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.

[Medication management of COPD]. / Prise en charge médicamenteuse de la BPCO.

MEDICATION MANAGEMENT OF COPD. The management of chronic obstructive pulmonary disease (COPD) is based on drug and non-drug measures. Inhaled therapies are the major issues including the use of short-acting bronchodilators for respiratory symptoms. If symptoms are daily, such as disabling dyspnea or frequent exacerbations, daily treatment with a long-acting bronchodilator is proposed: anti-muscarinic (LAMA) or ß2-agonist (LABA). If there is no improvement, escalation to dual and then triple therapy is proposed. Another major issue in the management of COPD is de-escalation in the event of ineffectiveness or side effects of inhaled corticosteroids (ICS). Finally, the role of blood eosinophils and other biomarkers is even more important that biotherapies could expand the therapeutic options for some subtypes of COPD patients.

PRISE EN CHARGE MÉDICAMENTEUSE DE LA BPCO. La prise en charge de la bronchopneumopathie chronique obstructive (BPCO) repose sur des mesures médicamenteuses et non médicamenteuses. Le principe des traitements médicamenteux dans la BPCO comprend des traitements inhalés, et notamment l'utilisation de bronchodilatateurs de courte durée d'action en cas de symptômes respiratoires. Si les symptômes sont quotidiens à type de dyspnée invalidante ou en cas d'exacerbations fréquentes, un traitement de fond quotidien par un bronchodilatateur de longue durée d'action est indiqué : antimuscarinique (LAMA) ou ß2-agoniste (LABA). En l'absence d'amélioration, une escalade est proposée par bithérapie puis trithérapie. Un autre enjeu majeur de la prise en charge de la BPCO est la désescalade thérapeutique en cas d'inefficacité ou d'effets indésirables des corticostéroïdes inhalés (CSI). Enfin, la place du dosage des éosinophiles et autres biomarqueurs sanguins est d'autant plus importante que les biothérapies pourraient venir élargir l'arsenal thérapeutique pour certains soustypes de patients atteints de BPCO.

Treatment pathways, economic burden and clinical outcomes in new users of inhaled corticosteroid/long-acting B2-agonist dual therapy with chronic obstructive pulmonary disease in a primary care setting in England: a retrospective cohort study.

OBJECTIVE: Management of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) improves lung function and health status and reduces COPD exacerbation risk versus monotherapy. This study described treatment use, healthcare resource utilisation (HCRU), healthcare costs and outcomes following initiation of single-device ICS/LABA as initial maintenance therapy (IMT). DESIGN: Retrospective cohort study. SETTING: Primary care, England. DATA SOURCES: Linked data from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. PARTICIPANTS: Patients with COPD and ≥1 single-device ICS/LABA prescription between July 2015 and December 2018 were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Treatment pathways, COPD-related HCRU and healthcare costs, COPD exacerbations, time to triple therapy, medication adherence (proportion of days covered ≥80%) and indexed treatment time to discontinuation. Data for patients without prior maintenance therapy history (IMT users) and non-triple users were assessed over a 12-month follow-up period. RESULTS: Of 13 451 new ICS/LABA users, 5162 were IMT users (budesonide/formoterol, n=1056; beclomethasone dipropionate/formoterol, n=2427; other ICS/LABA, n=1679), for whom at 3 and 12 months post-index, 45.6% and 39.4% were still receiving any ICS/LABA. At >6 to ≤12 months, the proportion of IMT users with ≥1 outpatient visit (10.1%) and proportion with ≥1 inpatient stay (12.6%) had increased from those at 3 months (9.0% and 7.4%, respectively). Inpatient stays contributed most to total COPD-related healthcare costs. For non-triple IMT users, at 3 and 12 months post-index, 4.5% and 13.7% had ≥1 moderate-to-severe COPD exacerbation. Time to triple therapy initiation and time to discontinuation of index medication ranged from 45.9 to 50.2 months and 2.3 to 2.8 months between treatments. Adherence was low across all time points (21.5-27.6%). Results were similar across indexed therapies. CONCLUSIONS: In the year following treatment initiation, ICS/LABA adherence was poor and many patients discontinued or switched therapies, suggesting that more consideration and optimisation of treatment is required in England for patients initiating single-device ICS/LABA therapy.

Effects of triple therapy on disease burden in patients of GOLD groups C and D: results from the observational COPD cohort COSYCONET.

