Objective To assess the utility of rate of disease progression (ΔFS) as a prognostic biomarker in amyotrophic laterals sclerosis (ALS).

Methods A total of 203 patients with ALS were prospectively recruited over a 10-year period. At initial visit, the following variables were collected: demographic details, symptom duration, site of onset, phenotype, riluzole use and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. The ΔFS score at initial visit was calculated by dividing the ALSFRS-R total score by symptom duration (months). The primary end point was survival. Kaplan-Meier survival curves were used to illustrate the distribution of survival from a specified point, while multiple Cox proportional hazards modelling with backward stepwise variable selection was used to identify the independent predictors of survival at initial visit.

Results The ΔFS score at initial visit was a significant predictor of survival in ALS (p<0.001), and remained significant when adjusted for age and site of onset (p<0.001). 3 prognostic subgroups emerged, with a ΔFS score of <0.47 associated with a median survival of 2.4 years, which was significantly greater when compared with an initial ΔFS score of between 0.47 and 1.11 (1.6 years, p<0.05) and a score >1.11 (0.7 years, p<0.001). Importantly, multiple Cox proportional hazards modelling identified ΔFS as a highly significant independent predictor of survival in ALS (p<0.001) along with site of disease onset (p<0.01).

Conclusions Rate of disease progression appears to be a simple and sensitive clinical prognostic biomarker in ALS that could be potentially utilised in clinical practice and future therapeutic trials.