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.

Asthma patients' and physicians' perspectives on the burden and management of asthma: Post-hoc analysis of APPaRENT 1 and 2 to assess predictors of treatment adherence.

INTRODUCTION: Patient adherence to maintenance medication is critical for improving clinical outcomes in asthma and is a recommended guiding factor for treatment strategy. Previously, the APPaRENT studies assessed patient and physician perspectives on asthma care; here, a post-hoc analysis aimed to identify patient factors associated with good adherence and treatment prescription patterns. METHODS: APPaRENT 1 and 2 were cross-sectional online surveys of 2866 adults with asthma and 1883 physicians across Argentina, Australia, Brazil, Canada, China, France, Italy, Mexico, and the Philippines in 2020-2021. Combined data assessed adherence to maintenance medication, treatment goals, use of asthma action plans, and physician treatment patterns and preferences. Multivariable logistic regression models assessed associations between patient characteristics and both treatment prescription (by physicians) and patient treatment adherence. RESULTS: Patient and physician assessments of treatment goals and adherence differed, as did reporting of short-acting ß2-agonist (SABA) prescriptions alongside maintenance and reliever therapy (MART). Older age and greater patient-reported severity and reliever use were associated with better adherence. Patient-reported prescription of SABA with MART was associated with household smoking, severe or poorly controlled asthma, and living in China or the Philippines. CONCLUSIONS: Results revealed an important disconnect between patient and physician treatment goals and treatment adherence, suggesting that strategies for improving patient adherence to maintenance medication are needed, focusing on younger patients with milder disease. High reliever use despite good adherence may indicate poor disease control. Personalised care considering patient characteristics alongside physician training in motivational communication and shared decision-making could improve patient management and outcomes.

[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.

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis.

INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757.

Real-World Treatment Patterns and Switching Following Moderate/Severe Chronic Obstructive Pulmonary Disease Exacerbation in Patients with Commercial or Medicare Insurance in the United States.

Purpose: There is limited literature regarding real-world treatment patterns of patients with COPD, particularly since the introduction of once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol in 2017. Here, we evaluated treatment patterns of patients with COPD before and after a COPD exacerbation. Patients and Methods: Retrospective, descriptive study using medical and pharmacy claims data and enrollment information from the Optum® Clinformatics® Data Mart database. Patients aged ≥40 years with ≥1 COPD exacerbation on or after September 18, 2017 were included. The index date was the last day of the first COPD exacerbation (ie day of visit for a moderate exacerbation or discharge date for a severe exacerbation). The baseline period was 12 months prior to index and the follow-up period (≥3 months) spanned from index until the earliest of health plan disenrollment, end of data availability (September 30, 2020), or death. Treatment patterns were evaluated during baseline and follow-up, with a focus on medication switching in the 90 days pre- and post-index. Results: COPD exacerbations were identified in 307,727 patients (125,942 severe; 181,785 moderate). Mean age at index was 72.8 years; 56.3% were female. Before and after first exacerbation, 37.7% and 48.2% of patients used ≥1 controller medication, respectively. In the 90 days pre-index, ICS, LABA, and LAMA medications were used by 27.5% of patients. Of these users, 64.3% remained on the same medication class, 21.7% discontinued, and 14.1% switched medication in the 90 days post-index. Among switchers, 44.0% switched to triple therapy. Most common switches were ICS/LABA to ICS/LABA/LAMA (20.7%) and LAMA to ICS/LABA/LAMA (16.4%). Conclusion: Many COPD exacerbations occur among patients not on controller medications. Although the percentage of patients receiving a controller medication increased following a first exacerbation, it remained below 50%. Of patients receiving controller medications pre-exacerbation, only a small proportion escalated to triple therapy post-exacerbation.

Clinical Characteristics and Economic Burden of Asthma in China: A Multicenter Retrospective Study.

Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy. We aim to obtain a better understanding of the clinical status and disease burden of patients with asthma in China. A retrospective study was carried out based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (available data from 38 hospitals). The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to Global Initiative for Asthma 2020 (GINA 2020). The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) at emergency department visits had lower frequencies of exacerbations compared with non-ICS/LABA-treated patients. The incidence rates for 1, 2, 3, and 4 exacerbation of the patients treated with ICS/LABA are lower than those treated without ICS/LABA (14.49 vs. 15.01%, 11.94% vs. 19.12%, 6.51% vs.12.92% and 4.10% vs. 9.35%). The difference got a statistical significance Chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations (mean costs are ï¿¥3,339.67 vs. ï¿¥968.45 separately).  These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for people living with asthma.

