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Recent data suggest differences in effectiveness of single-inhaler triple therapies (SITTs) for patients with chronic obstructive pulmonary disease (COPD); however, data specifically from patients previously treated with dual bronchodilator therapy are lacking. This real-world comparative effectiveness study assessed patients with COPD treated with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM) who stepped up from dual therapy.
Methods
This retrospective study used healthcare claims from the Komodo Research database to identify patients with COPD and Medicare Fee-for-Service insurance on dual therapy as their most recent treatment in the 90 days pre-index, stepping up to FF/UMEC/VI or BUD/GLY/FORM between January 1, 2016 and December 31, 2023. Primary outcome was annualized rate of moderate–severe exacerbations per patient-year (PPY) compared using rate ratios (RRs) and 95% confidence intervals (CIs) from Poisson regression models after adjustment with overlap weighting. Secondary outcomes were time to first moderate–severe exacerbation (analyzed as a composite and separately), reported using Kaplan–Meier (KM) analysis and compared using hazard ratios (HRs) with 95% CIs from weighted Cox regression models. All-cause mortality (KM analysis) was included as an exploratory outcome.
Results
Overall, 10,093 FF/UMEC/VI and 3926 BUD/GLY/FORM patients stepping up from dual therapy were included. Patients stepping up to FF/UMEC/VI experienced an 18% significantly lower rate of moderate–severe COPD exacerbations compared with BUD/GLY/FORM [0.80 vs. 0.98 PPY; RR (95% CI) 0.82 (0.77, 0.88); P < 0.001]. Stepping up to FF/UMEC/VI was also associated with a 14% lower risk of moderate–severe COPD exacerbations [HR (95% CI) 0.86 (0.81, 0.92); P < 0.001] and 18% lower risk of all-cause mortality [HR (95% CI) 0.82 (0.68, 0.99); P = 0.040] at 12 months compared with BUD/GLY/FORM.
Conclusion
In this real-world study, SITT with FF/UMEC/VI was associated with a significantly lower rate and risk of exacerbations compared with BUD/GLY/FORM in patients stepping up from dual therapy.
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Key Summary Points
Why carry out this study?
• Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM) are single-inhaler triple therapies (SITTs) approved as maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
• In many countries outside the United States (US), SITTs are indicated for patients who are inadequately controlled with dual therapy of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) or long-acting muscarinic antagonist/LABA (LAMA/LABA). There is a lack of comparative effectiveness data for these SITTs in patients stepping up from dual therapy.
• This real-world comparative effectiveness study aimed to assess moderate–severe exacerbations in patients treated with FF/UMEC/VI compared with patients treated with BUD/GLY/FORM who had previously received dual therapy, using data from US patients with Medicare Fee-for-Service insurance.
What was learned from this study?
• Patients receiving FF/UMEC/VI had a significantly lower annualized rate and lower 12-month risk of moderate–severe exacerbations compared with those receiving BUD/GLY/FORM.
• The 12-month risk of all-cause mortality, assessed as an exploratory endpoint, was also significantly lower in the FF/UMEC/VI group.
• Findings from this real-world comparative effectiveness study may help inform treatment recommendations for the management of COPD in patients who are inadequately controlled with dual combination therapy and require step up to SITT.
Introduction
Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM) are single-inhaler triple therapies (SITTs) that contain an inhaled corticosteroid (ICS; FF and BUD), a long-acting muscarinic antagonist (LAMA; UMEC and GLY), and a long-acting β2-agonist (LABA; VI and FORM) [1]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends the use of triple therapies in patients with chronic obstructive pulmonary disease (COPD) with ≥ 2 moderate exacerbations (or ≥ 1 exacerbation leading to hospitalization) and levels of blood eosinophils ≥ 300 cells/µL [2]. In the United States (US), both FF/UMEC/VI and BUD/GLY/FORM are approved for the maintenance treatment of patients with COPD [3, 4]; in the European Union, both products are approved as a maintenance treatment in adult patients with moderate–severe COPD who are not adequately treated by dual therapy (ICS/LABA or LAMA/LABA) [5, 6].
