Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

INTRODUCTION: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed. METHODS: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting ß2-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted. The objective was to refine current algorithms to identify moderate exacerbations in claims data and assess the refined algorithm's performance. Positive and negative predictive values (PPV and NPV) were assessed via chart review of 150 moderate exacerbations events and 50 patients without exacerbations. Sensitivity analyses assessed alternative algorithms and compared healthcare resource utilization (HRU) between algorithm-identified patients (claims group) and those confirmed by chart review (confirmed group) to have experienced a moderate exacerbation. RESULTS: Algorithm-identified moderate exacerbations were: visit of ≤1 day with an asthma exacerbation diagnosis OR visit of ≤1 day with selected asthma diagnoses AND ≥1 respiratory pharmacy claim, excluding systemic corticosteroids, within 14 days after the first claim. The algorithm's PPV was 42%; the NPV was 78%. HRU was similar for both groups. CONCLUSION: This algorithm identified potential moderate exacerbations from claims data; however, the modest PPV underscores its limitations in identifying moderate exacerbations, although performance was partially due to identification of previously unidentified severe exacerbations. Application of this algorithm in future claims-based studies may help quantify the economic burden of moderate and severe exacerbations in asthma when an algorithm identifying severe exacerbations is applied first.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Comparison of COPD health care utilization and associated costs across patients treated with LAMA+LABA fixed-dose therapies.

BACKGROUND: There is limited clinical trial and/or real-world evidence comparing differences among currently approved fixed-dose combination (FDC) long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) treatments. OBJECTIVE: To compare chronic obstructive pulmonary disease (COPD)-related and all-cause health care resource utilization (HCRU) and costs between COPD patients initiating tiotropium (TIO) + olodaterol (OLO) versus (a) other LAMA + LABA FDCs and (b) umeclidinium (UMEC) + vilanterol (VI), specifically. METHODS: In this retrospective observational study, patients initiating fixed-dose LAMA + LABA therapy (earliest fill date = index date) between January 1, 2014, and September 30, 2018, were identified using administrative claims data from the Optum Research Database. Patients were followed post-index for 1-12 months. Follow-up was censored at the earliest occurrence of index therapy discontinuation or switch, health plan disenrollment, study end date, or reaching the maximum 12-month allowed duration. Propensity score matching of 1:2 was used to balance differences in baseline characteristics between cohorts for each of the 2 comparisons. Annualized population averages of HCRU and costs were calculated for each cohort as [sum of visits (or costs) for all individuals during the follow-up period] ÷ [sum of follow-up on-treatment time for all individuals] × 365 days. RESULTS: After matching, compared with patients who initiated other LAMA + LABAs or UMEC + VI, patients who initiated TIO + OLO had 14.29% and 16.95% fewer mean annualized per-patient COPD-related emergency department (ED) visits (vs. other LAMA + LABAs: 0.49 vs. 0.59, P = 0.005; vs. UMEC + VI: 0.48 vs. 0.56, P = 0.026) and 3.07% and 3.14% fewer mean annualized per-patient pharmacy fills (vs. other LAMA + LABAs: 12.66 vs. 13.07, P = 0.016; vs. UMEC + VI: 12.62 vs. 13.02, P = 0.022), leading to 17.39% and 21.47% lower mean annualized per-patient COPD-related ED costs (vs. other LAMA + LABAs: $289 vs. $368, P = 0.003; vs. UMEC + VI: $285 vs. $345, P = 0.027) and 4.56% and 5.67% lower mean annualized per-patient pharmacy spending (vs. other LAMA + LABAs: $3,570 vs. $3,741, P < 0.001; vs. UMEC + VI: $3,556 vs. $3,770, P < 0.001) in the follow-up period. Similarly, patients in the TIO + OLO cohort had 15.63% and 21.17% fewer mean annualized per-patient all-cause ED visits (vs. other LAMA + LABAs: 1.08 vs. 1.37, P < 0.001; vs. UMEC + VI: 1.08 vs. 1.28, P = 0.001), 8.29% fewer mean annualized per-patient outpatient visits (vs. UMEC + VI: 13.28 vs. 14.48, P = 0.031), 3.41% fewer mean annualized per-patient pharmacy fills (vs. other LAMA + LABAs: 56.92 vs. 58.93, P = 0.028), 19.48% and 22.28% lower mean annualized per-patient all-cause ED costs (vs. other LAMA + LABAs: $755 vs. $971, P < 0.001; vs. UMEC + VI: $749 vs. $930, P < 0.001), and 10.86% lower mean annualized per-patient outpatient setting costs (vs. UMEC + VI: $3,348 vs. $3,756, P = 0.050). There were no statistically significant differences for the other outcome measures. CONCLUSIONS: In a real-world setting, differences in HCRU and costs were observed between FDC LAMA + LABAs, with patients initiating TIO + OLO having lower ED visits/costs, COPD-related pharmacy fills/costs, and all-cause pharmacy use and outpatient visits/costs than those initiating other FDC LAMA + LABAs or UMEC + VI specifically. The remaining HCRU and cost measures were not significantly different. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI; Ridgefield, CT). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations. Palli is an employee of BIPI. Xie, Chastek, Elliott, and Bengtson are employees of Optum, which was contracted by BIPI to conduct this study. The authors received no direct compensation related to the development of the manuscript. Part of the results of this study were accepted and presented at the 30th European Respiratory Society (ERS) International Congress (September 7-9, 2020; virtual).

