Neurofilament to monitor extended interval dosing.


When there is inflammation due to lesion formation that results in nerve damage, his damage can be picked up by monitoring neurofilaments.Natalizumab is typically dosed at monthly intervals but to reduce the risk of PML 6 weekly dosing has been used. In this study they do not find disease activity associated with the the extended dosing. Likewise they did not find evidence of increased neurofilament during this time. They suggest that monitoring neurofilaments may replace MRI and this may be true but in this cohort as no-one had disease activity using MRI or clinical outcomes, it is less clear cut. However monitoring neurofilament can be easier than having an MRI. Remember if you can’t get neurofilament done locally, NDG offers a service via the NHS. Details on the blog

Valentino et al. sNFL applicability as additional monitoring tool in Natalizumab Extended Interval Dosing regimen for RRMS patien MSARD, 2022

Introduction: Extended interval dosing (EID) of Natalizumab (NAT) has been proposed to reduce progressive multifocal leukoencephalopathy (PML) risk associated with standard interval dosing (SID) in people with multiple sclerosis (MS). Previous studies have suggested that NAT effectiveness is maintained in the great majority of patients who switch from SID to EID; monitoring of disease activity is currently based exclusively on clinical and MRI parameters. Frequent MRI are expensive and not always applicable, underlining the need for biological markers able to detect central nervous system lesions. Serum Neurofilament-light chain (sNFL) currently represents the most promising biomarker of disease activity, prognosis and treatment response in MS, and their clinical suitability is increasingly evident. The objective of the present study is to assess the applicability of sNFL as additional/alternative measure of treatment efficacy during EID regimen.

Methods: We measured sNFL…in longitudinal samples from 63 Relapsing Remitting (RR) MS patients switched from SID to EID. Inclusion criteria: diagnosis of RRMS, age 18-60 years; NAT SID for at least 12 months; NEDA-3 (no evidence of disease activity) for at least 12 months; availability of at least 2 serum samples collected 6 months apart. Patients’ follow-up time during EID was at least 12 months and 2 blood samples were collected after at least 6 and 12 months. Clinical examination was performed before each infusion, while MRI 6 and 12 months after NAT initiation and according to PML risk during the whole study.

Results: No patients showed clinical or MRI activity during the whole follow-up. sNFL levels measured during SID and EID were comparable, without significant difference between groups. The effect of EID on NFL levels did not show significant effects and sNFL levels did not vary with time during SID or EID protocols. Intra-individual sNFL levels demonstrated overall stability during SID and EID). According to our previously published reference values, sNFL levels were in the normal range in all samples, both during SID and EID.

Conclusions: Our results suggest that sNFL quantification can be used as an alternative/additional approach to MRI in managing individual patients. The present work provides a new clinical application of sNFL to monitor NAT efficacy.

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  • My experience of Natalizumab was that I functioned better for 2 weeks after an infusion and then struggled for the next 2 weeks. JCV positivity prevented shorter dosing intervals and I switched to Ocrelizumab. I suspect we’ll see SNFL levels rising in some individuals shortly after Natalizumab infusions and tailored dosing regimens, guided by SNFL levels and MRI activity. SNFL measurement will need to be more frequent than 6 monthly, possibly even a few times per week to guide dosing intervals in an individual. Twice a year SNFL measurement lacks the resolution to effectively guide dosing frequency, but maybe there is a significant lag between disease activity and SNFL level change.

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