Moderate and Severe Exacerbations and Healthcare Resource Utilization in Chinese Patients with COPD on Triple Therapy: A Retrospective Database Study.

N-acetylcysteine for COPD: the evidence remains inconclusive – Authors' reply

BackgroundThe benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid–LABA or LAMA–LABA), are uncertain.MethodsIn this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate–vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium–vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.ResultsThe rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).ConclusionsTriple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513.)

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...

RATIONALE In patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, early treatment with triple therapy (TT) has been shown to reduce the risk of exacerbations, healthcare resource utilization (HRU), and costs. However, many patients with COPD in China at risk of exacerbations are not prescribed TT. One reason for this is that characteristics of patients most likely to benefit from TT are not always identified. This study aimed to describe demographics, characteristics, and disease burden for patients with COPD in China who initiated TT. METHODS This retrospective analysis using data from the Tianjin electronic medical database identified patients aged ≥40 years who initiated single-inhaler TT (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or budesonide/glycopyrronium/formoterol (BUD/GLY/FOR), or multiple-inhaler TT (MITT) between January 1, 2019-June 30, 2023. Index date was the first date of an episode for which TT was prescribed for 30 consecutive days. Patient characteristics and demographics, COPD-related HRU and costs, and eosinophil levels (EOS) were captured on the index date and during the baseline period (12 months pre-index). RESULTS Overall, 7871 patients were included in the overall population; 3582 and 4289 patients were included in the MITT and SITT subgroups, respectively. Among patients in the SITT subgroup, 508 received FF/UMEC/VI and 3781 received BUD/GLY/FOR. In the overall population, median age was 66 years, 64.8% of patients were male, and the annualized rate of exacerbations was 0.34 (Table). The most common comorbidities at baseline were hypertension (36.8%) and asthma (33.0%). The proportions of patients in the overall population with ≥1 COPD-related emergency department (ED) visit, inpatient admission, and outpatient admission were 7.0%, 10.8%, and 62.4%, respectively. The annualized rate of COPD-related ED visits, inpatient admissions, and outpatient admissions was 0.15, 0.15, and 2.71, respectively. The median COPD-related total direct medical cost (RMB) was 2068 per patient and 361 per patient per visit in the overall population. Of the 653 patients with reported EOS, 43.5% had EOS &amp;lt;100 cells/μL, 42.1% had EOS 100-&amp;lt;300 cells/μL, and 14.4% had EOS ≥300 cells/μL. The annualized rate of exacerbations was 0.84 among patients with available EOS and 0.30 among patients without available EOS. CONCLUSIONS This study found that patients with COPD who were prescribed TT in China had a median age of 66 years and 64.8% were male. The most common comorbidities at baseline were hypertension and asthma, and more than half of patients with reported EOS had EOS &amp;gt;100 cells/μL.

BackgroundTriple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking.MethodsIn a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.ResultsThe modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg–budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg–budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate–formoterol group (2120 patients), and 1.24 in the budesonide–formoterol group (2131 patients). The rate was significantly lower with 320-μg–budesonide triple therapy than with glycopyrrolate–formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide–formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P=0.003). Similarly, the rate was significantly lower with 160-μg–budesonide triple therapy than with glycopyrrolate–formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide–formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P=0.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate–formoterol group.ConclusionsTriple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.)

PurposePatients with chronic obstructive pulmonary disease (COPD) may experience moderate (requiring outpatient care) or severe (requiring hospitalization) disease exacerbations. Guidelines recommend escalation from dual to triple therapy (inhaled corticosteroid + long-acting beta agonist + long-acting muscarinic antagonist) after two moderate or one severe exacerbation in a year. This study examined whether prompt initiation of triple therapy lowers risk of future exacerbations and reduces healthcare costs, compared to delayed/very delayed triple therapy after an exacerbation.Patients and MethodsThis retrospective observational study of US healthcare claims included patients ≥40 years old with COPD who initiated triple therapy (1/1/2011–3/31/2020) after ≥2 moderate or ≥1 severe exacerbation in the prior year. The earliest of the second moderate or first severe exacerbation was the index date. Patients were stratified by triple therapy timing: prompt (≤30 days post-index), delayed (31–180 days), very delayed (181–365 days). COPD exacerbations, all-cause and COPD-related healthcare utilization and costs were assessed during 12 months post-index (follow-up). Multivariable regression estimated the effect of each 30-day delay in triple therapy on the odds of exacerbations, number of exacerbations, and costs during follow-up, controlling for patient characteristics.ResultsA total of 24,770 patients were included: 7577 prompt, 9676 delayed, 7517 very delayed. Each 30-day delay of triple therapy was associated with 11% and 7% increases in the odds of any exacerbation and a severe exacerbation, respectively (odds ratio [95% CI]: 1.11 [1.10–1.13] and 1.07 [1.05–1.08]), a 4.3% (95% CI: 3.9–4.6%) increase in the number of exacerbations, a 1.8% (95% CI: 1.3–2.3%) increase in all-cause costs, and a 2.1% (95% CI: 1.6–2.6%) increase in COPD-related costs during follow-up.ConclusionPromptly initiating triple therapy after two moderate or one severe exacerbation is associated with decreased morbidity and economic burden in COPD. Proactive disease management may be warranted to prevent future exacerbations and lower costs among patients with COPD.

