| Title: |
Natural history of the revised ALS functional rating scale and its association with survival:the PRECISION-ALS Extant Study |
| Authors: |
van Eijk, Ruben P A; Weemering, Daphne N; Opie-Martin,Sarah; van Unnik, Jordi W J; Caravaca Puchades,Alejandro; Chiò,Adriano; Corcia,Philippe; Galvin,Miriam; Hardiman,Orla; Heverin,Mark; Hobin,Frederik; Holmdahl,Oskar; Ingre,Caroline; Lamaire,Nikita; Mac Domhnaill,Éanna; McDonough,Harry; Manera,Umberto; McDermott,Christopher J; McFarlane,Robert; Mouzouri,Mohammed; Ombelet,Fouke; Povedano Panadés,Mónica; Sennfält,Stefan; Shaw,Pamela J; Terrafeta Pastor,Cristina; Van Damme,Philip; Vasta,Rosario; Veldink, Jan H; Al-Chalabi,Ammar; van den Berg, Leonard H; Projectafdeling ALS; Brain; Neurologen; Genetic Risks |
| Publication Year: |
2025 |
| Subject Terms: |
ALS; ALSFRS-R; joint model; survival; Neurology; Clinical Neurology |
| Description: |
Objective: To characterize the natural history of the revised ALS functional rating scale (ALSFRS-R) over a 24-month period following initial assessment, and to assess its associations with survival. Methods: Longitudinal ALSFRS-R measurements and survival data were obtained from seven population-based, European cohorts. Different models for the ALSFRS-R trajectory were evaluated, including tests for linearity and between-cohort differences. We employed a joint modeling framework to factor in mortality, thereby aiming to derive a more precise estimate of the population’s rate of decline, while simultaneously delineating its relationship with survival. Results: In total, 7,030 patients were included who produced 31,746 ALSFRS-R measurements during a follow-up period of 10,285 person-years. There was substantial evidence for a non-linear time trend within all cohorts (all p < 0.001), with faster progression rates at the beginning of follow-up. The average rate over 24 months was 0.89 points per month; 95% of the patients had a rate between 0.04 and 1.96. Overall, two components of the ALSFRS-R trajectory were found to be associated with survival: (1) the actual value of the ALSFRS-R total score and (2) the rate of change at any given time (both p < 0.001). Conclusions: Functional loss in ALS follows a decelerating trajectory, where the current functional status and the rate of change have a direct impact on the patient’ s probability of survival. Given the pivotal role of the ALSFRS-R in drug development, these results help to separate treatment benefit from the disease’s natural trajectory and to estimate the impact on survival. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2167-8421 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/466023 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/466023 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.385DF526 |
| Database: |
BASE |