Abstract
BACKGROUND AND OBJECTIVES: The average survival of patients with amyotrophic lateral sclerosis (ALS) ranges from 2 to 5 years from symptom onset. However, it remains unclear whether this estimate has improved over time. The objective of this study was to analyze the survival trend of a large population-based cohort of patients with ALS over a 24-year period. METHODS: Patients from the Piemonte and Valle d'Aosta registry for ALS (PARALS) were categorized into the first (1995-2002), second (2003-2010), or third (2011-2018) epoch based on their diagnosis date. Survival was defined as the time from diagnosis to death, tracheostomy, or censoring date. A Cox proportional hazard model was developed with diagnosis epoch as the primary variable of interest, adjusted for sex, site of onset, age at onset, diagnostic delay, forced vital capacity at diagnosis, Δbody mass index from onset to diagnosis, noninvasive mechanical ventilation use, gastrostomy use, and site of follow-up. A subset analysis comparing the 2007-2012 and 2013-2018 cohorts was conducted, incorporating riluzole prescription, genetics, and preslope category as additional covariates. RESULTS: A total of 3,134 patients were included, evenly distributed across the 3 epochs (990, 1,023, and 1,121, respectively). The median survival remained stable during the first and second epoch (18.6 months vs 18.3 months) but improved during the third epoch (20.1 months; p = 0.0041), with a hazard ratio (HR) of 0.76 (95% CI 0.67-0.87, p = 0.00003). In the subset analysis, the most recent epoch (2013-2018) showed a continued survival advantage (HR 0.77, 95% CI 0.65-0.90). Of interest, the survival benefit was only evident among intermediate progressors (HR 0.60, 95% CI 0.45-0.80). DISCUSSION: In the PARALS, ALS survival increased over time. In a subset analysis, the beneficial effect of the epoch was only evident among intermediate progressors. The improvement in multidisciplinary care provided by tertiary centers may be one possible explanation for this finding, although further dedicated studies are needed to confirm this hypothesis.