Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab

Flon, Pierre de; Gunnarsson, Martin; Laurell, Katarina; Söderström, Lars; Birgander, Richard; Lindqvist, Thomas; Krauß, W.; Dring, Ann; Bergman, Joakim; Sundström, Peter; Svenningsson, Anders

doi:10.1212/wnl.0000000000002832

Cited by 80 publications

(74 citation statements)

References 20 publications

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“…In CIS/RRMS patients, the decrease in sNfL levels correlated inversely with longer time since start of DMTs independent of recent relapses. Notably, treatment effects on CSF NfL levels have already been shown for fingolimod, natalizumab, and rituximab in MS patients 13, 14, 15, 16, 17, 47. Although this study was not primarily designed to investigate treatment effects, our results suggest that DMTs reduce sNfL levels, supporting their value for monitoring treatment response.…”

Section: Discussionsupporting

confidence: 68%

“…Notably, treatment effects on CSF NfL levels have already been shown for fingolimod, natalizumab, and rituximab in MS patients. [13][14][15][16][17]47 Although this study was not primarily designed to investigate treatment effects, our results suggest that DMTs reduce sNfL levels, supporting their value for monitoring treatment response.…”

Section: Discussionmentioning

confidence: 65%

“…[4][5][6][7][8][9] CSF NfL levels are further increased during relapses and are positively associated with magnetic resonance imaging (MRI) lesion load and disability scores in MS. [10][11][12] Noteworthy, CSF NfL levels have also been shown to be a marker of treatment response in this disease. [13][14][15][16][17] However, lumbar punctures are relatively invasive procedures, limiting the value of CSF NfL in routine clinical settings.…”

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confidence: 99%

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Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

Disanto

Barro

Benkert

et al. 2017

Annals of Neurology

909

1,069

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ObjectiveNeurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single‐molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).MethodssNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross‐sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow‐up = 3.1 years, interquartile range [IQR] = 2.0–4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.ResultssNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2–65.3) or both brain and spinal gadolinium‐enhancing lesions (62.5pg/ml, IQR = 42.7–71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9–41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease‐modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC‐based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21–3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07–5.42, p = 0.034).InterpretationThese results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857–870

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

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Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

Disanto

Barro

Benkert

et al. 2017

Annals of Neurology

909

1,069

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“…Rituksimab er ikke godkjent for bruk mot multippel sklerose, men brukes hyppig utenfor indikasjon mot sykdommen i Sverige (23). Et annet B-celleantistoff -ocrelizumab -forventes å bli registrert som behandling mot multippel sklerose i 2017 (22).…”

Section: Alemtuzumab Og Rituksimabunclassified

Familieplanlegging, graviditet og amming ved multippel sklerose

Holmøy

Torkildsen²

2016

Tidsskriftet

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“…10,15 Despite this growing knowledge, it is still a remaining challenge to establish the appropriate use of s/p-NFL as a tool in clinical trials as well as in clinical routine. 17 The objective of this study was to evaluate the use of p-NFL as an endpoint measure in a clinical MS trial, here represented by the STRIX-trial. 17 The objective of this study was to evaluate the use of p-NFL as an endpoint measure in a clinical MS trial, here represented by the STRIX-trial.…”

Section: Introductionmentioning

confidence: 99%

Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial

et al. 2019

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Objective:The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis. Materials and methods:Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA. Results:The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 [SD 393] to 354 [SD 174] pg/mL; P = 0.006) and was statistically significant. The corresponding reduction in plasma NFL was 18% (from 9.73 [SD 7.04] to 7.94 [SD 3.10] pg/mL; P = 0.055) and did not reach statistical significance. Conclusion:This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimize the use in clinical trials.

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Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab

Abstract: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.

Cited by 80 publications

References 20 publications

Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

Familieplanlegging, graviditet og amming ved multippel sklerose

Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial

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