Implementation of 2023 Canadian Thoracic Society Guidelines for Single-Inhaler Triple Therapy Could Reduce Exacerbation and Mortality Rates in COPD: PROMETHEUS Canada.

PurposeRandomized trials report that single-inhaler triple therapy is more effective than dual bronchodilators at reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this effect may have been influenced by the forced withdrawal of inhaled corticosteroids (ICS) at randomization. We used an adaptive selection new-user design to compare single-inhaler triple therapy with dual bronchodilators in real-world clinical practice.Patients and MethodsWe identified a cohort of COPD patients, 40 years or older, treated during 2017–2020, from the United Kingdom’s Clinical Practice Research Datalink, a real-world practice setting. ICS-naïve patients initiating single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, after adjustment by propensity score weighting.ResultsThe cohort included 4106 new users of single-inhaler triple therapy and 29,702 of dual bronchodilators. Single-inhaler triple therapy was the first maintenance treatment in 44% of the users and 43% had no COPD exacerbations in the prior year. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with triple therapy relative to dual bronchodilators was 1.08 (95% confidence interval (CI): 1.00–1.16). Among patients with two or more prior exacerbations the HR was 0.83 (95% CI: 0.74–0.92), while for those with prior asthma diagnosis it was 0.86 (95% CI: 0.70–1.06) and with blood eosinophil count >300 cells/µL it was 0.89 (95% CI: 0.76–1.05). The incidence of severe pneumonia was increased with triple therapy (HR 1.50; 95% CI: 1.29–1.75).ConclusionIn a real-world setting of COPD treatment among ICS-naïve patients, thus unaffected by ICS withdrawal, single-inhaler triple therapy was not more effective than dual bronchodilators at reducing the incidence of exacerbation, except among patients with multiple exacerbations. Single-inhaler triple therapy should be initiated mainly in patients with multiple exacerbations while, for most others, dual bronchodilators are just as effective whilst avoiding the excess risk of severe pneumonias.

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Rationale : COPD exacerbations are associated with elevated risk for further COPD exacerbations and increased morbidity and mortality. Patients with COPD and concurrent asthma may have higher risk of exacerbations than those with COPD or asthma alone; it is unknown whether timely intervention with single-inhaler triple therapy would have benefits on their exacerbation risk. This study investigated whether prompt initiation of Budesonide/Glycopyrrolate/Formoterol Fumarate (BGF) after an exacerbation among patients with COPD and asthma is associated with reduced subsequent COPD exacerbations compared to delayed and very-delayed initiation strategies. Methods: The MITOS EROS+CP (US) study was a retrospective analysis of patients with COPD from the United States using the Inovalon More2 Registry and Medicare Fee-for-Service claims; this analysis focused on a sub-group of patients with concurrent asthma diagnosis (COPD+asthma). Patients were aged ≥40 years, with 12-months baseline history, initiating BGF therapy between July 2020-May 2023, and within 1 year of a qualifying COPD exacerbation: (a) ≥1 severe exacerbation, (b) ≥2 moderate exacerbations without prior inhaled maintenance therapy or (c) ≥1 moderate exacerbation while on prior therapy. The first observed qualifying exacerbation event defined the index date. Negative binomial regressions were used to assess the adjusted risks for subsequent exacerbations by initiation group: prompt (≤30 days), delayed (31-180 days), and very-delayed (181-365 days); adjustments were made for age, gender, race, comorbidity, payer group, index event type, and baseline exacerbations. Results: 8837 patients with COPD+asthma were identified; 1090 (12.3%) prompt, 3292 (37.3%) delayed, and 4455 (50.4%) very-delayed initiators. Overall, mean age was 66.1 years, 72.0% were female, and mean follow-up was 479.3 days. Crude post-index exacerbation rates per person-year (95% CI) were 1.38 (1.30-1.45) for prompt compared to 1.90 (1.85-1.94) and 2.48 (2.45-2.52) for delayed and very-delayed initiators, respectively (Figure 1). After adjustments, prompt initiators had 20% and 25% lower incidence of subsequent exacerbations compared to delayed (IRadj: 0.80 [0.75-0.85]) and very-delayed initiators (IRadj: 0.75 [0.71-0.80]) (Figure 1). Conclusion: Among patients with COPD who have a concurrent diagnosis of asthma, promptly initiating BGF following a moderate or severe COPD exacerbation was associated with a 20% and 25% lower annualized rate of subsequent exacerbations compared to delayed and very delayed BGF initiation, respectively. Proactive use of BGF even after a single moderate COPD exacerbation among patients with COPD and asthma, who have higher disease burden than either condition by itself, may be warranted to prevent further exacerbations and reduce their morbidity.