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Studies have shown that FF/UMEC/VI (one inhalation once daily) was more efficacious in reducing the annual rates of moderate or severe exacerbations, COPD-related hospitalizations, and mortality than dual therapies such as FF/VI (ICS/LABA) and UMEC/VI (LAMA/LABA); greater improvements in lung function and health status were also evident [7, 8]. Additionally, higher rates of treatment adherence and persistence were seen in those initiating FF/UMEC/VI compared with multiple-inhaler triple therapy, along with better symptom control (i.e., reduced rate of exacerbations) [9, 10]. Studies have also shown that BUD/GLY/FORM (two inhalations twice daily) reduced moderate or severe exacerbation rates and mortality, and improved forced expiratory volume in 1 second (FEV1), compared with dual therapies such as BUD/FORM (ICS/LABA) or GLY/FORM (LAMA/LABA) [11‐13].
Head-to-head randomized controlled trials (RCTs) of FF/UMEC/VI and BUD/GLY/FORM have not been conducted, although data are available from two real-world comparative effectiveness studies conducted in the US [1, 14]; both reported substantially lower rates of moderate–severe COPD exacerbations following treatment with FF/UMEC/VI than with BUD/GLY/FORM in patients with COPD from claims databases (commercial insurance and/or Medicare). FF/UMEC/VI was also associated with a 10% lower 12-month risk of moderate–severe exacerbations and an 11% lower 12-month risk of all-cause mortality in one of the studies; furthermore, approximately half of the patients used dual therapy prior to SITT [1]. No difference in all-cause mortality or the safety profile with FF/UMEC/VI versus BUD/GLY/FORM was found in the second study [14]. This current study builds on these findings, using similar methods with claims data to compare COPD exacerbations and all-cause mortality in patients with Medicare Fee-for-Service (FFS) insurance stepping up to FF/UMEC/VI and BUD/GLY/FORM who had used dual therapy as their latest treatment. This group of patients is of particular interest in countries/regions where SITTs are indicated for patients with COPD not adequately controlled with prior dual combination therapy (either ICS/LABA or LAMA/LABA) [15].
Methods
Data Source
This study sourced secondary data from the Komodo Research Data (KRD) administrative claims database between January 1, 2016 and December 31, 2023 for patients with Medicare FFS insurance. The open-source data subset in the KRD database contains data directly from healthcare providers and claims clearinghouses. Data on patients with Medicare FFS insurance, available in the open-source subset, did not include information on patients’ insurance eligibility. Continuous clinical activity was defined as consecutive quarters with at least one medical and one pharmacy claim, and was used as a proxy for continuous insurance coverage. Death information was sourced from vital statistics, such as national and state government public records, public listings (e.g., cemeteries, funeral homes), private claims, and obituary data.
Study Design
This was a retrospective weighted cohort study of patients with COPD treated with FF/UMEC/VI or BUD/GLY/FORM. The index date was defined as the first pharmacy claim for FF/UMEC/VI (100 µg/62.5 µg/25 µg) or BUD/GLY/FORM on or after January 1, 2021 that defined group assignment (Fig. 1). Patients initiating FF/UMEC/VI or BUD/GLY/FORM before January 1, 2021 were not included in order to mitigate any impact of temporal differences when comparing treatments (BUD/GLY/FORM was approved on July 23, 2020; FF/UMEC/VI was approved on September 18, 2017) [1]. Patient demographics and clinical characteristics were evaluated during the baseline period (12 months prior to the index date). The observation (follow-up) period was defined as the period from the day after the index date to the end of clinical activity, data availability, death, or switch to the other SITT, whichever occurred first. Patients were allocated to one of two exclusive comparison groups based on their SITT at index (either FF/UMEC/VI or BUD/GLY/FORM; cross-over not permitted).
