Abstract
Introduction
For patients with asthma who remain symptomatic on medium-dose inhaled corticosteroid/long-acting β2-agonist, add-on long-acting muscarinic antagonist is a treatment option, which can be administered as multiple-inhaler triple therapy (MITT). A high proportion of patients (61.5%–88.2%) discontinue MITT use within 1 year postinitiation; however, which patients discontinue and their treatment patterns at initiation are unknown. This study aimed to understand the demographic, clinical and treatment-related characteristics of patients with asthma who newly initiated MITT, by discontinuation status.
Methods
This retrospective cohort study used administrative data from IBM Truven MarketScan Commercial Claims and Encounters Database with Medicare supplement between 1 January 2016 and 31 December 2019. Adult patients with asthma who initiated MITT between 1 January 2017 and 31 March 2019 were included and were classified based on their discontinuation status. ‘Continuous users’ had continuous use of MITT and ‘discontinuers’ discontinued treatment within the 6-month period postinitiation. Demographics and clinical characteristics, asthma treatment use prior to MITT initiation (12-month baseline period), mode of MITT initiation and complexity of regimen were described.
Results
Of 4132 patients (mean age: 49.0 years, 67.9% female), 78.0% (n=3224) were discontinuers; 22.0% (n=908) were continuous users. Demographic and other clinical and treatment-related characteristics during baseline were broadly similar between cohorts. A significantly higher proportion of continuous users versus discontinuers had ≥6 dispensed claims for short-acting β2-agonist canisters (16.0% vs 12.5%; p=0.006) during baseline and initiated a once-daily MITT regimen (35.2% vs 26.2%; p<0.001). Fewer continuous MITT users used a mix of once-daily and twice-daily regimens than those who discontinued MITT (64.3% vs 72.3%; p<0.001).
Conclusions
Most patients with asthma discontinued MITT within 6 months. Results indicate that patients with a history of uncontrolled, symptomatic asthma and those using less complex triple therapy regimens at initiation are less likely to discontinue MITT than patients with controlled asthma and those using a complex MITT regimen.
Keywords: asthma, asthma epidemiology
WHAT IS ALREADY KNOWN ON THIS TOPIC.
Observational studies in the USA, Japan and England have shown a high proportion of patients with asthma (61.5%–88.2%) discontinue multiple-inhaler triple therapy (MITT) within 1 year postinitiation. However, further studies are needed to better understand the characteristics and treatment patterns of patients who discontinue MITT compared with continuous users.
WHAT THIS STUDY ADDS
This retrospective cohort study confirmed high discontinuation of MITT (78.0%) in patients with asthma. Results suggest that patients with poorer asthma control before MITT initiation may be more likely to continue using the treatment, and those who initiate MITT using less complex regimens may be less likely to discontinue MITT than patients using complex regimens.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Results of this study indicate that patients’ history of asthma control and the complexity of triple therapy regimen at MITT initiation may be linked to the discontinuation of MITT.
Introduction
Asthma affects approximately 300 million people worldwide, contributing to a substantial clinical and economic burden.1 2 For adult patients with asthma who remain poorly controlled on at least medium-dose inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, the Global Initiative for Asthma report recommends the addition of a long-acting muscarinic antagonist (LAMA) as a supplementary controller to ICS/LABA, administered as either multiple-inhaler triple therapy (MITT) or single-inhaler triple therapy (SITT).2
In observational studies in the USA, Japan and England, 61.5%–88.2% of patients discontinued MITT within 1 year postinitiation.3–5 However, further studies are needed to understand which patients with asthma are discontinuing MITT and their treatment patterns. The present study aimed to understand which patients discontinued MITT by describing demographics, clinical and treatment-related characteristics of patients with asthma who were new users of MITT by discontinuation status.
Methods
Study design
This retrospective cohort study used administrative data from the IBM Truven MarketScan Commercial Claims and Encounters Database with the Medicare supplement. The study period ranged from 1 January 2016 to 31 December 2019 and the index date was the date of first initiation of MITT between 1 January 2017 and 31 March 2019. The 12-month period before index was defined as the baseline period, and the 6-month period after index was the follow-up period (figure 1). Patients were required to have at least 9 months of follow-up data to enable classification of discontinuation status at 6 months after MITT initiation, accounting for the maximal allowable gap before discontinuation criteria were met.
