RESUMO
BACKGROUND: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count - focusing on blood EOS count 100 to < 300 cells/mm3 - as a function of exacerbation history and COPD severity. METHODS: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12-24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses. RESULTS: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD. CONCLUSIONS: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).
Assuntos
Broncodilatadores , Budesonida , Eosinófilos , Fumarato de Formoterol , Glicopirrolato , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Glicopirrolato/administração & dosagem , Feminino , Idoso , Pessoa de Meia-Idade , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Eosinófilos/efeitos dos fármacos , Fumarato de Formoterol/administração & dosagem , Método Duplo-Cego , Progressão da Doença , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Administração por Inalação , Resultado do Tratamento , Antagonistas Muscarínicos/administração & dosagem , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/fisiologiaRESUMO
Traditionally, developing inhaled drug formulations relied on trial and error, yet recent technological advancements have deepened the understanding of 'inhalation biopharmaceutics' i.e. the processes that occur to influence the rate and extent of drug exposure in the lungs. This knowledge has led to the development of new in vitro models that predict the in vivo behavior of drugs, facilitating the enhancement of existing formulation and the development of novel ones. Our prior research examined how simulated lung fluid (SLF) affects the solubility of inhaled drugs. Building on this, we aimed to explore drug dissolution and permeability in lung mucosa models containing mucus. Thus, the permeation of four active pharmaceutical ingredients (APIs), salbutamol sulphate (SS), tiotropium bromide (TioBr), formoterol fumarate (FF) and budesonide (BUD), was assayed in porcine mucus covered Calu-3 cell layers, cultivated at an air liquid interface (ALI) or submerged in a liquid covered (LC) culture system. Further analysis on BUD and FF involved their transport in a mucus-covered PAMPA system. Finally, their dissolution post-aerosolization from Symbicort® was compared using 'simple' Transwell and complex DissolvIt® apparatuses, alone or in presence of porcine mucus or polymer-lipid mucus simulant. The presence of porcine mucus impacted both permeability and dissolution of inhaled drugs. For instance, permeability of SS was reduced by a factor of ten in the Calu-3 ALI model while the permeability of BUD was reduced by factor of two in LC and ALI setups. The comparison of dissolution methodologies indicated that drug dissolution performance was highly dependent on the setup, observing decreased release efficiency and higher variability in Transwell system compared to DissolvIt®. Overall, results demonstrate that relatively simple methodologies can be used to discriminate between formulations in early phase drug product development. However, for more advanced stages complex methods are required. Crucially, it was clear that the impact of mucus and selection of its composition in in vitro testing of dissolution and permeability should not be neglected when developing drugs and formulations intended for inhalation.
Assuntos
Albuterol , Budesonida , Liberação Controlada de Fármacos , Fumarato de Formoterol , Muco , Permeabilidade , Brometo de Tiotrópio , Muco/metabolismo , Administração por Inalação , Suínos , Animais , Budesonida/farmacocinética , Budesonida/administração & dosagem , Budesonida/química , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/farmacocinética , Humanos , Albuterol/administração & dosagem , Albuterol/farmacocinética , Albuterol/química , Brometo de Tiotrópio/administração & dosagem , Brometo de Tiotrópio/farmacocinética , Brometo de Tiotrópio/química , Solubilidade , Linhagem Celular , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Broncodilatadores/química , Pulmão/metabolismo , Composição de Medicamentos/métodosRESUMO
BACKGROUND: The extrafine single inhaler triple therapy (efSITT) containing beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 µg has proved to be efficacious in patients with chronic obstructive pulmonary disease (COPD) in randomized control trials. OBJECTIVE: TRIWIN study evaluated the effectiveness of efSITT delivering beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 µg in COPD patients previously treated with multiple-inhaler triple therapy (MITT) in a real-world study in Greece. DESIGN: Prospective, multicenter, observational, non-interventional study was conducted over 24 weeks. METHODS: A total of 475 eligible patients had moderate-to-severe COPD, an indication for treatment with efSITT, and were symptomatic despite receiving MITT. COPD Assessment Test (CAT) score, pulmonary function parameters, use of rescue medication, and adherence to inhaler use were recorded at baseline (Visit 1), 3 (Visit 2), and 6 months (Visit 3) after treatment. RESULTS: Mean CAT score decreased from 21.4 points at Visit 1, to 16.6 at Visit 2 and 15.1 at Visit 3 (p < 0.001 for all pair comparisons). At Visit 3, 79.8% of patients reached a CAT improvement exceeding minimal clinically important difference (⩾2), compared to baseline. Mean forced expiratory volume in 1 s (%pred.) increased from 55.4% at Visit 1 to 63.5% at the end of study period (p < 0.001), while mean forced vital capacity (%pred.) increased from 71.1% at Visit 1, to 76.7% at Visit 3 (p < 0.001). The mean Test of Adherence to Inhalers score increased from 42.5 to 45.3 and 46.3 points, for the three visits, respectively (p < 0.001 comparing Visits 1/2 and Visits 1/3; p = 0.006 comparing Visits 2/3). The percentage of patients showing good adherence rose from 33.7% at baseline to 58.3% at Visit 3. The percentage of patients using rescue medication during the last month dropped from 16.2% to 7.4% at the end of study period (p < 0.001). Pulmonary function parameters also improved. CONCLUSION: The TRIWIN results suggest that extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium is effective in improving health status, pulmonary function, and adherence and in reducing rescue medication use in COPD patients previously treated with MITT, in a real-world setting in Greece.
