ABSTRACT
OBJECTIVE: To assess the impact of the HealthPrize RespiPoints™ program on treatment adherence and persistence in adults with chronic obstructive pulmonary disease (COPD). METHODS: In this retrospective cohort study, program participants and nonparticipants receiving tiotropium bromide (TIO) or TIO and olodaterol between 1 January 2015-31 March 2020 were propensity score matched (PSM), from the linked database of the HealthPrize patient list and IQVIA PharMetrics® Plus. Treatment adherence, persistence, healthcare resource utilization, and costs were compared. Multivariable logistic regression models assessed the odds of adherence (≥80% proportion of days covered [PDC]), adjusted risk of discontinuation, and adjusted total healthcare costs. RESULTS: Program participants (n = 262) demonstrated a 44% greater adherence during followup than nonparticipants (n = 262) (mean [standard deviation] PDC: 0.72 [0.27] vs 0.50 [0.36], p < 0.0001). Participants had higher odds of adherence vs nonparticipants (adjusted odds ratio: 2.51; 95% confidence interval: 1.72-3.66, p < 0.0001) and a lower percentage of participants discontinued their index medication (19.85% vs 33.59%, p = 0.0004). Fewer participants were hospitalized during follow-up (13.74% vs 17.56%, p = 0.23); adjusted total medical costs were 24% lower (p = 0.08). Higher pharmacy costs partially offset lower healthcare costs. CONCLUSIONS: Program participants showed improved COPD medication adherence and persistence compared to nonparticipants.
Subject(s)
Bronchodilator Agents , Medication Adherence , Pulmonary Disease, Chronic Obstructive , Tiotropium Bromide , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/economics , Tiotropium Bromide/administration & dosage , Medication Adherence/statistics & numerical data , Male , Retrospective Studies , Female , Middle Aged , Aged , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/economics , Bronchodilator Agents/therapeutic use , Cohort Studies , Benzoxazines/administration & dosage , Benzoxazines/economics , Health Care Costs/statistics & numerical data , Drug Combinations , Administration, Inhalation , Follow-Up StudiesABSTRACT
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.
Subject(s)
Albuterol , Budesonide , Drug Liberation , Formoterol Fumarate , Mucus , Permeability , Tiotropium Bromide , Mucus/metabolism , Administration, Inhalation , Swine , Animals , Budesonide/pharmacokinetics , Budesonide/administration & dosage , Budesonide/chemistry , Formoterol Fumarate/administration & dosage , Formoterol Fumarate/pharmacokinetics , Humans , Albuterol/administration & dosage , Albuterol/pharmacokinetics , Albuterol/chemistry , Tiotropium Bromide/administration & dosage , Tiotropium Bromide/pharmacokinetics , Tiotropium Bromide/chemistry , Solubility , Cell Line , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/chemistry , Lung/metabolism , Drug Compounding/methodsABSTRACT
INTRODUCTION: To date, there is limited evidence on the effects of bronchodilators on respiratory dynamics in chronic obstructive pulmonary disease (COPD). Dynamic chest radiography (DCR) is a novel radiographic modality that provides real-time, objective and quantifiable kinetic data, including changes in the lung area (Rs), tracheal diameter, diaphragmatic kinetics and pulmonary ventilation during respiration, at a lower radiation dose than that used by fluoroscopic or CT imaging. However, the therapeutic effect of dual bronchodilators on respiratory kinetics, such as chest wall dynamics and respiratory muscle function, has not yet been prospectively evaluated using DCR. AIM: This study aims to evaluate the effects of bronchodilator therapy on respiratory kinetics in patients with COPD using DCR. METHODS AND ANALYSIS: This is an open-label, prospective, single-centre, non-controlled, comparative study. A total of 35 patients with COPD, aged 40-85 years, with a forced expiratory volume in the first second of 30-80%, will be enrolled. After a 2-4 weeks washout period, patients will receive tiotropium/olodaterol therapy for 6 weeks. Treatment effects will be evaluated based on DCR findings, pulmonary function test results and patient-related outcomes obtained before and after treatment. The primary endpoint is the change in Rs after therapy. The secondary endpoints include differences in other DCR parameters (diaphragmatic kinetics, tracheal diameter change and maximum pixel value change rate), pulmonary function test results and patient-related outcomes between pre-therapy and post-therapy values. All adverse events will be reported. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Ethics Committee of Chiba University Hospital. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs032210543.