BackgroundIn some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs. LABA/LAMA or ICS/LABA using a single device.MethodsWe systematically reviewed randomized controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. We searched the PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy compared with single-inhaler dual therapy on all-cause mortality, the risk of acute exacerbation of COPD (AECOPD), and some safety endpoints. The Cochrane Collaboration tool was used to assess the quality of each randomized trial and the risk of bias.ResultsA total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than LABA/LAMA FDC (risk ratio, 0.70; 95% CI 0.56‐0.88). Single-inhaler triple therapy reduced the risk of exacerbation and prolonged the time to first exacerbation compared with single-inhaler dual therapy. The FEV1 increased significantly more under single-inhaler triple therapy than under ICS/LABA FDC (mean difference, 103.4 ml; 95% CI 64.65‐142.15). The risk of pneumonia was, however, significantly higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC (risk ratio, 1.55; 95% CI 1.35–1.80).ConclusionsThis meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of death of any cause and of moderate or severe exacerbation in COPD patients. However, the risk of pneumonia is higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC.Trial registration PROSPERO #CRD42020186726.

IntroductionFrom 2018 single inhaler triple therapy (SITT) became available in France to treat moderate-to-severe chronic obstructive pulmonary disease (COPD). Given its simplified inhaler use compared with multiple inhaler triple therapy...

Data analysis of numerous studies was carried out and trends and directions in the management of patients with сhronic obstructive pulmonary disease (COPD) were analysed. Studying the characteristics of factors contributing to disease development без коми allows us to understand that the smoking epidemic, the aging of the world population and the lack of disease-modifying therapy will lead to a further increase in mortality from COPD. Each COPD exacerbation increases both the risk and frequency of subsequent exacerbations, and the development of local or systemic changes and complications has also been established. Not only severe but also moderate COPD exacerbations (those that do not require hospitalization and could be treated on an outpatient basis) also increased the risk of subsequent exacerbations and death. The degree of increase in risk was proportional to the number of exacerbations per year. Thus, two moderate exacerbations per year increased the risk of death by 80 % (hazard ratio — 1.80 (95 % confidence interval (CI): 1.19—2.70)), while increased frequency of exacerbations to 5 increased the hazard ratio to 2.33 (95 % CI: 1.45—3.76).The effectiveness of the treatment of patients with COPD and the dependence of the latter on various factors were evaluated. Based on the received data, the specialists have concluded that the presence of one severe or two or more moderate COPD exacerbations during one year indicates a high risk of exacerbations in the future and is associated with an increased risk of premature death. Therefore, a high-risk group patient requires special attention when choosing the tactics of his management. This is reflected both in international and national consensus documents. A single-inhaler triple therapy (specifically a fixed combination of budesonide/glycopyrronium/formoterol), administered within the first 30 days after an exacerbation, is currently the only pharmacotherapeutic option that has been proven to reduce mortality in COPD patients.

PurposeClinical phenotypes of chronic obstructive pulmonary disease (COPD) include chronic bronchitis and emphysema, which have a high degree of overlap. In the phase 3 BOREAS (NCT03930732) trial, add-on dupilumab vs...

