A large real-world analysis among older Medicare patients compared asthma biologics and found mepolizumab performed comparably to dupilumab for preventing asthma hospitalizations. The same dataset reported significantly fewer exacerbations with mepolizumab, offering rare head-to-head guidance in a population where treatment choice is often driven by access, comorbidity profiles, and prior response patterns. Real-world comparative effectiveness is particularly valuable in asthma biologics because trials may not reflect the age, polypharmacy, and adherence patterns seen in practice. The study’s signal suggests that selection algorithms could incorporate outcome differences beyond healthcare utilization endpoints. For payers and clinicians, the immediate application is to refine formulary and prescribing logic for older patients, where safety tolerability and exacerbation reduction drive quality-of-life gains.