Subject(s)
Benzoxazines , Bronchodilator Agents , Drug Combinations , Pulmonary Disease, Chronic Obstructive , Tiotropium Bromide , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/physiopathology , Tiotropium Bromide/administration & dosage , Tiotropium Bromide/therapeutic use , Prospective Studies , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Aged , Benzoxazines/therapeutic use , Benzoxazines/administration & dosage , Middle Aged , Male , Aged, 80 and over , Female , Adult , Radiography, Thoracic , Forced Expiratory Volume/drug effects , Lung/diagnostic imaging , Lung/physiopathology , Lung/drug effectsABSTRACT
Background: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation. Methods: Using the Korean National Health Insurance Service database, we enrolled COPD patients initiating treatment with LAMA or LABA/ICS between January 2005 and April 2015. Propensity score matched individuals were compared on all-cause and COPD-related medical costs and HCRU over a three-year follow-up period. Results: A total of 2444 patients were enrolled in each treatment group. LAMA group was associated with significantly lower costs than LABA/ICS group, both in all-cause (403.08 vs 474.50 USD per patient per month [PPPM], cost ratio 1.18, 95% confidence interval [CI]=1.10-1.26, p<0.0001) and COPD-related (216.37 vs 267.32 USD PPPM, cost ratio 1.24, 95% CI=1.13-1.35, p<0.0001) medical costs. All-cause HCRU was not significantly different between groups, while COPD-related HRCU was higher in LAMA group (0.66 vs 0.60 medical visits PPPM, p<0.0001). Conclusion: COPD patients initiating treatment with LAMA were associated with lower all-cause and COPD-related medical costs than those starting with LABA/ICS despite the similar all-cause HCRU and higher COPD-related HCRU. Initiation with LAMA is a cost-efficient option for the treatment of COPD.
Subject(s)
Adrenergic beta-2 Receptor Agonists , Bronchodilator Agents , Databases, Factual , Drug Costs , Pulmonary Disease, Chronic Obstructive , Tiotropium Bromide , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/economics , Pulmonary Disease, Chronic Obstructive/diagnosis , Republic of Korea/epidemiology , Male , Female , Aged , Middle Aged , Adrenergic beta-2 Receptor Agonists/economics , Adrenergic beta-2 Receptor Agonists/administration & dosage , Tiotropium Bromide/administration & dosage , Tiotropium Bromide/economics , Treatment Outcome , Bronchodilator Agents/economics , Bronchodilator Agents/administration & dosage , Time Factors , Administration, Inhalation , Muscarinic Antagonists/economics , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/economics , Drug Combinations , Cost-Benefit Analysis , Retrospective Studies , Cost Savings , Health Resources/statistics & numerical data , Health Resources/economics , Lung/physiopathology , Lung/drug effectsABSTRACT
Objective: To investigate the clinical efficacy of combining budesonide formoterol with tiotropium bromide for treating asthmachronic obstructive pulmonary disease overlap syndrome (AOCS). Methods: The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone). Patients clinical efficacy, pulmonary function, fractioned exhaled nitric oxide (FeNO), immune function, endothelial function, serum lipid peroxidation injury indexes, adverse reactions, and quality of life scores were compared. Results: Prior to treatment, no significant differences were observed in various pulmonary function indicators, FeNO, immune function, endothelial function, and lipid peroxidation injury indexes between the two groups (P > 0.05). However, after treatment, all observation indexes in both groups improved to different levels, with the experimental group -demonstrating -significantly superior improvement, compared to the conventional group (P < 0.05). We also observed that adverse reactions in the experimental group were significantly lower than in the conventional group (P < 0.05). Conclusion: The combination of budesonide formoterol to tiotropium bromide in treating asthmaCOPD overlap syndrome may significantly improve pulmonary function, endothelial function, and immune status of patients and encourage the recovery of serum lipid peroxidation injury; therefore, this may deserve widespread adoption and application (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Budesonide, Formoterol Fumarate Drug Combination/administration & dosage , Anti-Asthmatic Agents/administration & dosage , Tiotropium Bromide/administration & dosage , Bronchodilator Agents/administration & dosage , Asthma/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Drug Therapy, Combination , Treatment Outcome , SyndromeABSTRACT
El curso natural de la enfermedad pulmonar obstructiva crónica incluye habitualmente exacerbaciones. Los pacientes con enfermedad pulmonar obstructiva crónica sufren de 1-4 exacerbaciones al año de media. Estas se asocian a un empeoramiento de la calidad de vida y a un aumento de la mortalidad. Disminuir y controlar el número de exacerbaciones es uno de los objetivos principales del tratamiento de la enfermedad pulmonar obstructiva crónica. Entre los tratamientos actuales, tiotropio es el principio activo que dispone de la evidencia más sólida en la reducción de exacerbaciones moderadas/graves, acompañado de un buen perfil de seguridad y tolerabilidad. La suma de olodaterol a tiotropio ofrece una doble broncodilatación bien tolerada y eficaz en la mejora de la función pulmonar, calidad de vida y disminución de la disnea en comparación con sus monocomponentes, y reduce un 7% la tasa anual de exacerbaciones moderadas/graves vs. tiotropio, no alcanzando el nivel de significación estadística preespecificado de p < 0,01