BACKGROUND: Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting. METHODS: Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes. RESULTS: In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed. CONCLUSION: Without statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds.

Clinical and economic outcomes in patients with chronic obstructive pulmonary disease initiating maintenance therapy with tiotropium bromide/olodaterol or fluticasone furoate/umeclidinium/vilanterol.

BACKGROUND: Clinical practice guidelines recommend dual long-acting muscarinic antagonists (LAMAs)/long-acting ß2agonists (LABAs) as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD) and dyspnea or exercise intolerance. Escalation to triple therapy (TT) (LAMA/LABA/inhaled corticosteroid) is conditionally recommended for patients with continued exacerbations on dual LAMA/LABA therapy. Despite this guidance, TT use is widespread across COPD severities, which could impact clinical and economic outcomes. OBJECTIVE: To compare COPD exacerbations, pneumonia events, and disease-related and all-cause health care resource utilization and costs (in 2020 US dollars) in patients initiating fixed-dose combinations of either LAMA/LABA (tiotropium/olodaterol [TIO + OLO]) or TT (fluticasone furoate/umeclidinium/vilanterol [FF + UMEC + VI]). METHODS: This retrospective observational study of administrative claims included patients with COPD aged 40 years or older initiating TIO + OLO or FF + UMEC + VI from June 2015 to November 2019. TIO + OLO and FF + UMEC + VI cohorts in the overall and maintenance-naive populations were 1:1 propensity score matched on baseline demographics, comorbidities, COPD medications, health care resource utilization, and costs. Multivariable regression compared clinical and economic outcomes up to 12 months in FF + UMEC + VI vs TIO + OLO postmatched cohorts. RESULTS: After matching, there were 5,658 and 3,025 pairs in the overall and maintenance-naive populations, respectively. In the overall population, the risk of any (moderate or severe) exacerbation was 7% lower in FF + UMEC + VI vs TIO + OLO initiators (adjusted hazard ratio [aHR] = 0.93; 95% CI = 0.86-1.0; P = 0.047). There was no difference in the adjusted risk of any exacerbation in the maintenance-naive population (aHR = 0.99; 95% CI = 0.88-1.10). Pneumonia risk was not statistically different between cohorts in the overall (aHR = 1.12; 95% CI = 0.98-1.27) and maintenance-naive (aHR = 1.13; 95% CI = 0.95-1.36) populations. COPD- and/or pneumonia-related adjusted total annualized costs (95% CI) were significantly greater for FF + UMEC + VI vs TIO + OLO in the overall ($17,633 [16,661-18,604] vs $14,558 [13,709-15,407]; P < 0.001; differences [% of relative increase] = $3,075 [21.1%]) and maintenancenaive ($19,032 [17,466-20,598] vs $15,004 [13,786-16,223]; P < 0.001; $4,028 [26.8%]) populations, with significantly higher pharmacy costs with FF + UMEC + VI (overall: $6,567 [6,503-6,632] vs $4,729 [4,676-4,783]; P < 0.001; $1,838 [38.9%]; maintenance-naive: $6,642 [6,560-6,724] vs $4,750 [4,676-4,825]; P < 0.001; $1,892 [39.8%]). CONCLUSIONS: A lower risk of exacerbation was observed with FF + UMEC + VI vs TIO + OLO in the overall population but not among the maintenance-naive population. Patients with COPD initiating TIO + OLO had lower annualized costs than FF + UMEC + VI initiators in the overall and maintenance-naive populations. Thus, in the maintenance-naive population, initiation with dual LAMA/LABA therapy per practice guidelines can improve real-world economic outcomes. Study registration number: ClinicalTrials.gov (identifier: NCT05127304). DISCLOSURES: The study was funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, BIPI grants all external authors access to relevant clinical study data. In adherence with the BIPI Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Dr Sethi has received honoraria/fees for consulting/speaking from Astra-Zeneca, BIPI, and GlaxoSmithKline. He has received consulting fees for serving on data safety monitoring boards from Nuvaira and Pulmotect. He has received consulting fees from Apellis and Aerogen. His institution has received research funds for his participation in clinical trials from Regeneron and AstraZeneca. Ms Palli was an employee of BIPI at the time the study was conducted. Drs Clark and Shaikh are employees of BIPI. Ms Buysman and Mr Sargent are employees and Dr Bengtson was an employee of Optum, which was contracted by BIPI to conduct this study. Dr Ferguson reports grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants from Novartis, Altavant, and Knopp; grants and personal fees from AstraZeneca, Verona, Theravance, Teva, and GlaxoSmithKline; and personal fees from Galderma, Orpheris, Dev.Pro, Syneos, and Ionis outside the submitted work. He was a paid consultant for BIPI for 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.

