Abstract Rationale Amyotrophic lateral sclerosis (ALS) is characterized by a highly variable clinical course, making management complex, especially regarding respiratory support. Non-invasive ventilation (NIV) is known to improve quality of life and survival in ALS, but the optimal timing of NIV initiation remains unclear. This study aimed to characterize the disease trajectories surrounding NIV therapy in a large national cohort, to explore the relationship between NIV initiation timing and survival, and to identify patient subgroups with distinct health trajectories. Methods We conducted a retrospective analysis of individuals with ALS identified in the French national health insurance database who received NIV between 2015 and 2019. Incident cases aged 25 or older with at least one ALS diagnostic code were included. Using time sequence analysis and K-clustering, we identified clusters of patients with similar health trajectories based on timing of NIV initiation and survival outcomes. Key clinical events, comorbidities, and healthcare utilization patterns were examined. Results A total of 3,443 patients were included (58% male, median age 67 y.o). Tracheostomy and gastrostomy were performed in 3.9% and 33.4% of patients, respectively. Median time from ALS diagnosis to NIV initiation was 10.8 months, with death occurring at a median of 21.5 months post-diagnosis. Four clusters were identified: Cluster A (21%) and Cluster B (26%) had late NIV initiation; Clusters C (25%) and D (28%) had early initiation. Patients with late NIV initiation were younger, had fewer comorbidities, and more physiotherapy sessions. Survival after NIV was longer in Clusters B and C, which included more males, fewer psychiatric comorbidities, higher rates of obstructive sleep apnea, and less frequent emergency hospitalizations. Notably, Cluster B combined late NIV initiation with prolonged survival and was distinguished by predominantly spinal onset and low comorbidity burden. Conclusions Our findings highlight substantial heterogeneity in ALS patient profiles and care pathways surrounding NIV therapy. Importantly, there was no consistent or universal relationship between timing of NIV initiation and survival across the cohort. These results suggest that NIV initiation should be tailored to individual patient characteristics and disease progression rather than following a uniform timing strategy. Further research is warranted to clarify the interplay between comorbidities such as obstructive sleep apnea and respiratory support outcomes. This abstract is funded by: ARSLA, Resmed
Tankéré et al. (2026) studied this question.