Fig. 1
Study design. BUD/GLY/FORM budesonide/glycopyrrolate/formoterol fumarate, COPD chronic obstructive pulmonary disease, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, KRD Komodo Research Data, SITT single-inhaler triple therapy. aContinuous clinical activity was defined as consecutive quarters with ≥ 1 medical and ≥ 1 pharmacy claim in KRD open-source data and was used as a proxy for continuous insurance coverage. bKRD data ranged from January 1, 2016 to December 31, 2023
The term ‘step up’ is used for the study population whose latest treatment was a dual therapy (either ICS/LABA or LAMA/LABA) prior to escalating to SITT. Patients had not been previously exposed to SITT. Patients diagnosed with COPD who stepped up to SITT per the approved label of FF/UMEC/VI (one inhalation once daily) or BUD/GLY/FORM (two inhalations twice daily) were included if they had ≥ 1 dispensing of FF/UMEC/VI (100 µg/62.5 µg/25 µg) or BUD/GLY/FORM on or after January 1, 2021 (as a step up from dual therapy as their latest treatment); ≥ 12 months of continuous clinical activity prior to the index date; ≥ 2 medical claims with a diagnosis of COPD in primary, secondary, or tertiary position of diagnosis codes in the claims database and in any setting on separate dates of service during the baseline period or on the index date; and use of dual therapy (ICS/LABA; LAMA/LABA) as the latest COPD treatment in the 90 days prior to step up to SITT. Patients were excluded if they were < 40 years of age on the index date; had ≥ 1 SITT dispensing any time prior to the index date (to ensure patients were newly stepping up to SITT); dispensing for both FF/UMEC/VI and BUD/GLY/FORM on the index date; ≥ 1 diagnosis of asthma in any position during the baseline period; and ≥ 1 diagnosis of cystic fibrosis, lung cancer, interstitial lung disease, or alpha-1 antitrypsin in any position during the baseline period.
Study Outcomes
COPD exacerbations were compared between the FF/UMEC/VI and BUD/GLY/FORM groups during the follow-up period. All study endpoints assessed during the follow-up period were weighted to adjust for confounding.
Primary Outcome
The primary outcome was the annualized rate of moderate or severe COPD exacerbations between patients treated with FF/UMEC/VI and BUD/GLY/FORM who used dual therapy as their latest treatment before stepping up to SITT. A moderate COPD exacerbation was defined as ≥ 1 outpatient (OP) or emergency department (ED) visit with a COPD exacerbation diagnosis code in the primary position and ≥ 1 pharmacy dispensing or medical administration in any care setting (e.g., hospitalization, OP, ED) for a systemic corticosteroid or guideline-recommended antibiotic within 5 days following, or prior to, the visit. A severe COPD exacerbation was defined as a hospitalization with a COPD exacerbation diagnosis code in the primary position. Definitions for moderate and severe COPD exacerbations were mutually exclusive and exacerbations occurring within 14 days of each other were considered as a single episode and classified according to the highest-severity contributing event. The date of the beginning of the first exacerbation was assigned as the date of the exacerbation. If the first exacerbation was on the index date, then neither exacerbation was counted as an exacerbation in the follow-up period.
Secondary Outcomes
The secondary outcomes were the time to first moderate–severe COPD exacerbation (analyzed as a composite), and time to first moderate and time to first severe exacerbation (analyzed separately) between patients treated with FF/UMEC/VI and BUD/GLY/FORM who used dual therapy as their latest treatment before stepping up to SITT.
Exploratory Outcome
The rate of all-cause mortality between patients treated with FF/UMEC/VI and BUD/GLY/FORM who used dual therapy as their latest treatment before stepping up to SITT was an exploratory endpoint.
Data Analysis
To minimize potential confounding, the overlap weighting (OW) approach based on the propensity score (PS) was used to evaluate the average treatment effect of the overlapped population of being treated with FF/UMEC/VI. PS and corresponding OW weights were calculated separately for the study population and groups of interest as 1–PS for the FF/UMEC/VI group, and as PS for the BUD/GLY/FORM group.
PS were generated using probability estimates from a logistic regression model in which treatment with FF/UMEC/VI (yes/no) was the binary dependent variable and patient characteristics were used as predictors of being treated with FF/UMEC/VI. Adjustment methods based on PS such as OW aim to simulate the balance achieved by a randomized trial by reducing differences in patient characteristics between groups prior to weighting. Differences between unweighted and weighted groups were assessed using standardized differences, with values >10% considered a meaningful difference between groups.
Rates of moderate or severe COPD exacerbations were calculated as the number of events divided by the patient-years of observation and reported per patient-year (PPY) during the follow-up period. Differences between weighted groups were evaluated using Poisson regression models with a log-link function and robust standard errors and reported as rate ratios (RRs) and 95% confidence intervals (CIs). Time to first moderate or severe COPD exacerbation and all-cause mortality were assessed using Kaplan–Meier (KM) analysis, and event rates at specific time periods (3, 6, 9, and 12 months) were compared between weighted groups using hazard ratios (HRs) and 95% CIs evaluated from weighted Cox proportional regression models. An intention-to-treat approach was utilized across the available follow-up, and only patients who crossed over to comparator treatment were censored from the analysis. P values for the secondary and exploratory outcomes have not been adjusted for multiplicity.
