Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies

doi:10.1016/j.jaci.2003.10.011

Journal of Allergy and Clinical Immunology

Volume 113, Issue 2, February 2004, Pages 245-251

https://doi.org/10.1016/j.jaci.2003.10.011 Get rights and content

Abstract

Background

Improved adherence to inhaled corticosteroids (ICSs) has also been associated with decreased asthma-associated morbidity and mortality.

Objective

The purpose of this study was to assess patient medication refill persistence with fluticasone propionate (FP) and salmeterol combination in a single inhaler (FSC), FP and salmeterol in combination from 2 separate inhalers, FP and montelukast in combination, FP as monotherapy, and montelukast as monotherapy.

Methods

We performed a retrospective, observational, 24-month (12-month baseline and 12-month follow-up) database study using medical and pharmacy claims from a large managed care organization. We identified 2511 subjects 12 years of age or older with a claim for asthma (International Classification of Diseases, Ninth Revision: 493.XX): 563 patients receiving FSC, 224 receiving FP plus salmeterol, 75 receiving FP plus montelukast, 798 receiving FP only, and 776 receiving montelukast only. Refill rates of FP, as a measure of adherence, were compared for each FP-containing cohort during the 12-month follow-up period. In addition, refill rates were compared between FSC, an inhaler, and montelukast, an oral medication.

Results

Twelve-month baseline asthma medication use and patient demographics were comparable among cohorts. Patients in the FSC cohort obtained significantly more refills compared with the number of FP refills in the other FP-containing cohorts (4.06 for FSC vs 2.35 for FP plus salmeterol, 1.83 for FP plus montelukast, and 2.27 for FP alone) over the 12-month follow-up period. In addition, patients taking FSC had similar refill persistence compared with patients taking the oral leukotriene modifier montelukast (4.51).

Conclusion

FSC might increase ICS refill persistence compared with FP alone in a single inhaler, FP in combination with salmeterol from 2 separate inhalers, and FP in combination with montelukast. In addition, FSC in a dry powdered inhaler had similar refill rates compared with an oral asthma agent, montelukast. Use of a single inhaler containing both an ICS (FP) and a long-acting bronchodilator (salmeterol) might increase the likelihood that patients are getting more optimal ICS therapy, as well as the benefits from the long-acting bronchodilator, with patient adherence comparable to an oral agent.

Section snippets

Data source

This is a retrospective observational cohort study using linked medical and pharmacy claims. The analysis was conducted by Ingenix, Inc, a UnitedHealth Group Company, which has access to a proprietary, Health Insurance Portability Accountability Act-compliant research database containing information from a noncapitated, managed, fee-for-service national health plan. This database is geographically diverse, containing more than 5 million annual covered lives, with integrated enrollment,

Subjects

A total of 7899 subjects were identified with a medical claim for asthma and at least one of the specified pharmacy prescription claims in the capture period. A total of 2436 subjects satisfied the inclusion criteria and were classified in the 5 study cohorts on the basis of their index drug use and medication use within 60 days of the index date (FSC, n = 563; FP plus salmeterol, n = 224; FP plus montelukast, n = 75; FP alone, n = 798; and montelukast alone, n = 776). The groups had similar

Discussion

The results from this study demonstrate that the use of FSC increases the refill persistence of ICSs over 12 months compared with using FP and salmeterol in separate inhalers, using FP with a leukotriene modifier, or even using FP alone. The annual refill rate for FSC was significantly higher when compared with the number of FP claims in the FP plus salmeterol cohort, the number of FP claims in the FP plus montelukast cohort, and the number of FP claims by patients using FP as a single