Commercial valved spacers versus home-made spacers for delivering bronchodilator therapy in pediatric acute asthma: a cost-effectiveness analysis.

OBJECTIVE: Although valved spacers are the preferred method for administering metered-dose inhaler bronchodilators such as albuterol in pediatric acute asthma, their high cost and their lack of availability have limited their use, especially in low- and middle-income countries (LMICs). Because of this, it is a common practice to use home-made spacers, although a formal analysis evaluating their cost-effectiveness is lacking. Therefore, the objective of this study was to analyze the cost-effectiveness of home-made spacers compared to commercial valved spacers for delivering bronchodilator therapy in pediatric acute asthma. METHODS: A decision-analysis model was used to estimate health outcomes and costs of a simulated cohort of pediatric patients treated for acute asthma. Effectiveness parameters were obtained from a systematic review of the literature. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia, a middle-income country (MIC). The main outcome of the model was avoidance of hospital admission. RESULTS: Base-case analysis showed that compared to commercial valved spacers, administering bronchodilators with home-made spacers results in lower overall treatment costs (US$126.75 vs. US$128.59 average cost per patient) without a significant difference in the probability of hospitalization avoided (0.8500 vs. 0.8500). CONCLUSIONS: The present study shows that in Colombia, an MIC, compared with commercial valved spacers, the use of home-made spacers for administering bronchodilator therapy is more cost-effective because it yields a similar probability of hospital admission at lower overall treatment costs.

Differences in Real-World Health and Economic Outcomes Among Patients with COPD Treated with Combination Tiotropium/Olodaterol Versus Triple Therapy.

BACKGROUND: The 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends combination long-acting muscarinic antagonists/long-acting beta2-agonists (LAMA + LABA) as preferred maintenance therapy for patients with symptomatic chronic obstructive lung disease (COPD) after monotherapy and stepping up to triple therapy (TT; LAMA + LABA + inhaled corticosteroids [ICS]) in case of further exacerbations. Restrictions on TT recommendations have primarily been driven by higher pneumonia risk associated with regular ICS use. Evidence suggests that TT is overprescribed, which may affect economic and clinical outcomes. OBJECTIVE: To compare health plan-paid costs, COPD exacerbations, and pneumonia diagnoses among patients newly treated with a LAMA + LABA regimen composed of tiotropium (TIO) + olodaterol (OLO) in a fixed-dose combination inhaler (TIO + OLO) or TT in a U.S. Medicare Advantage Part D insured population. METHODS: This retrospective study identified COPD patients aged ≥ 40 years who were initiating TIO + OLO or TT (index regimen) between January 1, 2014, and March 31, 2018, from a national administrative claims database. Continuous insurance coverage for 12 months pretreatment (baseline) and ≥ 30 days posttreatment (follow-up) was required. Patients were followed until the earliest of study end (May 31, 2018), discontinuation of index regimen (≥ 60-day gap in index regimen coverage), switch to a different regimen, or health plan disenrollment. Before analysis of outcomes, TIO + OLO and TT patients were 1:1 propensity score-matched on baseline demographics, comorbidities, COPD medication use, medical resource use, and costs. Cohort differences in post-match outcomes were assessed by Wald Z-test (annualized costs) and Kaplan-Meier method (time to first COPD exacerbation and pneumonia diagnosis). RESULTS: After matching, each cohort had 1,454 patients who were well balanced on baseline characteristics. Compared with TT, the TIO + OLO cohort incurred $7,041 (41.1%) lower mean COPD-related total costs ($10,094 vs. $17,135; P < 0.001); cohort differences in the medical component ($3,666 lower for TIO + OLO) were driven by lower mean acute inpatient costs ($3,053 lower for TIO + OLO). Combined mean COPD plus pneumonia-related medical costs were $5,212 (39.0%) lower for TIO + OLO versus TT ($8,209 vs. $13,421; P = 0.006), and total mean all-cause costs were $9,221 (30.4%) lower for TIO + OLO versus TT ($21,062 vs. $30,283; P < 0.001). Kaplan-Meier analysis found longer time to first severe COPD exacerbation (P = 0.020) and first pneumonia diagnosis (P = 0.002) for TIO + OLO versus TT and a lower percentage of TIO + OLO patients experiencing these events (severe COPD exacerbation: 9.0% vs. 16.1%; pneumonia: 14.5% vs. 19.3%). A secondary analysis, which expanded the TIO + OLO cohort to include any LAMA + LABA regimen, had similar findings for all outcomes. CONCLUSIONS: COPD patients initiating TIO + OLO incurred lower costs to health plans and experienced fewer COPD exacerbation and pneumonia events relative to TT. These findings provide important real-world economic and clinical insight into the GOLD recommendations for TIO + OLO and LAMA + LABA therapy. The study findings also indicate the continued inconsistency between the recommendations and real-world clinical practices pertaining to TT. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). Palli and Franchino-Elder are employees of BIPI. Frazer, DuCharme, Buikema, and Anderson are employees of Optum, which was contracted by BIPI to conduct this study. The authors received no direct compensation related to the development of the manuscript. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

The cost-saving switch from inhaled corticosteroid-containing treatments to dual bronchodilation: a two-country projection of epidemiological and economic burden in chronic obstructive pulmonary disease.

PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 recommendations support maintenance treatment with long-acting bronchodilators in most symptomatic patients with chronic obstructive pulmonary disease (COPD). While restricting the overuse of inhaled corticosteroids (ICS) may influence healthcare utilization required to treat inadvertent respiratory (exacerbations and pneumonia) and diabetes-related events, it may also change the total medication cost. This analysis was performed to estimate the 5-year budget impact of switching from ICS-containing treatment combinations to dual bronchodilation, in line with the recommendations. METHODS: The model quantified the budget impact of treatment and healthcare resource utilization when COPD patients were anticipated to switch from ICS-containing treatments to dual bronchodilation. Three switch scenarios were calculated with increasing proportions of patients on dual long-acting bronchodilators, to the detriment of ICS-containing double and triple combinations. Clinical and cost input data were based on results from clinical trials and Greek and Portuguese healthcare cost databases. RESULTS: Healthcare resource use to manage exacerbations, pneumonia and diabetes-related events were projected to increase between 2019 and 2023 in parallel with the growing COPD patient population and associated costs were estimated at 52-57% of the total disease cost in the Greek and Portuguese base case scenarios. Total cost savings between 21 and 112 million EUR were projected when the proportion of patients on double and triple ICS-containing treatments was gradually reduced to 50% in scenario A, 20% in scenario B and 7% in scenario C. Sensitivity analyses showed that none of the model assumptions had a major impact on the projected savings. CONCLUSION: The alignment of COPD treatment with current recommendations may bring clinical benefits to patients, without substantial cost increases and even cost savings for payers. The reviews of this paper are available via the supplemental material section.

Clinical characteristics, treatment patterns, disease burden, and persistence/adherence in patients with asthma initiating inhaled triple therapy: real-world evidence from Japan.

Objectives: To help optimize triple therapy use, treatment patterns and disease burden were investigated in patients in Japan with persistent asthma who initiated multi-inhaler triple therapy (inhaled corticosteroid/long-acting ß2-agonist/long-acting muscarinic antagonist; ICS/LABA/LAMA).Methods: This retrospective, observational cohort study using health insurance claims data included adults with persistent asthma who initiated triple therapy in 2016. Patients who were prescribed ICS/LABA in 2016 were included as an ICS/LABA-matched cohort. Patients were stratified into those with asthma only and those with asthma and chronic obstructive pulmonary disease (COPD) codes (asthma-COPD overlap [ACO]). Patient data from 1-year prior to 1 year post index date were analyzed.Results: For patients with asthma only in the triple therapy and ICS/LABA cohorts, baseline demographics were similar. A higher proportion of the triple-therapy cohort than the ICS/LABA cohort was receiving high-dose ICS at index (68.2% and 27.6%, respectively), and had experienced an exacerbation in the last year (64.0% and 29.4%, respectively). The proportion of patients with asthma only who developed any exacerbation was lower in the year following initiation of triple therapy compared with the year prior to initiation of triple therapy (45.8% vs 64.0%, respectively). For asthma only patients receiving triple therapy, the mean (standard deviation) proportion of days covered and medication possession ratio was 0.51 (0.36) and 0.86 (0.16), respectively. Similar trends were seen in patients with ACO in the triple-therapy and ICS/LABA cohorts.Conclusion: Evidence from this study may serve as a reference for the use of inhaled triple therapy for asthma.

Functional respiratory imaging assessment of glycopyrrolate and formoterol fumarate metered dose inhalers formulated using co-suspension delivery technology in patients with COPD.

BACKGROUND: Functional respiratory imaging (FRI) is a quantitative postprocessing imaging technique used to assess changes in the respiratory system. Using FRI, we characterized the effects of the long-acting muscarinic antagonist (LAMA), glycopyrrolate metered dose inhaler (GP MDI), and the long-acting ß2-agonist (LABA), formoterol fumarate metered dose inhaler (FF MDI), on airway volume and resistance in patients with moderate-to-severe chronic obstructive pulmonary disease. METHODS: Patients in this phase IIIb, randomized, double-blind crossover study received twice-daily GP MDI (18 µg) and FF MDI (9.6 µg). Primary endpoints were specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and specific image-based airway resistance (siRaw), measured using FRI. Secondary and other endpoints included additional FRI, spirometry, and body plethysmography parameters. Postdose efficacy assessments were performed within 60-150 min of dosing on day 15. RESULTS: A total of 23 patients were randomized and 19 completed both treatment periods. GP MDI and FF MDI both achieved significant improvements from baseline to day 15 in siVaw [11% (p = 0.0187) and 23% (p < 0.0001) increases, respectively] and siRaw [25% (p = 0.0219) and 44% (p < 0.0001) reductions, respectively]. Although, on average, improvements were larger for FF MDI than GP MDI, some individuals displayed greater responses with each of the two treatments. These within-patient differences increased with airway generation number. Spirometry and body plethysmography endpoints showed significant improvements from baseline in inspiratory capacity for both treatments, and numeric improvements for other endpoints. CONCLUSION: Both GP MDI and FF MDI significantly improved siRaw and siVaw at day 15 versus baseline. FRI endpoints demonstrated increased sensitivity relative to spirometry and body plethysmography in detecting differences between treatments in a small number of patients. Intra-patient differences in treatment response between the LAMA and the LABA provide further support for the benefit of dual bronchodilator therapies. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT02937584 The reviews of this paper are available via the supplemental material section.

