UNASSIGNED: In the management of chronic obstructive pulmonary disease (COPD), inhalation therapy plays a pivotal role. However, clinicians often face the dilemma of choosing between single and multiple inhaler therapies for their patients. This choice is critical because it can affect treatment efficacy, patient adherence, and overall disease management.
UNASSIGNED: This article examines the advantages and factors to be taken into consideration when selecting between single and multiple inhaler therapies for COPD.
UNASSIGNED: Both single and multiple inhaler therapies must be considered in COPD management. While single inhaler therapy offers simplicity and convenience, multiple inhaler therapy provides greater flexibility and customization. Clinicians must carefully evaluate individual patient needs and preferences to determine the most appropriate inhaler therapy regimen. Through personalized treatment approaches and shared decision-making, clinicians can optimize COPD management and improve patient well-being. Nevertheless, further research is required to compare the effectiveness of single versus multiple inhaler strategies through rigorous clinical trials, free from industry bias, to determine the optimal inhaler strategy. Smart inhaler technology appears to have the potential to enhance adherence and personalized management, but the relative merits of smart inhalers in single inhaler regimens versus multiple inhaler regimens remain to be determined.

BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear.
METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified.
RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared.
CONCLUSIONS: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants\' daily lives.
BACKGROUND: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

The value of treating asthma with the triple regimen of inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) delivered using multiple inhalers (MITT), or a single inhaler (SITT) is supported by a growing body of evidence, although research is still limited regarding the use of MITT.
Clinical characteristics, treatment patterns, disease burden, and persistence/adherence associated with MITT use in asthma. The MEDLINE database was searched to identify references from inception until October 2022.
The use of MITT is not very frequent in asthma patients, although it improves lung function and reduces the incidence of severe exacerbations. This may be due to existing concerns about using different devices on adherence and persistence to treatment, with a negative influence on outcomes, and to the fear that the patient will discontinue ICS/LABA but not LAMA. Nevertheless, although the current trend favors the SITT approach, some physicians may be induced to prescribe MITT over SITT because it allows the titration of individual components of triple therapy to be increased or decreased. Therefore, there is an evident need for pragmatic real-life studies to document when to prefer SITT and when MITT should be used.

Evidence from non-randomized studies shows benefits for single-inhaler users compared with multiple-inhaler users who receive the same medication. As a result, comparative cost-effectiveness studies are required to inform treatment decisions with an increasing choice of medications and devices for chronic obstructive pulmonary disease (COPD). This study conducted a systematic literature review to evaluate the cost-effectiveness of using a single combination inhaler regimen for patients with severe COPD. This review also investigated the health impact on patients in different settings.
A systematic literature search was conducted in PubMed (MEDLINE), EMBASE, Web of Science, Scopus, Cochrane Library, EBSCO Host (including CINAHL and EconLit), Health Technology Assessment Database, National Institute for Health Research Economic Evaluation Database, Cost-Effectiveness Analysis Registry and Google Scholar.
Based on the primary findings of 13 included studies: (1) single-inhaler triple therapy was a cost-effective treatment option for patients with severe COPD, and (2) triple therapy also resulted in better health outcomes (reduced exacerbations, life-years gained) and increased QALYs for patients with severe COPD. Nonetheless, eleven out of the thirteen selected studies were funded by the pharmaceutical industry, and none were conducted in the least developed countries. Therefore, the results should be interpreted with caution.

This study aimed to compare the efficacy and safety of single inhaler triple therapy and separate triple therapy in the treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD).
PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases were searched, and the search date was set from database inception until February 15, 2022. Randomized controlled trials of single inhaler triple therapy versus separate triple therapy, from which the results related to efficacy and safety profiles were extracted, and the methodologic quality and risk of bias were evaluated.
Five published articles (6 clinical trials) were screened from 3437 articles with a total of 4075 patients receiving single inhaler triple therapy and 3533 patients receiving separate triple therapy. Compared with separate triple therapy, single inhaler triple therapy significantly increased the change in forced expiratory volume in 1 second from baseline (mean difference = 0.02 L; 95% CI, 0.00-0.05L; P < 0.01), and there was a statistical difference between the 2 groups. No significant difference was found between the single inhaler triple therapy and separate triple therapy groups in terms of moderate to severe exacerbation rate (relative risk [RR] = 0.97; 95% CI, 0.85-1.10; P = 0.63), the change in St. George\'s Respiratory Questionnaire from baseline (mean difference = 0.34; 95% CI, -0.88 to 1.57; P = 0.58), proportion of St. George\'s Respiratory Questionnaire responders (RR = 0.99; 95% CI, 0.92-1.06; P = 0.77), adverse events (RR= 1.07; 95% CI, 0.90-1.27; P = 0.42), serious adverse events (RR = 1.02; 95% CI, 0.88-1.18; P = 0.81), mortality (RR = 1.10; 95% CI, 0.65-1.86; P = 0.72), risk of pneumonia (RR = 0.86; 95% CI, 0.62-1.18; P = 0.34), and risk of cardiovascular events (RR = 1.22; 95% CI, 0.91-1.65; P = 0.18).
Compared with separate triple therapy, single inhaler triple therapy appears to improve lung function in patients with moderate to severe COPD, especially in terms of forced expiratory volume in 1 second advantages. Single inhaler triple therapy may be a feasible and simplified option for patients with moderate to severe COPD; however, this conclusion needs to be further confirmed by future randomized controlled trials. (Clin Ther. 2022;XX:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

