Modeled reductions in COPD exacerbation rates, mortality, and related medical costs due to increased SITT adoption: PROMETHEUS Italy

Introduction: COPD is a leading cause of death and significant healthcare burden in Italy. The ETHOS (NCT02465567||5/2015) and IMPACT (NCT02164513||6/2014) randomized controlled trials (RCTs) have evaluated single-inhaler triple therapy (SITT) and have shown SITT efficacy and safety in reducing exacerbations and all-cause mortality in COPD patients. Despite benefits seen in RCTs, there are currently no studies that evaluate the long-term implications of broader and appropriate SITT use in Italy. We therefore evaluated the potential impact of broader SITT adoption on mortality, exacerbations, and related medical costs in Italy. Methods: We developed a 10-year (2025-2034) microsimulation model using literature-based patient demographic and clinical characteristics, incidence, therapy distribution and changes, COPD severity changes, mortality, and exacerbations to simulate the Italian COPD population. We modeled two scenarios: "status quo" and "increased SITT," and used patients' airflow limitation and exacerbation history (per GOLD guidelines) to choose patients for SITT. The model simulated annual changes in patient characteristics and related changes in medication therapy over 10-years. Patients' progression reflected reductions in % of FEV1 predicted and annual clinical characteristics. Flagged patients were those that qualified for SITT. Results: A starting population of approximately 1,550,000 diagnosed prevalent and incident COPD patients were included in the analysis. Based on our modeled "increased SITT" simulation and medication transition algorithm, at the end of the 10-year projection, the prevalent and incident COPD population in Italy increased to 1,881,000 patients, of which 45.4% received SITT. Over 10 years, modeled increased SITT treatment reduced severe and moderate Exacerbations by 12% and 13%, respectively, and all-cause mortality by 14%, avoiding 40,000 deaths, compared to status quo treatment for flagged COPD patients. Consequently, higher than current SITT adoption could reduce associated medical costs by €646 million for flagged COPD patients. Conclusion: Assuming RCTs effects and adherence translate to clinical practice, our model shows that higher than current SITT use in the Italian COPD population may lead to lower mortality rates and exacerbations, ensuring a substantial savings in associated medical costs. The results of this modeling study could provide rationale to modify existing practices on SITT prescribing with the aim of alleviating the burden of COPD.