Tiotropium for children and adolescents with severe asthma.

INTRODUCTION: An important proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, such as tiotropium bromide has been recommended for this subgroup of patients. The purpose of this study was to assess the cost-effectiveness of tiotropium as add-on therapies to ICS + LABA for children and adolescents with uncontrolled allergic asthma. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYS of two interventions including standard therapy (ICS + LABA), and add-on therapy with tiotropium, were calculated over a time horizon from 6 to 18 years. Probability sensitivity analyses were conducted. RESULTS: For a patient with severe asthma, our Markov model showed that compared to standard therapy, add-on therapy with tiotropium was associated with higher treatment costs and QALY. The incremental cost-effectiveness ratio estimated was US$2,017 in the probabilistic model after Monte-Carlo simulation. Our base-case results were robust to variations in all assumptions and parameters. The incremental net monetary benefit of US$327 with a 95% credible interval of US$396 to US425. CONCLUSION: Add-on therapy with tiotropium was cost-effective when added to usual care in children and adolescents with severe asthma who remained uncontrolled despite treatment with medium or high-dose ICS/LABA. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Economic impact of implementing prescription of single-inhaler triple therapies versus current multiple-inhaler triple therapies for COPD in the Apulia Region.

BACKGROUND: The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. METHODS: A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). RESULTS: Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. CONCLUSION: A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

Inclusão de nova apresentação de omalizumabe (150 mg/mL) solução injetável em seringa preenchida para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2- agonista de longa ação (LABA) / Inclusion of new presentation of omalizumab (150 mg/mL) solution for injection in pre-filled syringe for treatment of severe allergic asthma that is uncontrolled despite use of inhaled corticosteroids (ICS) associated with a beta2- long-acting agonist (LABA)

INTRODUÇÃO: A asma é uma doença inflamatória crônica das vias aéreas inferiores que se caracteriza por aumento da responsividade dessas vias a diferentes estímulos, com consequente obstrução ao fluxo aéreo, de forma recorrente e reversível. A OMS estima que cerca de 235 milhões de pessoas sofrem de asma. No Brasil, a asma foi a 3ª causa de internação hospitalar pelo SUS em 2008, com cerca de 300.000 hospitalizações naquele ano. Em 2013, ocorreram 129.728 internações e 2.047 mortes. Já em 2018, o número de internações foi de aproximadamente 87.000. De acordo com o PCDT de asma, do Ministério da Saúde, o omalizumabe é uma terapia inespecífica anti-IgE indicada exclusivamente para adultos e crianças com pelo menos 6 anos de idade com asma alérgica, moderada a grave (etapas IV e V), cujos sintomas são inadequadamente controlados apesar do uso de corticoide inalatório associado a um beta-2 agonista de longa ação. RECOMENDAÇÃO PRELIMINAR: Os membros do Plenário, presentes na 111ª Reunião Ordinária da Conitec, no dia 03 de agosto de 2022, deliberaram por unanimidade que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à inclusão da nova apresentação de omalizumabe (150 mg/mL) solução injetável em seringa preenchida, ao SUS, para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2-agonista de longa ação (LABA). A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: Foram recebidas 14 contribuições, sendo nove pelo formulário de experiência e opinião e cinco pelo formulário técnico-científico. Os nove respondentes do formulário de experiência e opinião apresentaram-se favoráveis à recomendação inicial da Conitec. Os participantes mencionaram a facilidade de administração do omalizumabe em seringa preenchida, a melhora na qualidade de vida e a necessidade de incorporação dessa apresentação do medicamento no SUS. Os benefícios desse formato de administração foram mencionados como uma facilidade do medicamento. No formulário para contribuições técnico-científicas quatro não apresentaram argumentação técnica sobre as evidências, mas argumentação de cunho pessoal acerca do uso da tecnologia, três foram positivas à incorporação. A contribuição enviada pela empresa fabricante do omalizumabe teceu comentários sobre as justificativas científicas e sobre o impacto orçamentário apresentadas na apreciação inicial da matéria, reforçando que não haverá ônus ao Ministério da Saúde na incorporação da nova apresentação de omalizumabe. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário presentes na 113ª Reunião Ordinária da Conitec, realizada no dia 06 de outubro de 2022, deliberaram por unanimidade, recomendar a incorporação da nova apresentação de omalizumabe (150 mg/mL) solução injetável em seringa preenchida, ao SUS, para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2-agonista de longa ação (LABA). Não foram adicionadas evidências, durante a Consulta Pública, que alterassem a recomendação preliminar da Comissão. Foi assinado o Registro de Deliberação nº 774/2022. DECISÃO: Incorporar, no âmbito do Sistema Único de Saúde - SUS, a nova apresentação de omalizumabe (150 mg/mL), solução injetável em seringa preenchida, para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2- agonista de longa ação (LABA), conforme a Portaria nº 143, publicada no Diário Oficial da União nº 214, seção1, página 92, em 11 de novembro de 2022.

