MS in 2018: new therapies and biomarkers

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jimmylegs
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Re: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Wed Mar 18, 2020 4:39 am

Association Between Serum Neurofilament Light Chain Levels and Long-term Disease Course Among Patients With Multiple Sclerosis Followed up for 12 Years (2019)
https://jamanetwork.com/journals/jamane ... le=2749888

Key Points
Question Can serum neurofilament light chain measurements serve as a reliable biomarker of disease worsening for patients with multiple sclerosis?

Findings In this cohort study of 607 patients with multiple sclerosis, serum neurofilament light chain levels increased significantly faster in those experiencing disability worsening than in those who remained clinically stable. Serum neurofilament light chain level was associated with brain fraction loss, whereas this was less the case for clinical outcomes such as relapses or EDSS worsening.

Meaning The association of serum neurofilament light chain level with changes in relevant clinical and neuroimaging outcomes in multiple sclerosis was confirmed, strengthening the potential of this biomarker as a measure of disease activity in multiple sclerosis; however, the clinically useful prognostic value of serum neurofilament light chain level for the individual patient was limited.

Abstract
Importance Blood sample–based biomarkers that are associated with clinically meaningful outcomes for patients with multiple sclerosis (MS) have not been developed.

Objective To evaluate the potential of serum neurofilament light chain (sNFL) measurements as a biomarker of disease activity and progression in a longitudinal MS data set.

Design, Setting, and Participants Single-center, ongoing, prospective observational cohort study of 607 patients with MS from the longitudinal EPIC (Expression, Proteomics, Imaging, Clinical) study at the University of California, San Francisco from July 1, 2004, through August 31, 2017. Clinical evaluations and sample collection were performed annually for 5 years, then at different time points for up to 12 years, with a median follow-up duration of 10 (interquartile range, 7-11) years. Serum NFL levels were measured using a sensitive single molecule array platform and compared with clinical and magnetic resonance imaging variables with the use of univariable and multivariable analyses.

Main Outcomes and Measures The main outcomes were disability progression defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score and brain fraction atrophy.

Results Mean (SD) age of the 607 study participants at study entry was 42.5 (9.8 ) years; 423 (69.7%) were women; and all participants were of non-Hispanic European descent. Of 3911 samples sequentially collected, 3904 passed quality control for quantification of sNFL. Baseline sNFL levels showed significant associations with EDSS score (β, 1.080; 95% CI, 1.047-1.114; P < .001), MS subtype (β, 1.478; 95% CI, 1.279-1.707; P < .001), and treatment status (β, 1.120; 95% CI, 1.007-1.245; P = .04). A significant interaction between EDSS worsening and change in levels of sNFL over time was found (β, 1.015; 95% CI, 1.007-1.023; P < .001). Baseline sNFL levels alone were associated with approximately 11.6% of the variance in brain fraction atrophy at year 10. In a multivariable analysis that considered sex, age, and disease duration, baseline sNFL levels were associated with 18.0% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNFL, with high-potency treatments associated with the greater decreases in sNFL levels compared with platform therapies (high-potency vs untreated: β, 0.946; 95% CI, 0.915-0.976; P < .001; high-potency vs platform: β, 0.972; 95% CI, 0.948-0.998; P = .04).

Conclusions and Relevance This study found that statistically significant associations of sNFL with relevant clinical and neuroimaging outcomes in MS were confirmed and extended, supporting the potential of sNFL as an objective surrogate of ongoing MS disease activity. In this data set of patients with MS who received early treatment, the prognostic power of sNFL for relapse activity and long-term disability progression was limited. Further prospective studies are necessary to assess the assay’s utility for decision-making in individual patients.
https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

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jimmylegs
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Re: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Wed Mar 18, 2020 9:51 am

Vitamin D3 supplementation and neurofilament light chain in multiple sclerosis (2019)
https://onlinelibrary.wiley.com/doi/abs ... /ane.13185

Abstract
Objectives
Low circulating vitamin D levels are associated with an increased risk of active MRI lesions and relapses in several cohorts with relapsing remitting multiple sclerosis (RRMS). Randomized controlled supplementation trials are, however, negative on their primary endpoints, while secondary MRI endpoints suggest anti‐inflammatory effects. Circulating levels of neurofilament light chain (NfL) are a biomarker of disease activity in RRMS. We explored whether 48‐week high‐dose vitamin D3 supplements were associated with lower circulating NfL levels.

Materials & Methods
Of N = 40 Dutch interferon beta‐treated participants with RRMS of the SOLAR trial, plasma samples at baseline and 48‐week follow‐up were available. Of these participants, N = 24 were supplemented with 14 000 IU/d vitamin D3 and N = 16 with placebo. Twenty‐five hydroxyvitamin D3 (25(OH)D3) levels were measured with LC‐MS/MS, and NfL levels were measured in duplicate with Simoa.

Results
Serum 25(OH)D3 levels at 48 weeks were increased in the vitamin D3 when compared to placebo group (median level 281 [IQR 205‐330] vs 72 [39‐88] nmol/L; P < .01). NfL levels at 48 weeks did not differ between the treatment groups (median level 25.4 [IQR 19.6‐32.2] vs 25.3 [17.9‐30.1] pg/mL; P = .74). Higher week 48 NfL level showed a trend toward association with a higher risk of combined unique active lesions on the week 48 MRI scan (OR 2.39 [95% CI 0.93‐6.12] for each 10 pg/mL increase; P = .07).

Conclusions
Supplementation of high‐dose vitamin D3 for 48 weeks was not associated with lower NfL levels. This study does not support an effect of vitamin D3 on this biomarker of neuro‐axonal injury.
https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

take control of your own health.
pursue optimal self care, with or without a diagnosis.

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