Best step-up treatments for children with uncontrolled asthma: a systematic review and network meta-analysis of individual participant data.

BACKGROUND: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting ß2-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo. RESULTS: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control. CONCLUSIONS: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

Longitudinal changes in the prevalence of adult asthma: An epidemiological survey among Japanese salaried employees and their dependents using healthcare insurance claim from 1999 to 2019.

BACKGROUND: Information on changes in asthma prevalence and the treatment status for asthma is used as basic information for taking medical and administrative measures against asthma. However, this information among adults is relatively limited. METHODS: To elucidate changes in the prevalence of asthma and treatment status over time among Japanese adults, health insurance claim data from some health insurance societies covering salaried employees and their dependents were studied longitudinally. Claim data from FY1999 to 2007 were obtained from two health insurance societies, and data from FY 2011 to 2019 were obtained from three different health insurance societies, and changes in standardized asthma prevalence among subjects aged 20-59 years, proportion of asthma patients prescribed ICS, leukotriene receptor antagonist (LTRA), and LABA, and the mean number of acute asthma exacerbations per year were analyzed. RESULTS: The prevalence of asthma increased from 1.6% in 1999 to 3.0% in 2007 and 2.9% in 2011 to 4.6% in 2019. Increased trends in asthma prevalence from 2011 to 2019 were more noticeable in subjects in their 50s than those in their 20s for both sexes. The number of emergency visits related to asthma was 1.5 per year in 1999, which decreased to 0.8 per year in 2019. The proportion of people prescribed all anti-asthma medications (ICS, LTRA, and LABA) increased over time. CONCLUSIONS: The prevalence of adult asthma among Japanese salaried employees and their dependents has increased over the last 20 years, suggesting more attention should be paid to the prevention of this disease in adults.

Tratamento da UCE refratária aos anti-histamínicos e na impossibilidade do omalizumabe, nos adultos / Treatment of CSU refractory to antihistamines and in the impossibility of omalizumab therapy in adults

Há o empenho contínuo de especialistas no desenvolvimento de tratamentos resolutivos ou eficazes nos controles das doenças, no entanto, a entidade urticária crônica espontânea (UCE), quando refratária à primeira linha de tratamento, os anti-histamínicos, apresenta um prognóstico desfavorável. Existe um arsenal de medicamentos biológicos disponíveis já consolidados como eficazes e seguros, porém eventualmente nos defrontamos com a inacessibilidade a estes medicamentos, devido aos custos dos mesmos e aos trâmites necessários para dar início ao tratamento. Tais fatos fundamentam a discussão sobre terapias alternativas com outros fármacos, visando manter o manejo adequado da doença e a qualidade de vida dos pacientes.

Specialists have made a continuous effort for the development of effective treatments for disease control; however, chronic spontaneous urticaria (CSU), when refractory to the first line of treatment, ie, antihistamines, has an unfavorable prognosis. There are biological medicines available, which have been consolidated as effective and safe, but we are occasionally faced with a lack of access to these medicines due to their costs and the necessary procedures to start treatment. Such facts support the discussion about alternative therapies with other drugs, aiming at maintaining the adequate management of the disease and the quality of life of patients.

Informe diário de evidências COVID-19: busca realizada em 19 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 19, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 19 artigos e 17 protocolos.

Weight status and nonadherence to asthma maintenance therapy among children enrolled in a public drug insurance plan.

