Is the assessment of asthma treatment efficacy sufficiently comprehensive?

The goal of asthma guideline therapy is to achieve disease control, by minimizing impairment and decreasing the risk of exacerbations and adverse effects of the disease and its treatment. The primary objective of most clinical trials of biologics for severe asthma is a reduction in exacerbation rate. Recently, studies with patients at the lower guideline steps have also selected exacerbation reduction as a primary objective. These trials in patients with milder disease frequently demonstrate statistically significantly fewer exacerbations, but their power calculations reflect larger sample size and smaller effect size. Exacerbations have a precise consensus definition, although a minimal clinically important difference has not been established. Reduction of exacerbations in severe asthma is commonly 10-fold greater than in mild disease. Further, reduction in exacerbations is not always associated with reduced impairment. If superior control is the objective, both domains should demonstrate consistent and parallel improvement. The disconnect may reflect the need for alternative tools for measurement of impairment or, possibly, different therapeutic mechanisms of action. Determining response to biologics or discussion of disease remission requires assessing symptoms that may occur daily rather than focusing on exacerbations that occur once or twice a year for patients at the highest steps of care according to the guidelines.

Effectiveness and economic impact of Dupilumab in asthma: a population-based cohort study.

RATIONALE: Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed. OBJECTIVES: To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation ("post-intervention period") and (i) the 6 months before Dupilumab initiation ("wash-out period") and (ii) the corresponding 6 months of the prior year ("pre-intervention period"). MAIN RESULTS: In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting ß2-agonists, inhaled corticosteroids (ICS)/long-acting ß2-agonists and ICS alone) when comparing the "pre-intervention" to the "post-intervention" period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the "pre-intervention" and "post-intervention" period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change. CONCLUSIONS: Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

Patient characteristics and eligibility for biologics in severe asthma: Results from the Greek cohort of the RECOGNISE "real world" study.

BACKGROUND: Some patients with severe asthma do not achieve sufficient symptom control despite guideline-based treatment, and therefore receive oral (OCS) and systemic corticosteroids (SCS) on regular basis. The side effects of corticosteroid use negatively impact patients' health-related quality of life (HRQoL) and increase the disease burden. Biologics have shown promise in asthma therapy; however, identifying patients who might benefit from biologic therapy is complex due to the heterogeneous pathophysiology of the disease. METHODS: The European, non-interventional, multicentre RECOGNISE study (NCT03629782) assessed patient characteristics, asthma medication and control, HRQoL as assessed by St. George's Respiratory Questionnaire (SGRQ), and health care resource use in patients with severe asthma, as well as their eligibility for biologic treatment. Here, data from the Greek cohort (N = 97) are reported. RESULTS: In Greece, patients with severe asthma were more often female (71%) and never smokers (68%). 87% of patients were assessed as eligible for biologic treatment by investigator's judgement (per label criteria: 76%). Most patients had been previously treated with SCS (82% eligible vs 85% non-eligible), with OCS use being more common in non-eligible patients (23.1% vs 11.9%). More eligible patients had poorly controlled asthma (76% vs 54%), and more impaired HRQoL (mean total SGRQ score: 46% vs 39%); symptom burden was significantly higher (mean symptom score: 60% vs. 44%, p: 0.0389). CONCLUSIONS: A high proportion of Greek patients with severe asthma are eligible for biologic therapy; however, individual risk factors and differences between asthma types must be considered before the introduction of targeted therapy.

Assessment of Drug Usage Pattern among Bronchial Asthma Patients in a Tertiary Care Teaching Hospital, Tamilnadu: A Cross-sectional Study.

BACKGROUND: Asthma is a chronic inflammatory disease of the small airways. Chronic inflammation often causes hyper responsiveness of airways with wheezing, breathing difficulty, cough and chest tightness. OBJECTIVE: The present study aimed to evaluate the drug usage pattern of anti-asthma drugs among asthma patients. METHODS: The present study was a prospective, observational cross-sectional study carried out among 422 outpatients being treated at the respiratory medicine department, SRM Medical College Hospital and Research Centre. Data regarding the prescribing indicators and patient indicators were collected from the patients' prescription slips and entered in the preformed proforma. Prescribing indicators were taken into consideration in evaluating the rationality of prescriptions. RESULTS: In the present study, 49% of patients were between the age group of 20-40 years. Genderwise distribution showed 58.05% of males and 41.95% of females. A family history of asthma was seen in 68% of the study population. The present study reported smoking among 51% and tobacco chewing in 21% of the study population. Low economic strata were observed in 77.9% of the study population. According to asthma grading, 65.8% were in the mild intermittent, and 25% were in the mild persistent group. Patients were on ß2 agonists (35.4%) and corticosteroids (32%). The most commonly used fixed drug combination was a short-acting ß2 agonist with corticosteroid (40.5%). A total of 68% of drugs were used by the inhalational route and 29% by the oral route. CONCLUSION: The findings showed that, the most frequently prescribed drug was a short-acting ß2 agonist with corticosteroid in a fixed-dose combination via inhalational route.