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Persistence results were consistent in sensitivity analyses that used varying definitions of nonpersistence, illustrating their robustness. Our results are consistent with existing observational studies among patients with asthma, which show that adherence and persistence are higher when using a single inhaler versus multiple inhalers in dual therapy.34,35 In 2 retrospective cohort studies in the United States examining adherence to dual therapy via a single inhaler versus 2 inhalers, the mean number of prescription refills and treatment days were higher for single inhaler versus multiple inhalers.34,35
Treatment guidelines recommend triple therapy for patients with asthma who remain uncontrolled on inhaled corticosteroid/long-acting β₂-agonist therapy. Previously, triple therapy was only available via multiple inhalers. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) is approved as maintenance treatment for asthma; however, real-world information on adherence and persistence is limited.
To compare adherence and persistence among adult patients with asthma receiving single-inhaler FF/UMEC/VI versus multiple-inhaler triple therapy (MITT) in the United States.
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Both medium- and high-dose BDP/FF/G were cost-effective vs BDP/FF, with ICERs of £12,224 and £15,587 per QALY gained. High-dose BDP/FF/G was dominant vs BDP/FF + tiotropium, as it was both cheaper and gained QALYs. Sensitivity analyses were consistent with the base model: medium- and high-dose BDP/FF/G had 94.3% and 88.3% likelihoods to be cost-effective vs BDP/FF; high-dose BDP/FF/G had 100% likelihood to be a dominant strategy vs BDP/FF + tiotropium.
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To describe real-world prevalence, outcomes, and treatment patterns associated with MITT.
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Use of separate inhalers for LABA, LAMA and ICS can lead to non-adherence to treatment over time, leading to increased morbidity and healthcare expenditures [6]. The use of LABA/LAMA/ICS combinations in a single inhaler is expected to be an effective treatment option for patients with persistent asthma and could also contribute to improved patient adherence which has been shown for other fixed-dose combination products [7,8]. Indacaterol acetate (IND [LABA]), is co-formulated with glycopyrronium bromide (GLY [LAMA]) and mometasone furoate (MF [ICS]) as a once-daily (o.d.) combination (IND/GLY/MF), delivered using the Breezhaler® device, for maintenance treatment of asthma.
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Patients with asthma who are inadequately controlled on inhaled corticosteroid–long-acting β₂-adrenoceptor agonist (ICS–LABA) combinations might benefit from the addition of a long-acting muscarinic receptor antagonist. The aim of the IRIDIUM study was to assess the efficacy and safety of a once-daily, single-inhaler combination of mometasone furoate, indacaterol acetate, and glycopyrronium bromide (MF–IND–GLY) versus ICS–LABA in patients with inadequately controlled asthma.
In this 52-week, double-blind, double-dummy, parallel-group, active-controlled phase 3 study, patients were recruited from 415 sites across 41 countries. Patients aged 18 to 75 years with symptomatic asthma despite treatment with medium-dose or high-dose ICS–LABA, at least one exacerbation in the previous year, and a percentage of predicted FEV₁ of less than 80% were included. Enrolled patients were randomly assigned (1:1:1:1:1) via interactive response technology to receive medium-dose or high-dose MF–IND–GLY (80 μg, 150 μg, 50 μg; 160 μg, 150 μg, 50 μg) or MF–IND (160 μg, 150 μg; 320 μg, 150 μg) once daily via Breezhaler, or high-dose fluticasone–salmeterol (FLU–SAL; 500 μg, 50 μg) twice daily via Diskus. The primary outcome was change from baseline in trough FEV₁ with MF–IND–GLY versus MF–IND at week 26 in patients in the full analysis set, analysed by means of a mixed model for repeated measures. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02571777, and is completed.
Between Dec 8, 2015, and Jun 14, 2019, 3092 of 4851 patients screened were randomly assigned (medium-dose MF–IND–GLY, n=620; high-dose MF–IND–GLY, n=619; medium-dose MF–IND, n=617; high-dose MF–IND, n=618; high-dose FLU–SAL, n=618). 2747 (88·8%) patients completed the 52-week treatment and 321 (10·4%) started but discontinued study treatment prematurely. Medium-dose MF–IND–GLY (treatment difference [Δ] 76 mL [95% CI 41–111]; p<0·001) and high-dose MF–IND–GLY (Δ 65 mL [31–99]; p<0·001) showed superior improvement in trough FEV₁ versus corresponding doses of MF–IND at week 26. Improvements in trough FEV₁ were greater for both medium-dose MF–IND–GLY (99 mL [64–133]; p<0·001) and high-dose MF–IND–GLY (119 mL [85–154]; p<0·001) than for high-dose FLU–SAL at week 26. Overall, the incidence of adverse events was balanced across the treatment groups. Seven deaths were reported (one with medium-dose MF–IND–GLY, two with high-dose MF–IND–GLY, and four with high-dose MF–IND) during the study; none of these deaths was considered by the investigators to be caused by study drugs or other study-related factors.
Once-daily, single-inhaler MF–IND–GLY improved lung function versus ICS–LABA combinations (MF–IND and FLU–SAL) in patients with inadequately controlled asthma. The safety profile was similar across treatment groups. MF–IND–GLY therefore constitutes a good treatment option in these patients.
Novartis Pharmaceuticals.

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Asthma, Rhinitis, Other Respiratory DiseasesImproved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies☆

Abstract

Background

Objective

Methods

Results

Conclusion

Section snippets

Data source

Subjects

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Respir Med

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

Clin Ther

Surveillance for asthma—United States, 1980-1999

MMWR Morb Mortal Wkly Rep

A case-control study of deaths from asthma

Thorax

Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study

Thorax

Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma

Int J Epidemiol

A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists

Am J Respir Crit Care Med

Risk factors for readmission to hospital for asthma in childhood

Thorax

Hospital readmissions for childhood asthma, a 10-year metropolitan study

Am J Respir Crit Care Med

Expert Panel Report guidelines for the diagnosis and management of asthma—update on selected topics 2002

Global Strategy for Asthma Management and Prevention

Asthma, Rhinitis, Other Respiratory Diseases
Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies☆