Asthma control in the United States: relationships between short-acting ß2-agonist and systemic corticosteroid use.

BACKGROUND: Asthma control assessment is based on impairment (current symptoms) and risk (exacerbation history). OBJECTIVE: To understand the extent of uncontrolled asthma, we assessed relationships between prescription fills for systemic corticosteroids (SCS) and short-acting ß2-agonists (SABA) as risk and impairment markers, respectively. METHODS: Annual SCS and SABA fills among US patients with asthma were evaluated by a retrospective analysis of IQVIA Longitudinal Access and Adjudication Data. Patient severity was assigned based on GINA step-therapy level. Exacerbations were evaluated by SCS fills within 12 months of a first asthma prescription fill. Uncontrolled asthma was defined as ≥2 SCS and/or ≥3 SABA fills annually. Individual patient relationships between SCS and SABA fills were assessed by Pearson's correlation coefficient. RESULTS: 4,506,527 patients were included: 15% had ≥2 SCS fills, 29% had ≥3 SABA fills, 37% fulfilled either or both criteria. If only SCS were assessed, 22% treated as mild-to-moderate and 27% as severe asthma would have been misclassified as controlled. If only SABA use was evaluated, 8% treated as mild-to-moderate and 11% as severe asthma would have been misclassified. Overall, 81% of uncontrolled asthma occurred in patients treated for mild-to-moderate disease. Among patients with ≥2 SCS fills, mean SABA fills were 2.9; the correlation between SCS and SABA fills per patient was significant but weak (r=0.18; p<0.001). CONCLUSION: High symptom burden and SCS exposures are not limited to severe asthma but are also characteristic in patients treated for mild-to-moderate disease. Both impairment and risk assessments are required to understand the full extent of uncontrolled asthma across disease severities.

Assessing meaningful change in the Asthma Impairment and Risk Questionnaire.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, yes/no, equally weighted control tool. Lower scores indicate better control. Moreover, 7 impairment items reflect previous 2-week symptoms, and 3 risk items assess previous 12-month exacerbations. The Follow-up AIRQ for use between annual assessments has a 3-month recall period for exacerbation items. OBJECTIVE: To evaluate the responsiveness of the AIRQ over time and identify a minimal important difference (MID). METHODS: The AIRQ longitudinal study data were analyzed from patients with asthma aged 12 years and older. Anchor-based methods assessed differences in AIRQ scores relative to Patient Global Impression of Change, the accepted MIDs for St. George's Respiratory Questionnaire and Asthma Control Test, and exacerbation occurrence over 12 months. Baseline and 12-month data reflected 12-month recall AIRQ scores; Follow-up AIRQ scores were used for 3-, 6-, and 9-month analyses. RESULTS: A total of 1070 patients were included. The Patient Global Impression of Change rating of "much improved" was associated with AIRQ mean score changes from baseline to months 3, 6, 9, and 12 of -2.0, -1.9, -1.9, and -1.8, respectively. The mean AIRQ score change among patients who met the St. George's Respiratory Questionnaire MID (≥4-point decrease) was -1.8 at 6 and 12 months. The AIRQ mean scores decreased from baseline by -2.2 to -2.5 points at months 3, 6, 9, and 12 for patients who met the Asthma Control Test MID (≥ 3-point increase). A 2-point higher baseline AIRQ score was associated with a 1.7 odds ratio of 12-month exacerbation occurrence (95% CI, 1.53-1.89). CONCLUSION: A change score of 2 is recommended as the AIRQ MID.

Advancing assessment of asthma control with a composite tool: The Asthma Impairment and Risk Questionnaire.

