Predictive ALS survival using ALSFRS-R slope & NfL: insights from the ALS/MND Natural History Consortium data and biofluid collection
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with no known cure. Disease progression in people living with ALS is heterogeneous, hindering personalized treatment development. The current gold standard for measuring disease progression in ALS, the ALS Functional Rating Scale - Revised (ALSFRS-R), is widely used but based on subjective measurements. Blood-based neurofilament light (NfL) has been studied as a diagnostic and prognostic biomarker but less information exists on its utility as a disease progression biomarker.
Methods
We present results from blood draws of 300 participants in the FDA-funded Clinic-Based Multi-Site ALS Natural History and Biofluid study of the ALS Natural History Consortium (NHC). Plasma NfL levels were measured and analyzed against different disease progression metrics based on the ALSFRS-R.
Results
NfL levels were found to be correlated with the ALSFRS-R average rate of change (r=−0.53, 95% CI −0.62 to −0.42). This association differed at a cutoff value of 61 pg/mL, with stronger correlations below this cutoff (r=−0.51 vs r=−0.18). Survival differed stratifying by this cutoff value, with participants under the cutoff having higher survival probabilities. The predictive value of NfL when predicting time to death was higher compared with the first ALSFRS-R across different event horizons. A model including both was better when predicting events up to 2 years after diagnosis.
Conclusions
These results highlight the utility of NfL as a disease progression biomarker in ALS alongside ALSFRS-R based disease progression metrics. The cutoff value can aid in clinical trial stratification, pragmatic trial planning, and clinical care.
KEY MESSAGES
What is already known on this topic
Blood-based neurofilament light (NfL) has previously been identified as a diagnostic and prognostic biomarker in ALS, but its use as a disease progression biomarker has been less studied.
What this study adds
This manuscript presents findings related to the utility of NfL as a disease progression biomarker in ALS from the current largest natural history cohort of people living with ALS. Specifically, it shows the added utility of baseline NfL values in predicting both disease progression and survival.
How this study might affect research, practice, or policy
Evidence in favor of the use of NfL as a disease progression biomarker can impact the design of clinical trials, helping with patient stratification, and allowing for better tailored treatments for people living with ALS. NfL is also being collected more frequently in standard clinical care, making a cutoff value for disease progression useful for disease management and patient planning.