Ethical Approval
The study complied with all applicable laws regarding patient privacy, as described in the Declaration of Helsinki. No direct patient contact or primary collection of individual human patient data occurred in this study. This study used existing, fully de-identified data that complied with the requirements of the Health Insurance Portability and Accountability Act and the patient(s) cannot be identified, directly or through identifiers. Study results were in tabular form and aggregate analyses that omit patient identification; therefore, informed consent and ethics committee or Institutional Review Board approval were not required.
Results
Patient Disposition
Among 445,266 patients with Medicare FFS insurance stepping up to SITT on or after January 1, 2021, there were 10,093 patients on FF/UMEC/VI and 3926 on BUD/GLY/FORM included in the study who had dual therapy as their latest treatment before SITT (Supplementary Fig. S1).
Baseline Patient Demographics and Clinical Characteristics
The covariate balance before and after weighting is shown in Supplementary Fig. S2. The mean follow-up time was 360 days in the FF/UMEC/VI group and 347 days in the BUD/GLY/FORM group. In the weighted groups, the end of the study observation period occurred due to switch to the other SITT [from FF/UMEC/VI: n = 450 (4.5%); from BUD/GLY/FORM: n = 364 (9.3%)], death [n = 490 (4.9%); n = 224 (5.7%)], or end of continuous clinical activity or data availability [n = 9153 (90.7%); n = 3338 (85.0%)]. In both weighted groups, the mean age was 74 years, 54% of patients were female, and the mean Quan–Charlson Comorbidity Index score was 2.6 (Table 1; baseline demographics and clinical characteristics for unweighted groups are shown in Supplementary Table S1). The controller medications most used during the 12-month baseline period were ICS/LABA (66%) and LAMA/LABA (38%), and the rescue medications most used were short-acting β2-agonists (72%), antibiotics (72%), and systemic corticosteroids (66%); all patients had used ICS/LABA or LAMA/LABA as their latest treatment prior to step up to SITT. Most patients had comorbidities at baseline, most commonly hypertension (76%), cardiac arrhythmias (33%), and diabetes (32%). Approximately half (49%) of patients had a moderate–severe COPD exacerbation during the baseline period.
Table 1
Selected patient baseline demographics and clinical characteristics—weighted groups
All-cause healthcare costs, $US 2023,e,f mean (SD)
Total costs (medical and pharmacy)
21,302 (29,619)
21,302 (28,455)
0.0
Total medical costs
13,420 (26,669)
13,266 (24,574)
0.6
Pharmacy costs
7883 (11,105)
8036 (11,362)
1.4
BUD/GLY/FORM budesonide/glycopyrrolate/formoterol fumarate, COPD chronic obstructive pulmonary disease, ED emergency department, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, HRU healthcare resource utilization, ICS inhaled corticosteroid, LABA long-acting β2-agonist, LAMA long-acting muscarinic antagonist, MITT multiple-inhaler triple therapy, OP outpatient, OW overlap weighting, PPY per patient-year, PS propensity score, Quan-CCI Quan-Charlson Comorbidity Index, SABA short-acting β2-agonist, SAMA short-acting muscarinic antagonist, SCS systemic corticosteroid, SD standard deviation, SITT single-inhaler triple therapy, Std. diff standardized difference, US United States
aPatients were weighted using the OW approach based on the PS to adjust for confounding. Variables used in the PS calculation included the following: age, sex, race, year of index date, physician specialty at index, US region, pulmonary testing at baseline, Quan-CCI score, COPD exacerbations at baseline and on the index date, baseline medication use (agents with ≥ 5% use in either group), baseline all-cause HRU and medical costs, SITT pharmacy costs on the index date, and comorbidities (conditions with ≥ 5% prevalence in either group)
bFor continuous variables, the standardized difference was calculated by dividing the absolute difference in means of the control and the case by the pooled standard deviation of both groups. The pooled standard deviation is the square root of the average of the squared standard deviations
cFor dichotomous variables, the standardized difference was calculated using the following equation where P is the respective proportion of participants in each group: |(Pcase-Pcontrol)|/√[(Pcase(1-Pcase)+Pcontrol(1-Pcontrol))/2]
dEvaluated during the 12-month baseline period, not including the index date
eEvaluated during the 12-month baseline period, including the index date
fCosts were inflated to $US 2023 using the U.S. Medical Care consumer price index from the Bureau of Labor Statistics from the U.S. Department of Labor
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Rate of Moderate or Severe COPD Exacerbations (Primary Outcome)
Patients stepping up to FF/UMEC/VI experienced an 18% significantly lower rate of moderate–severe COPD exacerbations than those stepping up to BUD/GLY/FORM [0.80 vs. 0.98 PPY; absolute difference –0.18 exacerbations PPY; RR (95% CI) 0.82 (0.77, 0.88); P < 0.001; Fig. 2]. When analyzed separately, the rate of moderate exacerbations was significantly lower (20%) for patients treated with FF/UMEC/VI compared with BUD/GLY/FORM [0.68 vs. 0.85 PPY; absolute difference –0.17 exacerbations PPY; RR (95% CI) 0.80 (0.74, 0.86); P < 0.001]; the difference in the rate of severe exacerbations was similar and not significant between the two groups.