Figure 1.
Study design. aAll patients were required to contribute an additional 3 months of data (ie, ≥9 months of data) to allow for classification of discontinuation status at 6 months postinitiation, based on the longest allowable gap between episodes of MITT prescribing before the criteria for discontinuation were met. MITT, multiple-inhaler triple therapy.
Objective
The objective of this study was to describe the demographic, clinical and treatment-related characteristics of patients with asthma at the time of their first MITT initiation, by discontinuation status. Patients were characterised as either ‘continuous users’ (no discontinuation of MITT use within 6 months postinitiation) or ‘discontinuers’ (any discontinuation of MITT within 6 months postinitiation, with or without re-initiation, which included discontinuation of MITT to begin SITT).
Eligibility criteria
Patients were included in the study if they were ≥18 years of age on the earliest date of their first medical claim for asthma or first pharmacy claim for an asthma maintenance therapy, had ≥2 medical claims with an asthma code recorded ≥30 days apart and ≥1 pharmacy claim for an asthma maintenance therapy (alone or in combination: ICS, LABA, LAMA, xanthines, leukotriene receptor antagonists, chromones and biologics), during the study period. Patients were also required to have initiated MITT between 1 January 2017 and 31 March 2019, have ≥12 months of continuous enrolment and full health insurance coverage preindex date, and have ≥9 months of continuous enrolment and full health insurance coverage postindex date. Diagnosis codes for asthma and respiratory conditions were defined by the International Classification of Diseases, Tenth Revision (online supplemental table 1).6
bmjresp-2023-001702supp001.pdf (402.6KB, pdf)
Patients were excluded from the study if they had any MITT use during the baseline period, or any SITT use during the baseline period (including the index date). Patients with ≥1 medical claim of any of the following respiratory conditions at any point during the study period were also excluded: active respiratory tuberculosis, chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer.
MITT use and discontinuation
MITT initiation was identified based on overlapping dispensed prescriptions for all three MITT components. The discontinuation of MITT use was identified as a greater than 45-day gap in prescribing MITT components.7 The MITT algorithm was defined as any period of overlap (≥1 day) between ICS/LABA and LAMA dispensed on the same or different days. The recorded days of supply were used to calculate the prescription duration with no stockpiling or stretch periods applied.
Statistical analyses
Statistical analyses were intended to be descriptive in nature. However, a post hoc χ2 test was conducted to determine whether there were statistically significant differences in short-acting β2-agonist (SABA) use (proportion of patients with ≥6 dispensed claims for SABA canisters; cut-off based on Nwaru et al 8) and MITT dosing regimen (proportion of patients initiating each regimen) between patient cohorts. These outcomes were selected for statistical analysis post hoc as the between-group differences in these outcomes were particularly large, so quantification of the differences was of interest.
A post hoc Cox proportional hazards model was used to determine whether MITT regimen complexity and other factors were independently associated with time to MITT discontinuation (outcome). Before building the model, the proportional hazards assumption was tested by examining a Kaplan-Meier curve (survival function vs survival time) by categories of MITT dosing scheduling complexity. After fitting the model, the proportional hazards assumptions were examined using a Schoenfeld residuals plot.
Survival analysis was used to determine whether MITT regimen complexity was independently associated with time to MITT discontinuation within 6 months of initiation. The categorical, independent variable was defined at index, and was classified as ‘once-daily’ (once-daily ICS/LABA plus once-daily LAMA [least complex dosing regimen]), ‘twice-daily’ (twice-daily ICS/LABA plus twice-daily LAMA) or ‘mix of once-daily and twice-daily’ (once-daily ICS/LABA plus twice-daily LAMA or twice-daily ICS/LABA plus once-daily LAMA [most complex dosing regimen, with discordant dosing regimens; reference category]).
