scholarly journals Exploring CSF neurofilament light as a biomarker for MS in clinical practice; a retrospective registry-based study

2021 ◽  
pp. 135245852110391
Author(s):  
Igal Rosenstein ◽  
Markus Axelsson ◽  
Lenka Novakova ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Neurofilament Light ◽  
Hazard Ratios ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
Diagnostic Work ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Work Up

Background: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. Objective: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). Methods: RRMS patients ( n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001–2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. Results: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499–2744] ng/L) than those without relapse (264 [125–537] ng/L, p < 0.001) and patients with gadolinium-enhancing lesions had 3.3 times higher median NFL (1414 [606.8–3210] ng/L) than those without (426 [IQR 221–851] ng/L, p < 0.001). The sensitivity and specificity of cNFL to detect disease activity was 75% and 98.5%, respectively. High cNFL at MS onset predicted progression to Expanded Disability Status Scale (EDSS) ⩾ 3 ( p < 0.001, hazard ratios (HR) = 1.89, 95% CI = 1.44–2.65) and conversion to secondary progressive MS (SPMS, p = 0.001, HR = 2.5, 95% CI = 1.4–4.2). Conclusions: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.

Biological markers in body fluids for activity and progression in multiple sclerosis

1999 ◽  
Vol 5 (4) ◽  
pp. 287-290
Author(s):  
Per Soelberg Sùrensen
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Markers ◽  
Body Fluids ◽  
Therapeutic Effects ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
The Individual ◽  
Relapsing Remitting Multiple Sclerosis

Reliable biological markers in body fluids for disease activity and progression are important for our understanding of the pathophysiology and therapeutic decisions in various subtypes of multiple sclerosis. Sampling from body fluids such as cerebrospinal fluid, blood, and urine constitutes the problem that the local immuno-inflammatory process takes place in the central nervous system whereas the disease activity is only to some extent reflected in the systemic immune compartment. Promising results have been obtained in studies of adhesion molecules, pro-inflammatory cytokines, co-stimulatory molecules and neopterin as markers of disease activity in relapsing-remitting multiple sclerosis. However, these results apply to groups of patients but not necessarily to individual patients. Currently no single body fluid marker is sufficiently correlated to disease activity to be used in the individual patient in monitoring disease activity, progression, or therapeutic effects.

scholarly journals Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731880163
Author(s):  
Gordon Mazibrada ◽  
Charlotte Sharples ◽  
Ines Perfect
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Observational Study ◽  
Disease Activity ◽  
Relapse Rate ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
The Uk ◽  
Relapsing Remitting Multiple Sclerosis

Background Fingolimod is approved for the treatment of highly active relapsing–remitting multiple sclerosis in Europe. There is limited information on its effectiveness and safety in clinical practice within the UK. Objective To evaluate retrospectively the effectiveness and safety of fingolimod in patients with relapsing–remitting multiple sclerosis who were prescribed fingolimod by UK neurologists within the National Health Service. Methods This was a multicentre, observational study conducted in the UK. Patients were initiated on fingolimod 0.5 mg 12 months before inclusion in the study. Key efficacy outcomes included annualised relapse rate and the proportion of patients free from relapses, disability progression and clinical and radiological disease activity at 12 months following fingolimod initiation. Resource utilisation and safety outcomes were also assessed. Results In 12 months of treatment with fingolimod, the mean annualised relapse rate was reduced by 79%, the majority of patients were free from relapses (83.7%). Based on limited data, most patients were free from disability progression and clinical and radiological disease activity. More than 90% of patients continued on fingolimod. Lymphocyte count reductions and liver enzyme increases were observed. Conclusion Fingolimod was effective in reducing the disease activity in relapsing–remitting multiple sclerosis patients requiring an escalation from first-line therapies who were prescribed fingolimod in clinical practice in the UK.

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.