BACKGROUND: National and international asthma guidelines and reports do not include control tools that combine impairment assessment with exacerbation history in one instrument. OBJECTIVE: To analyze the performance of the composite Asthma Impairment and Risk Questionnaire (AIRQ) in assessing both domains of control and predicting exacerbation risk compared with the Global Initiative for Asthma (GINA) 4-question symptom control tool (GINA SCT), Asthma Control Test (ACT), and physician expert opinion (EO) informed by GINA SCT responses and appraisal of GINA-identified risk factors for poor asthma outcomes. METHODS: Multivariable logistic regressions evaluated AIRQ and GINA SCT as predictors of ACT. McNemar's test compared the proportion of patients categorized at baseline as completely or well-controlled by each assessment but with current impairment or previous-year and subsequent-year exacerbations. RESULTS: The analysis included 1064 patients aged 12 years or older; mean (SD) age 43.8 years (19.3); 70% female; 79% White; and 6% Hispanic or Latino. AIRQ and GINA SCT were highly predictive of ACT well-controlled vs not well-controlled and very poorly controlled (receiver operator characteristic area under curve AIRQ = 0.90, GINA SCT = 0.86, P = .03 AIRQ vs GINA SCT) and ACT very poorly controlled vs well-controlled and not well-controlled asthma (receiver operator characteristic area under curve AIRQ = 0.91, GINA SCT = 0.87, P = .01 AIRQ vs GINA SCT). AIRQ rated fewer patients as having completely or well-controlled asthma who had current impairment (P < .01) or with previous-year and subsequent-year exacerbations (P < .001) than did GINA SCT, ACT, and EO. CONCLUSION: AIRQ performs better in assessing both domains of current control and predicting exacerbation risk than do control tools and EO informed by GINA SCT and risk factors for poor asthma outcomes.

Patterns of rescue and maintenance therapy claims surrounding a clinical encounter for an asthma exacerbation.

BACKGROUND: A "window of opportunity" has been proposed where anti-inflammatory therapy administration in response to symptoms could prevent exacerbation. OBJECTIVE: To evaluate rescue and maintenance therapy claims surrounding a severe asthma exacerbation serious enough to require a face-to-face clinical encounter. METHODS: Merative MarketScan research databases (US administrative claims 2011 to 2017) were analyzed for patients aged ≥4 years, with an asthma diagnosis code, who filled short-acting ß2-agonist (SABA) and Global Initiative for Asthma Steps 3 to 5 maintenance therapies. Patients were indexed on a random SABA claim and had 12 months' continuous health plan eligibility pre- and post-index. Serious exacerbations were severe exacerbations requiring systemic corticosteroids prescribed from an outpatient clinic, urgent care or emergency department, or hospitalization for asthma. SABA and maintenance claims 30 days pre- and post-event were analyzed. RESULTS: Of 319,342 patients (30% children 4 to 11 years; 70% adults or adolescents ≥12 years), 27.2% of children and 16.8% of adolescents or adults experienced ≥ 1 serious exacerbation (unadjusted odds ratio [OR], 1.85 [95% confidence interval, 1.81-1.88]). In the 30 days pre-event, 42.6% filled ≥1 SABA (children: 44.3%; adolescents or adults: 41.5%; OR, 1.12 [1.09-1.16]) and 57.4% filled maintenance (children: 59.0%; adolescents or adults: 56.3%; OR, 1.12 [1.08-1.15]). In the 30 days post-event, 61.4% filled SABA (children: 69.7%; adolescents or adults: 55.6%; OR, 1.84 [1.78-1.90]) and 94.8% filled maintenance (children: 98.6%; adolescents or adults: 92.2%; OR, 6.09 [5.45-6.81]). CONCLUSION: Many patients treated as having moderate-to-severe asthma escalate SABA claims before a serious exacerbation, but approximately 40% have no anti-inflammatory maintenance fill, highlighting a "window of opportunity" to prevent exacerbations using inhaled corticosteroids concomitantly with SABA as rescue.

The Asthma Impairment and Risk Questionnaire enhances the assessment of asthma control.