IntroductionThe 24-week KRONOS study (NCT02497001) showed that fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate 320/14.4/10 µg (BGF 320) metered dose inhaler (MDI) was more efficacious at improving lung function than fixed-dose...

BackgroundPatients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5.MethodsWe performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were stratified according to blood eosinophil count (≥150 per cubic millimeter at screening or ≥300 per cubic millimeter during the previous year). In METREO, all patients had a blood eosinophil count of at least 150 per cubic millimeter at screening or at least 300 per cubic millimeter during the previous year. The primary end point was the annual rate of moderate or severe exacerbations. Safety was also assessed.ResultsIn METREX, the mean annual rate of moderate or severe exacerbations in the modified intention-to-treat population with an eosinophilic phenotype (462 patients) was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group (rate ratio, 0.82; 95% confidence interval [CI], 0.68 to 0.98; adjusted P=0.04); no significant between-group differences were found in the overall modified intention-to-treat population (836 patients) (rate ratio, 0.98; 95% CI, 0.85 to 1.12; adjusted P>0.99). In METREO, the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100-mg mepolizumab group, 1.27 per year in the 300-mg mepolizumab group, and 1.49 per year in the placebo group. The rate ratios for exacerbations in the 100-mg and 300-mg mepolizumab groups versus the placebo group were 0.80 (95% CI, 0.65 to 0.98; adjusted P=0.07) and 0.86 (95% CI, 0.70 to 1.05; adjusted P=0.14), respectively. A greater effect of mepolizumab, as compared with placebo, on the annual rate of moderate or severe exacerbations was found among patients with higher blood eosinophil counts at screening. The safety profile of mepolizumab was similar to that of placebo.ConclusionsMepolizumab at a dose of 100 mg was associated with a lower annual rate of moderate or severe exacerbations than placebo among patients with COPD and an eosinophilic phenotype. This finding suggests that eosinophilic airway inflammation contributes to COPD exacerbations. (Funded by GlaxoSmithKline; METREX and METREO ClinicalTrials.gov numbers, NCT02105948 and NCT02105961.)

To describe the patient profile and disease burden for patients with chronic obstructive pulmonary disease (COPD) in China who initiated triple therapy. This retrospective, observational cohort study used real-world data from the Tianjin database to identify patients with COPD who initiated triple therapy between 1 January 2019 and 30 June 2023. Index date was the first prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol or budesonide/glycopyrronium/formoterol fumarate) or multiple-inhaler triple therapy (MITT). Patient demographics, clinical characteristics, baseline medications, healthcare resource utilisation and costs were described. In total, 7871 patients were included; 3582 received MITT and 4289 received SITT. In the overall population, the mean age was 65.8 years and 64.8% of patients were male. Most patients were non-smokers (95.6%) and had a visit to a Tier 3hospital at index (89.8%). Hypertension (36.8%) and asthma (33.0%) were the most common comorbidities at index. Inhaled corticosteroid/long-acting β2-agonist (19.3%) was the most used treatment prior to initiating triple therapy. The median (interquartile range) number of COPD-related emergency department visits, inpatient admissions and outpatient admissions in the year prior to and including the index date was 1 (1), 1 (0) and 3 (5), respectively. The median COPD-related total direct medical costs were 2068 Renminbi per patient. The mean proportion of days covered (PDC) for baseline medications was 0.35. The median eosinophil count was 120 cells/μL. These results provide an overview of the profiles of patients with COPD in China. The high rates of COPD-related healthcare resource utilization and costs demonstrate the considerable burden of COPD in China, whilst the PDC results indicate medication adherence needs to be improved. These findings could help reduce the burden of COPD in China by supporting the planning and adjustment of patients' treatment strategies.