Missing values for variables were not imputed, rather a complete case analysis was performed for univariate and multivariate models; this assumes data were missing at random. For univariate models, the analysis was conducted among all patients with non-missing data for each specific covariate. For the final model, only those patients with complete data for the included covariates were included. Univariate associations between proposed covariates and time to MITT discontinuation were conducted. Unadjusted and adjusted HRs with 95% CIs (and p values) were provided for all variables included in univariate and multivariable models, respectively.
Statistical analysis was conducted using SAS. Statistical power for the Cox regression was estimated using NCSS PASS Software (V.19.0.1).
Patient and public involvement
No patients or public were involved in this study, and no direct subject contact or primary collection of individual human patient data occurred.
Results
A total of 4132 new MITT users were included in the study. Of these patients, 78.0% (n=3224) discontinued MITT within 6 months after initiation (discontinuers), while 22.0% (n=908) had continuous MITT use (continuous users) for the full 6-month period after initiation.
The mean (SD) age among patients at the time of their MITT initiation was 49.0 (12.1) years and most patients were female (67.9%) (table 1). The most common comorbidities among patients were atopy (60.5%) and general cerebrovascular disorders (44.1%). Demographic characteristics of patients who were discontinuers were broadly similar to those who were continuous users, and the two cohorts also had a broadly similar comorbidity burden (table 1). A high proportion of patients had asthma symptoms, including breathlessness (44.1%) and coughing (51.7%) (table 1). A higher proportion of discontinuers had cough symptoms than continuous users (53.0% vs 47.4%), whereas a higher proportion of continuous users had breathlessness than discontinuers (47.9% vs 43.1%) (table 1).
Table 1.
Patient demographics at the time of MITT initiation and clinical characteristics during baseline
| All MITT initiators N=4132 |
Discontinuers of MITT use within 6 months postinitiation N=3224 |
Continuous users of MITT within 6 months postinitiation N=908 |
|
| Age (years), mean (SD) | 49.0 (12.1) | 49.0 (12.2) | 50.0 (11.8) |
| Female, n (%) | 2806 (67.9) | 2222 (68.9) | 584 (64.3) |
| Region in the USA, n (%) | |||
| South | 1665 (40.3) | 1312 (40.7) | 353 (38.9) |
| Northeast | 931 (22.5) | 749 (23.2) | 182 (20.0) |
| North Central | 869 (21.0) | 640 (19.9) | 229 (25.2) |
| West | 648 (15.7) | 507 (15.7) | 141 (15.5) |
| Unknown | 19 (0.5) | 16 (0.5) | 3 (0.3) |
| Comorbidities, n (%)* | |||
| Atopy | 2498 (60.5) | 1933 (60.0) | 565 (62.2) |
| General cerebrovascular disorders | 1820 (44.1) | 1413 (43.8) | 407 (44.8) |
| Obesity | 1590 (38.5) | 1241 (38.5) | 349 (38.4) |
| GERD | 1343 (32.5) | 1048 (32.5) | 295 (32.5) |
| General cardiac disorders | 860 (20.8) | 665 (20.6) | 195 (21.5) |
| Anxiety | 779 (18.9) | 620 (19.2) | 159 (17.5) |
| Chronic rhinitis | 446 (10.8) | 350 (10.9) | 96 (10.6) |
| Pneumonia | 433 (10.5) | 340 (10.6) | 93 (10.2) |
| Asthma symptoms, n (%) | |||
| Coughing | 2137 (51.7) | 1707 (53.0) | 430 (47.4) |
| Breathlessness | 1823 (44.1) | 1388 (43.1) | 435 (47.9) |
| Chest tightness | 910 (22.0) | 726 (22.5) | 184 (20.3) |
| Fatigue | 774 (18.7) | 604 (18.7) | 170 (18.7) |
| Wheezing | 595 (14.4) | 480 (14. 9) | 115 (12.7) |
| Night-time awakening | 330 (8.0) | 265 (8.2) | 65 (7.2) |
| >1 severe asthma-related exacerbation during baseline, n (%) | |||
| Hospitalisation-defined exacerbation† | |||
| 1 | 182 (4.4) | 147 (4.6) | 35 (3.9) |
| ≥2 | 20 (0.5) | 16 (0.5) | 4 (0.4) |
| ER-defined exacerbation‡ | |||
| 1 | 288 (7.0) | 241 (7.5) | 47 (5.2) |
| ≥2 | 59 (1.4) | 50 (1.6) | 9 (1.0) |
| SCS-defined exacerbation§ | |||
| 1 | 1160 (28.1) | 924 (28.7) | 236 (26.0) |
| ≥2 | 704 (17.0) | 536 (16.6) | 168 (18.5) |
*Comorbidites in ≥5% of patients in any cohort were included.