A novel, once-daily (o.d.), fixed-dose combination (FDC) of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF), delivered by the inhaler Breezhaler® device, is the first long-acting beta2-adrenergic agonist/long-acting muscarinic antagonist/inhaled corticosteroid (LABA/LAMA/ICS) therapy to be approved for maintenance treatment of asthma in adults inadequately controlled on LABA/ICS. The approval of IND/GLY/MF in the European Union (EU) also included an optional electronic sensor and smartphone (or other suitable device) application, making it the first \"digital companion\" that can be prescribed with an asthma medication. As a result, the European Medicines Agency included this approval as one of the \"outstanding contributions to public health\" (for Pneumology/Allergology) in their 2020 highlights report. Alongside IND/GLY/MF, an o.d. LABA/ICS FDC, IND/MF, was also developed and approved. This review outlines the unique strategy used in the accelerated development of IND/GLY/MF that combined various approaches: (1) selecting individual components with established efficacy/safety, (2) bridging doses to optimize efficacy/safety of IND/GLY/MF and IND/MF delivered via the Breezhaler® device, (3) developing IND/GLY/MF and IND/MF in parallel, and (4) submission for regulatory approval before formal completion of the pivotal phase III studies. IND/GLY/MF and IND/MF were combined in a single-development plan (PLATINUM program), which comprised four phase III studies: QUARTZ and PALLADIUM evaluated IND/MF while IRIDIUM and ARGON evaluated IND/GLY/MF. A unique feature was the inclusion of two LABA/ICS comparators in the pivotal IRIDIUM study-IND/MF as an internal comparator, and high-dose salmeterol xinafoate/fluticasone propionate (SAL/FLU) as a marketed comparator. In the ARGON study, IND/GLY/MF was compared against o.d. tiotropium (via Respimat®) plus twice-daily (b.i.d.) high-dose SAL/FLU (via Diskus®). As a result of this development strategy, the development and approval of IND/GLY/MF was accelerated by ca. 4 years as against what would be expected from a traditional approach, novel data were generated, and a unique optional digital companion was approved in the EU. A Video Abstract by Dr Dominic Brittain, Global Drug Development, Novartis. (MP4 228293 kb).

This study aims to compare the effects of single inhaler triple therapy comprised of inhaled corticosteroids (ICSs), long-acting β2-agonists (LABAs), and long-acting muscarinic receptor antagonists (LAMAs) with dual therapies comprised of either LABA/LAMA, ICS/LABA or separate ICS/LABA plus LAMA triple therapy.
The Pubmed, Embase, and Cochrane databases were searched up to October 31st 2018. Only randomized controlled trials were included in the meta-analysis. The primary outcome was the rate of moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations.
Seven studies fulfilling the inclusion criteria were included in the meta-analysis. Single inhaler triple therapy was associated with a significantly lower risk of COPD exacerbation compared with LABA/LAMA (rate ratio, 0.69; 95% confidence interval [CI] 0.55 to 0.87, I2 =85%), and ICS/LABA (rate ratio, 0.81; 95% CI 0.73 to 0.89, I2 =29%) dual therapy. Single inhaler triple therapy led to a more significant improvement in lung function and quality of life compared with LABA/LAMA and ICS/LABA dual therapy. Single inhaler triple therapy was associated with a higher risk of pneumonia compared with LABA/LAMA (risk ratio, 1.38, 95% CI 1.14 to 1.67, I2 =0) dual therapy.
The use of single inhaler triple therapy for COPD patients can result in lower rates of moderate or severe exacerbations of COPD as well as improved lung function and quality of life compared with dual therapy with LABA/LAMA or ICS/LABA.

A good level of asthma control improves the quality of life of asthmatic patients and may prevent future risk in term of exacerbations and decline of pulmonary function. However, in a real-life setting, several factors contribute to generally low compliance to the treatment. A rapid-onset, long-lasting medication with few adverse effects may contribute to improve adherence to therapy, along with an effective patient education and a good physician-patient communication. Many clinical studies demonstrated the comparable efficacy of the new fluticasone propionate/formoterol (FP/F) combination in a single inhaler to other combinations of inhaled corticosteroids and β2agonists and the superiority of FP/F as compared to its individual components. Also the safety profile of this combination was encouraging in all studies, even at higher doses. By effectively and safely targeting both airway inflammation and smooth muscle dysfunction, the two pathological facets of asthma, and allowing the patient to adapt dose strength, FP/F combination in a single device represents a valid option to improve asthma control in patients with different levels of asthma severity.

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 μg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 μg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. (
BACKGROUND: ISRCTN60408425).