in the most demanding task. Finally, MS patients with DS were slower than MS patients without DS not only in the most demanding task but also in the task requiring a lower level of cognitive demands. Conclusion: The contribution of DS to slowness depends on the level of cognitive demands. However, its impact on MS is more deleterious than on the general population.

scholarly journals Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis

2016 ◽  
Vol 22 (10) ◽  
pp. 1297-1305 ◽  
Author(s):  
Ludwig Kappos ◽  
Nicola De Stefano ◽  
Mark S Freedman ◽  
Bruce AC Cree ◽  
Ernst-Wilhelm Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Volume ◽  
Objective Measure ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Background: ‘No evidence of disease activity’ (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression (‘NEDA-3’), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression. Objective: To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 (‘NEDA-4’) Methods: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%–1.2%). Results: At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01–4.41; p < 0.0001). Conclusion: NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.

scholarly journals Peginterferon beta-1a reduces disability worsening in relapsing–remitting multiple sclerosis: 2-year results from ADVANCE

2016 ◽  
Vol 10 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Scott D. Newsome ◽  
Bernd C. Kieseier ◽  
Shifang Liu ◽  
Xiaojun You ◽  
Elizabeth Kinter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional Status ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Point Increase ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Background: In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing–remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL). Methods: In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks. After 1 year, patients on placebo were re-randomized to peginterferon beta-1a every 2 or 4 weeks. CDP was defined as ⩾1.0 point increase from a baseline Expanded Disability Status Scale (EDSS) score ⩾ 1.0, or ⩾1.5-point increase from baseline 0, confirmed 12 or 24 weeks after onset. Results: Peginterferon beta-1a every 2 weeks significantly reduced risk of 12- and 24-week CDP at 1 year compared with placebo (12-week CDP: 6.8% versus 10.5%, p = 0.038; 24-week CDP: 4% versus 8.4%, p = 0.0069, peginterferon beta-1a every 2 weeks versus placebo, respectively). Benefits were maintained over 2 years (11.2% and 7.7%, peginterferon beta-1a every 2 weeks in 12- and 24-week CDP, respectively). Approximately 90% of patients with 24-week CDP had simultaneous worsening by ⩾1 point in at least one functional system score, most commonly pyramidal. Displaying a 24-week CDP was associated with worse scores on the Multiple Sclerosis Functional Composite (MSFC) scale and several HRQoL instruments; the impact of CDP was attenuated by treatment with peginterferon beta-1a every 2 weeks. Conclusions: Peginterferon beta-1a has the potential to prevent/delay worsening of disability in patients with relapsing–remitting multiple sclerosis. Furthermore, improved benefits in disability status with peginterferon beta-1a were also associated with improved functional status and HRQoL [ ClinicalTrials.gov identifier: NCT00906399].

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