Asthma, long-term asthma control medication and tooth wear in American adolescents and young adults.

OBJECTIVE: This study explored the associations of asthma and long-term asthma control medication with tooth wear among American adolescents and young adults. METHODS: Data from 2186 participants of the National Health and Nutrition Examination Survey (NHANES) were used. Asthma and prescribed long-term medication were collected through questionnaires. The number of surfaces with tooth wear was determined during clinical examinations. Associations were tested in Hurdle regression models adjusting for confounders. RESULTS: The prevalence of tooth wear was 58%, with an average of 6.1 (SD: 4.0) surfaces affected among those with the condition. The prevalence of asthma was 10.3%, with 2.9% of participants using long-term medication for asthma control. In the adjusted regression model, asthma was not associated with tooth wear. However, long-term control medication was associated with greater odds of having tooth wear (odds ratio: 3.33; 95%CI: 1.24-8.97), but it was not associated with the number of surfaces with tooth wear among those with the condition (rate ratio: 1.01; 95% CI: 0.58-1.75). CONCLUSION: This cross-sectional analysis of national data shows that taking long-term asthma medication was positively associated with having tooth wear.

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma.

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV1 increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.

A Systematic Review of Decision-Analytic Models for Evaluating Cost-Effectiveness of Asthma Interventions.

OBJECTIVE: To demonstrate the landscape of model-based economic studies in asthma and highlight where there is room for improvement in the design and reporting of studies. DESIGN: A systematic review of the methodologies of model-based, cost-effectiveness analyses of asthma-related interventions was conducted. Models were evaluated for adherence to best-practice modeling and reporting guidelines and assumptions about the natural history of asthma. METHODS: A systematic search of English articles was performed in MEDLINE, EMBASE, and citations within reviewed articles. Studies were summarized and evaluated based on their adherence to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). We also studied the underlying assumptions about disease progression, heterogeneity in disease course, comorbidity, and treatment effects. RESULTS: Forty-five models of asthma were included (33 Markov models, 10 decision trees, 2 closed-form equations). Novel biological treatments were evaluated in 12 studies. Some of the CHEERS' reporting recommendations were not satisfied, especially for models published in clinical journals. This was particularly the case for the choice of the modeling framework and reporting on heterogeneity. Only 13 studies considered any subgroups, and 2 explicitly considered the impact of comorbidities. Adherence to CHEERS requirements and the quality of models generally improved over time. CONCLUSION: It would be difficult to replicate the findings of contemporary model-based evaluations of asthma-related interventions given that only a minority of studies reported the essential parameters of their studies. Current asthma models generally lack consideration of disease heterogeneity and do not seem to be ready for evaluation of precision medicine technologies.

Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

A systematic review of the adverse events and economic impact associated with oral corticosteroids in asthma.

Background: Oral corticosteroids (OCSs) are often used to achieve asthma control. OCS-related comorbidities increase the burden of disease for patients and healthcare providers. Most studies characterizing OCS use and risk of adverse events (AEs) are in non-asthma patients. We sought to systematically review the literature on the burden of OCS use among adults with asthma. Methods: We systematically reviewed the literature including MEDLINE (1946-May 2017), EMBASE (1974-May 2017), and the Cochrane Library (2005-May 2017) to identify studies that considered AEs due to OCS treatment of adults with asthma, their burden on healthcare utilization, and costs. Results: We retrieved 9,589 citations; and 15 studies were included. AEs were significantly higher among OCS-users compared with non-OCS users with pooled adjusted odds ratio (OR) 1.68 (95% CI 1.15-2.46) for diabetes mellitus and 1.34 (95% CI 1.23-1.46) for hypertension. Among high dose OCS-users (>10 mg) compared with non-OCS users, the pooled adjusted ORs for development of any complication was 3.35 (95% CI 2.94-3.82), and bone and muscle complications 2.30 (95% CI 2.18-2.42). The risk of any complication increased with higher doses of OCS, with pooled adjusted OR from 2 studies of 2.26 (95% CI 1.37-3.72), 2.94 (95% CI 2.62-3.29) and 3.35 (95% CI 2.94-3.82) for low dose (<6 mg), medium dose (5-12 mg) and high dose (>10 mg) respectively compared with no OCS use. Conclusions: The use of OCS in the management of asthma is associated with a higher risk of complications. This risk is higher as the OCS dose increases.

Temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations: FAST.

BACKGROUND: Asthma exacerbations affect the quality of life of patients with asthma and have a major effect on the overall costs of asthma care. An asthma self-management plan that advises the temporary quadrupling of inhaled corticosteroid dose may prevent asthma exacerbations, but this needs to be confirmed before being adopted widely. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of an asthma self-management plan that advises patients to temporarily quadruple the dose of inhaled corticosteroid when asthma control starts to deteriorate with a standard self-management plan. DESIGN: A multicentre, parallel-group, pragmatic randomised trial, with follow-up for 12 months. SETTING: Primary and secondary care across 207 sites in the UK. PARTICIPANTS: Asthma patients aged ≥ 16 years treated with an inhaled corticosteroid who had experienced at least one exacerbation in the previous 12 months. INTERVENTIONS: Participants were randomised (1 : 1) to a usual-care self-management plan or to a modified self-management plan that advised a temporary quadrupling of the inhaled corticosteroid at the point of asthma deterioration, both of which were actively implemented and supported by local research staff. PRIMARY OUTCOME: The primary outcome of 'time to first asthma exacerbation' was defined as the need for systemic corticosteroids (for at least 3 consecutive days) and/or unscheduled health-care consultations for asthma (i.e. reaching zone 3 or 4 of the Asthma UK self-management plan). RESULTS: A total of 1922 participants were randomised: the primary analysis included 938 participants (97%) in the usual-care group and 933 participants (97%) in the modified self-management group. The number of participants having at least one exacerbation of asthma in the year after randomisation was 484 (51.6%) in the usual-care group and 420 (45.0%) in the modified self-management group [adjusted hazard ratio 0.81, 95% confidence interval (CI) 0.71 to 0.92; p = 0.002]. There were fewer serious adverse events reported in the modified self-management group than in the usual-care group (11 vs. 32, respectively). Eight and six events of pneumonia, lower respiratory tract infections or influenza were reported in the usual-care group and the modified self-management group, respectively. Health-care-related costs were lower in the modified self-management group. The modified self-management group was £24 (bootstrapped 95% CI -£122 to £71) less costly than usual care, with a greater quality-adjusted life-year gain of 0.02 (bootstrapped 95% CI -0.005 to 0.04). Therefore, the modified self-management group was 'dominant', with a 94-95% probability of being cost-effective at the £20,000-30,000 threshold. LIMITATIONS: As the Fourfold Asthma STudy (FAST) was an open-label pragmatic trial, the possibility of treatment bias that may have affected the participants in the modified self-management group cannot be ruled out. Poorer than expected completion of participant diary cards, particularly within the usual-care self-management group, could have led to a null bias, underestimating the true effect of the intervention. CONCLUSIONS: An asthma self-management plan that advises patients to temporarily quadruple their dose of inhaled corticosteroid at the point of asthma symptoms worsening does reduce clinically important asthma exacerbations. In addition, the plan is cost-effective compared with the usual-care self-management plan. FUTURE WORK: To effectively implement asthma self-management plans that advise a temporary quadrupling of inhaled steroid at asthma deterioration into routine practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15441965. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 70. See the NIHR Journals Library website for further project information.

Methods for the assessment of selection bias in drug safety during pregnancy studies using electronic medical data.

