Retrospective Spanish study links COPD triple therapy to lower costs and emissions

Initiation of single-inhaler triple therapy containing budesonide, glycopyrronium and formoterol was followed by less healthcare use, lower estimated annual costs and reduced greenhouse gas emissions among 718 adults with chronic obstructive pulmonary disease treated in routine practice across 20 Spanish hospitals. In the post hoc ORESTES analysis, annualized hospitalizations fell 12.9%, emergency room admissions fell 12.0% and actual use of short-acting beta-2 agonists dropped 25.5% during the year after treatment began. Applying Spanish healthcare unit costs and emission factors, investigators estimated that healthcare resource use cost €200.11 less per patient per year and generated 25.16 kg of carbon-dioxide equivalent fewer emissions per patient per year. These were descriptive before-and-after associations rather than proof that the therapy caused the changes, because the retrospective study had no concurrent control group.

The analysis used data from ORESTES, a multicenter, longitudinal, retrospective observational study registered as NCT06321731. Eligible patients were aged 40 years or older, had a confirmed COPD diagnosis, initiated budesonide/glycopyrronium/formoterol fumarate dihydrate before June 2023 and had at least 12 months of clinical data before initiation. The observation period covered the 12 months before treatment and up to 12 months afterward, ending earlier if a patient discontinued therapy, was lost to follow-up or died. Patients were identified retrospectively from electronic medical records, and treatment decisions were made by physicians during routine care rather than according to a research protocol. At 12 months, 89.3% of the cohort were persistent with triple therapy; 6.6% had discontinued treatment, 3.8% had died and 0.4% were lost to follow-up.

The cohort had a mean age of 70.17 years, a mean time since COPD diagnosis of 7.32 years, and several indicators of substantial disease burden. A total of 66.4% of patients had experienced at least one exacerbation during the preceding year, 72.3% were classified as having a high-risk GesEPOC phenotype, 78.4% had modified Medical Research Council dyspnea scores of at least 2, and 50.9% were classified as GOLD E. Before triple therapy, annualized rates were 0.53 hospitalizations, 4.47 hospitalized days, 0.71 emergency room admissions, 1.89 primary care visits and 1.28 specialist visits per patient. Emergency visits were treated as a separate category and did not include episodes resulting in hospitalization. Rescue-medication use was based on prescriptions documented as actually used by patients rather than prescriptions merely issued.

After budesonide/glycopyrronium/formoterol initiation, annualized hospitalization rates declined to 0.47 per patient and hospitalized days to 4.06, corresponding to reductions of 12.9% and 9.2%. Emergency room admissions decreased to 0.62, a 12.0% reduction, while primary care visits fell to 1.80, or 4.9%. Specialist visits moved in the opposite direction, increasing 17.5% to 1.51 per patient. The investigators said this rise might partly reflect the hospital-based study design and continued follow-up in specialist respiratory clinics, but the observational records could not establish whether closer follow-up caused any of the changes in acute care. The annualized rate of actual short-acting beta-2 agonist use fell from 1.19 to 0.89 prescriptions per patient, a decrease of 25.5%.

Researchers translated these utilization measures into economic estimates from the perspective of the Spanish National Health System. Published Spanish unit costs were updated to 2026 values using the general Consumer Price Index from Spain’s National Statistics Institute. The functional unit for the estimates was one patient over 12 months, and unit costs were applied to cohort-level annualized measures of resource use. Before triple-therapy initiation, estimated healthcare resource costs averaged €2,599.46 per patient per year. Hospitalizations accounted for 88.5% of that amount, or €2,300.13, while emergency room admissions accounted for €101.57, primary care visits for €53.57 and specialist visits for €144.19. Following initiation, the overall estimate decreased by €200.11 to €2,399.35 per patient. Hospitalization costs produced a €210.59 reduction, emergency room costs a €12.14 reduction and primary care costs a €2.61 reduction, while specialist visit costs increased by €25.22.