BACKGROUND: Asthma control is often overestimated in routine practice, and despite advances in the understanding of immunopathology and the availability of new precision therapies, the burden of disease remains unacceptably high. OBJECTIVE: To compare the performance of the Asthma Impairment and Risk Questionnaire (AIRQ) with patient and physician assessments and the Asthma Control Test (ACT) in identifying asthma control. METHODS: Baseline data from a longitudinal study of the AIRQ were analyzed. Patients with asthma in the United States aged 12 years and older followed in 24 specialty practices and 1 specialty-affiliated primary care clinic were enrolled between May and November 2019. At entry, participants completed AIRQ and ACT, and participants and physicians completed 5-point Likert scale assessments of control. RESULTS: A total of 1112 participants were enrolled (mean [SD] age = 43.9 [19.3] years, 70% of the female sex, 78% White). Overall, 62% of participants rated themselves as well- or completely controlled, and 54% were rated comparably by physicians. The ACT classified 49% of participants as well-controlled, with 35% similarly categorized by AIRQ. Previous-year exacerbations were experienced by 32% of participants who self-rated as well- or completely controlled, 30% who were rated as well- or completely controlled by physicians, and 29% assessed as well-controlled by ACT, but only 15% of those classified as well-controlled by AIRQ. CONCLUSION: The burden of asthma is substantial in patients cared for by asthma specialists, and asthma control is overestimated by patients, physicians, and the symptom-based ACT. The AIRQ assesses risk in addition to symptom control and may serve to improve asthma control determination by assessing previous exacerbations.

Mapping geographic variability of severe uncontrolled asthma in the United States: Management implications.

BACKGROUND: The US population-level data on asthma morbidity and mortality are available primarily through state-level surveys. We hypothesize that considerable county-level heterogeneity may be obscured by state-level data, thus impeding focused initiatives to improve asthma outcomes. OBJECTIVE: To assess heterogeneity in the prevalence of uncontrolled, severe, and severe uncontrolled asthma by evaluating state- and county-level morbidity reflected in large administrative claims data sets and identify relationships between pharmacotherapy-based morbidity and the Centers for Disease Control and Prevention's asthma mortality data. METHODS: Asthma prevalence and morbidity were identified using medical and pharmacy claims from the IQVIA Longitudinal Access and Adjudication Data database (July 2015-June 2018). Heat maps ranked the prevalence of severe uncontrolled asthma by deciles in all 50 states and the District of Columbia, plus 2935 counties. Mortality in states (2016) and 3147 counties (1999-2018) was similarly mapped and ranked and contrasted with claims-based morbidity. RESULTS: Among 4,506,527 individuals with asthma, 640,936 (14.2%) received age-specific therapy for severe asthma. Of those with severe asthma, 144,232 (22.5%) filled 2 or more annual courses of systemic steroids and were designated as having severe uncontrolled asthma. Most states with high mortality had relatively few patients with severe uncontrolled asthma. A marked correlation between mortality and morbidity and trends by urban vs rural and metropolitan status were found at the county level. CONCLUSION: Intrastate heterogeneity in the morbidity and mortality of severe uncontrolled asthma at the county level is not evident in state-level analyses. Increased local awareness of systemic corticosteroid use as an indicator of uncontrolled asthma should prompt regional educational and public health efforts to improve outcomes.

Evaluating construct validity of the Asthma Impairment and Risk Questionnaire using a 3-month exacerbation recall.

