Care pathway heterogeneity in Amyotrophic Lateral Sclerosis: effects of gender, age and onset

Background and objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration resulting in loss of muscle function. Care management is restricted to symptomatic and palliative strategies, while clinical manifestations are heterogeneous. However, assessing the timing and benefits of ALS major clinical interventions remains challenging, with varying and nonspecific time-to-events estimates reported in the literature. Consequently, we proposed a retrospective cohort study leveraging healthcare system data to investigate ALS patients care pathway stratified by gender, age class and onset site to describe strategies diversity and temporality. Methods: We developed an algorithm to identify incident ALS patients in the French hospitalization registry and assessed its quality through comparison with literature. We described 7 states, encompassing patient status regarding clinical intervention history, considered 15 transitions and stratified the analysis depending on 12 different patient profiles, defined according to gender, the presence of symptoms indicative of disease onset site and age class, to model profile-specific care pathway trajectories. Alongside analysis of median time before transition, we compared acceleration factors resulting from Accelerated Failure Time (AFT) and time-inhomogeneous models. Results: We identified 21,153 incident patients with ALS between 2013 and 2022 with a mean age of 67.7±13.1 years at time of in-registry detection, male/female and spinal/bulbar ratios of 1.2 and 1.9, respectively. Non-invasive ventilation (NIV), gastrostomy, tracheostomy or death at hospital was recorded for 55.24% of the study population. We identified significant variations in utilization based on gender, age class, and onset site. Notably, older age and bulbar onset site accelerated gastrostomy use and spinal onset site was associated with delayed NIV initiation while tracheostomy, mainly considered for younger patients (<64 years), is rarely indicated in ALS care management. Alongside investigation of time-to-event speed, we report extensively the patient profile-specific estimated median delay before clinical event start. Conclusion: Leveraging real-world data from hospital registries provides a large sample size to investigate low prevalence diseases. In conjunction with multi-state models such data enables a comprehensive analysis of care pathways which revealed variations in ALS management strategies based on patient profiles. By identifying these disparities, our study contributes to enhancing the foreseeability of support strategies for ALS patients.