David A. Stempel

Comparative effect of body mass index on response to asthma controller therapy.

Increases in body mass index (BMI) are reported to influence asthma severity and response to treatment. This analysis was designed to explore whether increasing BMI altered the comparative response to treatment with either fluticasone propionate (FP) or montelukast. Two double-blind, randomized, parallel-group trials of 12-weeks duration comparing FP, 88 micrograms, twice daily or montelukast, 10 mg, daily were evaluated. Subjects with mild-moderate persistent asthma were retrospectively stratified by BMI of <20 kg/m(2) (underweight), 20-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight), and > or =30 kg/m(2) (obese). Outcomes included mean changes in forced expiratory volume in 1 second (FEV(1)) and morning peak flow, daily albuterol use, and daily symptom scores. There were 1052 subjects evenly distributed between FP and montelukast by baseline parameters, including BMI. FP was statistically superior to montelukast for all BMI categories of normal, overweight, and obese subjects for FEV(1) (p < 0.008), morning peak flow (p < 0.002), albuterol use (p < 0.02), and symptom scores (p < 0.05). FP produced a significantly greater clinical response for normal, overweight, and obese subjects compared with montelukast. Irrespective of BMI, FP appears to be the more effective asthma controller therapy.

Effects of fluticasone propionate/salmeterol combination on asthma-related health care resource utilization and costs and adherence in children and adults with asthma

BACKGROUNDnClinical trials suggest that in patients with asthma inadequately controlled on low- to medium- dose inhaled corticosteroids (ICSs), the addition of a long-acting beta-agonist such as salmeterol (SAL is more effective than the addition of montelukast (MON) or a higher-dose ICS.nnnOBJECTIVEnThis study was designed to expand on these earlier findings by comparing asthma-related health care resource utilization and costs, as well as adherence to ICSs, in children and adults with asthma receiving ICS monotherapy who either were switched to fluticasone propionate plus SAL from a single inhaler (FSC) or initiated add-on therapy with SAL from a separate inhaler or MON.nnnMETHODSnThis retrospective study used an integrated managed-care database from >30 health plans. Patients were >or=5 years of age with a diagnosis of asthma (International Classification of Diseases, Ninth Revision, Clinical Modification 493.xx) and >or=2 claims for FSC, SAL, or MON. The date of first claim for the medication of interest was the index date. Patients were also required to have >or=1 claim for an ICS during the 12 months preindex and 12 months postindex. Utilization and costs of asthma-related care and adherence to ICS treatment postindex were compared using multivariate methods.nnnRESULTSnAfter adjusting for preindex characteristics, patients receiving FSC (n=1287) had fewer claims for short-acting beta-agonists, oral corticosteroids, and lower adjusted asthma-related costs postindex compared with ICS + SAL (n=562) and ICS + MON (n=420). FSC patients also had greater adherence to ICS therapy. Those who received FSC had lower risks for treatment failure (defined as asthma-related emergency department visits or hospitalization or receipt of alternative study medication or oral corticosteroids during the postindex period).nnnCONCLUSIONnIn this health insurance claims-based study of patients with asthma inadequately controlled with an ICS alone, those who received stepped-up therapy with FSC used fewer rescue medications and had greater persistence with ICSs compared with those in whom SAL or MON was added to ICS monotherapy.

Effect of increased body mass index on asthma risk, impairment and response to asthma controller therapy in African Americans