Respiratory tract infection-induced asthma exacerbations in adults with asthma: assessing predictors and outcomes.

Objective: To evaluate clinical and economic burden associated with respiratory tract infection (RTI)-induced asthma exacerbations and to identify risk factors associated with these exacerbations. Factors associated with these exacerbations are understudied and little information is available about consequent expenditures. Methods: In this retrospective case-control study, medical records and pharmacy data in King Abdullah University Hospital in Northern Jordan were reviewed for adults with asthma aged 40 years and older, over the period 2013-2016. Cases of RTI-induced asthma exacerbations were identified, and controls were selected randomly from asthmatic adults who did not experience any RTI-induced asthma exacerbation during the same period. Independent-samples t-tests and chi-square tests were conducted to compare patient characteristics of cases and controls. Predictors of RTI-induced asthma exacerbations and the resultant complications were evaluated using multivariable logistic regression. Multivariable regression on log-transformed charges was used to predict expenditures of these exacerbations. Results: A total of 137 cases and 548 controls were identified. Using inhaled corticosteroid + long-acting beta-agonists (ICS + LABA) was significantly associated with lower odds of RTI-induced asthma exacerbations (OR = 0.4; 95% CI, 0.21-0.77; p = 0.006), and lower odds of resultant serious complications (OR = 0.23; 95% CI, 0.07-0.69; p = 0.009), compared to being untreated with any asthma maintenance treatment. Asthma severity and co-morbidities were associated with increased susceptibility to these exacerbations. The average charges of RTI-induced asthma admissions and outpatient exacerbations were 1042.9 JD ($1471.0) and 81.1 JD ($114.4), respectively. Conclusions: ICS + LABA, asthma severity and co-morbidities appeared to affect the clinical and economic burden associated with RTI-induced asthma exacerbations. Efforts to prevent these exacerbations in patients with risk factors are warranted.

Omalizumabe para o tratamento de asma alérgica grave não controlada apesar do uso de corticoide inalatório associado a um beta-2 agonista de longa ação / Omalizumab for the treatment of severe uncontrolled allergic asthma despite the use of inhaled corticosteroids associated with a long-acting beta-2 agonist