†Based on a hospitalisation with an asthma diagnosis code in the primary position at any time during the hospitalisation.
‡Based on an ER visit with asthma diagnosis code in the primary position.
§Based on a medical claim with either (1) an asthma diagnosis in the primary position for a duration of 3–28 days based on pharmacy claims or (2) an injectable corticosteroid claim (medical or pharmacy) starting within ±7 days of the medical claim with an asthma diagnosis in the primary position.
ER, emergency room; GERD, gastro-oesophageal reflux disease; MITT, multiple-inhaler triple therapy; SCS, systemic corticosteroid.
During the baseline period, 45.1% of patients experienced one or more corticosteroid-defined exacerbations, 8.4% of patients had emergency room-defined exacerbations and 4.9% had hospitalisation-defined exacerbations (table 1). There were no differences in exacerbation history at baseline between discontinuers and continuous users (table 1).
Asthma treatment patterns and healthcare resource utilisation (HCRU) among patients were assessed during the baseline period. The proportion of patients using individual maintenance therapies was similar between cohorts, except for a few numerical differences. The most common maintenance medication was ICS/LABA (86.7% vs 80.2% in continuous users and discontinuers, respectively) (table 2). A lower proportion of continuous users had claims for LAMA than those who discontinued (22.0% vs 28.4%) (table 2). During baseline, the mean (SD) dispensed claims for SABA canisters was 3.0 (3.2) among all patients and was similar in continuous users and discontinuers (3.0 [3.3] vs 3.0 [3.1], respectively). However, a statistically higher (p=0.006) proportion of continuous MITT users (16.0%, n=145/908) had ≥6 dispensed claims for SABA canisters compared with MITT discontinuers (12.5%, n=402/3224) (table 2). All-cause and asthma-related HCRU were similar during baseline in patients who were continuous users of MITT and those who were discontinuers (table 2).
Table 2.
Mode of MITT initiation, asthma maintenance and reliever therapy use, and HCRU during baseline
| All MITT initiators N=4132 |
Discontinuers of MITT use within 6 months postinitiation N=3224 |
Continuous users of MITT within 6 months postinitiation N=908 |
|
| Mode of MITT initiation, n (%) | |||
| Step-up from ICS/LABA | 2165 (52.4) | 1634 (50.7) | 531 (58.5) |
| Direct initiation or step-up from other maintenance therapy | 1176 (28.5) | 947 (29.4) | 229 (25.2) |
| Step-up from LAMA | 791 (19.1) | 643 (20.0) | 148 (16.3) |
| Asthma maintenance therapy use, n (%) | |||
| ICS/LABA | 3373 (81.6) | 2586 (80.2) | 787 (86.7) |
| LTRA | 2594 (62.8) | 2014 (62.5) | 580 (63.9) |
| LAMA | 1116 (27.0) | 916 (28.4) | 200 (22.0) |
| ICS | 854 (20.7) | 667 (20.7) | 187 (20.6) |
| OCS (long-term)* | 386 (9.3) | 296 (9.2) | 90 (9.9) |
| Biologics | 264 (6.4) | 205 (6.4) | 59 (6.5) |
| Xanthines | 40 (1.0) | 24 (0.7) | 16 (1.8) |
| LABA | 37 (0.9) | 28 (0.8) | 9 (1.0) |
| Chromones | 9 (0.2) | 7 (0.2) | 2 (0.2) |
| Asthma reliever therapy use, n (%) | |||
| SABA canisters dispensed, mean (SD) | 3.0 (3.2) | 3.0 (3.1) | 3.0 (3.3) |
| ≥6 SABA canisters dispensed | 547 (13.2) | 402 (12.5) | 145 (16.0) |
| Asthma-related HCRU, mean (SD) | |||
| OP visits | 3.0 (3.8) | 3.0 (3.8) | 3.0 (4.0) |
| ER visits | 0.0 (0.6) | 0.0 (0.6) | 0.0 (0.4) |
| IP visits | 0.0 (0.3) | 0.0 (0.3) | 0.0 (0.2) |
| All-cause HCRU, mean (SD) | |||
| OP visits | 23.0 (19.2) | 23.0 (19.2) | 23.0 (19.3) |
| ER visits | 1.0 (1.4) | 1.0 (1.5) | 1.0 (1.1) |
| IP visits | 0.0 (0.5) | 0.0 (0.5) | 0.0 (0.4) |
*Long-term OCS use refers to OCS fills with ≥28 days’ supply.