Objective: The pediatric obese-asthma phenotype is associated with poor control, perhaps because of medication nonadherence. This study aimed to assess whether weight status is associated with nonadherence in children prescribed new asthma maintenance therapies.Methods: A historical cohort was constructed from a clinical database linking individual patient and prescription data to Quebec's prescription claims registry. Children aged 2-18 years with specialist-diagnosed asthma who were newly prescribed one of the following maintenance controllers: leukotriene receptor antagonists (LTRA); low-dose inhaled corticosteroids (ICS); medium/high-dose ICS; or combination therapy (ICS with long-acting beta-2 agonists and/or LTRA), at the Asthma Center of the Montreal Children's Hospital from 2000-2007 were included. Primary nonadherence was defined as not claiming any prescriptions, whereas secondary nonadherence was measured with the proportion of prescribed days covered (PPDC ≤ 50%) among primary adherers over a 6-month follow-up period. A modified Poisson regression model served to estimate the effect of excess weight (BMI > 85th percentile) on primary and secondary nonadherence.Results: Approximately one third of patients were primary nonadherers and 60% took less than 50% of prescribed therapy. Excess weight was associated with a trend toward increased risk of primary nonadherence in children newly prescribed low-dose ICS (RR 1.53, 95%CI 0.94-2.49), and of secondary nonadherence in children initiating medium/high-dose ICS (RR 1.24; 95%CI 0.98-1.59).Conclusions: Excess weight status is a possible determinant of primary nonadherence in children initiating low-dose ICS and secondary nonadherence to higher-dose ICS regimens. This hypothesis-generating study suggests that nonadherence may be a potential contributor to higher morbidity in children with obese-asthma.

Prescription Status and Clinical Outcomes of Methylxanthines and Leukotriene Receptor Antagonists in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Background: Methylxanthines and leukotriene receptor antagonists (LTRA) are not a first-line medical treatment for chronic obstructive pulmonary disease (COPD) but are frequently prescribed despite limited evidence. We aimed to elucidate the real prescribing status and clinical impacts of these agents in early COPD patients. Methods: Patients with mild-to-moderate COPD (FEV1>50%) were selected from the Korean National Health and Nutrition Examination Survey data between 2007 and 2012. Besides analyzing the prescription status of methylxanthines and LTRA and the contributing factors to the prescription, we evaluated the clinical impacts of these drugs on the exacerbation, hospitalization, and medical costs. Results: Of 2269 patients with mild-to-moderate COPD, 378 patients (16.7%) were under medical treatments, and the users of methylxanthines and/or LTRA were 279 patients (12.3%); however, only 139 patients (6.1%) were inhaler users. The contributing factors for the prescription of methylxanthines were a comorbidity of asthma or allergic disease, poor lung function, low quality of life, prescribing doctor from the specialty of internal medicine, and an institution type of private hospital. The prescription of LTRA was associated with the comorbidity of allergic disease. The methylxanthine and/or LTRA users had more hospital utilization but did not have significant differences in acute exacerbations and medical cost for hospital utilization, compared with the non-users. Conclusion: Methylxanthines and LTRA were used in a significant proportion of patients with mild-to-moderate COPD in real fields without favorable impacts on the exacerbations, hospitalizations, or medical costs. The use of more effective inhaled medications should be encouraged.

Economic Burden Associated with Receiving Inhaled Corticosteroids with Leukotriene Receptor Antagonists or Long-Acting Beta Agonists as Combination Therapy in Older Adults.

BACKGROUND: There is a paucity of literature on the health care expenditures associated with different pharmacologic treatments in older adults with asthma that is not well controlled on inhaled corticosteroids (ICS). OBJECTIVE: To compare asthma-related and all-cause health care expenditures associated with leukotriene receptor antagonists (LTRA) versus long-acting beta agonists (LABA) when added to ICS in older adults with asthma. METHODS: A retrospective cohort was constructed using 2009-2010 Medicare fee-for-service medical and pharmacy claims from a 10% random sample of beneficiaries continuously enrolled in Parts A, B, and D in 2009. The sample comprised patients who were aged 65 years and older, diagnosed with asthma, and treated exclusively with ICS + LABA or ICS + LTRA. Outcomes assessed were asthma-related expenditures (medical, pharmacy, and total) and all-cause health care expenditures (medical, pharmacy, and total). Outcomes were measured from the date of the first prescription for the add-on treatment (LABA or LTRA in combination with ICS) after having at least a 4-month "wash-in" period in which patients were receiving no controller, ICS alone, or ICS plus the add-on treatment of the follow-up period. Patients were followed until death, switching to or adding the other add-on treatment, or the end of the study (December 31, 2010). Multivariable regression models with nonparametric bootstrapped standard errors were used to compare all-cause and asthma-related expenditures per patient per month (PPPM) between ICS + LABA and ICS + LTRA users. All models were adjusted for demographics, comorbidities, and county-level health care access variables. RESULTS: The primary analysis included 14,702 patients, of whom 12,940 were treated with ICS + LABA and 1,762 were treated with ICS + LTRA. The mean (SD) follow-up periods were 12.3 (± 5.7) months for the ICS + LABA group and 15.3 (± 5.1) months for the ICS + LTRA group. Adjusted asthma-related expenditures PPPM were $400 for the ICS + LTRA group compared with $286 for the ICS + LABA group (P < 0.001). However, adjusted total all-cause expenditure PPPM was significantly lower for patients treated with ICS + LTRA ($6,087 for ICS + LTRA compared with $6,975 for ICS + LABA, P = 0.029). CONCLUSIONS: Older adults with asthma often experience economic burden from asthma and other chronic illnesses. Compared with ICS + LTRA, ICS + LABA was associated with lower asthma-related expenditures but with higher all-cause expenditures in older adults. DISCLOSURES: Support for this study was provided by the University of Pittsburgh School of Pharmacy and the Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA P30 AGAG024827). C. Thorpe reports grants from the National Institute of Aging during the conduct of this study. The other authors have nothing to disclose.