Electronic health data are routinely used for population drug studies. Due to the ethical dilemma in carrying out experimental drug studies on pregnant women, the effects of medication usage during pregnancy on fetal and maternal outcomes are largely evaluated using this data collection medium. One major limitation in this type of study is the delayed inclusion of pregnancies in the cohort. For example, in the province of Quebec, Canada, a major pregnancy cohort only captured pregnancies after 20 weeks gestation. The purpose of this study was to demonstrate three methods that can be used to assess the extent of selection bias due to the delayed inclusion of pregnancies. We use causal directed acyclic graphs to explain the source of this selection bias. In an example involving a cohort of pregnant asthmatic women reconstructed from the linkage of administrative health databases from the province of Quebec, we use numerical derivations, a simulation study and a sensitivity analysis to investigate the potential for bias and loss of power due to the delayed inclusion. We find that this selection bias can be partially mitigated by controlling for variables related to (spontaneous or therapeutic) abortion and the outcome of interest. The three proposed methods allow for the pre and post hoc ascertainment of the bias. While delayed pregnancy inclusion selection bias (which includes "live birth bias") can produce substantial bias in pregnancy drug studies, all three methods are effective at producing estimates of the size of the bias.

Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

BACKGROUND: Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. METHODS: We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. RESULTS: A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. CONCLUSIONS: In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965 .).

The impact of FDA regulatory activities on incident dispensing of LABA-containing medication: 2005-2011.

OBJECTIVE: Evidence of safety issues associated with long-acting beta2-agonist (LABA) treatment has led to multiple regulatory activities by the U.S. Food and Drug Administration (FDA) on this class of medications. This study describes the impact of the regulatory activities on incident LABA-containing medication dispensing. METHODS: A monthly rolling cohort of asthma patients who were eligible to initiate a LABA-containing product was created in the Mini-Sentinel Distributed Database between January 2005 and June 2011. Cohorts of individuals who initiated LABA were examined for the changes in the proportions of single-ingredient to fixed-dose inhaled corticosteroid (ICS)-LABA initiators, appropriate initiation of LABA-containing products, and use of controller medications. The impact of the 2005 and 2010 FDA regulatory activities associated with LABA-containing products was measured using interrupted time series with segmented regression. RESULTS: LABA-containing product initiation was declining prior to the 2005 regulatory activities and continued to decline over the study period, accompanied by increased initiation of fixed dose ICS-LABA among LABA initiators. While the 2010 regulatory activities had no immediate impact on the proportion of LABA initiation in patients with prior controller medication dispensing and/or poor asthma control, there was an increasing positive trend toward LABA initiation in the appropriate patient population after the regulatory activities. CONCLUSION: The 2005 and 2010 FDA regulatory activities likely had an impact on communicating the safety concerns of LABA products. However, the impact cannot be viewed independent of scientific publications, guidelines for asthma treatment and other regulatory activities.

FourFold Asthma Study (FAST): a study protocol for a randomised controlled trial evaluating the clinical cost-effectiveness of temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations.

BACKGROUND: Asthma is one of the commonest chronic diseases in the UK. Acute exacerbations of asthma are unpredictable, disruptive and frightening. They cause considerable morbidity and account for a large component of the health service costs of asthma. The widespread use of an asthma self-management plan, designed to encourage disease monitoring and timely intervention, can reduce exacerbations and is, therefore, recommended for all patients with asthma. Unfortunately, the majority of patients are not provided with such a plan. There are a variety of reasons for this but uncertainty about what to include in the plan when asthma control is deteriorating, but before the need for orally administered corticosteroids, is a contributing factor. The aim of this trial is to determine whether an asthma self-management plan, which includes a temporary quadrupling of the dose of inhaled corticosteroid when asthma control starts to deteriorate, reduces asthma exacerbations requiring orally administered corticosteroids or unscheduled health care consultation for asthma. METHODS: A multicentre, pragmatic, randomised trial in adults aged over 16 years with a clinical diagnosis of asthma, treated with a licensed dose of inhaled corticosteroid and at least one exacerbation in the previous 12 months requiring treatment with systemic corticosteroids. Participants will be randomised to either a self-management plan, which includes a temporary (maximum of 14 days) fourfold increase in inhaled corticosteroid or the same plan without an increase in inhaled corticosteroid. Participants will be followed up at 6 and 12 months and will attend the clinic for an additional visit if their asthma control deteriorates. The primary outcome is time to first asthma exacerbation, defined as the need for systemic corticosteroids and/or unscheduled health care consultation for asthma. The estimated sample size is 1800 participants. DISCUSSION: The FAST trial is an independent study that has been prioritised and commissioned by the National Institute for Health Research (NIHR) in the United Kingdom. It will provide high-quality evidence to inform clinical decision-making on the role of an asthma self-management plan, which includes a temporary fourfold increase of inhaled corticosteroid, when asthma control starts to deteriorate. The first participant was randomised on 17th May 2013 and recruitment will close on 31 January 2016 with the last patient last visit taking place in January 2017. TRIAL REGISTRATION: ISRCTN: 15441965 , registered on 25 April 2013.