ER, emergency room; HCRU, healthcare resource utilisation; ICS, inhaled corticosteroid; IP, inpatient; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; MITT, multiple-inhaler triple therapy; OCS, oral corticosteroid; OP, outpatient; SABA, short-acting β2-agonist.
The regimen for MITT treatment components was assessed at the time of MITT initiation. Most MITT initiators (70.6%) used a mix of once-daily and twice-daily ICS/LABA and LAMA (the most complex regimen), with 28.2% using both once-daily ICS/LABA and once-daily LAMA (the least complex regimen), and 1.3% using both ICS/LABA and LAMA as a twice-daily regimen. A significantly higher (p<0.001) proportion of continuous users (35.2%, n=320/908) initiated a once-daily regimen of MITT than discontinuers (26.2%, n=843/3224), while more discontinuers (72.3%, n=2332/3224) used a mix of once-daily and twice-daily regimens than continuous users (64.3%, n=584/908) (online supplemental figure 1). A large increase in MITT discontinuation (decrease in survival probability) was observed around 30 days after initiation, with a subsequent smaller increase at around 90 days. The probability of MITT discontinuation was highest among those on a twice-daily regimen, followed by a mix of once-daily and twice-daily and once-daily regimens (figure 2). Post hoc analysis showed that compared with a mix of once-daily and twice-daily ICS/LABA and LAMA, patients on once-daily regimens were less likely to discontinue MITT (HR 0.8 [95% CI 0.8, 0.9]; p<0.001), whereas patients on twice-daily regimens were more likely to discontinue MITT (HR 1.3 [95% CI 1.0, 1.8]; p=0.0421). Further details on the Cox proportional hazards regression analysis and univariate and multivariate analyses for the association between MITT regimen and time to MITT discontinuation can be found in online supplemental tables 2–4.
Figure 2.
Kaplan-Meier survival curve for time to discontinuation in patients initiating MITT, stratified by MITT regimen complexity. MITT, multiple-inhaler triple therapy.
Most patients initiated MITT following previous asthma maintenance therapy. The highest proportion of MITT initiators stepped up from ICS/LABA (52.4%), followed by direct MITT initiators or those who stepped up from other maintenance therapy (28.5%) and those who stepped up from LAMA (19.1%) (table 2).