Access to affordable medicines and diagnostic tests for asthma and COPD in sub Saharan Africa: the Ugandan perspective.

BACKGROUND: Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management. METHODS: Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days' wages it would cost the least paid public servant were analysed. RESULTS: The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days' wages for inhaled salbutamol to 17.1 days' wages for formoterol/budesonide inhalers and 27.8 days' wages for spirometry. CONCLUSION: Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

Comparing effectiveness and outcomes in asthma and cystic fibrosis.

As technology yields new treatments, pediatric pulmonologists need determine how best to use them and how to decide which ones are best for any specific group or individual patient. Physicians have always customized therapies based upon patient response, but the new concept of "Personalized (or precision) medicine" focuses attention to a greater degree on the individual needs of patients based on their genetic, biomarker, phenotypic, or psychosocial characteristics. The newly developed biologics for treatment of asthma and CFTR modulators for treatment of cystic fibrosis (CF) highlight this newer approach. As we have more treatments available, new approaches to testing efficacy and effectiveness of these new therapies is necessary in order to efficiently bring them to market and compare their benefits in real world practice. While comparative effectiveness can be tested in pragmatic clinic trials, the most common approaches make use of observational data such as administrative databases and patient registries but their use for this is fraught with pitfalls that may or may not be methodologically surmountable. Once new therapies have been shown to be efficacious and effective, it is important to be cognizant of methods for ensuring that all patients actually receive the treatments that will be best for them. Comparisons of the effectiveness of clinical practice in the form of benchmarking is helpful for this, and consideration of costs and cost-effectiveness is essential to judging the best treatment for patients in a real-world setting.

Self-assessment of Allergic Rhinitis and Asthma (SACRA) Questionnaire-based Allergic Rhinitis Treatment Improves Asthma Control in Asthmatic Patients with Allergic Rhinitis.

Objective This study was conducted to investigate whether the add-on treatment of allergic rhinitis (AR) based on the Self-assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire for assessing AR control improves both AR and asthma control in asthmatic patients with AR. Methods This multi-center prospective study was performed in Nagano prefecture, Japan. Two hundred five asthmatic patients and 23 respiratory physicians participated in the study. We administered add-on AR treatments based on the results of the SACRA questionnaire. After the first SACRA questionnaire, 67 asthmatic patients agreed to receive an add-on AR treatment. Three months after the AR treatment, a secondary SACRA questionnaire, asthma control test (ACT), and pulmonary function tests were performed. Results After the add-on AR treatment, the visual analogue scales (VASs) for AR and asthma, as assessed by the SACRA questionnaire and ACT score, were significantly improved in the patients of the AR+ group. With regard to the pulmonary function tests, the percent predicted vital capacity, and percent predicted forced expiratory volume in one second were also significantly improved. Regardless of whether the patients had previously undergone leukotriene receptor antagonists (LTRA) treatment, the VASs for AR and asthma and the ACT score were significantly improved in the AR+ group. However, the vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume (FEV1) were only significantly improved in the AR+ group that had previously undergone LTRA treatment. Conclusion SACRA questionnaire-based add-on AR treatment would be convenient for the detection of AR by respiratory physicians and would offer improved asthma control. This questionnaire can also be used to assess the therapeutic effects.