BACKGROUND: Recurrent assessment of asthma control is essential to evaluating disease stability and intervention impacts. An assessment that can be administered between annual clinic visits is needed. The Asthma Impairment and Risk Questionnaire (AIRQ) is a cross-sectionally validated, 10-item, yes or no, composite control tool evaluating previous 2-week symptoms and previous 12-month exacerbations. OBJECTIVE: To evaluate the construct validity of the AIRQ using a 3-month recall period for exacerbation-based risk questions and retaining the 2-week recall for symptom-based impairment items. METHODS: At baseline, patients completed the AIRQ with 12-month recall exacerbation items, Asthma Control Test (ACT), St. George's Respiratory Questionnaire (SGRQ), and global self-assessments of asthma risk, control, and symptom severity. Patient-reported exacerbations were captured monthly. The AIRQ with 3-month recall exacerbation items, ACT, and global self-assessments was administered at months 3, 6, and 9, and SGRQ at month 6. RESULTS: A total of 1112 patients aged 12 years or older were enrolled (mean [SD] age, 43.9 [19.5] years). The AIRQ and each administration of the AIRQ with 3-month recall exacerbation items classified asthma control similarly to an ACT plus exacerbation validation standard. For both AIRQ versions, SGRQ scores were higher with worsening asthma control (P < .001). At months 3, 6, and 9, worse AIRQ control levels were associated with higher proportions of patients with 1 or more and 2 or more exacerbations in the previous 3 months and patient global self-assessments indicating greater asthma morbidity (all P < .001). CONCLUSION: The AIRQ using exacerbation risk items with a 3-month recall period exhibits construct validity for classifying current asthma control and can be administered between annual AIRQ assessments.

Real-world patterns and implications of short-acting ß2-agonist use in patients with asthma in the United States.

BACKGROUND: Short-acting ß2-agonist (SABA) use is one measure reflecting asthma control. OBJECTIVE: To evaluate the associations between real-world SABA use and severe asthma exacerbations in the United States. METHODS: Patients with asthma 12 years of age or older receiving SABA in the IBM MarketScan research databases of US administrative claims from September 30, 2014, to September 30, 2016, were evaluated. Patients with 12 months' continuous eligibility before and after their first SABA claim (index SABA), an asthma diagnosis before through 60 days postindex, and either one additional SABA or at least 1 maintenance fill(s) were included. SABA claims postindex (including index fill) were grouped as follows: low: index only; medium: 2 to 3 canisters per year; and high: 4 or more canisters per year. Differences in SABA exposure with respect to disease severity groups and severe asthma exacerbations (hospitalizations, emergency visits, or outpatient systemic corticosteroids) were analyzed by analysis of variance and χ2 (significance, P ≤ .05). RESULTS: A total of 135,540 patients were included: 62.8% women; mean (SD) age, 40.9 (18.3) years; SABA fills per 12-months postindex: 3.0(2.7). Furthermore, 28% of patients filled 1 SABA, 47% 2 to 3, and 25% 4 or more canisters per year. Despite higher maintenance medication possession ratio with increasing SABA (low, 0.53 (0.37); medium, 0.59 (0.35); high, 0.66 (0.32)), annual exacerbation rate per person per year and percent of patients within each SABA group having at least 1 exacerbation rose as SABA fills increased (low, 1.00 (1.45), 45.8%; medium, 1.20 (1.62), 54.3%; high, 1.50 (1.94), 58.7%). Mean SABA fills differed between patients with 0 exacerbation, 2.8 (2.6); 1 exacerbation, 2.9 (2.5); and 2 or more exacerbations, 3.3 (2.9). CONCLUSION: Exacerbation risk increased with increasing SABA fills. Management strategies ensuring adequate anti-inflammatory therapy delivered to the airways when symptoms occur may be needed to mitigate asthma morbidity.

Current practice patterns, challenges, and educational needs of asthma care providers in the United States.

OBJECTIVE: For severe, uncontrolled asthma (SUA), a gap exists between recent scientific advances and their incorporation into clinical practice. Using a Knowledge-to-Action Framework, new knowledge can be translated into evidence-based interventions to improve outcomes. The AstraZeneca U.S. PRECISION initiative aims to apply this Framework to improve recognition and management of SUA. The study objective was to identify factors contributing to gaps in care for patients with SUA. Results from a needs assessment survey of U.S. pulmonologists and allergists/immunologists were assessed within the Knowledge-to-Action Framework to advance bench-to-bedside care. METHODS: Pulmonologists and allergists/immunologists from across the United States were invited to complete a customized, quantitative severe asthma survey in person at the 2017 American Thoracic Society annual meeting or via the Internet. Responses were summarized descriptively, and chi-squared tests evaluated associations between variables of interest. RESULTS: Overall, 140 U.S. providers responded, most of whom were pulmonologists (84%). Most (60%) practiced in a community-based setting; 40% practiced at an academic medical center. Key challenges to providing care for patients with severe asthma included insurance company requirements and identification of the pathophysiology of an individual patient's severe asthma. Traditional measures of asthma-related morbidity were ranked as highly important by significantly more respondents compared with assessment of biomarkers (p < 0.0001). Respondents generally valued online virtual self-education. CONCLUSIONS: Survey results identified unmet needs for the identification and management of patients with SUA and opportunities to improve patient outcomes through evidence-based management of SUA, including testing for biologic eligibility and subsequent use of biologic therapies.

Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease: a discrete choice experiment.

BACKGROUND: A variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies. METHODS: A self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes. Selection of attributes was informed by patient focus groups and literature review. RESULTS: The discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD. Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1. Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1. Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids. Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations. CONCLUSIONS: The most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations. Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important.

Efficacy and safety of budesonide/formoterol pMDI vs budesonide pMDI in asthmatic children (6-<12 years).

BACKGROUND: The efficacy and safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI) have been demonstrated in patients with asthma at least 12 years old. OBJECTIVE: To evaluate the efficacy of 2 formoterol doses added to budesonide as fixed combinations vs budesonide alone in children 6 to younger than 12 years with asthma. METHODS: This randomized, double-blinded, parallel-group, multicenter study (NCT02091986; CHASE 3) included children 6 to younger than 12 years with asthma previously receiving a medium-dose inhaled corticosteroid (ICS) or an ICS plus a long-acting ß2-agonist. Children symptomatic during a 7-28-day run-in on low-dose ICS, 1 inhalation of budesonide dry powder inhaler 90 µg twice daily (BID), were randomized to receive 2 inhalations of budesonide/formoterol pMDI 80/4.5 µg (160/9 µg) BID (n = 92), budesonide/formoterol pMDI 80/2.25 µg (160/4.5 µg) BID (n = 95), or budesonide pMDI 80 µg (160 µg) BID (n = 92) for 12 weeks. RESULTS: Change in forced expiratory volume in 1 second from baseline to 1 hour after dosing (primary end point), change in forced expiratory volume in 1 second 15 minutes after dosing, and peak expiratory flow 1 hour after dosing at week 12 were statistically significantly greater for budesonide/formoterol 160/9 µg vs budesonide (P ≤ .015 for all comparisons), but not for budesonide/formoterol 160/4.5 µg vs budesonide. Bronchodilator effects, evident 15 minutes after the dose on day 1, were maintained at week 12. Incidence of protocol-defined asthma exacerbations and improvements in asthma symptom-related and quality-of-life outcomes were similar across treatments. There were no notable safety differences among treatments. CONCLUSION: Budesonide/formoterol pMDI 160/9 µg showed statistically significant and clinically meaningful lung function improvements vs budesonide pMDI 160 µg, demonstrating appropriateness as a therapeutic option for children 6 to younger than 12 years with asthma symptomatic on ICS alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02091986.

Impact of Clinical Characteristics and Biomarkers on Asthma Impairment and Risk Questionnaire Exacerbation Prediction Ability.