Assuntos
Beclometasona , Broncodilatadores , Combinação de Medicamentos , Fumarato de Formoterol , Glicopirrolato , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Masculino , Feminino , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Administração por Inalação , Fumarato de Formoterol/administração & dosagem , Resultado do Tratamento , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Glicopirrolato/administração & dosagem , Glicopirrolato/efeitos adversos , Grécia , Pulmão/fisiopatologia , Pulmão/efeitos dos fármacos , Índice de Gravidade de Doença , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Fatores de Tempo , Volume Expiratório Forçado , Adesão à Medicação , Glucocorticoides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversosRESUMO
BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.
Assuntos
Asma , Álcoois Benzílicos , Clorobenzenos , Combinação de Medicamentos , Humanos , Masculino , Feminino , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/uso terapêutico , Estudos Retrospectivos , Asma/tratamento farmacológico , Pessoa de Meia-Idade , Clorobenzenos/administração & dosagem , Clorobenzenos/uso terapêutico , Adulto , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Administração por Inalação , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Idoso , Fumarato de Formoterol/administração & dosagem , Resultado do Tratamento , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Testes de Função Respiratória , Eosinófilos/efeitos dos fármacosRESUMO
OBJECTIVES: To evaluate the cost-effectiveness of budesonide/formoterol reliever and maintenance therapy compared with salmeterol/fluticasone plus salbutamol as reliever therapy for asthma patients ≥12 years from the societal perspective in China. METHODS: A Markov model was developed with three health states (non-exacerbation, exacerbation, and death) with a lifetime horizon. The exacerbation rates were obtained from a prospective cohort study conducted in Chinese asthma patients. Healthcare resources utilization data were estimated based on current clinical asthma management guidelines. Asthma-related mortality, cost input and utility values were derived from public database and literature. Model robustness was assessed with one-way sensitivity and probabilistic sensitivity analyses. RESULTS: Compared with salmeterol/fluticasone plus salbutamol, budesonide/formoterol reliever and maintenance therapy led to fewer exacerbation events (13.6 vs. 15.9) and 0.0077 quality-adjusted life years (QALY) gain at an additional cost of ¥196.38 over lifetime. The base case incremental cost-effectiveness ratio (ICER) was ¥25,409.98 per QALY gained. The variables that had most impact on the model output included drug costs and medication adherence. At a willingness-to-pay threshold of ¥257,094/QALY (3 times of gross domestic product per capita in China in 2022), the probability of budesonide/formoterol maintenance and reliever therapy being cost-effective versus salmeterol/fluticasone plus as-needed salbutamol was 83.00%. CONCLUSION: From the societal perspective, budesonide/formoterol reliever and maintenance therapy is likely to be a cost-effective option compared with salmeterol/fluticasone plus as-needed salbutamol for Chinese asthma patients ≥12 years.