Fig. 2
Rates of moderate and severe COPD exacerbations—weighted groups. BUD/GLY/FORM budesonide/glycopyrrolate/formoterol fumarate, CI confidence interval, COPD chronic obstructive pulmonary disease, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, PPY per patient-year, RR rate ratio. *P < 0.001
Time to First Moderate or Severe COPD Exacerbation (Secondary Outcomes)
Stepping up to FF/UMEC/VI was associated with a 14% significantly lower risk of time to first moderate–severe COPD exacerbation up to 12 months compared with stepping up to BUD/GLY/FORM [KM-estimated exacerbation risk 43.6% vs. 49.0%, absolute difference –5.4%; HR (95% CI) 0.86 (0.81, 0.92); P < 0.001; Fig. 3a]. There was also a 15% lower risk of moderate COPD exacerbations in patients who stepped up to FF/UMEC/VI versus BUD/GLY/FORM [KM-estimated exacerbation risk 38.8% vs. 43.9%, absolute difference –5.1%; HR (95% CI) 0.85 (0.80, 0.91); P < 0.001; Fig. 3b]. The risk of severe COPD exacerbations trended lower in those stepping up to FF/UMEC/VI compared with BUD/GLY/FORM [KM-estimated exacerbation risk 9.6% vs. 10.6%, absolute difference –1.0%; HR (95% CI) 0.92 (0.80, 1.05); P = 0.213; 8% lower risk] at 12 months (Fig. 3c).
Fig. 3.
Time to first moderate and severe COPD exacerbations—weighted groups. BUD/GLY/FORM budesonide/glycopyrrolate/formoterol fumarate, CI confidence interval, COPD chronic obstructive pulmonary disease, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, HR hazard ratio. *P < 0.001. aHRs and P values were calculated using Cox proportional hazards regression models. bNumber of patients without event still observed at the specific point in time
Patients stepping up to FF/UMEC/VI had an 18% significantly lower risk of all-cause mortality up to 12 months compared with those patients stepping up to BUD/GLY/FORM [KM-estimated risk of death 4.9% vs. 6.0%, absolute difference –1.1%; HR (95% CI) 0.82 (0.68, 0.99); P = 0.040; Fig. 4].
Fig. 4.
All-cause mortality of patients with COPD—weighted groups. BUD/GLY/FORM budesonide/glycopyrrolate/formoterol fumarate, CI confidence interval, COPD chronic obstructive pulmonary disease, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, HR hazard ratio. *P = 0.040. aHRs and P values were calculated using Cox proportional hazards regression models. bNumber of patients without event still observed at the specific point in time
To our knowledge, this is the first real-world comparative effectiveness study of FF/UMEC/VI versus BUD/GLY/FORM among patients with COPD who were stepped up to SITT from prior dual combination therapy. This meets an important knowledge gap, and our findings have implications for clinical practice in those countries where SITTs are indicated for patients with COPD not adequately controlled with prior dual therapy (either ICS/LABA or LAMA/LABA).
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In this real-world comparative effectiveness study using US Medicare FFS claims data, a similar proportion of patients in the two treatment groups had comorbidities at baseline, including a prevalence of those related to cardiovascular disease. Patients receiving FF/UMEC/VI had significant reductions in the rate of moderate–severe COPD exacerbations and the risk of exacerbations at 12 months post-step up compared with those receiving BUD/GLY/FORM.
