We are happy to announce that our new paper on how to use cerebrospinal fluid neurofilament light chain (CSF NfL) in daily clinical practice has appeared online (open access) in the journal of Neurology Neuroimmunology and Neuroinflammation.
In this paper, we have documented how the BartsMS team is already using for more than four years NfL values obtained with a lumbar puncture to advise pwMS on which disease-modifying treatment strategy would be best for them. This means that we only accept that pwMS are free of disease activity when the following three domains are evaluated:
1. Clinical – Presence of relapses
2. Radiological – New or enhancing lesions on brain or spinal cord MRI
3. Cerebrospinal fluid – Neurofilament light chains above age-related references values
This three-layered approach is novel, as the majority of current MS neurologists base their treatment strategies solely on the first/clinical and second/radiological domains. However, we demonstrate that MS disease activity is most frequently represented by elevated CSF NfL (85 out of 203 pwMS) compared to clinical (81 out of 203 pwMS) and MRI activity (65 out of 203 pwMS).
In addition, it was also apparent that 22 out of 203 pwMS (approximately 10 %) had increased CSF NfL as the only sign of disease activity, and this was especially true for people with the progressive disease stage.
The implications of these findings are tantalising, as it adds a whole new layer on top of the traditional disease activity work-up. It also means that those with progressive disease are no longer side-lined as inactive in so far as their disease is concerned. The technique we have used to measure the NfL values is CE-certified and available for commercial use in the European Union. This means that European MS neurologist can pick up the phone as we speak and discuss with their clinical laboratories how to implement CSF NfL measurements in their clinical practice.
Our findings also question the current classifications of MS, moving towards a more biological signature of disease activity than a clinical one. The current MS classification system that Lublin et al. introduced in 2013 still makes the distinction between relapsing and progressive pwMS. However, as our data show that progressive pwMS can still manifest with very high CSF NfL levels reflecting ongoing and undoubtfully harmful inflammation this classification system feels outdated. Shouldn’t we be focusing on active versus inactive disease instead? . Labelling pwMS as active versus inactive based on our three-layered disease-activity cake would therefore reflect much better the treatment dilemmas neurologists face today. What do you think?
Saúl Reyes*, Ide Smets*, David Holden, Karina Carrillo-Loza, Tatiana Christmas, Lucia Bianchi, Francesca Ammoscato, Benjamin Turner, Monica Marta, Klaus Schmierer, Gavin Giovannoni, Sharmilee Gnanapavan
Objective To evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.
Methods This was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.
Results Of 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).
Conclusions CSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.