IntroductionChronic obstructive pulmonary disease (COPD) is a progressive lung condition associated with high morbidity and mortality. Single-inhaler triple therapy (SITT), such as budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF), is recommended for patients with COPD who are not adequately controlled by dual therapy (DT). Escalation from DT or switching from triple therapy (TT)—SITT or multiple-inhaler TT (MITT)—are key real-world treatment pathways.MethodsThe observational, retrospective, multicenter ORESTES study included adults (≥ 40 years) with COPD initiating BGF in routine clinical practice. This secondary analysis focuses on the following treatment pathways: escalation from DT and switch from TT. Patients’ characteristics, exacerbations, additional COPD treatments, and healthcare resource utilization (HCRU) were assessed.ResultsA total of 295 patients escalated from DT and 356 switched from TT (SITT: 147; MITT: 209) to BGF. 66.8% of patients escalating from DT and 78.5% switching from TT showed a high-risk GesEPOC phenotype; 77.9% and 80.0% had mMRC grade ≥ 2, and 91.2% and 96.1% had ≥ 3 comorbidities. Following BGF initiation, the annualized exacerbation rate decreased by 11.6% (from 1.06 to 0.94) in patients escalating from DT and by 15.5% (from 1.60 to 1.35) in patients switching from TT (after SITT: 17.8% reduction; after MITT: 14.1%). Rescue medication use declined overall, and specifically short-acting beta-2 agonists (SABA) use declined by 23.2% and 19.4% (SITT: 21.9%; MITT: 18.4%). Emergency room visits and hospitalizations decreased by 19.7% and 19.0% in patients escalating from DT, and by 29.4% and 25.5% among those switching from TT (SITT: 25.0%/18.3%; MITT: 32.4%/29.9%).ConclusionsIn this real-world Spanish cohort of patients with COPD not adequately controlled with DT or TT, reductions in exacerbations, rescue medication use, and HCRU were observed after BGF initiation, supporting the potential value of earlier introduction of BGF in patients with persistent symptoms and/or frequent exacerbations despite high-intensity therapy.Clinical Trial RegistrationNCT06321731.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-026-00341-6.

Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial

IntroductionCOPD 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.MethodsWe 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.ResultsA 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.ConclusionAssuming 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.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12931-025-03358-8.

BackgroundThis study aims to compare the effects of single inhaler triple therapy comprised of inhaled corticosteroids (ICSs), long-acting β2-agonists (LABAs), and long-acting muscarinic receptor antagonists (LAMAs) with dual therapies comprised of either LABA/LAMA, ICS/LABA or separate ICS/LABA plus LAMA triple therapy.MethodsThe Pubmed, Embase, and Cochrane databases were searched up to October 31st 2018. Only randomized controlled trials were included in the meta-analysis. The primary outcome was the rate of moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations.ResultsSeven studies fulfilling the inclusion criteria were included in the meta-analysis. Single inhaler triple therapy was associated with a significantly lower risk of COPD exacerbation compared with LABA/LAMA (rate ratio, 0.69; 95% confidence interval [CI] 0.55 to 0.87, I2=85%), and ICS/LABA (rate ratio, 0.81; 95% CI 0.73 to 0.89, I2=29%) dual therapy. Single inhaler triple therapy led to a more significant improvement in lung function and quality of life compared with LABA/LAMA and ICS/LABA dual therapy. Single inhaler triple therapy was associated with a higher risk of pneumonia compared with LABA/LAMA (risk ratio, 1.38, 95% CI 1.14 to 1.67, I2=0) dual therapy.ConclusionsThe use of single inhaler triple therapy for COPD patients can result in lower rates of moderate or severe exacerbations of COPD as well as improved lung function and quality of life compared with dual therapy with LABA/LAMA or ICS/LABA.

Impact of Increased Single-Inhaler Triple Therapy Use in Appropriate Patients on Chronic Obstructive Pulmonary Disease Exacerbations, Mortality, and Medical Costs: PROMETHEUS Spain

Objective In Japan, the optimal initiation timing and efficacy of single-inhaler triple therapy (SITT) in asthma management remain unexplored. This study investigated SITT initiation timing following an asthma exacerbation, and examined patient demographics and clinical characteristics. Methods Observational, retrospective cohort study in patients with asthma aged ≥15 years who initiated SITT following their earliest observed asthma exacerbation (February–November 2021), using data from Japanese health insurance claims databases (JMDC and Medical Data Vision [MDV]). The study period ended May 2022 for JMDC and September 2022 for MDV. Descriptive analyses were performed independently by database. Variables evaluated included timing of SITT initiation post exacerbation (prompt, delayed and late, ≤30, 31–180 and >180 days post index, respectively), patient demographics, clinical characteristics, and pre-index treatment. Results Of patients in the JMDC and MDV databases, most initiated SITT promptly after an asthma exacerbation, 60.8% (n = 951/1565) and 44.4% (n = 241/543), respectively. Delayed initiation occurred in 22.6% (n = 354/1565) and 26.3% (n = 143/543) of patients, and late initiation occurred in 16.6% (n = 260/1565) and 29.3% (n = 159/543), respectively. Most patients were indexed on a moderate asthma-related exacerbation, 97.1% (n = 1519/1565) and 68.7% (n = 373/543), respectively. Conclusion Most patients with asthma initiated SITT promptly following a moderate exacerbation, with delayed and late initiation more common among patients with complex clinical profiles. The findings underscore the necessity for future research to examine the interaction between patient characteristics, clinical outcomes, and the timing of SITT initiation to optimize treatment strategies, as clinical practice may vary by exacerbation severity.

