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Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT.

ABSTRACT: Rationale: In the IMPACT (Informing the Pathway of COPD Treatment) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy reduced exacerbation risk versus FF/VI and UMEC/VI and mortality risk versus UMEC/VI. However, pneumonia incidence was higher in the inhaled corticosteroid (FF)-containing arms, raising questions about the relative benefit of exacerbation reduction compared with the increased risk of pneumonia.Objectives: Determine benefit-risk of the three treatments by evaluating time-to-first and rates of composite exacerbation or pneumonia outcomes.Methods: We evaluated time-to-first (prespecified) and rates (post hoc) of investigator-reported pneumonia, serious pneumonia leading to hospitalization or death, and the composite endpoints of 1) moderate (required antibiotics/corticosteroids)/severe (hospitalized) exacerbation or pneumonia and 2) severe exacerbation or serious (hospitalized) pneumonia. Analyses were repeated for radiographically confirmed pneumonia (post hoc).Results: Moderate/severe exacerbations occurred in 47%, 49%, and 50% of patients randomized to FF/UMEC/VI, FF/VI and UMEC/VI, and pneumonias in 8%, 7%, and 5%, respectively. FF/UMEC/VI reduced the risk of combined moderate/severe exacerbation or pneumonia (time-to-first) versus FF/VI (hazard ratio, 0.87 [95% confidence interval (CI), 0.82-0.92]) and UMEC/VI (0.87 [0.81-0.94]), as well as the risk of combined severe exacerbation or serious pneumonia versus UMEC/VI (0.83 [0.72-0.96]). FF/UMEC/VI reduced the rate of combined moderate/severe exacerbation or pneumonia (rate ratio, 0.78 [0.72-0.84]) and combined severe exacerbation or serious pneumonia (rate ratio, 0.76 [0.65-0.89]) versus UMEC/VI. Results were similar for radiographically confirmed pneumonia endpoints.Conclusions: Despite higher incidence of pneumonia in FF-containing arms, these composite exacerbation/pneumonia outcomes support a favorable benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.

SUBMITTER: Dransfield MT

PROVIDER: S-EPMC8086537 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aim: This study sought to compare treatment persistence, adherence, and risk of exacerbation among patients with COPD treated with single-inhaler triple therapy (SITT) and multiple-inhaler triple therapy (MITT) in the Chinese population. Methods: This was a multicenter, prospective observational study. Patients with COPD from ten hospitals in Hunan and Guangxi provinces in China were recruited from 1 January 2020 to 31 November 2021 for the study and were followed up for one year. Treatment persistence, adherence, and exacerbation rates during the 12-month follow-up were analyzed in COPD patients treated with SITT and MITT. Results: A total of 1,328 patients were enrolled for final analysis, including 535 (40.3%) patients treated with SITT and 793 (59.7%) treated with MITT. Of these patients, the mean age was 64.9 years and most patients were men. The mean CAT score was 15.2 ± 7.1, and the median (IQR) FEV1% was 54.4 (31.2). The SITT group had a higher mean CAT score, more patients with mMRC >1, and lower mean FEV1% and FEV1/FVC than the MITT patients. Moreover, the proportion of patients with ≥1 exacerbation in the previous year was higher in the SITT cohort. SITT patients had, compared to MITT patients, a higher proportion of adherence (proportion of days covered, PDC) ≥0.8 (86.5% vs. 79.8%; p = 0.006), higher treatment persistence [HR: 1.676 (1.356-2.071), p < 0.001], lower risk of moderate-to-severe exacerbation [HR: 0.729 (0.593-0.898), p = 0.003], and severe exacerbation [HR: 0.675 (0.515-0.875), p = 0.003], as well as reduced all-cause mortality risk [HR: 0.475 (0.237-0.952), p = 0.036] during the 12-month follow-up. Persistence was related to fewer future exacerbations and mortality than non-persistence in the SITT and MITT groups. Conclusion: Patients with COPD treated with SITT showed improved treatment persistence and adherence, as well as a reduction in the risk of moderate-to-severe exacerbation, severe exacerbation, and mortality compared to patients treated with MITT in the Chinese population. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR-POC-17010431.

