Supplementary Material for: Impact of increased single-inhaler triple therapy use in appropriate patients on COPD exacerbations, mortality, and medical costs: PROMETHEUS Spain.

Introduction: COPD is the third cause of death in Spain. The ETHOS (NCT02465567) and IMPACT (NCT02164513) RCTs showed reduced exacerbations and all-cause mortality for single-inhaler triple therapy (SITT), but no studies have evaluated the potential impact on COPD outcomes of higher SITT adoption in Spain.

Methods: We used literature-based data on patient characteristics, incidence, COPD severity changes, treatment distributions/transitions, mortality, exacerbations, and medical costs, to inform a stochastic simulation of the Spanish COPD population for 2025-2034 under two scenarios: “Status Quo” and “Increased SITT”, in which higher SITT use is driven by airflow limitation, exacerbation history (as per 2025 GOLD guidelines) and SITT replacing multiple-inhaler triple therapy (MITT). Additionally, we present results separately for the subset of patients that met the criteria for SITT use, referred to as “flagged population.”

Results: In our 10-year simulation, increased SITT use in the flagged population could lead to 51,000 deaths avoided resulting in a 14.6% reduction in mortality rates and extended patient life by 1.2 years per COPD flagged patient. Additionally, increased SITT use in the flagged population reduced severe and moderate exacerbations by 62,000 (an 11.5% reduction) and 366,000 (an 11.6% reduction), respectively, resulting in total medical savings of €384 million.

Conclusion: Based on our simulation, increased use of SITT in the Spanish COPD population, consistent with the most recent 2025 GOLD guidelines’ recommendations, could reduce mortality and exacerbations and their corresponding medical costs. Increasing SITT utilization in patients with COPD may constitute a long-term strategy with relevant clinical and economic benefits.

引言：慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）是西班牙的第三大死亡病因。ETHOS（NCT02465567）与IMPACT（NCT02164513）两项随机对照试验（Randomized Controlled Trial, RCT）证实，单吸入器三联疗法（Single-Inhaler Triple Therapy, SITT）可减少急性加重事件与全因死亡率，但尚无研究评估西班牙境内更广泛应用SITT对COPD转归的潜在影响。
方法：本研究采用基于文献的患者特征、发病率、COPD严重程度变化、治疗分布与转换、死亡率、急性加重事件及医疗成本数据，针对2025至2034年的西班牙COPD人群开展两种场景下的随机模拟研究：「现状场景」与「SITT增量使用场景」。该场景下SITT使用量提升的驱动因素包括气流受限、急性加重史（符合2025年全球慢性阻塞性肺疾病防治指南（Global Initiative for Chronic Obstructive Lung Disease, GOLD）标准），且以SITT替代多吸入器三联疗法（Multiple-Inhaler Triple Therapy, MITT）。此外，本研究将针对符合SITT使用标准的患者亚组（即「标记人群」）单独呈现分析结果。
结果：在本次10年模拟周期中，标记人群内SITT使用量的提升可避免51000例死亡，使死亡率降低14.6%，且每名标记COPD患者的生存期可延长1.2年。此外，标记人群中SITT使用量的提升可分别减少62000例重度急性加重（降幅11.5%）与366000例中度急性加重（降幅11.6%），累计实现医疗成本节约3.84亿欧元。
结论：基于本次模拟结果，契合2025年GOLD指南推荐的西班牙COPD人群增量使用SITT策略，可降低死亡率与急性加重事件发生率，并减少相应医疗成本。提升COPD患者的SITT使用率或可成为兼具临床与经济效益的长期干预方案。