No increase of serum neurofilament light in relapsing-remitting multiple sclerosis patients switching from standard to extended-interval dosing of natalizumab

Johnsson, Magnus; Farman, Helen H; Blennow, Kaj; Zetterberg, Henrik; Malmeström, Clas; Axelsson, Markus; Lycke, Jan

doi:10.1177/13524585221108080

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…active RRMS/CIS patients was 9.1 ng/L (IQR; 4.2-25.8), that is 2.5 times higher than in patients with stable disease, 16 and the individual sNfL CV was 33%, which was twice that of stable RRMS controls.…”

Section: Discussionmentioning

confidence: 78%

Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Johnsson,

Stenberg,

Farman

et al. 2024

Mult Scler

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Background: Serum neurofilament light (sNfL) reflects neuroaxonal damage and is now used as an outcome in treatment trials of relapsing-remitting multiple sclerosis (RRMS). However, the diagnostic properties of sNfL for monitoring disease activity in individual patients warrant further investigations. Method: Patients with suspected relapse and/or contrast-enhancing lesions (CELs) were consecutively included and performed magnetic resonance imaging (MRI) of the brain at baseline and weeks 28 and 48. Serum was obtained at baseline and 2, 4, 8, 16, 24, and 48 weeks. Neurofilament light concentration was measured using Single molecule array technology. Results: We included 44 patients, 40 with RRMS and 4 with clinically isolated syndrome. The median sNfL level peaked at 2 weeks post-baseline (14.6 ng/L, interquartile range (IQR); 9.3–31.6) and reached nadir at 48 weeks (9.1 ng/L, IQR; 5.5–15.0), equivalent to the median sNfL of controls (9.1 ng/L, IQR; 7.4–12). A baseline Z-score of more than 1.1 (area under the curve; 0.78, p < 0.0001) had a sensitivity of 81% and specificity of 70% to detect disease activity. Conclusion: One out of five patients with relapse and/or CELs did not change significantly in post-baseline sNfL levels. The utility of repeated sNfL measurements to monitor disease activity is complementary rather than a substitute for clinical and MRI measures.

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Section: Discussionmentioning

confidence: 78%

Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Johnsson,

Stenberg,

Farman

et al. 2024

Mult Scler

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“…While other DMTs have shown convincing decreases of plasma/ serum NfL, the effect has been modest with teriflunomide [25,30]. Although, our study population was limited to only 12 patients, who were of older age where the variability of plasma NfL is higher [31], our results warrant further investigations to explore if teriflunomide affects the penetrans of NfL from CSF to blood.…”

Section: Discussionmentioning

confidence: 80%

Teriflunomide Concentrations in Cerebrospinal Fluid and Plasma in Patients with Multiple Sclerosis: A Pharmacokinetic Study

2023

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Background Teriflunomide is a disease modifying treatment (DMT) approved for relapsing-remitting multiple sclerosis (RRMS) in adults and children. It reduces lymphocyte proliferation by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and thereby the pyrimidine synthesis. Although most DMTs in multiple sclerosis (MS) modulate or inhibit the immune system in the periphery, the efficacy may improve if the agent also targets immune activity within the central nervous system (CNS), acts as a neuro-protective and enhances neuro-regeneration. The objective of this study was to determine the passage of teriflunomide over the blood-cerebrospinal fluid barrier (BCSFB). Methods Plasma and cerebrospinal fluid (CSF) teriflunomide concentrations were determined at steady state in 12 patients with RRMS, treated with oral teriflunomide 14 mg once daily. Included patients were all clinically stable without relapse or disability worsening within 6 months prior from baseline and were on no other immune modulating or immunosuppressive drugs. ResultsThe mean teriflunomide concentrations in plasma and CSF were 38775 (SEM ± 7256) ng/mL and 68 (SEM ± 15) ng/mL, respectively. The passage over the BCSFB was 0.17 % (SEM ± 0.01). While no correlation was found between the function of the BCSFB assessed with the albumin ratio and the CSF teriflunomide concentration, the CSF and plasma teriflunomide concentrations were highly correlated (r s = 0.90, < 0.0001). Conclusions Further studies are warranted to determine if the obtained CSF teriflunomide concentration reflects that in the CNS and is able to influence inflammatory and degenerative processes within the CNS.

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“…These results add to the growing body of evidence from real-world clinical practice that the effectiveness of natalizumab on clinical end points (relapses and disease progression) and MRI end points is maintained for patients who switch from Q4W dosing to EID 7–9 and are consistent with those of a recently published prospective study that found sNfL levels were unchanged during 12 months of follow-up in patients who switched from natalizumab Q4W to every - 6 -week (Q6W) dosing. 36…”

Section: Discussionmentioning

confidence: 99%

Serum neurofilament light levels in natalizumab-treated patients with multiple sclerosis who switch to extended interval dosing from every-4-week dosing in real-world clinical practice

et al. 2022

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Background: Serum levels of neurofilament light chain (sNfL) are a potentially useful biomarker for assessing the efficacy of multiple sclerosis (MS) treatments. Objective: To compare levels of sNfL in patients with MS who switched from natalizumab every 4 weeks (Q4W) to extended interval dosing (EID) and patients who remained on Q4W dosing in real-world clinical practice. Methods: This was a retrospective analysis of samples from patients treated with natalizumab from 2010 to 2015 at a single center in the United States. Levels of sNfL were compared in patients who stayed on Q4W dosing or who switched to EID (parallel-arm analyses) and during Q4W and EID periods in patients who switched to EID (pre- and post-switch analyses). Results: The analysis included 139 patients (Q4W: n = 79; EID: n = 60). After adjustment, levels of sNfL did not significantly differ between patients who remained on Q4W dosing and those who switched to EID in parallel-arm analyses (adjusted Q4W-EID difference = 0.51 pg/mL; p = 0.60) or pre- and post-switch analyses (adjusted difference = 0.96 pg/mL; p = 0.10). Conclusion: These sNfL biomarker results suggest that the effectiveness of natalizumab is maintained in patients who switch from Q4W dosing to EID.

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No increase of serum neurofilament light in relapsing-remitting multiple sclerosis patients switching from standard to extended-interval dosing of natalizumab

Cited by 11 publications

References 43 publications

Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Serum neurofilament light for detecting disease activity in individual patients in multiple sclerosis: A 48-week prospective single-center study

Teriflunomide Concentrations in Cerebrospinal Fluid and Plasma in Patients with Multiple Sclerosis: A Pharmacokinetic Study

Serum neurofilament light levels in natalizumab-treated patients with multiple sclerosis who switch to extended interval dosing from every-4-week dosing in real-world clinical practice

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