Variation in costs due to virtual switching from free- to fixed-triple LABA/LAMA/ICS combinations among COPD patients: an analysis using a primary care database.

Chronic obstructive pulmonary disease (COPD) is a condition with a relevant clinical and economic burden. Only 10% to 40% of COPD patients reporting a regular use of respiratory medications, including those who suffered from severe disease being prescribed with triple combination therapy, nominally long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid (ICS). The recent market launch of fixed-triple LABA/LAMA/ICS therapy might contribute to improve medications adherence and costs containment, given the use of a single instead of two or three inhalers. Few data are available on costs due to triple therapy prescribed for COPD. In specific, there are no studies providing data on the potential costs saving whether COPD patients exposed to free-triple combination therapy were switched to fixed-triple combination. In this respect, we simulated some scenarios of virtual switching and calculated the related cost savings.

Treatment Patterns and Disease Burden Associated with Multiple-Inhaler Triple-Therapy Use in Asthma.

BACKGROUND: Addition of a long-acting muscarinic antagonist is recommended for patients with asthma uncontrolled on inhaled corticosteroid/long-acting ß2-agonist therapy. This is the first large-scale, real-world study examining multiple-inhaler triple-therapy (MITT) use in asthma. OBJECTIVE: To describe real-world prevalence, outcomes, and treatment patterns associated with MITT. METHODS: This retrospective cohort study used medical and pharmacy claims from the Optum Research Database. Patients were diagnosed with asthma between January 01, 2013, and July 31, 2018, with evidence of MITT use (≥1 overlapping days' supply of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist). Annual MITT prevalence (primary end point) was assessed in the prevalent population; eligible patients were 18 years or older with 2 or more asthma diagnoses during the study period, and continuous enrollment for the entire year. Secondary outcomes (adherence [proportion of days covered], MITT persistence, health care resource utilization, costs) were assessed in the incident MITT population; eligible patients were 18 years or older, with 2 or more asthma diagnoses and continuous enrollment during both the 12-month baseline and 12-month follow-up periods. Patients with chronic obstructive pulmonary disease or cystic fibrosis were excluded. RESULTS: MITT prevalence was low but increased from 0.35% (95% CI, 0.32-0.37) in 2014/2015 to 1.00% (95% CI, 0.96-1.04) in 2017/2018. Among 1831 incident MITT users, there was a substantial disease burden, demonstrated by high health care resource utilization and exacerbation rates. Adherence and persistence to MITT was low (mean proportion of days covered, 0.31 ± 0.27), and 12% (n = 216) remained on MITT 12 months postinitiation. CONCLUSIONS: Overall, MITT use among patients with asthma is low. Patients initiating MITT have substantial disease burden and significant unmet needs.

Cost-utility of triple versus dual inhaler therapy in moderate to severe asthma.

BACKGROUND: An important proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids and long-acting beta-agonists. Clinical guidelines recommend, in these patients, using add-on long-acting muscarinic antagonists (triple therapy) to treatment with high doses of inhaled corticosteroids-long-acting beta2-agonist (dual therapy). The purpose of this study was to assess the cost-effectiveness of triple therapy versus dual therapy for patients with severe asthma. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYS of dual and triple therapy were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. RESULTS: The model suggests a potential gain of 1.55 QALYs per patient per year on triple therapy with respect to dual therapy. We observed a difference of US$304 in discounted cost per person-year on triple therapy with respect to dual therapy. The incremental cost-effectiveness ratio was US$196 in the probabilistic model. In the sensitivity analysis, our base-case results were robust to variations in all assumptions and parameters. CONCLUSION: In conclusion, triple therapy in patients with moderate-severe asthma was cost-effective. Using triple therapy emerges with our results as an alternative before using oral corticosteroids or biologics, especially in resource-limited settings.