BACKGROUND: Complex models combining impairment-based control assessments with clinical characteristics and biomarkers have been developed to predict asthma exacerbations. The composite Asthma Impairment and Risk Questionnaire (AIRQ) with adjustments for demographics (age, sex, race, and body mass index) predicts 12-month exacerbation occurrence similarly to these more complex models. OBJECTIVE: To examine whether AIRQ exacerbation prediction is enhanced when models are adjusted for a wider range of clinical characteristics and biomarkers. METHODS: Patients aged 12 years and older completed monthly online surveys regarding exacerbation-related oral corticosteroid use, emergency department or urgent care visits, and hospitalizations. Univariate logistic regressions to predict exacerbations were performed with sociodemographics, comorbidities, exacerbation history, lung function, blood eosinophils, IgE, and FeNO. Significant (P ≤ .05) variables were included in multivariable logistic regressions with and without AIRQ control categories to predict 12-month exacerbations (log odds ratio [95% Wald confidence interval]). Model performances were compared. RESULTS: Over 12 months, 1,070 patients (70% female; mean [SD] age, 43.9 [19.4] years; 22% non-White; body mass index [SD], 30.6 [8.7]) completed one or more survey (mean [SD], 10.5 [2.8] surveys). In the multivariable analysis, AIRQ control category adjusted for significant clinical characteristics and biomarkers was predictive of one or more exacerbations: odds ratio (95% CI) not well-controlled versus well-controlled: 1.93 (1.41-2.62), very poorly controlled versus well-controlled: 3.81 (2.65-5.47). Receiver operating characteristic area under the curve (AUC) for this more complex model of exacerbation prediction (AUC = 0.72) did not differ from AIRQ (AUC = 0.70). Models with AIRQ performed better than those without AIRQ (AUC = 0.67; P < .05). CONCLUSION: Costly and time-consuming complex modeling with clinical characteristics and biomarkers does not enhance the strong exacerbation prediction ability of AIRQ.

A Discrete Choice Experiment to Assess Patient Preferences for Asthma Rescue Therapy and Disease Management.

BACKGROUND: With the expanding treatment landscape for asthma, the process of identifying best-fit, individualized management options is becoming increasingly complicated. Understanding patients' preferences can inform shared decision-making between clinicians and patients. OBJECTIVES: To examine preferences of adults with asthma for therapeutic and management attributes and determine how these preferences vary among patients. METHODS: We conducted an online discrete choice experiment survey in US adults with asthma. Patient preferences were analyzed using logit models. Factors affecting patients' preferences were identified by least absolute shrinkage and selection operator analysis. RESULTS: A total of 1,184 patients completed the survey (60% female; mean [SD] age, 49.2 [15.0] years). Patients most valued fewer asthma attacks requiring urgent health care professional visits, fewer exacerbations requiring oral corticosteroids, and a reduced risk for oral thrush. Higher value was placed on reducing the risk of short-term (oral thrush) versus long-term side effects (diabetes). Patients were willing to increase rescue medication use in exchange for decreasing exacerbations requiring oral corticosteroids and attacks requiring urgent health care professional visits. Patients preferred a single inhaler for rescue and maintenance and least valued asthma action plans. Demographic, socioeconomic, and clinical factors affected patient preferences. CONCLUSIONS: Patients sought convenient management options that focused mainly on decreasing the short-term morbidity associated with asthma exacerbations and therapies. Preferences varied by demographics, clinical factors, and socioeconomics. It is important for shared decision-making discussions to include conversations about morbidity and how available therapeutic options align with individual patient preferences.

Relationship Between Asthma Control as Measured by the Asthma Impairment and Risk Questionnaire (AIRQ) and Patient Perception of Disease Status, Health-Related Quality of Life, and Treatment Adherence.