Abstract Objective: To explore whether obesity alters the risk, impairment and response to treatment in African Americans with asthma. Methods: The data used for this secondary analysis are from a 1-year study in African American subjects comparing fluticasone propionate/salmeterol 100/50u2009µg combination (FSC) and fluticasone propionate 100u2009µg (FP). Subjects were retrospectively stratified by body mass index (BMI) <20 [underweight], 20–24.9 [normal weight], 25–29.9 [overweight], 30–34.9 [obese I], 35–39.9 [obese II], and ≥40 [obese III] kg/m2. Outcomes studied included impairment domains: FEV1, morning and evening peak expiratory flow (AM and PM PEF), daily albuterol use, daily symptom scores and future risk domain: exacerbations. Clinical trial registration: www.clinicaltrials.gov; NCT00102765 Results: There were 475 subjects evenly distributed between FSC and FP by baseline parameters. There were 207 subjects with a BMI ≥30, including 70 subjects with a BMI ≥40. Baseline BMI ≥40 was associated with numerically lower baseline AM and PM PEF. There was an attenuation of response to both treatments for only PM PEF (pu2009<u20090.05). By contrast, subjects with lower degrees of obesity or overweight did not differ from those with normal weight. The total population exacerbation rate was 2-fold greater in obese III subjects (39%) compared with subjects in other BMI categories (16–21%) (pu2009<u20090.05). A potential study limitation is the retrospective analysis of existing data. Discussion: Response to treatment was attenuated for PM PEF for subjects with BMI ≥40 and was also associated with an increased rate of asthma exacerbations.

Association between adherence with fixed dose combination fluticasone propionate/salmeterol on asthma outcomes and costs

ABSTRACT Objective: To assess the association between adherence with fluticasone propionate/salmeterol combination (FSC) product in a single inhaler and asthma care utilization and costs in asthma patients in typical US clinical practice. Methods: Retrospective longitudinal analysis using linked medical and pharmacy claims from a managed care database representing >70 US health plans. Subjects included those with two prescriptions for FSC after January 1, 2000 (first prescription = ‘index date’) and diagnosis of asthma. Follow-up was defined as time from index date to disenrollment or discontinuation of FSC (180 days without supply), receipt of different controller, or 24 months post-index. Patients were excluded if: <12 months continuous enrollment pre-index, <12 months of follow-up, diagnoses of COPD or respiratory cancer, use of ipratropium, or age <12 years. Effect of FSC adherence on asthma-related outcomes (short-acting beta-agonist use (SABA), corticosteroid use (CS), emergency department (ED) visit/hospitalizations) and asthma-related health plan costs during each quarter post-index and FSC adherence in prior quarter controlling for demographics, time since index, season, comorbidities, pre-index medications, utilization, and cost. Results: 12 907 patients were identified: mean age, 40 years; mean follow-up, 20 months; mean quarterly FSC adherence, 54%; mean quarterly incidence of asthma-related ED visit/hospitalization, 1.12%. After adjusting for baseline characteristics, each 25% improvement in adherence was associated with a 10% reduction in the odds of asthma-related ED visit or hospitalization (p < 0.001), a 10% reduction in the odds of receiving SABA (p < 0.001), a 3% reduction in the odds of receiving a CS (p = 0.027). However, total asthma-related costs also increased 23% for each 25% increase in the use of FSC. Conclusions: Despite the limitations of the study, this analysis shows that improving compliance with an asthma controller medication such as FSC may help reduce the burden of asthma.

Which patients with chronic obstructive pulmonary disease benefit from the addition of an inhaled corticosteroid to their bronchodilator? A cluster analysis