Project description:Background: The US population includes 24 million to 29 million people with diagnosed and undiagnosed chronic obstructive pulmonary disease (COPD). Studies have demonstrated the safety and efficacy of single-inhaler triple therapy (SITT) in reducing COPD exacerbations. Long-term population implications of SITT use have not been quantified. Objectives: This simulation-based projection aimed to estimate the potential impact of widespread SITT use on the US COPD population. Methods: Exacerbation and all-cause mortality reductions reported in the Efficacy and Safety of Triple Therapy in Obstructive Lung Disease trial (ETHOS; NCT02465567) were used to project clinical outcomes in US patients meeting ETHOS trial eligibility criteria (ETHOS-Eligible) and patients meeting a practical definition of SITT eligibility (Expanded ETHOS-Eligible). The US COPD population was modeled with 1000 simulations of patient progression over 10 years. Agent characteristics were based on literature and claims analysis of the 2016-2018 Medicare 100% fee-for-service and IBM MarketScan® databases. Agent annual characteristics reflected incident cases, changes in COPD severity, treatment, mortality, and exacerbations under status quo treatment patterns and scenarios for the adoption of SITT. The scenarios assumed the reduced exacerbation and mortality rates associated with SITT according to ETHOS trial outcomes mean values. Results: Higher than current SITT adoption over 10 years would be expected to substantially reduce COPD exacerbation-associated hospitalizations by 2 million. Applying mean improvements reported in ETHOS for SITT would extend average patient life expectancy 2.2 years for ETHOS-Eligible patients and 1.7 years for Expanded ETHOS-Eligible patients. The number needed to treat to extend the average patient life by 1 year was 8 for the ETHOS-Eligible population and 10 for the Expanded ETHOS-Eligible population. Discussion: Widespread SITT adoption may be impeded by competitive pressures from generic treatments and nonadherence, and efficacy observed in clinical trials may not occur in real-world populations. Conclusions: Assuming ETHOS treatment effects and adherence translate to clinical practice, higher than current use of SITT can substantially reduce COPD exacerbations and hospitalizations and extend survival. These results should be viewed cautiously, because the improved outcomes for SITT in the ETHOS final retrieved vital statistics data were not statistically significant for all comparator therapy groups.

Project description:PurposeThe 24-week INTREPID trial demonstrated the clinical benefits of once-daily single-inhaler triple therapy (SITT) with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) versus non-ELLIPTA multiple-inhaler triple therapy (MITT) in patients with symptomatic chronic obstructive pulmonary disease (COPD). This analysis assessed the cost-effectiveness of FF/UMEC/VI versus non-ELLIPTA MITT for the treatment of symptomatic COPD from a United Kingdom (UK) National Health Service (NHS) perspective.Patients and methodsThe analysis was conducted using the validated GALAXY COPD disease progression model. Baseline characteristics, treatment effect parameters (forced expiratory volume in 1 second and St. George's Respiratory Questionnaire score [derived from exploratory COPD Assessment Test score mapping]), and discontinuation data from INTREPID were used to populate the model. UK healthcare resource and drug costs (2020 British pounds) were applied, and costs and outcomes were discounted at 3.5%. Analyses were conducted over a lifetime horizon from a UK NHS perspective. Model outputs included exacerbation rates, total costs, life years (LYs), quality-adjusted LYs (QALYs) and incremental cost-effectiveness ratio per QALY. Sensitivity analyses were conducted to assess the robustness of the results by varying parameter values and assumptions.ResultsOver a lifetime horizon, FF/UMEC/VI provided an additional 0.174 (95% confidence interval [CI]: 0.024, 0.344) LYs (approximately 2 months), and 0.253 (95% CI: 0.167, 0.346) QALYs (approximately 3 months), at a cost saving of £1764 (95% CI: -£2600, -£678) per patient, compared with non-ELLIPTA MITT. FF/UMEC/VI remained the dominant treatment option, meaning greater benefits at lower costs, across all scenario and sensitivity analyses.ConclusionBased on this analysis, in a UK setting, FF/UMEC/VI would improve health outcomes and reduce costs compared with non-ELLIPTA MITT for the treatment of patients with symptomatic COPD. SITT may help to reduce the clinical and economic burden of COPD and should be considered by physicians as a preferred treatment option.

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Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT.

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