Assessment of the efficacy and safety of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler in patients with asthma.

BACKGROUND: In developing countries, there is a need for access to affordable inhaled respiratory medicines. This study tested the clinical non-inferiority of fluticasone propionate/salmeterol combination (FSC) 50/250 µg Rotacaps®/Rotahaler® compared with FSC 50/250 µg Diskus®. METHODS: A multi-centre, randomised, double-blind, double-dummy study evaluated 12 weeks, twice daily treatment of FSC 50/250 µg administered using Rotacaps/Rotahaler or Diskus inhaler in a crossover design in patients with asthma (pre-bronchodilator forced expiratory volume in 1 s (FEV1) 40%-85% of predicted, FEV1 reversibility ≥12%, prior stable dose with inhaled corticosteroid (ICS) or ICS/long acting beta-agonist). The primary efficacy endpoint, change from baseline in trough morning FEV1 at Day 85, was analysed using a model for repeated measures analysis. The pre-defined criterion for non-inferiority was the lower limit of the CI (0.025, one-sided significance level) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than -125 mL. Secondary endpoints included serial FEV1 measurements, morning peak expiratory flow (PEF), rescue medication use, day- and night-time asthma symptoms, Asthma Control Test (ACT) scores, and serial cortisol measured over 12 h (area under the curve (AUC0-12)). RESULTS: Treatment with FSC 50/250 µg via Rotacaps/Rotahaler or Diskus resulted in a similar LS mean increase from baseline in trough FEV1 at Day 85 (231 mL and 203 mL respectively). The difference in the model-adjusted LS mean change was 28 mL (95% CI -24 mL, 80 mL), fulfilling the criterion for non-inferiority. Data for all secondary endpoints were similar for the two treatments, supporting the primary endpoint findings. Both treatments were well tolerated and demonstrated similar safety profiles. CONCLUSION: This study demonstrated the clinical non-inferiority of FSC 50/250 µg when administered using Rotacaps/Rotahaler compared with administration using Diskus in patients with asthma, and suggests there is no difference in the risk:benefit profile between the two FSC inhalers.

Pediatric asthma medication therapy management through community pharmacy and primary care collaboration.

OBJECTIVES: To design and implement a collaborative medication therapy management (MTM) program targeting pediatric patients with high-risk asthma in a community pharmacy. SETTING: Underserved inner city of Cincinnati, OH. PRACTICE DESCRIPTION: A large national grocery store chain pharmacy and an academic hospital developed a partnership aimed at improving asthma care for shared patients. An interdisciplinary project team was formed, including 2 clinical pharmacists, 1 pharmacy district clinical coordinator, 1 pharmacy division clinical coordinator, 1 associate professor at a college of pharmacy, 1 pharmacy resident, and 3 pediatric physicians. This pilot project involved 2 Kroger Pharmacy sites and Cincinnati Children's Hospital Medical Center's (CCHMC) 3 pediatric primary care centers. PRACTICE INNOVATION: Kroger and CCHMC staff identified shared high-risk asthma patients (those cared for at the included primary care centers who used Kroger for their medication fills) with the use of information from validated symptom assessments (Asthma Control Test), refill history, and recent health care utilization. Community pharmacists recruited jointly identified patients and provided a targeted MTM intervention. Education focused on asthma diagnosis, types of asthma medications, appropriate medication administration, and environmental triggers. Pharmacists suggested medication changes to prescribers via facsimile. Pharmacists followed up with patients in 30 days to assess asthma control, provide additional education, and propose further recommendations. EVALUATION: Outcomes evaluated included the average number of recommendations made to patients and prescribers and acceptance rates for each of those measures. RESULTS: Six patients completed the project. Pharmacists provided an average of 3.7 recommendations to each patient and 1.5 to prescribers for each patient; 77.3% and 100% recommendations were accepted, respectively. CONCLUSION: This pilot project describes the design and implementation of a pharmacist-physician collaborative program for high-risk pediatric asthma patients. The greatest outcome of this project was the formation of a collaborative team between pharmacists and physicians that continues to work together on additional family-centered initiatives.

Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial.

OBJECTIVES: Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations. Therefore, we aimed to compare the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combination in patients of AR. MATERIALS AND METHODS: Seventy patients with AR participated in a prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial. The patients between the age group of 18-65 years of either gender having moderate-severe intermittent or mild persistent AR were included in the study. The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher. The patients were randomly divided into two treatment groups with montelukast-levocetirizine (10 mg and 5 mg) in one group and montelukast-fexofenadine (10 mg and 120 mg) in another group. TNSS parameter was the main effectiveness parameter. RESULTS: Evaluation of TNSS revealed significant difference (P < 0.05) when compared from baseline to 4th week in both groups. The mean change of TNSS, i.e., 9.46 was significant (P < 0.05) in montelukast-fexofenadine group. The cost-effectiveness ratio was less in montelukast-levocetirizine group than in montelukast-fexofenadine group. CONCLUSION: The decrease in TNSS was more in montelukast-fexofenadine group, but the cost-effectiveness is more with montelukast-levocetirizine combination.

Asthma Controller Medication Adherence, Risk of Exacerbation, and Use of Rescue Agents Among Texas Medicaid Patients with Persistent Asthma.

BACKGROUND: Adherence to asthma long-term controller medications is one of the key drivers to improve asthma management among patients with persistent asthma. While suboptimal use of controller medications has been found to be associated with more frequent use of oral corticosteroids (OCS), few studies exist regarding the relationship between adherence to controller therapy and the use of short-acting beta2-agonists (SABAs). A better understanding of the association between adherence to asthma controller agents and use of reliever medications will help health care providers and decision makers enhance asthma management. OBJECTIVE: To determine if there is a relationship between asthma controller adherence, risk of exacerbation requiring OCS, and use of asthma rescue agents. METHODS: Texas Medicaid claims data from January 1, 2008, to August 31, 2011, were retrospectively analyzed. Continuously enrolled patients aged 5-63 years with a primary diagnosis of asthma (ICD-9-CM code 493) and with 4 or more prescription claims for any asthma medication in 1 year (persistent asthma) were included. The index date was the date of the first asthma controller prescription, and patients were followed for 1 year. The primary outcome variables were SABA (dichotomous: less than 6 vs. ≥ 6) and OCS (continuous) use. The primary independent variable was adherence (proportion of days covered [PDC]) to asthma long-term controller medications. Covariates included demographics and nonstudy medication utilization. Multivariate logistic and linear regression analyses were employed to address the study objective. RESULTS: The study sample (n = 32,172) was aged 15.0 ± 14.5 years, and adherence to controller therapy was 32.2% ± 19.7%. The mean number of SABA claims was 3.7 ± 3.1, with most patients having 1-5 claims (73.2%), whereas 19.4% had ≥ 6 SABA claims. The mean number of OCS claims was 1.0 ± 1.4. Adherent (PDC ≥ 50%) patients were 96.7% (OR = 1.967; 95% CI = 1.826-2.120) more likely to have ≥ 6 SABA claims when compared with nonadherent (PDC less than 50%) patients (P less than 0.001). As for OCS use, adherent patients had 0.11 fewer claims compared with nonadherent patients (P less than 0.001). Importantly, patients with ≥ 6 SABA claims had 0.7 more OCS claims compared with patients with less than 6 claims for SABA (P less than 0.001). The odds of having ≥ 6 SABA claims were higher for concurrent dual therapy users, older age, males, African Americans and higher number of nonstudy medications (P less than 0.001). Dual therapy users, younger age, Hispanic ethnicity, and higher number of nonstudy medications were associated with an increase in OCS use (P less than 0.005). CONCLUSIONS: Adherence to long-term controller medications was suboptimal among patients with asthma. Adherent patients had fewer OCS claims, indicating that adherence to controller therapy is critical in preventing asthma exacerbations requiring OCS use. Although there was a positive relationship between adherence to long-term controller medication and SABA use, increased SABA use served as a predictor of increased OCS use, which indicates poor asthma control. Health care providers should be aware of OCS and SABA use among patients who are both adherent and nonadherent to asthma controller medications.