Several factors may have contributed to the favorable outcomes observed in patients treated with FF/UMEC/VI in this study. A prospective, phase 3 RCT showed that GLY/FORM was inferior to UMEC/VI on morning pre-dose trough FEV1 in patients with moderate–very severe COPD [17], suggesting differences in the efficacy of the component molecules of the two SITTs. Additionally, the dosing regimen of FF/UMEC/VI (one inhalation per day in a dry powder inhaler) versus BUD/GLY/FORM (two inhalations, twice daily in a metered-dose inhaler) may have implications for medication adherence [3, 4]. Patients initiating FF/UMEC/VI have been shown to have greater medication adherence and persistence compared with those initiating BUD/GLY/FORM in a recent retrospective real-world US dataset analysis [18]. Inhaler device type may also be a contributing factor. Patient preference for continuity of device may play an important role in the treatment prescribed. Nonetheless, differences in dosing, devices, and molecules are intrinsically linked with differences in effectiveness and preference noted in real-world experience.
Several of the factors discussed above may be considered as potential sources of bias (e.g., adherence differences, patient preference, or channeling/selection bias due to factors such as availability of treatment or patient prognosis/characteristics). We applied a robust methodology (OW based on high-dimensional PS) to ensure the two cohorts were as similar as possible, with available baseline characteristics carefully balanced between the groups (Fig. S2).
There are no head-to-head prospective RCTs comparing efficacy among SITTs; however, indirect comparisons and retrospective analyses have been conducted [1, 14, 19, 20]. A matching-adjusted indirect comparison of two RCTs reported that BUD/GLY/FORM was associated with a significant reduction in all-cause mortality versus FF/UMEC/VI in patients with moderate–very severe COPD [19]. Conversely, a network meta-analysis based on 17 RCTs showed improvements in the annualized rates of moderate–severe exacerbations with FF/UMEC/VI versus BUD/GLY/FORM [20]. Two real-world studies in patients from the US with COPD have previously assessed the comparative effectiveness of FF/UMEC/VI and BUD/GLY/FORM [1, 14]. Both studies included patients with COPD reflective of the approved indications and real-world practice in the US (including patients initiating treatment with SITT). As with the current study, dosing regimens were consistent with the approved labels (FF/UMEC/VI: one inhalation per day; BUD/GLY/FORM: two inhalations, twice daily). The studies showed that patients receiving FF/UMEC/VI had a lower rate and lower risk of moderate–severe COPD exacerbations compared with those receiving BUD/GLY/FORM [1, 14]. Furthermore, in one of the studies that assessed safety, there were no differences found in the safety profile between the SITTs, as assessed by the risk of hospitalization due to pneumonia [14]. In the present study, risk of all-cause mortality at 12 months post-initiation was significantly lower in patients receiving FF/UMEC/VI in an exploratory outcome. The two previous real-world studies reported different results for all-cause mortality. Mannino et al. (2025) observed an 11% lower 12-month risk of all-cause mortality (assessed as an exploratory outcome) in favor of FF/UMEC/VI, whereas no difference in the risk of all-cause mortality (secondary outcome) was observed in the other study in which patients were, on average, slightly younger than those studied by Mannino et al. [1, 14].
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Potential limitations should be considered when interpreting the findings from this observational claims-based study. The presence of a dispensed medication does not provide confirmation that it was used as prescribed, and medications such as over-the-counter products may not have been captured in the database. In addition, administrative claims data are vulnerable to inaccuracies of coding and missing data, and the possibility of residual confounding due to inaccurate or missing data cannot be completely excluded (despite the use of OW). Another potential source of residual confounding is the lack of information on clinical parameters (e.g., lung function, symptoms, smoking status, eosinophil count) that may inform prescriber treatment decisions and choice of inhaler [21]. Also, the use of a 90-day window pre-index (designed to include all step-up patients and exclude patients who do not have the intended treatment pattern) may have excluded some relevant patients or conversely included some irrelevant patients. There was a difference in sample size between the FFF/UMEC/VI and BUD/GLY/FORM groups; however, the analyses were conducted on the full study population rather than subsets, therefore ensuring all eligible patients were included. Also, the use of OW to balance baseline demographic and clinical characteristics mitigates potential confounding due to differences in sample size. Lastly, study findings are reflective of patients from the US with COPD and Medicare FFS insurance and generalization to patient populations from different healthcare systems may be limited.