Objective To identify subsets of chronic obstructive pulmonary disease (COPD) patients who are more protected from exacerbations with the use of an inhaled corticosteroid/long-acting β2 agonist (ICS/LABA) combination, compared with the use of LABA monotherapy. Design Post hoc cluster analysis of patients from two randomised clinical trials of salmeterol/fluticasone propionate (SFC) and salmeterol (SAL) that had primary endpoints of moderate/severe exacerbation rates. Setting Centres in North America. Participants 1543 COPD patients were studied. Interventions SFC 50/250u2005µg or SAL 50u2005µg, twice daily. Primary and secondary outcome measures The analysis identified clusters of COPD patients more responsive to SFC versus SAL with respect to the annual rate of moderate/severe exacerbations and compared their baseline clinical characteristics. Results Overall, SFC significantly reduced the annual rate of moderate/severe exacerbations as compared with SAL alone (rate ratio (RR)=0.701, p<0.001). Three-patient clusters were identified: COPD patients receiving diuretics (RR=0.56, p<0.001); patients not receiving diuretics but with forced expiratory volume in 1 s (FEV1) reversibility ≥12% (RR=0.67, p<0.001) exhibited a substantial reduction in the annual rate of moderate/severe exacerbations relative to SAL. A third cluster, consisting of patients not receiving diuretics and without FEV1 reversibility, demonstrated no difference for SFC versus SAL. Patients receiving diuretics had a significantly higher prevalence of comorbid cardiovascular disease. Conclusions COPD patients receiving diuretics and those not receiving diuretics but with FEV1 reversibility >12% at baseline were significantly more likely to experience a reduction in COPD-associated exacerbations with SFC versus SAL alone. Trial registration NCT00115492, NCT00144911

Fluticasone propionate/salmeterol and exercise-induced asthma in children with persistent asthma.

Exercise is a common trigger in children with persistent asthma and inhaled corticosteroids have been shown to effectively treat clinical manifestations of persistent asthma, including protection from decrements in lung function caused by exercise. The goal of this study was to evaluate the effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with fluticasone propionate 100 mcg for the prevention of airflow limitation triggered by standardized exercise challenge in pediatric and adolescent patients with persistent asthma.

Controller medications and their effects on asthma exacerbations temporally associated with upper respiratory infections

BACKGROUNDnExacerbations are a major risk and a cause of asthma morbidity and healthcare utilization. Viral-induced upper respiratory tract infections are the most frequent trigger of asthma-related exacerbations. Studies have traditionally assessed exacerbations without documentation regarding exacerbation etiology. Therefore, it remains unknown whether asthma medications can alter exacerbation susceptibility based on a specific etiology.nnnOBJECTIVEnTo examine whether treatment with inhaled corticosteroids plus long-acting beta(2)-agonists reduced the number of exacerbations associated with upper respiratory tract infections versus inhaled corticosteroids alone.nnnMETHODSnTwo large datasets comparing treatment with fluticasone propionate and fluticasone propionate plus salmeterol were analyzed, including the number of clinically reported upper respiratory tract infections, asthma-related exacerbations, and the presence of an exacerbation and concurrent report of an upper respiratory tract infection.nnnRESULTSnBoth treatment groups had similar incidences of upper respiratory tract infections. Of those reporting an upper respiratory tract infection, statistically significantly fewer reported an asthma-related exacerbation comparing fluticasone propionate plus salmeterol with fluticasone propionate (p=0.0057).nnnDISCUSSIONnThis retrospective analysis suggests that therapy with fluticasone propionate plus salmeterol provides protection against asthma exacerbations temporally associated with upper respiratory tract infections. This retrospective analysis supports the hypothesis that specific therapeutic approaches to mitigate virus-associated exacerbations may benefit asthma care. Well-controlled prospective studies are warranted.

Dispensing of fluticasone propionate/salmeterol combination in the summer and asthma-related outcomes in the fall.