Rationale: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays an upstream role in chronic obstructive pulmonary disease (COPD). In the phase 2a, multicenter, double-blind COURSE study (NCT04039113), tezepelumab reduced the annualized rate of COPD exacerbations that were moderate (resulting in systemic corticosteroids [SCS] and/or antibiotics use for ≥3 days [or one depot injection]) or severe (leading to hospitalization or death) by 37% versus placebo in patients with a baseline blood eosinophil count (BEC) of ≥150 cells/µL (95% CI: 7-57; rate ratio: 0.63 [95% CI: 0.43-0.93]). No reductions in exacerbations were observed in patients with BECs of <150 cells/µL (rate ratio: 1.19 [95% CI: 0.75-1.90]). It is not known whether the exacerbation reduction observed with tezepelumab varies based on whether moderate exacerbations with antibiotic use alone are counted. This exploratory analysis evaluated the efficacy of tezepelumab versus placebo in patients from COURSE, grouped by baseline BEC, in reducing COPD exacerbations based on whether antibiotic use alone was a criterion for moderate exacerbations. Methods: Patients (40-80 years old) with moderate to very severe COPD were randomized 1:1 to receive tezepelumab 420 mg or placebo subcutaneously every 4 weeks for up to 52 weeks. This analysis assessed the annualized rate of moderate or severe COPD exacerbations over 52 weeks in patients overall and by baseline BEC subgroup (≥150 cells/μL and <150 cells/μL) based on whether antibiotic use (for ≥3 days) alone was included in the definition of a moderate exacerbation during the study. Results: Overall, 165 patients received tezepelumab and 168 received placebo. During the study, there were a small number of moderate exacerbations with antibiotic use and without SCS use. When moderate exacerbations treated with antibiotics alone were excluded, tezepelumab recipients overall and patients with a baseline BEC ≥150 cells/µL experienced 20% and 39% fewer COPD exacerbations versus placebo, respectively, over 52 weeks. For moderate exacerbations treated with antibiotics alone, tezepelumab recipients overall and those with a baseline BEC of ≥150 cells/µL had 10% and 21% fewer exacerbations versus placebo, respectively, over 52 weeks. No reductions were seen in patients with a BEC <150 cells/μL (Table). Conclusions: Compared with placebo recipients, tezepelumab recipients overall and those with baseline BECs of ≥150 cells/µL had reduced rates of COPD exacerbations, regardless of whether moderate exacerbations were treated with SCS or antibiotics alone.

PurposeThe efficacy and safety of first-line triple and dual therapy remain unclear because the stepwise strategy is a worldwide standard in controller-naïve asthma. A preliminary retrospective cohort study was conducted to investigate the efficacy and safety of first-line triple and dual therapy for managing controller-naïve and symptomatic adult patients with asthma.Patients and MethodsPatients with asthma who received first-line single-inhaler triple therapy (SITT) or dual therapy (SIDT) for at least 8 weeks were selected between December 1, 2020, and May 31, 2021, in Fujiki Medical and Surgical Clinic, Miyazaki, Japan. Data on daytime and nighttime visual analog scale (VAS) scores, lung function tests, fractional exhaled nitrogen oxide (FENO), and adverse events were compared between SITT and SIDT pre- and post-treatment.ResultsThe SITT significantly improved the nighttime, but not daytime, VAS scores better than the SIDT 2 weeks post-treatment (P = 0.0026), whereas SITT and SIDT significantly improved daytime and nighttime VAS scores after treatment compared to baseline. Both therapies also significantly improved lung functions and FENO post-treatment. The proportion of patients achieving complete control in the nighttime VAS scores after SITT was significantly higher than that four (P = 0.0186) and 8 weeks (P = 0.0061) after SIDT. Only patients with SITT experienced dry mouth.ConclusionOur study demonstrated that first-line SITT and SIDT were effective, and SITT improved disease control faster than SIDT in controller-naïve and symptomatic adult patients with asthma. The first-line SITT may contribute to faster and better control levels in symptomatic patients with asthma.