The natural course of chronic obstructive pulmonary disease usually includes exacerbations. chronic obstructive pulmonary disease patients suffer from 1-4 exacerbations per year on average. These are associated with worsening quality of life and increased mortality. Reducing and controlling the number of exacerbations is one of the main goals of chronic obstructive pulmonary disease treatment. Among current treatments, tiotropium is the active substance with the strongest evidence in the reduction of moderate/severe exacerbations, together with a good safety and tolerability profile. The addition of olodaterol to tiotropium offers well-tolerated and effective double bronchodilation for improving lung function, quality of life, and decreased dyspnoea compared to its single components. This also reduces the annual rate of moderate/severe exacerbations vs. tiotropium by 7%, although not reaching the pre-specified statistical significance level of P<.01
Subject(s)
Humans , Bronchodilator Agents/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quality of Life , Benzoxazines/administration & dosage , Benzoxazines/adverse effects , Bronchodilator Agents/adverse effects , Drug Therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Tiotropium Bromide/administration & dosage , Tiotropium Bromide/adverse effectsABSTRACT
Abstract Objective: To compare a once-daily long-acting β2 agonist (indacaterol 150 µg) with a once-daily long-acting anticholinergic (tiotropium 5 µg) in terms of their effects on exercise endurance (limit of tolerance, Tlim) in patients with moderate COPD. Secondary endpoints were their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Methods: This was a randomized, single-blind, crossover pilot study involving 20 patients (mean age, 60.9 ± 10.0 years; mean FEV1, 69 ± 7% of predicted). Spirometric parameters, Transition Dyspnea Index scores, Tlim, and exertional dyspnea were compared after three weeks of each treatment (with a one-week washout period between treatments). Results: Nineteen patients completed the study (one having been excluded because of COPD exacerbation). Improvement in Tlim from baseline tended to be greater after treatment with tiotropium than after treatment with indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0.06). Tlim significantly improved from baseline after treatment with tiotropium (having increased from 396 ± 319 s to 493 ± 347 s; p = 0.010) but not after treatment with indacaterol (having increased from 393 ± 246 to 401 ± 254 s; p = 0.678). There were no differences between the two treatments regarding improvements in Borg dyspnea scores and lung hyperinflation at "isotime" and peak exercise. There were also no significant differences between treatments regarding Transition Dyspnea Index scores (1.5 ± 2.1 vs. 0.9 ± 2.3; p = 0.39). Conclusions: In patients with moderate COPD, tiotropium tends to improve Tlim in comparison with indacaterol. No significant differences were observed between the two treatments regarding their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Future studies, including a larger number of patients, are required in order to confirm our findings and explore mechanistic explanations. (ClinicalTrials.gov identifier: ...
RESUMO Objetivo: Comparar um β2-agonista de longa duração administrado uma vez por dia (indacaterol 150 µg) a um anticolinérgico de longa duração administrado uma vez por dia (tiotrópio 5 µg) quanto a seus efeitos na resistência ao exercício (limite de tolerância, Tlim) em pacientes com DPOC moderada. Os desfechos secundários foram seus efeitos na hiperinsuflação pulmonar, na dispneia causada pelo exercício e na dispneia na vida diária. Métodos: Estudo piloto randomizado cruzado e simples cego com 20 pacientes (média de idade: 60,9 ± 10,0 anos; média do VEF1: 69 ± 7% do previsto). Parâmetros espirométricos, pontuação no Transition Dyspnea Index, Tlim e dispneia aos esforços foram comparados após três semanas de cada tratamento (com uma semana de intervalo entre os tratamentos). Resultados: Dezenove pacientes completaram o estudo - um foi excluído por causa de exacerbação da DPOC. A melhora no Tlim tendeu a ser maior com tiotrópio do que com indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0,06). Em comparação com os valores basais, o Tlim melhorou significativamente com tiotrópio (aumentando de 396 ± 319 s para 493 ± 347 s; p = 0,010), mas não com indacaterol (aumentando de 393 ± 246 para 401 ± 254 s; p = 0,678). Não houve diferença entre os tratamentos quanto à melhora na pontuação na escala de dispneia de Borg e na insuflação pulmonar no "isotempo" e no pico do exercício. Também não houve diferenças significativas entre os tratamentos quanto à pontuação no Transition Dyspnea Index (1,5 ± 2,1 vs. 0,9 ± 2,3; p = 0,39). Conclusões: Em pacientes com DPOC moderada, o tiotrópio tende a melhorar o Tlim em comparação com o indacaterol. Não houve diferenças significativas entre os tratamentos quanto a seus efeitos na insuflação pulmonar, na dispneia durante o exercício e na dispneia na vida diária. São necessários mais estudos, com um número maior de pacientes, para confirmar nossos achados e explorar explicações mecanicistas. (ClinicalTrials.gov ...