Assuntos
Asma , Análise Custo-Benefício , Combinação Fluticasona-Salmeterol , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Asma/tratamento farmacológico , China , Combinação Fluticasona-Salmeterol/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Budesonida/uso terapêutico , Budesonida/economia , Budesonida/administração & dosagem , Antiasmáticos/uso terapêutico , Antiasmáticos/economia , Fumarato de Formoterol/uso terapêutico , Fumarato de Formoterol/administração & dosagem , Modelos Econométricos , Criança , Adulto Jovem , Estudos Prospectivos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Serviços de Saúde/estatística & dados numéricos , Serviços de Saúde/economia , Broncodilatadores/uso terapêutico , Broncodilatadores/economia , Broncodilatadores/administração & dosagem , Quimioterapia Combinada , Análise de Custo-Efetividade , População do Leste AsiáticoRESUMO
BACKGROUND: Short-acting ß2-agonists (SABA) overuse is associated with poor asthma control. The Global Initiative for Asthma (GINA) 2019-updated strategy report has therefore taken a paradigm shift in reliever therapy recommendations. OBJECTIVES: (I) To investigate the status of SABA overuse and medication dispensing patters in asthma in the Netherlands (II) validate dispensing data for SABA overuse identification and (III) understand patients' perspectives towards this SABA-taking behavior to inform future improvement strategies. METHODS: An annually repeated cross-sectional study was conducted from 2017 to 2021 using pharmacy dispensing data in a real-world setting, including asthma patients aged 18-45 with ≥1 inhaler. A following qualitative study was performed in identified SABA overusing patients with a questionnaire and semi-structured interviews, supported by theoretical frameworks. RESULTS: Dispensing data was available from 87 % of all community pharmacies (n = 1994) in 2017 and 95 % (n = 2005) in 2021. SABA overuse prevalence was constant for the five study-years with 20.6 % (±0.5 %). Increased ICS-formoterol and decreased SABA dispenses were observed in starters of inhalation therapy in 2021. 53 asthma patients completed the questionnaire of whom 43 patients confirmed SABA overuse, generating a positive predictive value of 81 %. Key behavioral drivers covered 7 themes regarding capability (knowledge; skills; memory, attention and decision process) motivation (emotion; beliefs about-capabilities; consequences) and opportunity (environmental context). CONCLUSION: SABA overuse remains in one-fifth of asthma patients across the Netherlands, requiring careful attention from healthcare professionals. Dispensing data is a valid measure for SABA overuse in a clinical setting, facilitating patient selection. To meet patients' varied supporting needs, integration of tailored behavioral interventions is essential.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Asma , Humanos , Asma/tratamento farmacológico , Asma/psicologia , Estudos Transversais , Adulto , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Pessoa de Meia-Idade , Masculino , Feminino , Países Baixos , Adulto Jovem , Adolescente , Inquéritos e Questionários , Administração por Inalação , Uso Excessivo de Medicamentos Prescritos , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , PercepçãoAssuntos
Antiasmáticos , Asma , Etanolaminas , Fumarato de Formoterol , Humanos , Asma/tratamento farmacológico , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Etanolaminas/uso terapêutico , Etanolaminas/administração & dosagem , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Administração por Inalação , Medicina Baseada em Evidências , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Resultado do TratamentoAssuntos
Asma , Etanolaminas , Fumarato de Formoterol , Humanos , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , Europa (Continente) , Asma/tratamento farmacológico , Etanolaminas/uso terapêutico , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Administração por Inalação , Broncodilatadores/uso terapêuticoRESUMO
INTRODUCTION: The use of pressurised metered-dose inhalers (pMDIs) and asthma exacerbations necessitating healthcare reviews contribute substantially to the global carbon footprint of healthcare. It is possible that a reduction in carbon footprint could be achieved by switching patients with mild asthma from salbutamol pMDI reliever-based therapy to inhaled corticosteroid-formoterol dry powder inhaler (DPI) reliever therapy, as recommended by the Global Initiative for Asthma. METHODS: This post hoc analysis included all 668 adult participants in the Novel START trial, who were randomised 1:1:1 to treatment with as-needed budesonide/formoterol DPI, as-needed salbutamol pMDI or maintenance budesonide DPI plus as-needed salbutamol pMDI. The primary outcome was carbon footprint of asthma management, expressed as kilograms of carbon dioxide equivalent emissions (kgCO2e) per person-year. Secondary outcomes explored the effect of baseline symptom control and adherence (maintenance budesonide DPI arm only) on carbon footprint. RESULTS: As-needed budesonide/formoterol DPI was associated with 95.8% and 93.6% lower carbon footprint compared with as-needed salbutamol pMDI (least-squares mean 1.1 versus 26.2â kgCO2e; difference -25.0, 95% CI -29.7 to -20.4; p<0.001) and maintenance budesonide DPI plus as-needed salbutamol pMDI (least-squares mean 1.1 versus 17.3â kgCO2e; difference -16.2, 95% CI -20.9 to -11.6; p<0.001), respectively. There was no statistically significant evidence that treatment differences in carbon footprint depended on baseline symptom control or adherence in the maintenance budesonide DPI arm. CONCLUSIONS: The as-needed budesonide/formoterol DPI treatment option was associated with a markedly lower carbon footprint than as-needed salbutamol pMDI and maintenance budesonide DPI plus as-needed salbutamol pMDI.