Discontinuation of disease-modifying therapies in multiple sclerosis – Clinical outcome and prognostic factors

2016 ◽  
Vol 23 (9) ◽  
pp. 1241-1248 ◽  
Author(s):  
Gabriel Bsteh ◽  
Julia Feige ◽  
Rainer Ehling ◽  
Michael Auer ◽  
Harald Hegen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Disease Activity ◽  
Cox Regression ◽  
Disability Progression ◽  
Hazard Ratios ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Disease Modifying Treatment ◽  
Relapsing Remitting Multiple Sclerosis

Background: Stable disease course may prompt consideration of disease-modifying treatment (DMT) discontinuation in relapsing–remitting multiple sclerosis (RRMS). Objective: To investigate the clinical outcome after DMT discontinuation and to identify predictive factors supporting decision-making. Methods: We included 221 RRMS patients, who discontinued DMT after ⩾12 months and had documented follow-up ⩾2 years after discontinuation. Hazard ratios (HRs) with 95% confidence intervals (CIs) regarding relapse and disability progression after DMT discontinuation were calculated from Cox regression models. Results: Age >45 years at discontinuation (HR = 0.47, CI = 0.23–0.95, p = 0.038), absence of relapses for ⩾4 years on DMT before discontinuation (HR = 0.29, CI = 0.10–0.82, p = 0.020) and absence of contrast enhancing lesions (HR = 0.46, CI = 0.28–0.78, p = 0.004) were independent predictors of absence of relapse after discontinuation. Age >45 years and absence of relapses ⩾4 years on DMT combined had an HR of 0.06 (CI = 0.01–0.44, p < 0.001). Higher Expanded Disability Status Scale (EDSS) at discontinuation, age >45 years and longer disease duration were significantly associated with disability progression after discontinuation. Conclusion: While freedom from further disease activity is generally unpredictable, there is a subset of patients (age ⩾45 years, DMT intake ⩾4 years without evidence of clinical or radiological disease activity) having a high likelihood of remaining relapse-free after DMT discontinuation. However, close clinical monitoring for recurrent disease activity is mandatory after discontinuing treatment.

No evidence of disease activity in patients receiving daclizumab versus intramuscular interferon beta-1a for relapsing-remitting multiple sclerosis in the DECIDE study

2016 ◽  
Vol 23 (13) ◽  
pp. 1736-1747 ◽  
Author(s):  
Ludwig Kappos ◽  
Eva Havrdova ◽  
Gavin Giovannoni ◽  
Bhupendra O Khatri ◽  
Susan A Gauthier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Interferon Beta ◽  
Composite Endpoint ◽  
Logistic Regression Models ◽  
Treatment Groups ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: No evidence of disease activity (NEDA) is a composite endpoint being increasingly applied as an outcome measure in clinical trials as well as proposed for individual therapeutic decisions in multiple sclerosis (MS). Objective: Assess the proportion of patients with relapsing-remitting MS achieving NEDA in the DECIDE study of daclizumab 150 mg subcutaneous versus intramuscular interferon beta-1a 30 µg for 96–144 weeks. Methods: NEDA was defined as no relapses, no onset of 12-week confirmed disability progression (CDP), no new/newly enlarging T2 hyperintense lesions (NET2), and no gadolinium-enhancing (Gd+) lesions. Logistic regression models adjusted for baseline covariates compared treatment groups for baseline to week 96, weeks 0–24, and weeks 24–96. Results: From baseline to week 96, more daclizumab versus intramuscular interferon beta-1a patients achieved NEDA (24.6% vs 14.2%; odds ratio (OR; 95% confidence interval): 2.059 (1.592−2.661); p < 0.0001). ORs for clinical NEDA (no relapses, no CDP) and magnetic resonance imaging (MRI) NEDA (no NET2, no Gd+ lesions) were 1.651 (1.357−2.007; p < 0.0001) and 2.051 (1.628−2.582; p < 0.0001), respectively. ORs in favor of daclizumab for weeks 24–96 were consistently higher than for weeks 0–24. Conclusion: More daclizumab versus intramuscular interferon beta-1a patients achieved NEDA early in DECIDE, with effects increasing over time.

scholarly journals Blood neurofilament light chain as a biomarker of MS disease activity and treatment response

Neurology ◽  
2019 ◽  
Vol 92 (10) ◽  
pp. e1007-e1015 ◽  
Author(s):  
Jens Kuhle ◽  
Harald Kropshofer ◽  
Dieter A. Haering ◽  
Uma Kundu ◽  
Rolf Meinert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Light Chain ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis.MethodsWe measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-β-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes.ResultsAt baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51–4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67–3.83]; p < 0.0001), brain volume loss (difference in means: −0.78% [−1.02 to −0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97–3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656–0.813] and IFN 0.789 [0.704–0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552–0.714] and IFN 0.794 [0.705–0.894]; p < 0.001, both studies at all assessments).ConclusionsBlood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response.

Sign in / Sign up

Export Citation Format

Share Document