BACKGROUNDnAsthma exacerbations occur year-round; however, peak asthma-related events occur in the fall and are frequently associated with viral respiratory infections.nnnOBJECTIVEnTo compare the rates of asthma-related emergency department (ED) visits and hospitalizations in the fall (September, October, November) between users and nonusers of fluticasone propionate plus salmeterol in a single inhaler (FSC) in the preceding summer.nnnMETHODSnThis was a retrospective, observational study using health care claims from a large managed care database. Patients age 4 to 55 years with both a medical claim for asthma and a pharmacy claim for FSC were categorized into 3 age groups: children (4-11 years), adolescents (12-18 years), and adults (19-55 years).nnnRESULTSnThere were 201,973 observations of FSC dispensings and 184,143 observations without FSC. Across all age groups, summertime dispensings of FSC were associated with a significantly lower (P < .001) risk of an asthma-related ED visit (4-11 years: adjusted odds ratio [OR], 0.54, 95% CI, 0.49-0.60; 12-18 years: OR, 0.59, 95% CI, 0.54-0.64; 19-55 years: OR, 0.53, 95% CI, 0.51-0.55) or hospitalization (4-11 years: OR, 0.43, 95% CI, 0.35-0.54; 12-18 years: OR, 0.49, 95% CI, 0.40-0.60; 19-55 years: OR, 0.61, 95% CI, 0.57-0.65) in the subsequent fall. This protective effect persisted even for patients with fall dispensings of FSC. The risk of oral corticosteroid dispensing in the fall was also significantly reduced in all age groups.nnnCONCLUSIONnSummertime dispensings of FSC were associated with a decreased risk of serious asthma-related outcomes in the subsequent fall. Continuous use of FSC before seasonal viral exposure may decrease seasonally related exacerbations.

An evaluation of asthma medication utilization for risk evaluation and mitigation strategies (REMS) in the United States: 2005–2011

Abstract Purpose: The purpose of this study was to assess drug utilization patterns of fluticasone propionate (FP)/salmeterol (SAL) combination (FSC) and SAL over the 7-year period of 2005–2011 in patients with asthma as part of the Risk Evaluation and Mitigation Strategies (REMS). Methods: A descriptive, retrospective observational study utilizing national pharmacy data and employer-based claims data to characterize drug utilization patterns. Results: For patients with asthma, the total number of FSC and SAL dispensings and users of FSC and SAL has declined between 2005 and 2011. During this period, FSC and SAL dispensing for asthma decreased 24% and 76%, respectively, with a more pronounced decline between 2010 and 2011 relative to other years. The total number of patients with asthma who were dispensed FSC has decreased by 10% among adults and by 40% in children and adolescents. While SAL-containing medications decreased, dispensing of FP monotherapy increased 39% during the same 7-year period. The number of patients dispensed FP for asthma has increased 47% in children 4–11 years of age, 72% in adolescents 12–17 years of age, and 6% in adults. SAL use without a controller was infrequent and decreasing, reported by 1.7% and 0.5% of patients with asthma in 2005 and 2011, respectively. Conclusions: In patients with asthma, use of FSC and SAL decreased between 2005 and 2011, while the use of FP increased. Use of SAL monotherapy was infrequent and declined during the study period. The data suggest that the substantial communication activities have encouraged appropriate prescribing of long-acting β2-adrenergic agonist (LABA).

A new focus on assessing and treating asthma control in the African-American community: a call to action.

Asthma continues to be a highly prevalent disease characterized by significant morbidity, unnecessary mortality, and substantial cost to the health care system. After decades of increasing prevalence, the number of current asthmatics in recent years has plateaued at approximately 22 million people in the United States. An additional 10 million Americans have a past history of asthma that is not active. The burden of asthma is higher among African Americans than in any other racial or ethnic group in America. The African-American community continues to experience a disproportional increase in asthma prevalence, morbidity, and mortality. The educational initiatives stemming from the newly revised National Heart Lung and Blood Institute (NHLBI) guidelines provide the opportunity to address the increased burden of asthma in the African American community. These new guidelines, released in August 2007, focus on asthma control as the primary goal of therapy, routine monitoring of asthma control, and use of asthma control assessments to direct treatment. The present review discusses the following: I. The impact of health disparities on outcomes of African Americans with asthma, II. The barriers that prevent asthmatic patients from achieving optimal control, III. The unique factors that challenge practitioners and patients in achieving optimal asthma control in the African American Community, IV. The impact of good asthma control and the need for patients and clinicians to assess asthma control in with a standardized assessment tool, and V. Strategic initiatives and the role of the End The Attacks NOW program in improving outcomes for African American patients with asthma.