Assuntos
Asma , Broncodilatadores , Budesonida , Pegada de Carbono , Inaladores de Pó Seco , Fumarato de Formoterol , Humanos , Asma/tratamento farmacológico , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Budesonida/administração & dosagem , Administração por Inalação , Fumarato de Formoterol/administração & dosagem , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Albuterol/administração & dosagem , Albuterol/uso terapêutico , Inaladores Dosimetrados , Resultado do Tratamento , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Método Duplo-Cego , IdosoRESUMO
INTRODUCTION: Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a. METHODS: The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 µg [medium-strength BDP]; Study 2: 200/6/12.5 µg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve between time zero and the last quantifiable timepoint (AUC0-t) for the analytes were between 80 and 125 %. RESULTS: In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for Cmax and 127.34 % for AUC0-t). In Study 1, GB AUC0-t lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for Cmax and 129.12 % for AUC0-t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0-t, although not for Cmax. Both formulations were similarly well tolerated in all three studies. CONCLUSIONS: Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.
Assuntos
Propelentes de Aerossol , Beclometasona , Estudos Cross-Over , Combinação de Medicamentos , Fumarato de Formoterol , Glicopirrolato , Inaladores Dosimetrados , Beclometasona/farmacocinética , Beclometasona/administração & dosagem , Humanos , Fumarato de Formoterol/farmacocinética , Fumarato de Formoterol/administração & dosagem , Masculino , Glicopirrolato/farmacocinética , Glicopirrolato/administração & dosagem , Administração por Inalação , Adulto , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Área Sob a Curva , Equivalência Terapêutica , Broncodilatadores/farmacocinética , Broncodilatadores/administração & dosagem , Antiasmáticos/farmacocinética , Antiasmáticos/administração & dosagem , FluorocarbonosRESUMO
INTRODUCTION/BACKGROUND: Mild asthma treatment recommendations include intermittent inhaled corticosteroid (ICS)/formoterol dosing or regular ICS dosing with short-acting ß2-agonist reliever. Due to the heterogeneity of asthma, identification of traits associated with improved outcomes to specific treatments would be clinically beneficial. AIMS/OBJECTIVES: To assess the impact of patient traits on treatment outcomes of regular ICS dosing compared with intermittent ICS/formoterol dosing, a systematic literature review (SLR) and network meta-analysis (NMA) was conducted. Searches identified randomised controlled trials (RCTs) of patients with asthma aged ≥12 years, containing ≥1 regular ICS dosing or intermittent ICS/formoterol dosing treatment arm, reporting traits and outcomes of interest. RESULTS: The SLR identified 11 RCTs of mild asthma, of 14,516 patients. A total of 11 traits and 11 outcomes of interest were identified. Of these, a feasibility assessment indicated possible assessment of three traits (age, baseline lung function, smoking history) and two outcomes (exacerbation rate, change in lung function). The NMA found no significant association of any trait with any outcome with regular ICS dosing relative to intermittent ICS/formoterol dosing. Inconsistent reporting of traits and outcomes between RCTs limited analysis. CONCLUSIONS: This is the first systematic analysis of associations between patient traits and differential treatment outcomes in mild asthma. Although the traits analysed were not found to significantly interact with relative treatment response, inconsistent reporting from the RCTs prevented assessment of some of the most clinically relevant traits and outcomes, such as adherence. More consistent reporting of respiratory RCTs would provide more comparable data and aid future analyses.
Assuntos
Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2 , Asma , Fumarato de Formoterol , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Asma/tratamento farmacológico , Fumarato de Formoterol/administração & dosagem , Administração por Inalação , Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Resultado do Tratamento , Antiasmáticos/administração & dosagem , Quimioterapia Combinada , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Fatores Etários , Fumar , AdolescenteRESUMO
Purpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany. Patients and Methods: Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period. Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period. Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.
Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019. In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years. The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).
Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Combinação de Medicamentos , Glicopirrolato , Antagonistas Muscarínicos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Feminino , Estudos Retrospectivos , Alemanha , Idoso , Administração por Inalação , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Glicopirrolato/administração & dosagem , Glicopirrolato/efeitos adversos , Clorobenzenos/administração & dosagem , Clorobenzenos/efeitos adversos , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Resultado do Tratamento , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/efeitos adversos , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Fumarato de Formoterol/administração & dosagem , Quimioterapia Combinada , Fatores de Tempo , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Sixty-five percent of people with severe asthma and a fractional exhaled nitric oxide (Feno) greater than or equal to 45 parts per billion (ppb) are nonadherent to inhaled corticosteroids (ICSs). Digital devices recording both time of use and inhaler technique identify nonadherence and ICS responsiveness but are not widely available. As the NEXThaler dose counter activates only at an inspiratory flow rate of 35 L/min, this may provide an alternative to identifying ICS responsiveness. OBJECTIVE: To assess ICS adherence and responsiveness in severe asthma using beclometasone/formoterol (200/6 µg) NEXThaler (BFN) dose-counting. METHODS: Patients with severe asthma with a Feno greater than or equal to 45 ppb were invited to use BFN in place of their usual ICS/long-acting ß2-agonist. Feno, 6-item Asthma Control Questionnaire score, lung function, and blood eosinophil count were monitored for 3 months. A log10ΔFeno of greater than or equal to 0.24 was used to define Feno suppression as the primary marker of ICS responsiveness at day 28. RESULTS: Twenty-seven of 48 (56%) patients demonstrated significant Feno suppression at month 1 (median pre-114, post-48 ppb, P < .001). A small but significant reduction occurred in Feno nonsuppressors. The 6-item Asthma Control Questionnaire score fell a median 1.2 units in Feno suppressors (P < .001) and 0.5 units in nonsuppressors (P = .025). These effects were sustained until month 3 in Feno suppressors, with a significant improvement in FEV1 and blood eosinophils. Sixty-seven percent (18 of 27) of those with baseline ICS/long-acting ß2-agonist prescription refills of 80% or more were Feno suppressors, suggesting prior nonadherence despite adequate prescription collection. Seventy-nine percent of Feno suppressors did not require biologics within mean 11.4 months from initial dose counting. CONCLUSIONS: BFN dose-counting identifies ICS responsiveness in severe asthma with the implication that these patients may not need to progress to biological therapies.
Assuntos
Antiasmáticos , Asma , Beclometasona , Fumarato de Formoterol , Óxido Nítrico , Humanos , Asma/tratamento farmacológico , Masculino , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , Feminino , Beclometasona/administração & dosagem , Beclometasona/uso terapêutico , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico/análise , Adulto , Administração por Inalação , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Adesão à Medicação , Etanolaminas/uso terapêutico , Etanolaminas/administração & dosagem , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Idoso , Combinação de Medicamentos , Resultado do Tratamento , Eosinófilos/imunologia , Testes de Função RespiratóriaRESUMO
PURPOSE OF REVIEW: Asthma is the most common chronic respiratory disorder, characterized by recurring, reversible airflow obstruction due to inflammation and airway hyperresponsiveness. Although biologics have provided significant advances in the treatment of asthma, they are expensive, and their use remains restricted to more severe asthma. Additional approaches in the management of moderate-to-severe asthma are necessary. RECENT FINDINGS: ICS-formoterol as maintenance and reliever therapy in asthma and its effect on improved asthma control has been demonstrated in multiple cohorts of asthma. Although ICS-formoterol as maintenance and reliever therapy has been widely validated, there are significant design considerations including the requirement for exacerbation and bronchodilator response and the lack of evidence for effectiveness in patients who use nebulized reliever therapies, which may limit the use of this therapy in selected populations. More recent trials of as-needed ICS have demonstrated effectiveness in reducing asthma exacerbations and improvements in asthma control and may provide an additional therapeutic strategy for individuals with moderate-to-severe asthma. SUMMARY: Both ICS-formoterol as a maintenance and a reliever as well as as-needed ICS have demonstrated significant improvements in the control of moderate-to-severe asthma. Future investigational work will be necessary to elucidate whether a strategy of ICS-formoterol as maintenance and reliever therapy or an as-needed ICS strategy demonstrates superiority in asthma control in the context of the cost to individual patients and health systems.