INTRODUÇÃO: A asma é uma doença crônica não transmissível, associada a inflamação crônica das vias aéras e a hiper-responsividade aos estímulos diretos e indiretos. Os sintomas variam na sua duração e intensidade, sendo alguns deles: falta de ar, dor no peito, tosse e limitação do fluxo expiratório. No Sistema Único de Saúde são disponibilizados medicamentos para o tratamento da asma, de acordo com o Protocolo Clínico e Diretrizes Terapêuticas vigente. Um dos fenótipos é a asma alérgica, que ocorre em maioria na infância e está associada ao histórico de doença alérgica. A asma ainda pode ser classificada de acordo com a gravidade, sendo a grave aquela que requer altas doses de corticoide inalatório associado a beta-2 agonista de longa duração para prevenir o descontrole ou aquela que permanece não controlada mesmo com o tratamento. O omalizumabe, anticorpo monoclonal que se liga a IgE circulante, é indicado para esse grupo de pacientes que tem asma alérgica grave não controlada. PERGUNTA: O omalizumabe é eficaz e seguro como terapia adicional ao tratamento padrão em pacientes diagnosticados com asma alérgica grave não controlada apesar do uso de corticoide inalatório associado a um beta-2 agonista de longa duração, quando comparado a terapia padrão isolada? TECNOLOGIA: Omalizumabe (Xolair®). EVIDÊNCIAS CIENTÍFICAS: Segundo metanálise de baixa qualidade metodológica omalizumabe adicionado à terapia padrão em comparação a terapia padrão isolada resultou em melhora de 10% no volume expiratório forçado em um segundo (FEV1) após 4 meses de utilização com diferença estatisticamente significativa, o que representou um efeito de magnitude moderada (teste d de Cohen de 0,47); magnitude de efeito mantida após 24 meses de acompanhamento. Segundo revisão sistemática de qualidade moderada, o uso do medicamento está associado a uma diminuição das exacerbações clinicamente significativas (razão de taxas RR 0,74 IC 95% 0,55 a 1,00). Em três revisões sistemáticas de qualidade baixa a moderada a utilização do medicamento foi associada a uma discreta diminuição no número de hospitalizações. Em um dos estudos o número de pacientes que deveriam receber o tratamento para evitar uma hospitalização foi de 36 e em outro observou-se 0,5 menos hospitalizações após 12 e 24 meses. de tratamento (teste d de Cohen 0,36 e 0,48, respectivamente). Em estudo observacional identificou-se uma redução estatisticamente significativa no número de visitas a emergências em função do uso do medicamento emergência por qualquer causa (39,1% vs 27,6%, pré e pós-omalizumabe, p<0,0001). Houve também uma redução estatisticamente significativa no consumo de corticoides inalatórios e orais, assim como aferido em estudos observacionais, com uma magnitude entre 40 e 50%. AVALIAÇÃO ECONÔMICA: O demandante realizou uma avaliação de custo-efetividade comparando os cenários terapia padrão e terapia padrão com a adição do omalizumabe. A razão de custo-efetividade incremental encontrada foi de R$ 39.161,00. Na análise de sensibilidade, o RCEI variou de R$ 15.559,00 a R$ 58.111,00. A avaliação econômica apresentou algumas limitações, como o desenho do modelo e suas transições, bem como terem sido considerados apenas os respondedores ao omalizumabe no braço de tratamento. MONITORAMENTO DO HORIZONTE tecnológico: Foram encontrados três medicamentos com indicação para asma alérgica grave, sendo que nenhum deles atua na mesma via que o omalizumabe (benralizumabe, mepolizumabe e tezepelumabe). Também foram identificadas duas empresas com estudos em andamento fase 3 de biossimilares do omalizumabe. CONSIDERAÇÕES: A evidência disponível é baseada em estudos clínicos randomizados, alguns abertos, e, em sua maioria, nos estudos observacionais que compararam período pré-omalizumabe e pós-omalizumabe. O omalizumabe adicionado a terapia comparado com a terapia padrão isolada demonstrou melhora nos desfechos avaliados (função pulmonar, hospitalização, exacerbações, resposta ao tratamento), porém a avaliação da qualidade dos estudos foi considerada baixa. A razão de custo-efetividade incremental foi de R$ 39.161,00 e o impacto orçamentário incremental no primeiro ano de aproximadamente R$ 71 milhões e R$ 481 milhões em cinco anos. Há limitações importantes na avaliação econômica e no impacto orçamentário que podem ter gerado uma subestimação dos valores. RECOMENDAÇÃO PRELIMINAR: Durante a 80ª reunião da Conitec, o plenário discutiu aspectos como a baixa qualidade da evidência científica; a ausência de novas evidências de qualidade desde a última avaliação pela comissão; a presença de eventos adversos (inclusive a exacerbação da asma); e a subestimação da população que seria beneficiada pela tecnologia. Diante do exposto, a Conitec, em 08/08/2019, recomendou a não incorporação no SUS do omalizumabe para asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2-agonista de longa duração (LABA). CONSULTA PÚBLICA: Foram recebidas 274 contribuições técnico-científicas e 2.098 contribuições de experiência ou opinião, sendo a maioria (87,67%) discordante da recomendação preliminar da Conitec. As contribuições realizadas convergiam para os aspectos de efetividade da medicação, como a melhora dos sintomas clínicos da asma, controle da doença, diminuição de crises e exacerbações e consequentemente redução do número de hospitalizações. Além disso, ficou claro que o omalizumabe é um medicamento que deve ser indicado para uma população específica, na qual foi descartada toda e qualquer causa do não controle da doença. Estados que utilizam o omalizumabe relataram suas experiências positivas, assim como outros profissionais e pacientes, no que diz respeito ao controle da asma em grupos bem selecionados. Após a Consulta Pública, a Conitec entendeu que houve argumentação suficiente para alterar sua recomendação inicial. RECOMENDAÇÃO FINAL: Os membros da Conitec em 07/11/2019 deliberaram por recomendar a incorporação no SUS do omalizumabe para o tratamento de asma alérgica grave não controlada apesar do uso de corticoide inalatório associado a um beta-2 agonista de longa ação. Foi assinado o Registro de Deliberação nº 490/2019. DECISÃO: Incorporar o omalizumabe para o tratamento de asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta-2 agonista de longa ação, no âmbito do Sistema Único de Saúde - SUS, conforme a Portaria nº 64, publicada no Diário Oficial da União nº 251, seção 1, página 1417, em 30 de dezembro de 2019.

Higher short-acting beta-agonist use is associated with greater COPD burden.

INTRODUCTION: The COPD Assessment Test (CAT) is a self-administered questionnaire that measures symptomatic burden. CAT is used as part of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines refined ABCD tool and is usually performed during office visit assessment. Electronic medication monitors (EMMs) capture utilization of short-acting beta-agonists (SABA) that may indicate disease worsening in real-time. The primary objective was to assess the relationship of CAT with SABA utilization. METHODS: From 8/2017-1/2019, COPD patients ≥40 years of age were enrolled in a digital health platform consisting of EMMs and a mobile application to track time and date of SABA use. Patients with a completed CAT and ≥81 days of continuous EMM data were included in analyses. Using one-way ANOVA, SABA use and maintenance medication adherence were compared by CAT score categories: <10 (low burden), 10-20 (medium), 21-30 (high), and 31-40 (very high). Associations were additionally estimated in patients who used ≥1 puff/week of their rescue and maintenance medication. RESULTS: The population included 2196 COPD patients (mean age: 60 years). CAT scores from low to high burden were associated with greater SABA use, from 0.8 to 1.9 puffs/day (+1.1 [95% CI: 0.6, 1.6 puffs/day], P < 0.001), and lower adherence, from 69% to 59%, (-10% [95% CI: -1, -19%], P = 0.04). Sensitivity analyses yielded similar results. CONCLUSIONS: This study found a significant association between greater SABA use and lower adherence with higher burden CAT scores. This finding may suggest that passive collection of inhaled medications could serve as a surrogate for CAT.