Eficacia y seguridad del uso de bromuro de tiotropio en el tratamiento de pacientes con asma severa no controlada con ics/laba y ltra, y no tributarios a teofilina / Efficacy and safety of the use of tiotropium bromide in the treatment of patients with severe asthma not controlled with ics / laba and ltra, and not tributaries to theophylline

INTRODUCCIÓN: El presente dictamen presenta la evaluación de tecnología de la eficacia y seguridad de bromuro de tiotropio en el tratamiento de dolor neuropático. El asma es una enfermedad respiratoria crónica que se manifiesta de manera heterogénea entre los que la padecen, usualmente caracterizada por inflamación crónica de las vías aéreas. El asma puede ser clasificado como leve, moderada o severa. La severidad del asma se evalúa de manera retrospectiva y está en función del tratamiento requerido para controlar los síntomas y exacerbaciones. La prevalencia global de asma se ha estimado entre 1% y 16% en la población entre 13 y 14 años de edad, aunque varían entre países por la ausencia de una definición de asma universal. En cuanto a la población adulta general, en Estados Unidos, la prevalencia de asma se estima cerca al 8%, mientras que la prevalencia de asma en adultos mayores de 65 años se encuentra entre 4% y 8%. El asma severa se da en 5-10% del total de casos de asma. TECNOLOGIA SANITARIA DE INTERÉS: El bromuro de tiotropio, también llamado únicamente tiotropio, es un agente anticolinérgico de acción prolongada que presenta afinidad especifica por los receptores muscarínicos (M 1 a M 5 ), particularmente por los subtipos M 1 y M 3 . La acción del bromuro de tiotropio se da a nivel de vías áreas, donde inhibe los receptores muscarínicos de músculo liso, lo cual tiene como resultado la broncodilatación. A los medicamentos de su clase se les conoce como antagonistas muscarínicos de acción prolongada (LAMA, por sus siglas en inglés). METODOLOGIA: Se llevó a cabo una búsqueda de la literatura con respecto a la eficacia y seguridad de de bromuro de tiotropio en el tratamiento de asma severa en las bases de datos de PubMed, TRIPDATABASE, The Cohrane Library y www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como Organización mundial de la Salud (OMS), National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), Canadian Agency for Drugs and Technologies in Health (CADTH), Instituto de efectividad clínica y sanitaria (IECS), Instituto de Evaluación de Tecnología en Salud (IETS); y especializados en neumología como American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), Asociación Latinoamericana de Tórax (ALAT), National Heart, Lung and Blood Institute (NHLBI), British Thoracic Society (BTS). RESULTADOS: En la actualidad el Petitorio Farmacológico de EsSalud cuenta con ICS, LABA, LTRA y teofilina para el tratamiento de pacientes con asma severa. Sin embargo, existe un grupo de pacientes en quienes el tratamiento con dosis máximas de ICS más LABA y terapia complementaria con LTRA o teofilina no ha logrado controlar la enfermedad, en ellos se requiere contar con otras alternativas de tratamiento. Adicional a ello, existen pacientes para quienes alguna de las terapias complementarias está contraindicada, dejando de ser una opción adicional de tratamiento. En este contexto, se ha solicitado al IETSI la evaluación del uso fuera del petitorio de bromuro de tiotropio. El bromuro de tiotropio, también llamado únicamente tiotropio, es un agente anticolinérgico de acción prolongada que presenta afinidad especifica por los receptores muscarínicos (M 1 a M 5 ). La acción del fármaco se da a nivel de vías áreas, donde inhibe los receptores muscarínicos del músculo liso, generando broncodilatación. A los medicamentos de su clase se les conoce como antagonistas muscarínicos de acción prolongada (LAMA, por sus siglas en inglés). A la fecha (Julio 2017) la evidencia identificada en relación al uso de bromuro de tiotropio en el tratamiento de asma severa corresponde a dos GPC (GINA 2017 y BTS/SIGN 2016), una ETS (SMC), un documento de consejo (NICE), un metanálisis (MA), y dos ECAs gemelos (PrimoTinA I y II). Las GPC de GINA y BTS/SIGN son homogéneas en sus recomendaciones. Así, ambas GPC mencionan el uso de tiotropio como una alternativa de tratamiento complementario en pacientes con asma pobremente controlada a pesar del uso de dosis máximas de ICS más LABA, al mismo nivel que el uso de LTRAs o teofilina. Dichas recomendaciones responden indirectamente a la pregunta PICO de interés del dictamen en la medida en que no especifican el uso consecutivo de las alternativas mencionadas frente a ausencia de mejoría de los síntomas, por lo que no hacen referencia específicamente a la población de interés del dictamen. Tanto el MA como los ensayos gemelos PrimoTinA I y II evidencian que el uso de tiotropio como terapia complementaria no ofrece ningún beneficio sobre el uso de ICS/LABA en cuanto a las variables de relevancia clínica como la ocurrencia de exacerbaciones, la calidad de vida y el control de la enfermedad, en pacientes con asma severa. Ambos estudios (el MA y los ensayos) constituyen evidencia indirecta para responder a la pegunta PICO ya que incluyen únicamente a la población de asmáticos que ha recibido ICS/LABA o solo ICS, mientras que la población de la pregunta PICO incluye también a aquellos que han recibido además LTRAs y no son tributarios a teofilina. A pesar de ser evidencia indirecta, es posible aplicar dichos resultados a la población de interés del dictamen ya que se observan resultados no favorables en una población que ha recibido menos líneas de tratamiento, por lo que se esperaría que en una población que ha pasado por más tratamientos este resultado negativo se mantenga. A manera de información adicional de relevancia, los elaboradores de las guías resaltan que para pasar a una siguiente alternativa de tratamiento es necesario corroborar la adherencia a los tratamientos empleados previamente, así como la ausencia de factores externos irritantes que puedan provocar exacerbaciones y la presencia de comorbilidades no controladas apropiadamente. Asimismo, hacen hincapié en que se debe evaluar la técnica empleada por los pacientes al usar el inhalador, ya que ello influye grandemente en la eficacia del fármaco. CONCLUSIÓN: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) no aprueba el uso de bromuro de tiotropio en pacientes con asma severa no controlada con ICS/LABA y LTRAs y no tributarios a teofilina.