The environmental model expressed resource use in kilograms of carbon-dioxide equivalent, combining published emission factors for hospitalizations, emergency room admissions, primary and specialist visits, patient transport and actual short-acting beta-2 agonist use. Transport-related emissions were estimated separately with Spanish travel-distance data and transport assumptions because the proxy distances used in the multinational framework were not considered sufficiently representative. Before initiation, total emissions associated with the selected care components were estimated at 245.43 kg CO2e per patient per year. Hospitalizations contributed 79.0%, or 193.96 kg CO2e, and actual rescue-medication use contributed 11.1%, or 27.27 kg CO2e. Emergency room admissions accounted for 5.2%, primary care visits 1.4% and specialist visits 3.2%. After initiation, the total fell by 25.16 kg CO2e to 220.27 kg CO2e.

Hospitalization-related emissions declined by 17.88 kg CO2e after treatment initiation, rescue-medication emissions by 6.94 kg CO2e, emergency room emissions by 1.53 kg CO2e and primary care emissions by 0.17 kg CO2e. Specialist-visit emissions increased by 1.37 kg CO2e. The emissions estimate was then tested under alternative assumptions about generic healthcare-contact factors, transport choices, vehicle electrification and travel distances. The modeled annual reduction ranged from 21.66 to 33.70 kg CO2e per patient across these scenarios, compared with the base-case estimate of 25.16 kg CO2e. Tested scenarios included varying generic healthcare-contact factors by plus or minus 25%, assuming all hospital and emergency travel used ambulances and other travel used private cars, increasing the electric-vehicle share from less than 1% to 20%, and applying the shortest and longest average travel distances reported across Spanish provinces. These sensitivity analyses supported the direction of the modeled result, although they did not remove the limitations of the observational comparison.

For system-level context, the authors multiplied the per-patient estimates by an external proprietary market estimate of 65,000 patients initiating triple therapy in Spain during 2025. This illustrative scenario implied approximately €13.0 million in annual healthcare-resource cost savings and 1,635 tons of avoided CO2e. The authors explicitly cautioned that the projection should not be interpreted as an observed national saving or emissions reduction. The economic and environmental analyses excluded maintenance inhaled therapies because complete longitudinal data for the pre-initiation period were unavailable and the previous inhaler devices could not be reliably inferred from recorded ingredients. Short-acting bronchodilator acquisition costs were omitted because their expected contribution was considered minimal. The selected resource and medication components also did not constitute a full environmental sustainability assessment of the COPD care pathway.

The results need to be interpreted within the design and scope of ORESTES. Its retrospective before-and-after comparison cannot establish that budesonide/glycopyrronium/formoterol caused the changes; regression to the mean and confounding by indication remain possible, and no paired longitudinal model, covariate adjustment, formal hypothesis testing or missing-data imputation was used. Data came from hospital-based records, potentially limiting generalizability to primary-care-led COPD services, and the analysis did not separately compare patients escalating from dual therapy with those switching from another triple regimen. It also was not a cost-effectiveness study: it included no concurrent comparator, health-utility outcome or incremental cost-effectiveness ratio. The multicenter cohort, use of routine electronic records and integration of economic and environmental estimates nevertheless provide descriptive real-world evidence that improvements in acute healthcare use after treatment optimization can coincide with lower modeled costs and emissions.

Subject of Research: Estimated healthcare costs, resource use and greenhouse gas emissions after COPD triple-therapy initiation in Spain

Article Title: Impact of Budesonide/Glycopyrronium/Formoterol Initiation on Healthcare Resource Utilization and Estimated Associated Costs and Greenhouse Gas Emissions Across COPD Care in Spain (ORESTES* Study)

Article References: Figueira-Gonçalves, J. M., Alcázar-Navarrete, B., Ancochea, A., Lastres, T., de Andrés-Nogales, F., Corregidor-García, C., Fitas, E., & Sánchez-Covisa, J. (2026). Impact of Budesonide/Glycopyrronium/Formoterol Initiation on Healthcare Resource Utilization and Estimated Associated Costs and Greenhouse Gas Emissions Across COPD Care in Spain (ORESTES* Study). Advances in Therapy. https://doi.org/10.1007/s12325-026-03817-8

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03817-8

Keywords: COPD, triple therapy, budesonide, glycopyrronium, formoterol, healthcare utilization, healthcare costs, greenhouse gas emissions, Spain, retrospective cohort, Impact, Initiation