BACKGROUND: Severe exacerbations requiring hospitalization contribute a substantial portion of the morbidity and costs of chronic obstructive pulmonary disease (COPD). Triple therapy (inhaled corticosteroid + long-acting β-agonist + long-acting muscarinic antagonist) is a recommended option for patients who experience recurrent COPD exacerbations or persistent symptoms. Few real-world studies have specifically examined the effect of prompt initiation of triple therapy, specifically among patients hospitalized for a COPD exacerbation. OBJECTIVE: To assess whether prompt initiation of triple therapy following a severe COPD exacerbation was associated with lower risk of subsequent exacerbations and lower health care use and costs and the effects of each 30-day delay of initiation. METHODS: Adults aged 40 years or older with COPD were identified in the Merative MarketScan Databases between January 1, 2010, and December 31, 2019, and were required to meet the following criteria: open or closed triple therapy (date of first closed prescription or last component of open=index treatment date), more than 1 inpatient admission with a primary COPD diagnosis (ie, severe exacerbation) in the prior 12 months (index exacerbation), 12 months of continuous enrollment before (baseline) and after (follow-up) index exacerbation, and absence of select respiratory diseases and cancer. Patients were stratified based on timing of open or closed triple therapy after the index exacerbation: prompt (≤30 days), delayed (31-180 days), or very delayed (181-365 days). Multivariable regression controlled for baseline characteristics (age, sex, insurance type, index year, comorbidities, prior treatment, and prior exacerbations) and estimated the odds of subsequent exacerbations, change in the number of exacerbations, and change in health care costs during 12-month follow-up associated with each 30-day delay of triple therapy initiation. RESULTS: A total of 6,772 patients met inclusion criteria (2,968 [43.8%] prompt, 1,998 [29.5%] delayed, and 1,806 [26.7%] very delayed). The adjusted odds of any exacerbation and a severe exacerbation during 12-month follow-up increased by 13% (odds ratio [95% CI]: 1.13 [1.11-1.15]) and 10% (1.10 [1.08-1.12]), respectively, for each 30-day delay in triple therapy initiation, and the mean number of exacerbations increased by 5.4% (95% CI = 4.7%-6.1%). There was a 3.0% increase (95% CI = 2.2%-3.8%) in mean all-cause costs and a 3.7% increase (95% CI = 2.9%-4.6%) in total COPD-related costs for each 30-day delay of triple therapy initiation. CONCLUSIONS: Longer delays in triple therapy initiation after a COPD hospitalization result in greater risk of subsequent exacerbations and higher health care resource use and costs. Adequate post-discharge follow-up care and earlier consideration of triple therapy may improve clinical and economic outcomes among patients with COPD. DISCLOSURES: This study was funded by AstraZeneca. Dr Evans is employed by Merative, formerly IBM Watson Health, and Mr Tkacz was employed by IBM Watson Health at the time of this study; Merative/IBM Watson Health received funding from AstraZeneca to conduct this study. Mr Pollack, Dr Staresinic, Dr Feigler, and Dr Patel are employed by AstraZeneca. Dr Touchette, Dr Portillo, and Dr Strange are paid consultants to AstraZeneca. Dr Strange also participates in research grants paid to the Medical University of South Carolina by AstraZeneca, CSA Medical, and Nuvaira, and is a consultant to GlaxoSmithKline, Morair, and PulManage regarding COPD.

PurposeTriple therapy of chronic obstructive pulmonary disease (COPD), consisting of inhaled corticosteroid (ICS), long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) has shown benefits in patients with COPD. However, little is known about the use of triple therapy in Chinese patients. This study aims to describe the treatment patterns and the utilization of triple therapy in COPD patients based on real-world data from China.Patients and MethodsThis retrospective study included patients with COPD from the Yinzhou database. Patients aged ≥ 40 years with a diagnosis of COPD were included. Different combinations of ICS, LAMA and LABA prescribed during follow-up were categorized as single, dual, or triple therapies. Descriptive analysis was performed to depict the treatment patterns of each therapy.ResultsA total of 7888 patients were prescribed at least one COPD therapy during the follow-up. Among them, 29.1% were prescribed triple therapy (ICS+LABA+LAMA) with a median (IQR) treatment duration of 3.27 (7.17) months. The majority (68.6%) of patients were prescribed dual therapy with ICS+LABA, while 27.3% and 23.3% of patients were prescribed single therapy with ICS or LAMA, respectively. Regarding treatment sequences during follow-up, 30.1% of patients received dual therapy with ICS+LABA, followed by 11.4% receiving only triple therapy and 10.4% receiving single therapy with ICS alone.ConclusionOur study assessed treatment patterns and triple therapy utilization among patients with COPD in China. The majority of patients were treated with ICS+LABA dual therapy. Triple therapy was also widely used, with most patients transitioning from other treatment modalities.

Dupilumab for chronic obstructive pulmonary disease with type 2 inflammation: a pooled analysis of two phase 3, randomised, double-blind, placebo-controlled trials.

Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies

ObjectiveTo compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review and meta-analysis of randomised...

BackgroundGuidelines recommend that treatment with a long-acting β2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base.MethodsWe conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations.ResultsWe identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15–52% compared with LAMA/LABA, 15–35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25–50 (preventing one patient from having an event) and the event-based number needed to treat of around 3–11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons.ConclusionThe decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials.Trial registrationPROSPERO #CRD42018102125.