Discussion
Among patients who initiated MITT for the first time, nearly 80% discontinued the treatment within 6 months. Previous studies in the UK, the USA and Japan reported similarly high levels of discontinuation (ranging from 61.5% to 88.0%) in the year after MITT initiation.3–5 Generally, similar trends were observed in demographic and clinical characteristics during baseline between continuous users and those who discontinued MITT use within 6 months, with a few differences. Notably, a higher proportion of continuous users had ≥6 dispensed claims for SABA canisters in the year prior to MITT initiation compared with discontinuers. Given that high levels of SABA use can be viewed as a proxy for asthma control, this suggests that patients with poorer asthma control prior to MITT initiation may be more likely to use the therapy long-term.2 8 9 In previous studies, the majority of patients with asthma used SABA as rescue medication before MITT initiation (54.8%–82.7%), with a study in Japan showing that the proportion of patients with SABA use decreased post-MITT initiation versus baseline (47.1% vs 54.8%).3 4 In addition, in the current study, a significantly greater proportion of continuous users were dispensed a simple MITT regimen at index (once-daily ICS/LABA plus once-daily LAMA), with more discontinuers using complex MITT regimens (a combination of once-daily and twice-daily ICS/LABA plus LAMA). In an observational study of patients with COPD in the USA, complex regimens (three inhalers including ICS+LABA+LAMA) have been associated with poorer adherence than simple regimens (two inhalers including ICS/LABA+LAMA or ICS+LABA/LAMA).10 Indeed, in the current study, once-daily regimens were associated with a lower probability of discontinuing MITT compared with complex MITT regimens. Possible causes of discontinuation of MITT may include the inconvenience of using multiple inhalers and burdensome regimens, inadequate insurance coverage, out-of-pocket expenses, switching to biologics treatment, etc.2 Though this is not the focus of this analysis, it is worth noting that future studies could quantify the above to shed light on the causes of MITT discontinuation.
This study used a real-world database to characterise the demographic, clinical and treatment-related characteristics of patients with asthma in the USA. Unlike in previous studies of MITT where patient characteristics were described for the full cohort of initiators,3–5 we stratified our analysis to better understand how characteristics of patients with continuous MITT use over 6 months differed from those who discontinued during that time. When interpreting the findings from this study, a few limitations should be considered. The MarketScan database provided a large sample of patients covered by private US insurance plans and some patients using Medicare; therefore, the results may not be entirely generalisable to the US population. However, the results likely better reflect a real-world patient population compared with prospective cohort or randomised controlled trials with more selective eligibility criteria than the current study. Administrative claims data may be vulnerable to coding inaccuracies and the presence of a diagnosis code may not indicate the presence of disease, which may lead to misclassification bias. To minimise these limitations, code lists were developed with clinical coding experts to appropriately identify an asthma diagnosis. MITT components may also be used to treat COPD, and therefore the algorithms for MITT may have included patients without recorded evidence of COPD who were not necessarily taking MITT for their asthma. As with other claims database studies, pharmacy claims data indicate the date on which the medication was dispensed. However, they do not guarantee that the medication was taken exactly as prescribed or on what exact days patients are taking their medications, leading to a risk of misclassifying MITT users and non-users. To mitigate this, the performance of several existing algorithms was tested and assessed in exploratory analyses, to identify a single robust algorithm for the main analyses.7 As there were no external standards or validated algorithms against which to compare, the assessment was subjective, and each metric was recalculated following adaptations to the original, existing algorithms. To explore the findings from this study, further observational studies, randomised controlled trials or prospective studies should be conducted using other secondary datasets.
Conclusion
Discontinuation of MITT is high in patients with asthma. Findings from this observational study indicate that patients with a history of uncontrolled, symptomatic asthma and those who initiate MITT using less complex regimens may be less likely to discontinue MITT than patients with controlled asthma and those using complex MITT regimens.
bmjresp-2023-001702supp002.pdf (59.7KB, pdf)
Acknowledgments
The authors would like to thank George Mu (GSK, R&D Global Medical, Collegeville, USA) for their contribution to the study. Editorial support in the form of preparation of the first draft based on input from all authors, and collation and incorporation of author feedback to develop subsequent drafts was provided by Evelin O Szalai, PhD, of Fishawack Indicia, UK, part of Avalere Health, and was funded by GSK.
Footnotes
Contributors: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors, take responsibility for the integrity of the work as a whole, contributed to the writing and reviewing of the manuscript, and have given final approval for the version to be published. All authors take complete responsibility for the integrity of the data and accuracy of the data analysis. BN, SZ, AC and YLiu were involved in the conception or design of the study, and in data analysis or interpretation. YLu was involved in data analysis or interpretation. AC, BN, SZ, YLiu and YLu act as guarantors of the manuscript.