Assuntos
Antiasmáticos , Asma , Fumarato de Formoterol , Glucocorticoides , Humanos , Administração por Inalação , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Budesonida/efeitos adversos , Quimioterapia Combinada , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêuticoRESUMO
El asma se caracteriza por su impacto deletéreo que incluye gran coste económico para el sistema de salud. En pacientes con asma mal controlada a pesar del tratamiento, se propone un régimen de mantenimiento con corticoides inhalados y formoterol. El objetivo del presente estudio observacional retrospectivo fue evaluar las modificaciones espirométricas tras el cambio del medicamento controlador en pacientes con asma moderada a severa asistidos en el Hospital Clínico de Magallanes de Punta Arenas, así como también cuantificar la modificación en el número de exacerbaciones graves (consulta a un servicio de urgencia y/u hospitalización por asma). Participaron 61 adultos con asma moderada a severa (mediana de edad: 60 años [rango: 21-87], mujeres: 69,4%; comorbilidad atópica/alérgica: 79%; otras comorbilidades: 46,8%) en los que se cambió el tratamiento con fluticasona/salmeterol 250/25 μg por budesónida/formoterol 160/4,5 μg. No se observaron cambios significativos en los índices espirométricos tras el cambio. Con el tratamiento inicial, el 46,9% presentó ≥ 1 visita a urgencias (total: 50 consultas). Tras el cambio por budesonida/formoterol, el 21% requirió al menos una visita a urgencias (total: 14 consultas; p < 0,01). La proporción de pacientes con ≥ 2 consultas a urgencias fue de 19,7% con el tratamiento basal y de 1,6% tras el cambio a budesonida/formoterol (p < 0,01). No se observaron diferencias significativas en la cantidad de hospitalizaciones. En este estudio del mundo real de pacientes con asma moderada a grave, el cambio del tratamiento a budesonida/formoterol se asoció con reducción significativa de las consultas a urgencias, a pesar de no detectarse cambios de significación estadística en los índices espirométricos habituales.
Asthma is characterized by its deleterious impact, including a high cost to the healthcare system. In patients with poorly controlled asthma despite treatment, a maintenance regimen of inhaled corticosteroids and formoterol is proposed. The aim of this retrospective, observational study was to evaluate the spirometric changes after switching the controller medication in patients with moderate to severe asthma attended in our institution ("Hospital Clínico de Magallanes"), as well as the variation in the number of severe exacerbations (consultation to an emergency department and/or hospitalization for asthma). Sixty-one adults with moderate to severe asthma (median age: 60 years-old [range: 21-87], women: 69.4%; atopic/allergic comorbidity: 79%; other comorbidities: 46.8%) in whom treatment with fluticasone/salmeterol 250/25 μg was switched to budesonide/formoterol 160/4.5 μg participated in our study. No significant changes in spirometric parameters were observed after the replacement treatment. With the initial treatment, 46.9% patients presented ≥ 1 visit to the emergency department (total: 50 visits). After the switch to budesonide/formoterol, 21% required at least one emergency department visit (total: 14 consultations; p < 0.01). The proportion of patients with ≥ 2 emergency department visits was 19.7% with baseline treatment and 1.6% after switching to budesonide/formoterol (p < 0.01). No significant differences were observed in the number of hospitalizations. In this real-world study of moderate to severe asthma patients, switching to budesonide/formoterol was associated with a significant reduction in emergency department visits, despite no statistically significant changes in the usual spirometric parameters.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Asma/tratamento farmacológico , Espirometria , Budesonida/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Broncodilatadores/administração & dosagem , Esquema de Medicação , Volume Expiratório Forçado , Estudos Retrospectivos , Quimioterapia Combinada , Combinação Fluticasona-Salmeterol/administração & dosagemRESUMO
BACKGROUND: Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tightness and coughing. Inhaled drugs on a daily basis are the cornerstone of asthma treatment, therefore, patient adherence is very important. METHODS: We performed a multicenter, open, non-interventional, observational, prospective study of 716 adult patients diagnosed with asthma receiving FDC (Fixed-dose combination) budesonide/formoterol via the Elpenhaler device. We assessed the adherence to treatment at 3 and 6 months (based on the MMAS-8: 8-item Morisky Medication Adherence Scale), the quality of life and change in forced expiratory volume in 1 s (FEV1) from baseline to follow-up. RESULTS: Approximately 80% of the patients showed medium to high adherence throughout the study. The mean (SD) MMAS-8 score at 6 months was 6.85 (1.54) and we observed a statistically significant shift of patients from the low adherence group to the high adherence group at 6 months. Moreover, after 6 months of treatment with FDC budesonide/formoterol, we observed an increase in the patients' quality of life that as expressed by a change 2.01 (95%CI 1.93-2.10) units in Mini AQLQ (p < 0.0001) that was more pronounced in the high adherence group. The same trend was also observed in terms of spirometry (mean FEV1 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline) with a higher improvement in the medium and high adherence groups. CONCLUSIONS: Treatment with FDC of budesonide/formoterol via the Elpenhaler device was associated with improvement in asthma-related quality of life and lung function over 6 months that were more prominent in patients with higher adherence. TRIAL REGISTRATION: 2017-HAL-EL-74 (ClinicalTrials.gov Identifier: NCT03300076).