Conclusions
This real-world comparative effectiveness study of US patients with Medicare insurance is the first to compare outcomes in patients with COPD treated with FF/UMEC/VI versus BUD/GLY/FORM who were previously treated with dual combination therapy before stepping up to SITT. Patients stepping up to FF/UMEC/VI had a lower rate and risk of moderate–severe COPD exacerbations relative to those stepping up to BUD/GLY/FORM. Findings from this real-world comparative effectiveness study may help inform treatment recommendations for the management of patients with COPD who are inadequately controlled with dual combination therapy and require a step up to SITT.
Medical Writing/Editorial Assistance
Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing, and referencing) was provided by Tony Reardon and Nina Kureishy of Luna, OPEN Health Communications, and was funded by GSK, in accordance with Good Publication Practice (GPP) guidelines (www.ismpp.org/gpp-2022).
Declarations
Conflict of Interest
Jadwiga A. Wedzicha reports grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, and Novartis, consulting fees from AstraZeneca, EpiEndo Pharmaceuticals, GSK, Gilead, Novartis, Pfizer, Roche, and Empirico, honoraria for lectures, presentations or educational events from AstraZeneca, Boehringer Ingelheim, Glenmark, GSK, Novartis, Recipharm, Roche, and Sanofi, and participation as the data safety monitoring board chair for Virtus. Stephen G. Noorduyn, Valentina Di Boscio, Anurita Majumdar, Rosirene Paczkowski, and Stephen Weng are employees of GSK and/or hold financial equities in GSK. Stephen G. Noorduyn is also a PhD candidate at McMaster University. Olivier Le Rouzic is a principal investigator of CSL Behring and Vertex studies and reports receiving personal fees and/or congress support from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Grifols, GSK, LFB, and Sanofi outside the submitted work. Guillaume Germain and François Laliberté are employees of Groupe d’analyse which received funding from GSK to conduct this study but not for manuscript development. David Mannino is a consultant for AstraZeneca, the COPD Foundation, Genentech, GSK, Regeneron, and UpToDate. David Mannino is also an expert witness on behalf of people suing the tobacco and vaping industries.
Ethical Approval
The study complied with all applicable laws regarding patient privacy, as described in the Declaration of Helsinki. No direct patient contact or primary collection of individual human patient data occurred in this study. This study used existing, fully de-identified data that complied with the requirements of the Health Insurance Portability and Accountability Act and the patient(s) cannot be identified, directly or through identifiers. Study results were in tabular form and aggregate analyses that omit patient identification; therefore, informed consent and ethics committee or Institutional Review Board approval were not required.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
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Comparative Effectiveness of FF/UMEC/VI and BUD/GLY/FORM in Patients with COPD Stepping Up From Dual Therapy
Verfasst von
Jadwiga A. Wedzicha
Stephen G. Noorduyn
Valentina Di Boscio
Olivier Le Rouzic
Anurita Majumdar
Rosirene Paczkowski
Stephen Weng
Guillaume Germain
François Laliberté
David Mannino
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Die Annahme, dass beim außerklinischen Kreislaufstillstand (OHCA) die Zahl der notwendigen Defibrillationen den Schweregrad einer zugrunde liegenden KHK widerspiegelt, trifft wohl nicht zu. Als Selektionskriterium für eine Koronarangiografie taugt sie daher nicht.
Metastatische Rezidive sind bei Jugendlichen und jungen Erwachsenen mit Krebs häufig und verschlechtern die Prognose deutlich. Eine umfassende Kohortenstudie aus Kalifornien zeigt klare Unterschiede nach Tumorart, Stadium und Diagnosejahr.
Daten der Phase-III-Studie STELLAR sprechen für eine klinisch relevante Aktivität der Therapiekombination aus Eflornithin und Lomustin bei Personen mit rezidivierten Grad-3-Astrozytomen. Besonderheiten im Studiendesgin machen die Interpretation indes nicht ganz leicht.
Geht es nach einer aktuellen Metaanalyse, ist die kurzzeitige Verabreichung von niedrigdosierten systemischen Kortikosteroiden bei schweren Nicht-COVID-19-Pneumonien bzw. ARDS mit Blick auf das Überleben eher vorteilhaft. Die Sicherheit der Evidenz ist allerdings ausbaufähig.