Cost-Utility Analysis of Long-Acting Beta Agonists versus Leukotriene Receptor Antagonists in Older Adults with Persistent Asthma Receiving Concomitant Inhaled Corticosteroid Therapy.

BACKGROUND: Long-acting beta agonists (LABA) and leukotriene receptor antagonists (LTRA) are the major add-on treatments in older adults with persistent asthma when inhaled corticosteroids (ICS) fail to achieve adequate asthma control. OBJECTIVES: To evaluate the cost-utility of ICS + LABA treatment compared with ICS + LTRA treatment in older adults with asthma. METHODS: A Markov model was used to estimate the incremental costs and quality-adjusted life expectancy associated with ICS + LABA treatment versus ICS + LTRA treatment in older adults with asthma in the United States from the health system perspective. The HCUPnet 2010 national statistics were used to extract the costs associated with asthma and cardiovascular hospitalizations, and inpatient mortality associated with these events. Event probabilities were predicted using Medicare 2009-2010 claims for older adults with asthma. Treatment costs were estimated on the basis of average wholesale drug price listings, and utility estimates were extracted from the literature. To account for uncertainty, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. RESULTS: The model predicted that, compared with ICS + LTRA treatment, ICS + LABA treatment costs $5,823 more while gaining 0.03 quality-adjusted life-years (QALYs), resulting in an incremental cost-effectiveness ratio of $209,090 per QALY. Hospitalization probabilities and posthospitalization utilities were the most influential parameters in the one-way sensitivity analysis. Probabilistic uncertainty analysis using Monte-Carlo simulations showed that the probabilities that ICS + LTRA treatment is cost-effective compared with ICS + LABA treatment are 77% and 62% at $50,000 and $100,000 per QALY gained willingness-to-pay thresholds, respectively. CONCLUSIONS: The cost-effectiveness of ICS + LABA treatment is economically unfavorable in older adults when compared with LTRA as add-on treatment.

Comparative safety and costs of stepping down asthma medications in patients with controlled asthma.