Assuntos
Asma , Budesonida/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Qualidade de Vida , Adulto , Asma/tratamento farmacológico , Asma/psicologia , Broncodilatadores/administração & dosagem , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Combinação de Medicamentos , Etanolaminas/efeitos adversos , Fumarato de Formoterol/uso terapêutico , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Patients with stable chronic obstructive pulmonary disease (COPD) have been observed to benefit from tiotropium bromide. However, there are few studies of tiotropium bromide on sputum and sputum viscosity. To evaluate the effect of tiotropium bromide on mucus hypersecretion, a randomized, double-blind controlled trial was performed. METHODS: 120 cases of patients with pulmonary function grade II were divided into two groups, which include the treatment group given tiotropium bromide powder inhalation (18 µg, inhalation, QD) and the control group given formoterol fumarate powder inhalation (12 µg, inhalation, BID) plus ambroxol hydrochloride tablets (60 mg, oral, TID). After 3 months of treatment, the pulmonary function and α 1-acid glycoprotein (α 1-AGP) in sputum were detected, and the changes of glycoprotein and Ca2+ content were evaluated by Miller classification. RESULTS: Three patients (2 cases in the treatment group and 1 case in the control group) were dropped due to loss of follow-up, and 117 cases of patients were enrolled in this study. After 3 months of treatment, the sputum character score, α1-acid glycoprotein, Ca2+ content, and lung function of the two groups were significantly improved; group comparison analyses revealed that there was no significant difference in the content of α 1-AGP, Ca2+ in sputum, and lung function between the two groups (P > 0.05), but the improvement of sputum properties was significant (P < 0.05), and the treatment group was better than the control group (t = -2.77; P = 0.007). CONCLUSIONS: Inhaled tiotropium bromide can effectively inhibit the mucus hypersecretion in stable COPD patients, improve the sputum properties and lung function of patients, and improve the quality of life of patients.
Assuntos
Muco/efeitos dos fármacos , Muco/fisiologia , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Brometo de Tiotrópio/uso terapêutico , Administração por Inalação , Ambroxol/administração & dosagem , Cálcio/metabolismo , Biologia Computacional , Método Duplo-Cego , Fumarato de Formoterol/administração & dosagem , Humanos , Antagonistas Muscarínicos/administração & dosagem , Orosomucoide/metabolismo , Ventilação Pulmonar/efeitos dos fármacos , Qualidade de Vida , Escarro/efeitos dos fármacos , Escarro/fisiologia , Brometo de Tiotrópio/administração & dosagemRESUMO
A large proportion of asthmatic patients are treated with protocols resulting from data obtained by randomized controlled trials (RCTs) for which they would not have been eligible. Therefore, the aim of this study was to undertake a quantitative synthesis on real-world evidence comparing single inhaled corticosteroid (ICS)/formoterol maintenance and reliever therapy (SMART) and maintenance ICS/long-acting ß2-adrenoceptor agonist (LABA) + as-needed short-acting ß2-adrenoceptor agonist (SABA). A network meta-analysis of real-world studies was performed to compare SMART with ICS/LABA + as-needed SABA therapies in asthmatic patients. The surface under the cumulative ranking curve analysis was used to rank efficacy. The posterior probability distribution was reported as 95% credible interval (95%CrI). Data of 11,360 asthmatic patients were extracted from 6 studies. SMART including an ICS at medium-dose (MD) was more effective than MD ICS/LABA FDC + as-needed SABA (RR 0.54 95%CrI 0.42-0.69; P < 0.001) and low-dose (LD) SMART (RR 0.82 95%CrI 0.70-0.95; P < 0.05) against severe asthma exacerbation. MD SMART improved the Asthma Control Questionnaire score more than MD ICS/LABA FDC + as-needed SABA (delta effect -0.33 95%CrI -0.62 to -0.01; P < 0.05). The efficacy rank was: MD SMART > LD SMART > ICS + LABA free combination + as-needed SABA > ICS/LABA FDC + as-needed SABA > MD ICS/LABA FDC + as-needed SABA. The findings of this network meta-analysis of real-world evidence, and concordance with the effect estimates resulting from previous meta-analyses of RCTs, suggest that SMART may represent the preferred therapeutic option to reduce the risk of severe exacerbation in adults with moderate to severe asthma.
Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antiasmáticos/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Administração por Inalação , Asma , Quimioterapia Combinada , Humanos , Quimioterapia de ManutençãoRESUMO
OBJECTIVE: To provide an overview of the risk factors and mechanisms underlying asthma exacerbations and the role of inhaled corticosteroids (ICSs) in preventing exacerbations. DATA SOURCES: Queries for asthma exacerbations and ICSs were conducted using PubMed, searching for primary articles and reviews. STUDY SELECTIONS: Studies written in English, with a focus on well-designed randomized controlled clinical trials. RESULTS: Asthma exacerbations remain a major source of morbidity, with future exacerbations most likely among patients with previous exacerbations and among those with peripheral blood eosinophilia. Exacerbations are often triggered by viral respiratory tract infections, but recent evidence supports nonviral triggers as well. In terms of exacerbation prevention, several approaches to ICS therapy have been found to be effective, including intermittent high-dose ICS without use of background controller in preschool children with recurrent episodic wheezing, intermittent high-dose ICS without use of background controller in adults with mild asthma, and as-needed ICS dosing whenever rescue treatment is needed among children, adolescents, and adults with mild asthma not receiving daily controller therapy. CONCLUSION: ICSs are highly effective in preventing exacerbations of asthma. Multiple dosing strategies have been found to reduce exacerbation risk, allowing for a personalization of approaches based on individual patient phenotypes and preferences.
Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Antiasmáticos/administração & dosagem , Asma/patologia , Asma/prevenção & controle , Criança , Pré-Escolar , Eosinofilia/patologia , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , Humanos , Lactente , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sons Respiratórios/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: The 2021 Global Initiative for Asthma (GINA) report recommends as-needed inhaled corticosteroid (ICS)/formoterol irrespective of severity, and maintenance and reliever treatment (MART) from GINA Step 3 as part of Treatment Track 1, partly based on the SYGMA studies. We investigated how current clinical practice in Australia, Canada, China and the Philippines relates to latest GINA recommendations. METHODS: Patients and physicians were recruited from online panels between July and August 2020 and invited to complete an online survey. INCLUSION CRITERIA: age ≥18 years, current/past physician diagnosis of asthma (patients); primary care (Canada also included respirologists/respiratory therapists), treating ≥4 patients with asthma per month, ≥3 years in clinical practice (physicians). RESULTS: Overall, 1216/70,183 patients and 803/8376 physicians replied and were eligible for inclusion. Only 8-15% of patients were using MART; 66-81% used regular maintenance therapy with/without an as-needed reliever. Across the four countries, physicians classified 48-63% of their patients as mild (GINA Steps 1-2) and 28-36% as moderate (GINA Steps 3-4). Generally, physicians rated symptom control over exacerbation reduction as their main treatment goal; patients also ranked symptom relief as very important. Approximately 9-29% of patients and 24-45% of physicians were unaware of MART, and among those who prescribed MART, 80-95% prescribed an additional (non-ICS) as-needed reliever. INTERPRETATION: Most physicians prioritized managing asthma symptoms over exacerbations. A lack of awareness and understanding of MART dosing exists among physicians. Practical strategies are required to implement GINA recommendations effectively in real-world clinical practice and to identify appropriate patients for MART.