Trends in prescriptions and costs of inhaled medications in chronic obstructive pulmonary disease: a 19-year population-based study from Canada.

Background: The patterns of medication use in chronic obstructive pulmonary disease (COPD) may change over time due to the availability of new medications, updates in guideline-based recommendations, and changes in patient and care provider preferences. Objectives: To document population-level trends of filled prescriptions and costs for major classes of inhaled COPD therapies. Method: We used administrative health databases of the province of British Columbia, Canada, from 1997 to 2015, to create a retrospective cohort of COPD patients. We documented the percentage of patients receiving major inhaled COPD-related medications, including short-acting beta-2 adrenoreceptor agonists (SABA), long-acting beta-2 adrenoreceptor agonists (LABA), inhaled corticosteroids (ICS), short-acting muscarinic receptor antagonists (SAMA), and long-acting muscarinic receptor antagonists (LAMA). We quantified the average, and relative annual change in, dispensed quantities and costs (in 2015 Canadian dollars [$]) of medications. Combination therapy was assessed as the proportion of time covered by two or more long-acting medications of different classes. Results: A total of 176,338 patients were included in the final cohort (mean age at entry 68.7, 48.5% female). In 2015, the most common medication was ICS (45.7% of the patients), followed by LABA (36.5%). LAMA was the least used medication (18.9%). The number of filled prescriptions per patient per year for LAMA (+7.8% per year) and LABA (+4.9%) increased, while they decreased for SAMA (-6.3%) and SABA (-3.8%), and remained relatively constant for ICS. The average annual per-patient costs of inhaled medications were $570.8 in 2015, which was double the costs from 1997. Single-inhaler ICS/LABA had the highest rate of increase (11.6% per year), and comprised 53.7% of the total costs of inhalers in 2015. In 2015, 28.5% of the patient time was on combination therapies, with 7.1% on triple ICS/LABA/LAMA therapy. Conclusion: Utilization of inhaled therapies for COPD has changed significantly over time. The low utilization of LAMA and high utilization of combination therapies (particularly those containing ICS) do not seem to be aligned with COPD treatment guidelines.

Economic impact of delaying initiation with multiple-inhaler maintenance triple therapy in Spanish patients with chronic obstructive pulmonary disease.

Purpose: Guidelines recommend the use of triple therapy with an inhaled corticosteroid (ICS), a long-acting ß2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA) to reduce the risk of future exacerbations in symptomatic COPD patients with a history of exacerbations. This study aimed to estimate COPD-related healthcare resource use and costs, and subsequent exacerbation rates, for patients initiating multiple-inhaler triple therapy (MITT) early (≤30 days) versus late (31-180 days) following an exacerbation, in a real-world clinical setting. Patients and methods: This was an observational, longitudinal, retrospective study using electronic medical records from the Spanish database of the Red de Investigación en Servicios Sanitarios Foundation. Patients ≥40 years old with a confirmed COPD diagnosis who were newly prescribed MITT up to 180 days after an exacerbation between January 2013 and December 2015 were included. Patients were followed from the date of MITT initiation for up to 12 months to assess COPD-related health care resource use (routine and emergency visits, hospitalizations, pharmacologic treatment), exacerbation rate, and costs (€2017); these endpoints were compared between early versus late groups. Results: The study included 1280 patients who met selection criteria: mean age 73 years, 78% male, and 41% had severe/very severe lung function impairment. The proportion of patients initiating MITT early versus late was 61.6% versus 38.4%, respectively. There were no statistically significant differences in baseline characteristics between groups. During follow-up, health care resource consumption was lower in the early versus late group, especially primary care and ED visits, leading to lower total costs (€1861 versus €1935; P<0.05). In the follow-up period, 28.0% of the patients in the early group experienced ≥1 exacerbation versus 36.4% in the late group (P=0.002), with an exacerbation rate of 0.5 versus 0.6 per person per year (P=0.022), respectively. Conclusion: Initiating MITT early (≤30 days after an exacerbation) may reduce health care costs and exacerbation rate compared with late MITT initiation.

Patient-reported outcomes of dual bronchodilator fixed-dose combination versus bronchodilator monotherapy in individuals with COPD.