BACKGROUND: Limited data exist regarding outcomes after stepping down asthma medication. OBJECTIVE: We sought to compare the safety and costs of stepping down asthma controller medications with maintaining current treatment levels in patients with controlled asthma. METHODS: Patients with persistent asthma were identified from the US Medical Expenditure Panel Survey years 2000-2010. Each patient had Medical Expenditure Panel Survey data for 2 years, and measurement was divided into 5 periods of 4 to 5 months each. Eligibility for stepping down asthma controller medications included no hospitalizations or emergency department visits for asthma in periods 1 to 3 and no systemic corticosteroid and 3 or less rescue inhalers dispensed in periods 2 and 3. Steps were defined by type and dose of chronic asthma medication based on current guidelines when comparing period 4 with period 3. The primary outcome of complete asthma control in period 5 was defined as no asthma hospitalizations, emergency department visits, and dispensed systemic corticosteroids and 2 or fewer dispensed rescue inhalers. Multivariable analyses were conducted to assess safety and costs after step down compared with those who maintained the treatment level. RESULTS: Overall, 29.9% of patients meeting the inclusion criteria (n = 4235) were eligible for step down; 89.4% (95% CI, 86.4% to 92.4%) of those who stepped down had preserved asthma control compared with 83.5% (95% CI, 79.9% to 87.0%) of those who were similarly eligible for step down but maintained their treatment level. The average monthly asthma-related cost savings was $34.02/mo (95% CI, $5.42/mo to $61.24/mo) with step down compared with maintenance of the treatment level. CONCLUSION: Stepping down asthma medications in those whose symptoms were controlled led to similar clinical outcomes at reduced cost compared with those who maintained their current treatment level.

Unmet medical needs for chronic spontaneous urticaria patients: highlighting the real-life clinical practice in Taiwan.

BACKGROUND: Treatment guidelines for chronic spontaneous/idiopathic urticaria (CSU) are available; however, only 50% of patients are well controlled with approved doses of H1-antihistamines, and certain patients remain symptomatic despite receiving up to 4× the approved dose of H1-antihistamines plus H2 antihistamines and/or leucotriene-receptor antagonists. OBJECTIVES: To highlight real-life clinical practice in Taiwan and to understand the unmet medical needs of CSU patients. METHODS: A nationwide cross-sectional, observational survey of 50 dermatologists and 200 CSU patients was conducted between June 2013 and November 2013. Face-to-face interviews of dermatologists and online interviews of CSU patients were conducted independently. RESULTS: Dermatologists reported that dermographism and blood tests were the most commonly used diagnostic methods to confirm the diagnosis. The key driving factor for most clinic-based dermatologists (70%) in choosing a treatment was 'response to my medicines', and most preferred H1-antihistamines and steroids for treating CSU patients, whereas most hospital-based dermatologists (85%) gave higher priority to 'severity and impact of the conditions'. Patients were reported to have high psychological pressures and significant impact of CSU on their daily activity. In addition, CSU patients were not satisfied with their current treatment and 69% of patients switched their first-consulted physician. Furthermore, lack of information and concerns about side-effects were major factors which held back patients from seeking Western treatment. CONCLUSIONS: There is an unmet medical need of CSU patients in Taiwan highlighting gaps among guidelines, real-life clinical practice, patients' perceptions and patients' knowledge of their disease.

