Chitinase 3-like 1 is associated with the response to interferon-beta treatment in multiple sclerosis

Matute-Blanch, Clara; Río, Jordi; Villar, Luisa M.; Midaglia, Luciana; Malhotra, Sunny; Álvarez‐Cermeño, José C.; Vidal-Jordana, Ángela; Montalbán, Xavier; Comabella, Manuel

doi:10.1016/j.jneuroim.2016.12.006

Cited by 20 publications

(17 citation statements)

References 10 publications

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“…Our results showing no significant association with either MRI activity or EDSS score are supported by a recent study that also found no significant differences in CHI3L1 levels and disease activity. 23 Indeed, this study 23 suggested that CHI3L1 may reflect the response to IFNB-1a treatment in patients with RRMS. Our study did not support this conclusion.…”

Section: Discussionmentioning

confidence: 79%

Neurofilament light chain predicts disease activity in relapsing-remitting MS

Varhaug

Barro

Bjørnevik

et al. 2018

Neurol Neuroimmunol Neuroinflamm

123

128

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Objective:To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS).Methods:A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models.Results:NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9–52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1–48.5) compared with those without (28.0 pg/mL, IQR 21.9–36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8–35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.Conclusion:Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity.ClinicalTrials.gov identifier:NCT00360906.

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Section: Discussionmentioning

confidence: 79%

Neurofilament light chain predicts disease activity in relapsing-remitting MS

Varhaug

Barro

Bjørnevik

et al. 2018

Neurol Neuroimmunol Neuroinflamm

123

128

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“…We have previously shown that treatment with natalizumab and methylprednisolone reduces sCD27 concentrations in the CSF of patients with progressive MS and that sCD27 is associated with neuroaxonal damage assessed by the CSF concentration of NFL in progressive MS. 24 CHI3L1 has shown response to treatment with disease-modifying treatments in patients with RRMS. [25][26][27][28] Thus, the inability of dimethyl fumarate to normalize the CSF levels of these 2 biomarkers suggests lack of efficacy of dimethyl fumarate. This conclusion is supported by the observation that dimethyl fumarate also had no effect on the inflammatory biomarkers BCMA and CD14.…”

Section: Discussionmentioning

confidence: 99%

Dimethyl Fumarate Treatment in Patients With Primary Progressive Multiple Sclerosis

Chow

Talbot

Lundell

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectiveTo study whether dimethyl fumarate is superior to placebo in decreasing CSF concentrations of neurofilament light chain (NFL) in patients with primary progressive MS (PPMS).MethodsIn the double-blind, placebo-controlled phase 2 study dimethyl FUMArate treatment in Progressive Multiple Sclerosis (FUMAPMS), patients with PPMS were randomly assigned to treatment with 240 mg dimethyl fumarate or placebo in a 1:1 ratio for 48 weeks. The primary endpoint was change in concentration of NFL in the CSF. Secondary endpoints included other CSF biomarkers and clinical and MRI measures. Efficacy was evaluated for the full data set by multiple imputations to account for missing data. Safety was assessed for the full data set.ResultsFifty-four patients (mean age 54.9 years [SD 6.1], median Expanded Disability Status Scale 4.0 [nterquartile range 4.0–6.0], disease duration 14.1 [SD 9.4], and 21 [39%] female) were randomized to either placebo (n = 27) or dimethyl fumarate (n = 27) therapy. At screening CSF concentrations, adjusted for age and sex, of NFL, myelin basic protein (MBP), soluble CD27, chitinase 3-like 1, and B-cell maturation antigen were higher than in a group of symptomatic controls. Twenty-six patients (96%) in the dimethyl fumarate group and 24 patients (89%) in the placebo group completed the randomized phase. Mean change in CSF concentrations of NFL did not differ between groups (mean difference 99 ng/L; 95% CI −292 to 491 ng/L). MBP in CSF decreased in the treatment group (−182 ng/L, 95% CI −323 to −41 ng/L compared with placebo). The difference observed in the multiple imputation data set was not significant in a per protocol analysis. This was nominally significant in the multiple imputation data set but not in the per protocol analysis This was not found in the per protocol analysis Other secondary and tertiary outcomes were not affected. Various infections, lymphopenia, flushing, and gastrointestinal side effects were more frequent in the dimethyl fumarate group. Serious adverse events were similar between groups.DiscussionDimethyl fumarate treatment for 48 weeks had no effect on any of the investigated efficacy measures in patients with PPMS. We did not observe adverse events not anticipated for dimethyl fumarate treatment.Trial Registration InformationClinicaltrials.gov identifier NCT02959658.Classification of EvidenceThis study provides Class I evidence that for patients with PPMS, dimethyl fumarate treatment has no effect on CSF NFL levels compared with placebo treatment.

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“…Cantó and colleagues showed in a multicentre longitudinal cohort study with 813 participants that the CHI3L1 concentration is an independent risk factor for the conversion from CIS to MS. High CHI3L1 levels were also associated with faster disability progression [93]. Although CHI3L1 is not yet clinically established, it is a promising candidate as a biomarker of MS prognosis and probably treatment response [94].…”

Section: Molecular Biomarkers For Ms Prognosismentioning

confidence: 99%

Molecular biomarkers in multiple sclerosis

Ziemssen

Akgün

Brück

2019

J Neuroinflammation

181

141

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Multiple sclerosis (MS) is an inflammatory-neurodegenerative disease of the central nervous system presenting with significant inter- and intraindividual heterogeneity. However, the application of clinical and imaging biomarkers is currently not able to allow individual characterization and prediction. Complementary, molecular biomarkers which are easily quantifiable come from the areas of immunology and neurobiology due to the causal pathomechanisms and can excellently complement other disease characteristics. Only a few molecular biomarkers have so far been routinely used in clinical practice as their validation and transfer take a long time. This review describes the characteristics that an ideal MS biomarker should have and the challenges of establishing new biomarkers. In addition, clinically relevant and promising biomarkers from the blood and cerebrospinal fluid are presented which are useful for MS diagnosis and prognosis as well as for the assessment of therapy response and side effects.

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Chitinase 3-like 1 is associated with the response to interferon-beta treatment in multiple sclerosis

Cited by 20 publications

References 10 publications

Neurofilament light chain predicts disease activity in relapsing-remitting MS

Neurofilament light chain predicts disease activity in relapsing-remitting MS

Dimethyl Fumarate Treatment in Patients With Primary Progressive Multiple Sclerosis

Molecular biomarkers in multiple sclerosis

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