Background: This study compared real-world patient-reported outcomes (PROs) measured by the Clinical COPD Questionnaire (CCQ), the London Chest Activities of Daily Living (LCADL) scale, and the Work Productivity and Activity Impairment (WPAI) questionnaire between individuals with COPD initiating LAMA/LABA fixed-dose combination (FDC) dual therapy versus either long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) monotherapy. Methods: Individuals with COPD aged ≥40 years initiating a LAMA/LABA FDC dual therapy or a LAMA or LABA monotherapy (index date = first prescription date) between January 1, 2016 and December 31, 2016 were identified from a large US administrative claims database. Individuals were excluded if they were prescribed an inhaled corticosteroid (ICS) or ICS/LABA two months prior to the index date or were diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma. The cohorts were propensity score matched (PSM) 1:1 for COPD severity using baseline measures. Each participant completed a survey. Results: Surveys were completed by 399 participants in the dual therapy cohort, and 718 participants in the monotherapy cohort. Following PSM, 379 participants remained in each cohort for analysis (monotherapy: 369 LAMA and 10 LABA). The dual therapy cohort reported fewer COPD-related symptoms (CCQ symptom score 2.75 vs 2.97, respectively, P=0.023), and, fewer limitations in leisure activities (LCADL leisure score 4.78 vs 5.17, respectively, P=0.021) versus the monotherapy cohort. No significant differences were found in the WPAI. A greater percentage of participants in the dual therapy cohort stayed on index therapy (63.1%) when compared with the monotherapy cohort (30.3%, P<0.0001). Conclusions: Only 30% of the participants prescribed monotherapy, usually with a LAMA, remained on index therapy alone at the time of survey administration. In the dual therapy cohort, 63% of the participants remained on the index medication and had fewer COPD-related symptoms and fewer limitations in leisure activities compared with participants in the monotherapy cohort.

Assessment of physical functioning and handling of tiotropium/olodaterol Respimat® in patients with COPD in a real-world clinical setting.

Background: Patients with chronic obstructive pulmonary disease (COPD) show signs of reduced physical activity from the early stages of the disease, impacting morbidity and mortality. Data suggest treatment with tiotropium, a long-acting muscarinic antagonist, and olodaterol, a long-acting ß2-agonist (LABA), as monotherapies and in combination, increases exercise capacity. This study assessed the effects of fixed-dose tiotropium/olodaterol (delivered via Respimat®) on physical function in Global Initiative for Chronic Obstructive Lung Disease A-D patients requiring long-acting dual bronchodilation treatment in a real-world setting. Methods: This open-label, single arm, noninterventional study measured changes in physical function in COPD patients treated with tiotropium/olodaterol 5/5 µg for approximately 6 weeks (between Visit 1 [baseline] and Visit 2). Primary end point was therapeutic success, defined as a minimum 10-point increase in Physical Functioning Questionnaire (PF-10) score. Secondary end points included change in PF-10 from Visit 1 to Visit 2, the patient's general condition (measured by Physician's Global Evaluation score) at Visit 1 and Visit 2, and patient satisfaction with treatment delivered via the Respimat® device (assessed by Patient Satisfaction Questionnaire) at study end. Results: Therapeutic success was observed in 51.5% of 1578 patients (95% confidence interval [CI] 49.0, 54.0) after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 11.6 points (95% CI 10.7, 12.6). Patient general condition improved as indicated by a general improvement in scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment (82.5%), inhalation (87.5%), and handling of Respimat® (85.2%). One percent of patients reported an investigator-defined drug-related adverse events (AE). Conclusion: Tiotropium/olodaterol treatment improved physical functioning in COPD patients. An associated increase in patient general condition was observed. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment, inhaling, and handling of the Respimat® device. No unexpected drug-related AE occurred.

Long-acting muscarinic antagonist versus long-acting ß2 agonist/corticosteroid for moderate to severe chronic obstructive pulmonary disease patients: Exacerbation risk assessment.

BACKGROUND: Whether the beneficial effects of long-acting muscarinic antagonists (LAMA) are better than those of long-acting ß2 agonist/corticosteroids (LABA/ICS) in preventing exacerbations in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to assess the risk of exacerbations in moderate to severe COPD patients receiving LAMA versus LABA/ICS. METHODS: We retrospectively reviewed the medical records of patients diagnosed with COPD (2008-2010). The inclusion criteria were age ≥ 40 years, forced expiratory volume in 1 second (FEV1) 30% to 80% of predicted value and at least three prescriptions for COPD medication, including LAMA or LABA/ICS. RESULTS: Of the 557 COPD patients screened, 90 patients were enrolled in the analysis. The demographic characteristics of patients receiving LABA/ICS or LAMA were similar. The all exacerbation rates was significantly higher in patients with global initiative for chronic obstructive lung disease stage II COPD treated with LABA/ICS than in those treated with LAMA (p = 0.001), regardless of previous exacerbation history. Patients with previous exacerbation history showed an independent increase in the risk of moderate or severe exacerbation compared with those without exacerbation history (hazard ratio 3.86, 95% CI 1.75-8.53, p = 0.001). CONCLUSION: In comparison with LABA/ICS, LAMA is beneficial in reducing exacerbation risk for moderate COPD. Previous exacerbation history independently predicts the future risk of exacerbation regardless of treatment.

Medication management patterns among Medicare beneficiaries with chronic obstructive pulmonary disease who initiate nebulized arformoterol treatment.