Quantifying the Economic Impact of Delayed Multiple-Inhaler Triple Therapy Initiation in Patients with COPD: A Retrospective Cohort Study of Linked Electronic Medical Record and Hospital Administrative Data in England.

PURPOSE: To assess if early multiple-inhaler triple therapy (MITT) initiation in patients with chronic obstructive pulmonary disease (COPD) reduces subsequent healthcare resource utilization (HCRU), direct medical costs, and acute exacerbations of COPD (AECOPDs). PATIENTS AND METHODS: This retrospective, longitudinal cohort study used electronic health records and linked hospital administrative data in England. COPD patients with an AECOPD between July 2012 and May 2016 (index), and who subsequently started MITT within 180 days were eligible. Patients with an AECOPD 6 months prior to index were excluded. HCRU, direct healthcare costs, and AECOPDs were assessed in the following 24-month period for early (≤30 days) and delayed (31-180 days) MITT initiators. RESULTS: A total of 934 patients were included in the analysis and categorized as early (n=367, 39%) or delayed (n=567, 61%) MITT initiators. Mean patient age was 68.5 years and 53.2% were male. A significantly higher proportion of delayed MITT initiators required ≥1 outpatient appointment (all-cause) compared with early MITT initiators (87% vs 79%; p=0.0016). A significantly higher proportion of delayed MITT initiators required ≥1 COPD­related inpatient stay versus early MITT initiators (47% vs 40%; p=0.0262). Over the 24-month follow-up, mean all-cause and COPD-related total healthcare costs were significantly higher in delayed MITT initiators compared with early MITT initiators (all­cause: £11,348 vs £8126; p=0.0011; COPD-related: £7307 vs £4535; p=0.0009). CONCLUSION: Delayed initiation of multiple-inhaler triple therapy was associated with higher all-cause and COPD-related costs, suggesting that earlier initiation of triple therapy in COPD patients may help reduce the economic burden on the healthcare system.

Cost-effectiveness of the fixed-dose combination tiotropium/olodaterol versus tiotropium monotherapy or a fixed-dose combination of long-acting ß2-agonist/inhaled corticosteroid for COPD in Finland, Sweden and the Netherlands: a model-based study.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting ß2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands. METHODS: A previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV1), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively. RESULTS: Treatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer's incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries. CONCLUSIONS: Based on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.

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.

Broncodilatadores Antagonistas Muscarínicos de Longa Ação (LAMA) + Agonistas Beta2-Adrenérgicos de Longa Ação (LABA) para o tratamento de pacientes com Doença Pulmonar Obstrutiva Crônica / Muscarinic Antagonist Bronchodilators Long Acting (LAMA) + Long Acting Beta2-Adrenergic Agonists (LABA) for the treatment of patients with Chronic Obstructive Pulmonary Disease

INTRODUÇÃO: O diagnóstico de Doença Pulmonar Obstrutiva Crônica (DPOC) é feito com base em sinais e sintomas respiratórios crônicos. A prevalência da doença apresenta variação considerável, situando-se entre 4% e 10% em países europeus e norte-americanos, enquanto, no Brasil, a prevalência total de distúrbio ventilatório obstrutivo é de 15,8% na região metropolitana de São Paulo, entre indivíduos com mais de 40 anos, sendo 18% entre os homens e 14% entre as mulheres. A DPOC é considerada a quarta principal causa de morte no mundo, prevendo-se que seja a terceira em 2020, devido à continuidade da exposição aos fatores de risco e ao envelhecimento da população. Em relação à gravidade da obstrução, a DPOC é classificada em leve a muito grave, considerando o nível de redução no volume expiratório forçado em 1 segundo (VEF1) em relação ao previsto. O objetivo da terapia da DPOC é melhorar os sintomas, diminuir as exacerbações, melhorar a função pulmonar e a qualidade de vida do paciente. PERGUNTA: Os broncodilatadores LAMA + LABA são eficazes, seguros e custo-efetivos para o tratamento de pacientes com DPOC2? TECNOLOGIA: Combinação de um ß2-agonista de longa duração (LABA) e um anticolinérgico de longa duração (LAMA). EVIDÊNCIAS CIENTÍFICAS: Foram recuperadas 4.946 re

Symptom Burden and GOLD Classification in Medicare Advantage Patients with COPD Initiating Umeclidinium/Vilanterol or Fluticasone Propionate/Salmeterol Therapy.

