Progression of ALS based on adapted ALS Milano-Torino staging system in US Medical Claims: ALS-MITOS-C

Topic:

Clinical Management

Poster Number: P269

Author(s):

Daniel Gomes, Voxanalytica, San Francisco, CA, Tony Wang, PhD, Voxanalytica, San Francisco, CA, Sarah M England, PhD, Biogen, Cambridge, MA, Katie Stenson, Biogen, Cambridge, MA, Boyang Bian, PhD, Biogen, Cambridge, MA, Teresa E Fecteau, PhD, Biogen, Cambridge, MA

Background: Understanding natural history of ALS is critical for development of more effective management strategies and can support design of clinical trials for new therapies. Prospective studies from ALS centers of excellence have greatly enhanced our understanding of natural history of ALS. Medical claims can provide real world data on natural history of ALS from a broader sample of patients. However, we are not aware of claims-based studies that have adapted validated clinical staging systems such as ALS-MiToS.

Objectives: Retrospective study based on de-identified medical claims linked to mortality data covering October 2015 to 2024. Diagnosis of ALS was based on previously published algorithms. Threshold states for the 4 ALS-MiToS domains were translated into ICD/HCPCS/CPT codes: Movement (Walking/Self-Care), Communication, Breathing and Swallowing Impairment. Staging was aligned to original ALS-MiToS: Stages 0-4 based on count of domains and 5 for death. To adjust events with competing risk for death, composite endpoints were used: MiToS domains – Swallowing Impairment or Death; MiToS stages – Stage 4 or 5/Death. Age at onset of each MiToS-C domain and Stage were calculated by the Turnbull Estimator, an adaptation of Kaplan-Meier that explicitly handles patients with varying history and follow up duration.

Results: Final cohort included 7273 patients with a median age at ALS Diagnosis of 63.7 years (IQR 57.2-71.8), 44% female; 84% limb onset, 14% bulbar onset, and 1.8% both; 42% died during follow-up (n=3058). Median ages of impairment for Breathing 64.1 (56.4-72.9), Walking/Self Care 69.5 (61.3-78.8), Communication 69.2 (61.0-78.4), Swallowing or Death 70.7(62.6-79.1). Median (IQR) onset of MiToS-C Stages 2, 3, 4 or 5/Death: 65.2(59.0-73.3), 67.2(60.9-75.6), 69.9(62.7-77.5), respectively.

Conclusion: Real-world data can augment evidence from ALS natural history studies with a broader range of patients and adaptation of the ALS-MiToS staging can provide clinically meaningful endpoints to assess progression of disease in medical claims.