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.

Clinical and Economic Impact of Long-Term Inhaled Corticosteroid Withdrawal in Patients with Chronic Obstructive Pulmonary Disease Treated with Triple Therapy in Spain.

Purpose: To determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting ß2-agonist (LABA), and long-acting muscarinic antagonist (LAMA). Patients and Methods: This was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted. Results: Of 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57-0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001). Conclusion: ICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.

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 cost of exacerbations in patients with chronic obstructive pulmonary disease using multiple inhaler triple therapy in South Korea.

BACKGROUND: Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. METHODS: This was a retrospective cohort study using the South Korea National Health Insurance database (2014-2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months' data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). RESULTS: Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75-0.78); mean PPPY total healthcare costs were 2093 USD. CONCLUSIONS: Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Risk Assessment of Acute Myocardial Infarction and Stroke Associated with Long-Acting Muscarinic Antagonists, Alone or in Combination, versus Long-Acting beta2-Agonists.

Background: The long-acting muscarinic antagonist (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). A post-authorization safety study was initiated to assess potential cardiovascular risks associated with LAMAs versus long-acting beta2-agonists. Purpose: To estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction (AMI), stroke, and major adverse cardiac events (MACE) in new users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA compared with initiators of LABA. Patients and Methods: This population-based cohort study included patients with COPD aged ≥40 years initiating COPD medications in the UK Clinical Practice Research Datalink (CPRD) Aurum database from 2012 to 2019. Poisson regression models were used to estimate the IRR for AMI, stroke, and MACE in users of COPD medications versus LABA, adjusting for clinically relevant covariables. Results: The study included 11,121 new users of aclidinium, 4804 of aclidinium/formoterol, 56,198 of tiotropium, 23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods of continuous medication use after initiation (current use), crude incidence rates per 1000 person-years for AMI ranged from 8.7 (aclidinium/formoterol) to 12.4 (LAMA/LABA), for stroke ranged from 4.8 (aclidinium/formoterol) to 7.2 (LAMA/LABA), and for MACE ranged from 13.5 (aclidinium/formoterol) to 19.3 (LAMA/LABA). Using LABA as reference, adjusted IRRs [95% confidence intervals] were close to 1 for all study drugs for AMI (lowest for aclidinium/formoterol, 0.95 [0.60-1.52], and highest for LAMA/LABA, 1.23 [0.91-1.67]), stroke (lowest for aclidinium/formoterol, 0.64 [0.39-1.06], and highest for tiotropium, 1.02 [0.81-1.27] for tiotropium) and for MACE (lowest for aclidinium, 0.93 [0.75-1.16], and highest for LAMA/LABA, 1.24 [0.97-1.59]). Conclusion: Risks of AMI, stroke, and MACE in current users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS were similar to the risks among current users of LABA.

The Impact of the Pay-for-Performance Program on the Outcome of COPD Patients in Taiwan After One Year.

Objective: To investigate the impact of a multidisciplinary intervention on the clinical outcomes of patients with COPD. Methods: This study retrospectively extracted the data of patients enrolled in the national pay-for-performance (P4P) program for COPD in four hospitals. Only COPD patients who received regular follow-up for at least one year in the P4P program between September 2018 and December 2020 were included. Results: A total of 1081 patients were included in this study. Among them, 424 (39.2%), 287 (26.5%), 179 (16.6%), and 191 (17.7%) patients were classified as COPD Groups A, B, C, and D, respectively. Dual therapy with long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) was the most used inhaled bronchodilator at baseline (n = 477, 44.1%) patients, followed by LAMA monotherapy (n = 195, 18.0%), triple therapy with inhaled corticosteroid (ICS)/LABA/LAMA (n = 184, 17.0%), and ICS/LABA combination (n = 165, 15.3%). After one year of intervention, 374 (34.6%) and 323 (29.9%) patients had their pre- and post-bronchodilator-forced expiratory volume in one second (FEV1) increase of more than 100 mL. Both the COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) scores had a mean change of -2.2 ± 5.5 and -0.3 ± 0.9, respectively. The improvement in pulmonary function and symptom score were observed across four groups. The decreased number of exacerbations was only observed in Groups C and D, and not in Groups A and B. Conclusion: This real-world study demonstrated that the intervention in the P4P program could help improve the clinical outcome of COPD patients. It also showed us a different view on the use of dual therapy, which has a lower cost in Taiwan.