Background: Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) provide greater improvements in lung function and symptoms than inhaled corticosteroid (ICS)/LABA in patients with chronic obstructive pulmonary disease (COPD). This study evaluated symptom burden and Global Initiative for Obstructive Lung Disease (GOLD) categorization among patients who recently initiated umeclidinium/vilanterol (UMEC/VI; LAMA/LABA) or fluticasone propionate/salmeterol (FP/SAL; ICS/LABA) single-inhaler dual therapy. Methods: COPD-diagnosed Medicare Advantage enrollees aged ≥65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores. Results: The final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (~40%) than GOLD B (~36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups. Conclusion: After controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.

Health and cost impact of stepping down asthma medication for UK patients, 2001-2017: A population-based observational study.

BACKGROUND: Guidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs. METHODS AND FINDINGS: We used nationwide UK primary care medical records, 2001-2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (long-acting ß2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown (adjusted hazard ratio, 95% CI, p-value: ICS inhaler dose = 0.86, 0.77-0.93, p < 0.001; ICS mean daily = 0.80, 0.74-0.87, p < 0.001; LABA = 1.01, 0.92-1.11, p = 0.87, other add-on = 1.00, 0.91-1.09, p = 0.79) and no increase in reliever prescriptions (adjusted odds ratio, 95% CI, p-value: ICS inhaler dose = 0.99, 0.98-1.00, p = 0.59; ICS mean daily = 0.78, 0.76-0.79, p < 0.001; LABA = 0.83, 0.82-0.85, p < 0.001; other add-on = 0.86, 0.85-0.87, p < 0.001). Prognostic factors to initiate stepdown included medication burden, but not medication side effects. National Health Service (NHS) indicative prices were used for cost estimates. Stepping down medication, either LABAs or ICSs, could save annually around £17,000,000 or £8,600,000, respectively. Study limitations include the possibility that prescribed medication may not have been dispensed or adhered to and the reason for stepdown was not documented. CONCLUSION: In this UK study, we observed that asthma patients were increasingly prescribed higher levels of treatment, often without clear clinical indication for such high doses. Stepping down medication did not adversely affect outcomes and was associated with substantial cost savings.

Association Between Adherence to Maintenance Medication in Patients with COPD and Acute Exacerbation Occurrence and Cost in China: A Retrospective Cohort Database Study.

Background: This study aimed to evaluate the association between adherence to maintenance medication (ie, inhaled bronchodilators, inhaled corticosteroid/long-acting beta-2 agonist [ICS/LABA] combinations, and oral therapy) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and related costs among patients with chronic obstructive pulmonary disease (COPD) in China. Patients and Methods: Claims data from the hospitals of a metropolitan city in south China between January 2014 and December 2016 were obtained. Patients with COPD with ≥2 maintenance medication claims during 1 year were included. Adherence was measured by the proportion of days covered (PDC). The interaction of medication class×adherence was considered when building models. Results: A total of 11,708 patients met the inclusion criteria, of whom 10.8% were highly adherent (PDC≥0.8). There were significant interaction effects of drug category on hospitalized AECOPD risk (P≤0.001), hospitalized AECOPD rate (P<0.001), and 1-year hospitalized AECOPD treatment costs (P=0.012). There was a relationship between high adherence and outcomes for ICS/LABA combinations (n=3,419), ie, relative risk of hospitalized AECOPD was reduced by 34.8% (adjusted odds ratio=0.65; 95% confidence interval (CI): 0.54-0.79; P<0.001) while the frequency of hospitalized AECOPD per patient-year was reduced by 24.4% (adjusted rate ratio=0.76; 95% CI: 0.65 to 0.87; P<0.001). Mean 1-year per-patient hospitalized AECOPD costs were reduced by 37.8% (mean difference=-848 USD; 95% CI: -1435-262 USD; P<0.001). Patients taking oral mucolytics and having high adherence had worse AECOPD outcomes than patients with poor adherence. Conclusion: High adherence to ICS/LABA maintenance therapy was associated with reduced hospitalized AECOPD rates and costs in Chinese patients with COPD.