Funding: This study was funded by GSK (study number: 207017). GSK also contributed to the design of the study and was involved in the collection, analysis, and interpretation of data, and GSK authors contributed to the writing and reviewing of the manuscript.
Competing interests: BN was an employee of CY Partners Recruitment Ltd and on assignment at GSK as a Complementary Worker at the time of the study. AC and YLiu were employees of GSK at the time of the study and hold shares/stocks in the company. SZ is an employee of GSK and holds shares/stocks in the company. YLu has no competing interests. AC, BN, SZ, YLiu, and YLu act as guarantors of the mansucript.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review: Not commissioned; externally peer reviewed.
Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Data availability statement
Data are available upon reasonable request. Anonymised individual participant data and study documents can be requested for further research from: https://www.gsk-studyregister.com/en/.
Ethics statements
Patient consent for publication
Not applicable.
Ethics approval
This study complied with all applicable laws regarding subject privacy. As this is an observational study based on a database that contains anonymised patient records, patient informed consent, ethics committee or Institutional Review Board approval are not required. Any publications and reports do not include subject identifiers.
References
- 1.G. B. D. Chronic Respiratory Disease Collaborators . Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet Respir Med 2017;5:691–706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Global Initiative for Asthma . Global strategy for asthma management and prevention. 2023. Available: https://ginasthma.org/wp-content/uploads/2023/07/GINA-2023-Full-report-23_07_06-WMS.pdf
- 3.Oppenheimer J, Bogart M, Bengtson LGS, et al. Treatment patterns and disease burden associated with multiple-Inhaler triple-therapy use in asthma. J Allergy Clin Immunol Pract 2022;10:485–94. 10.1016/j.jaip.2021.09.033 [DOI] [PubMed] [Google Scholar]
- 4.Suzuki T, Fairburn-Beech J, Sato K, et al. Clinical characteristics, treatment patterns, disease burden, and persistence/adherence in patients with asthma initiating inhaled triple therapy: real-world evidence from Japan. Curr Med Res Opin 2020;36:1049–57. 10.1080/03007995.2020.1763937 [DOI] [PubMed] [Google Scholar]
- 5.Meeraus W, Zhang S, Fowler A, et al. Treatment patterns in English asthma patients initiating multiple inhaler triple therapy: a cohort study. ERS International Congress 2020 abstracts; September 7, 2020:2277 10.1183/13993003.congress-2020.2277 [DOI] [Google Scholar]
- 6.World Health Organization . ICD-10: International Statistical Classification of Diseases and Realted Health Problems: 10th revision, 2nd edn, Available: https://apps.who.int/iris/handle/10665/42980
- 7.Meeraus W, Numbere B, Liu Y, et al. Assessing algorithms to identify asthma patients using multiple inhaler triple therapy (comprising ICS, LABA, LAMA) in a real-world database. ISPOR Europe 2021, Copenhagen, Denmark. 2021. Available: https://www.ispor.org/heor-resources/presentations-database/presentation/euro2021-3409/113734
- 8.Nwaru BI, Ekström M, Hasvold P, et al. Overuse of short-acting beta2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J 2020;55:1901872. 10.1183/13993003.01872-2019 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Azzi EA, Kritikos V, Peters MJ, et al. Understanding reliever overuse in patients purchasing over-the-counter short-acting beta2 agonists: an Australian community pharmacy-based survey. BMJ Open 2019;9:e028995. 10.1136/bmjopen-2019-028995 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Bogart M, Stanford RH, Laliberté F, et al. Medication adherence and persistence in chronic obstructive pulmonary disease patients receiving triple therapy in a USA commercially insured population. Int J Chron Obstruct Pulmon Dis 2019;14:343–52. 10.2147/COPD.S184653 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
bmjresp-2023-001702supp001.pdf (402.6KB, pdf)
bmjresp-2023-001702supp002.pdf (59.7KB, pdf)
Data Availability Statement
Data are available upon reasonable request. Anonymised individual participant data and study documents can be requested for further research from: https://www.gsk-studyregister.com/en/.