Purpose: Global evidence-based treatment strategies for chronic obstructive pulmonary disease (COPD) recommend using long-acting bronchodilators (LABDs) as maintenance therapy. However, COPD patients are often undertreated. We examined COPD treatment patterns among Medicare beneficiaries who initiated arformoterol tartrate, a nebulized long-acting beta2 agonist (LABA), and identified the predictors of initiation. Methods: Using a 100% sample of Medicare administrative data, we identified beneficiaries with a COPD diagnosis (ICD-9 490-492.xx, 494.xx, 496.xx) between 2010 and 2014 who had ≥1 year of continuous enrollment in Parts A, B, and D, and ≥2 COPD-related outpatient visits within 30 days or ≥1 hospitalization(s). After applying inclusion/exclusion criteria, three cohorts were identified: (1) study group beneficiaries who received nebulized arformoterol (n=11,886), (2) a subset of the study group with no LABD use 90 days prior to initiating arformoterol (n=5,542), and (3) control group beneficiaries with no nebulized LABA use (n=220,429). Logistic regression was used to evaluate predictors of arformoterol initiation. Odds ratios (ORs), 95% confidence intervals (CIs), and p values were computed. Results: Among arformoterol users, 47% (n=5,542) had received no LABDs 90 days prior to initiating arformoterol. These beneficiaries were being treated with a nebulized (50%) or inhaled (37%) short-acting bronchodilator or a systemic corticosteroid (46%), and many received antibiotics (37%). Compared to controls, beneficiaries who initiated arformoterol were significantly more likely to have had an exacerbation, a COPD-related hospitalization, and a pulmonologist or respiratory therapist visit prior to initiation (all p<0.05). Beneficiaries with moderate/severe psychiatric comorbidity or dual-eligible status were significantly less likely to initiate arformoterol, as compared to controls (all p<0.05). Conclusion: Medicare beneficiaries who initiated nebulized arformoterol therapy had more exacerbations and hospitalizations than controls 90 days prior to initiation. Findings revealed inadequate use of maintenance medications, suggesting a lack of compliance with evidence-based treatment guidelines.

Healthcare costs of the SATisfaction and adherence to COPD treatment (SAT) study follow-up.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by recurring exacerbations. We estimated the costs of healthcare resources for COPD management funded by the Italian National Healthcare Service (INHS) for one year. METHODS: We examined the demographic, clinical, and economic variables at enrolment and follow-up visits (at 6 and 12 months) of COPD patients participating in the SAT study and referred to 20 Italian pulmonary centres with different institutional characteristics. Costs were expressed in Euro (€) 2018. A random effects log-linear panel regression model was performed to predict the average cost per patient. RESULTS: Most of the centres were public institutions (90%; public university hospital: 30%). The total average cost of COPD was €2647.38/patient and ICS/LABA/LAMA therapy contributed the most (€1541.45). The average cost was €6206.19/patient for severe COPD (+139.67% vs the cost/patient with mild or moderate COPD). The regression model showed that, others things being equal, increases in the predicted average logged cost per patient were due to liquid oxygen therapy (+468.31%), three COPD exacerbations during the follow-up (+254.54%), and ICS/LABA or ICS/LABA/LAMA associated therapy (+59.26%). Moreover, a 1.19% increment was observed for each additional score of the CAT questionnaire. Conversely, a 36.52% reduction in the predicted average logged cost was reported for hospitals managed by local healthcare authorities. CONCLUSIONS: The health econometric approach is innovative in the management of COPD patients in Italy. The results of the random effects log-linear panel data regression model may help clinicians estimate INHS costs when managing COPD patients. Clinicaltrials.gov ID# NCT02689492.

Clinical burden of illness among patients with severe eosinophilic COPD.

Background: There are currently limited real-world data on the clinical burden of illness in patients with COPD who continue to exacerbate despite receiving triple therapy. The aim of this study was to compare the burden of COPD in patients with and without a phenotype characterized by a high blood eosinophil count and high risk of exacerbations while receiving triple therapy. Methods: This retrospective cohort study (GSK ID: 207323/PRJ2647) used UK Clinical Practice Research Datalink records linked with Hospital Episode Statistics. Eligible patients had a COPD medical diagnosis code recorded between January 1, 2004 and December 31, 2014, and a blood eosinophil count recorded on/after that date. Patients were followed from index date (first qualifying blood eosinophil count) until December 31, 2015. The study phenotype was defined as ≥2 moderate/≥1 severe acute exacerbation of COPD (AECOPD) in the year prior to the index date, current use of multiple-inhaler triple therapy (MITT), and blood eosinophil count ≥150 cells/µL on the index date. Outcomes measured during follow-up included moderate/severe AECOPDs, severe AECOPDs, all-cause mortality, primary care (GP) clinical consultations, and non-AECOPD-related unscheduled hospitalizations. Results: Of 46,814 patients eligible for inclusion, 2512 (5.4%) met the definition of the study phenotype. Adjusted rate ratios (95% CI) of moderate/severe AECOPDs and all-cause mortality in patients with the study phenotype versus those without were 2.32 (2.22, 2.43) and 1.26 (1.16, 1.37), respectively. For GP visits and non-AECOPD-related unscheduled hospitalizations, adjusted rate ratios (95% CI), in patients with the study phenotype versus those without, were 1.09 (1.05, 1.12) and 1.31 (1.18, 1.46), respectively. Conclusion: Patients with COPD and raised blood eosinophil counts who continue to exacerbate despite MITT represent a distinct subgroup who experience substantial clinical burden and account for high healthcare expenditure. There is a need for more effective management and therapeutic options for these patients.