Clinical practice guideline: Allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is one of the most common diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most common chronic disease in the United States overall. AR is estimated to affect nearly 1 in every 6 Americans and generates $2 to $5 billion in direct health expenditures annually. It can impair quality of life and, through loss of work and school attendance, is responsible for as much as $2 to $4 billion in lost productivity annually. Not surprisingly, myriad diagnostic tests and treatments are used in managing this disorder, yet there is considerable variation in their use. This clinical practice guideline was undertaken to optimize the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an assessment of the harm-benefit balance of various diagnostic and management options. PURPOSE: The primary purpose of this guideline is to address quality improvement opportunities for all clinicians, in any setting, who are likely to manage patients with AR as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The guideline is intended to be applicable for both pediatric and adult patients with AR. Children under the age of 2 years were excluded from the clinical practice guideline because rhinitis in this population may be different than in older patients and is not informed by the same evidence base. The guideline is intended to focus on a limited number of quality improvement opportunities deemed most important by the working group and is not intended to be a comprehensive reference for diagnosing and managing AR. The recommendations outlined in the guideline are not intended to represent the standard of care for patient management, nor are the recommendations intended to limit treatment or care provided to individual patients. ACTION STATEMENTS: The development group made a strong recommendation that clinicians recommend intranasal steroids for patients with a clinical diagnosis of AR whose symptoms affect their quality of life. The development group also made a strong recommendation that clinicians recommend oral second-generation/less sedating antihistamines for patients with AR and primary complaints of sneezing and itching. The panel made the following recommendations: (1) Clinicians should make the clinical diagnosis of AR when patients present with a history and physical examination consistent with an allergic cause and 1 or more of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing. Findings of AR consistent with an allergic cause include, but are not limited to, clear rhinorrhea, nasal congestion, pale discoloration of the nasal mucosa, and red and watery eyes. (2) Clinicians should perform and interpret, or refer to a clinician who can perform and interpret, specific IgE (skin or blood) allergy testing for patients with a clinical diagnosis of AR who do not respond to empiric treatment, or when the diagnosis is uncertain, or when knowledge of the specific causative allergen is needed to target therapy. (3) Clinicians should assess patients with a clinical diagnosis of AR for, and document in the medical record, the presence of associated conditions such as asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and otitis media. (4) Clinicians should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with AR who have inadequate response to symptoms with pharmacologic therapy with or without environmental controls. The panel recommended against (1) clinicians routinely performing sinonasal imaging in patients presenting with symptoms consistent with a diagnosis of AR and (2) clinicians offering oral leukotriene receptor antagonists as primary therapy for patients with AR. The panel group made the following options: (1) Clinicians may advise avoidance of known allergens or may advise environmental controls (ie, removal of pets; the use of air filtration systems, bed covers, and acaricides [chemical agents formulated to kill dust mites]) in patients with AR who have identified allergens that correlate with clinical symptoms. (2) Clinicians may offer intranasal antihistamines for patients with seasonal, perennial, or episodic AR. (3) Clinicians may offer combination pharmacologic therapy in patients with AR who have inadequate response to pharmacologic monotherapy. (4) Clinicians may offer, or refer to a surgeon who can offer, inferior turbinate reduction in patients with AR with nasal airway obstruction and enlarged inferior turbinates who have failed medical management. (5) Clinicians may offer acupuncture, or refer to a clinician who can offer acupuncture, for patients with AR who are interested in nonpharmacologic therapy. The development group provided no recommendation regarding the use of herbal therapy for patients with AR.

[Argentine guidelines for urticaria and angioedema]. / Guía argentina de urticaria y angioedema.

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20% of the population at some point in their lives. Acute urticaria (less than 6 weeks' duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU's diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40% of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.

Guía Argentina de urticaria y angioedema

Se actualiza el diagnóstico de la urticaria crónica (UC) y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas), y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE) o inducible (UCI). El diagnóstico es sencillo, pero incluye un minucioso estudio para descartar diagnósticos diferenciales; para UCI son útiles las pruebas de provocación en la caracterización y manejo. Los estudios complementarios se deben limitar y orientar según sospecha clínica. El tratamiento se divide en tres enfoques: evitación, eliminación o tratamiento del estímulo desencadenante o de la causa, y tratamiento farmacológico. Recientemente éste se modificó, con empleo de antihistamínicos de segunda generación como primera línea y aumento de dosis de antihistamínicos H1 no sedantes, hasta 4 veces, como segunda línea. Los antihistamínicos son fundamentales para tratar la UC; sin embargo, un 40% de los pacientes no logra un buen control pese al aumento de dosis y requiere otro medicamento adicional. La evidencia más reciente considera que un grupo de fármacos puede utilizarse como tercera línea en estos casos, para mejorar la calidad de vida y limitar la toxicidad por el uso frecuente o crónico de esteroides sistémicos. Se recomiendan para esta tercera línea solo 3 fármacos: omalizumab, ciclosporina A o antileucotrienos.

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20% of the population at some point in their lives. Acute urticaria (less than 6 weeks' duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU´s diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40% of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.