Disease Burden and Healthcare Utilization Among Patients with Chronic Obstructive Pulmonary Disease (COPD) in England.

Purpose: Clinical guidelines for COPD management suggest pharmacologic treatment algorithms based on symptoms and exacerbation history. As previous research has suggested that prescribing patterns are not always aligned with these recommendations, this study investigated the burden of disease in patients with COPD receiving, and persisting on, new inhaled maintenance therapy. Patients and Methods: This was a retrospective observational study using two linked electronic databases containing health records of patients in England. Patients aged ≥35 years with a confirmed diagnosis of COPD, and who initiated a new inhaled respiratory pharmacologic maintenance regimen between January 1, 2014 and December 31, 2016 (index date) were eligible for inclusion. New treatments could be long-acting muscarinic antagonist (LAMA) or long-acting ß2-agonist (LABA) monotherapy, inhaled corticosteroid (ICS)/LABA or LAMA/LABA dual therapy, or a multiple-inhaler triple therapy (MITT; LAMA/LABA/ICS). Patients were required to have 12 months of available medical history prior to, and after, the index date. Results: In total, 25,350 eligible patients were identified, of these 8282 (mean age: 70.9 years; 51.5% male) persisted with their newly prescribed inhaled therapy for ≥12 months and were included in the analysis. In the 12 months prior to index, 54% of patients had moderate or severe dyspnea (Medical Research Council score ≥3). The most common therapy initiated at index was MITT (42%), followed by ICS/LABA dual therapy (31.2%). The proportion of patients with moderate or severe dyspnea in the post-index period ranged from 29.0% of patients receiving ICS to 64.2% of patients receiving MITT. In the post-index period, 48.1% of patients experienced ≥1 exacerbation and 54.9% had ≥5 general practitioner visits. Conclusion: Many of the patients with COPD in our study continued to experience symptoms and exacerbations, despite persisting on the same treatment for ≥12 months. This suggests that some patients may benefit from treatment modification in accordance with guideline recommendations.

PRIMUS - Prompt Initiation of Maintenance Therapy in the US: A Real-World Analysis of Clinical and Economic Outcomes Among Patients Initiating Triple Therapy Following a COPD Exacerbation.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) may experience moderate (requiring outpatient care) or severe (requiring hospitalization) disease exacerbations. Guidelines recommend escalation from dual to triple therapy (inhaled corticosteroid + long-acting beta agonist + long-acting muscarinic antagonist) after two moderate or one severe exacerbation in a year. This study examined whether prompt initiation of triple therapy lowers risk of future exacerbations and reduces healthcare costs, compared to delayed/very delayed triple therapy after an exacerbation. PATIENTS AND METHODS: This retrospective observational study of US healthcare claims included patients ≥40 years old with COPD who initiated triple therapy (1/1/2011-3/31/2020) after ≥2 moderate or ≥1 severe exacerbation in the prior year. The earliest of the second moderate or first severe exacerbation was the index date. Patients were stratified by triple therapy timing: prompt (≤30 days post-index), delayed (31-180 days), very delayed (181-365 days). COPD exacerbations, all-cause and COPD-related healthcare utilization and costs were assessed during 12 months post-index (follow-up). Multivariable regression estimated the effect of each 30-day delay in triple therapy on the odds of exacerbations, number of exacerbations, and costs during follow-up, controlling for patient characteristics. RESULTS: A total of 24,770 patients were included: 7577 prompt, 9676 delayed, 7517 very delayed. Each 30-day delay of triple therapy was associated with 11% and 7% increases in the odds of any exacerbation and a severe exacerbation, respectively (odds ratio [95% CI]: 1.11 [1.10-1.13] and 1.07 [1.05-1.08]), a 4.3% (95% CI: 3.9-4.6%) increase in the number of exacerbations, a 1.8% (95% CI: 1.3-2.3%) increase in all-cause costs, and a 2.1% (95% CI: 1.6-2.6%) increase in COPD-related costs during follow-up. CONCLUSION: Promptly initiating triple therapy after two moderate or one severe exacerbation is associated with decreased morbidity and economic burden in COPD. Proactive disease management may be warranted to prevent future exacerbations and lower costs among patients with COPD.