Purpose: Critical asthma outcomes highlighted in clinical guidelines include asthma-related quality of life, asthma exacerbations, and asthma control. An easy-to-implement measure of asthma control that assesses both symptom impairment and exacerbation risk and reflects the impact of asthma on patients' lives is lacking. Hence, the objective of this study was to assess the Asthma Impairment and Risk Questionnaire (AIRQ®) construct validity relative to patient self-perception of asthma status and validated disease-specific patient-reported outcome (PRO) measures. Patients and methods: Baseline data were analyzed from patients (aged ≥ 12 years) with asthma participating in a 12-month observational study assessing the ability of AIRQ to predict exacerbations. At entry, patients completed a sociodemographic questionnaire, AIRQ, 3 questions addressing self-perceived asthma status, Saint George's Respiratory Questionnaire (SGRQ), mini-Asthma Quality of Life Questionnaire (AQLQ), and Adult Asthma Adherence Questionnaire (AAAQ). Descriptive statistics were calculated for demographic and clinical characteristics. AIRQ construct validity was evaluated by assessing correlations between total AIRQ score and patient self-assessments, SGRQ, mini-AQLQ, and AAAQ scores. Comparisons of SGRQ, mini-AQLQ, and AAAQ total and component/domain scores by AIRQ control category were performed using general linear models and Scheffe's post hoc adjustments for pairwise comparisons. Results: A total of 1112 patients were enrolled: 70% female, 78% White, mean (standard deviation) age 43.9 (19.5) years. There were highly significant correlations between AIRQ score and patient self-perception of overall control (r = 0.69; p < 0.001), total SGRQ (r = 0.74, p < 0.001), and mini-AQLQ (r = -0.78, p < 0.001) scores. As AIRQ control category worsened, so did total and domain SGRQ, mini-AQLQ, and AAAQ impediment-to-inhaled-corticosteroid-adherence scores (all pairwise comparisons p < 0.001). Conclusion: Findings demonstrate the construct validity of AIRQ relative to patient self-perception of asthma status, disease-specific PRO measures, and treatment adherence barriers. AIRQ can be a useful instrument to raise awareness of the unrecognized impacts of asthma on patients' lives.

The use of short-acting bronchodilators and cost burden of asthma across Global Initiative for Asthma-based severity levels: Insights from a large US commercial and managed Medicaid population.

BACKGROUND: Despite the availability of effective treatments, patients with asthma, regardless of severity, remain at risk of severe exacerbations resulting in significant burden to patients, the health care system, and insurance providers. OBJECTIVE: To examine severe exacerbations, treatment patterns, health care resource utilization (HCRU), and costs across all asthma severities. METHODS: In this retrospective study, patients aged 4 years and older filling 1 short-acting (ß2-agonist (SABA) and at least 1 maintenance fill or at least 2 SABAs with or without maintenance fills were identified from administrative claims data from the IBM MarketScan Commercial and IBM MarketScan Multistate Medicaid Research databases (January 2010 to December 2017). Patients were indexed on a random SABA fill (2011-2016) and had 12 months of continuous eligibility pre-index and post-index. Patients were classified into Global Initiative for Asthma (GINA) 2018 severity steps and by asthma control, as measured by SABA fill use in the 12 months pre-index: low (1 SABA fill per year), medium (2-3 SABA fills per year), and high (≥ 4 SABA fills per year); well controlled, not well controlled, and very poorly controlled, respectively. Severe asthma exacerbation events, health care costs, and asthma-related HCRU and costs were assessed relative to asthma severity and asthma control post-index. RESULTS: Of 1,005,522 patients, 50.3% filled GINA Step 1; 19.7% GINA Step 2; 10.9% GINA Step 3; and 19.1% GINA Steps 4-5 treatments. Overall, 953,337 severe exacerbation events occurred (approximately 0.95 events per patient), equating to 0.96, 0.67, 0.83, and 1.28 events per patient for patients filling GINA Step 1 through Steps 4-5, respectively. GINA Step 1 had the highest proportion of patients experiencing at least 1 event (57.0%), followed by GINA Steps 4-5 (55.2%), GINA Step 3 (45.0%), and GINA Step 2 (41.9%) treatments (P < 0.05). For GINA Step 1, 64.4% of well-controlled patients experienced at least 1 exacerbation event vs 50.4% of not well-controlled and 53.0% of very poorly controlled patients (P < 0.05). For patients filling GINA Step 2-5 treatments, a greater proportion of very poorly controlled patients experienced at least 1 exacerbation event vs well-controlled patients (P < 0.05). The average total annual health care cost per patient was $7,148 and total annual asthma-related costs were $1,741. Each additional SABA fill was associated with a 26.0%, 10.8%, and 34.6% increase in incidence of total exacerbations, all-cause costs, and asthma-related costs, respectively (P < 0.05). CONCLUSIONS: In this real-world database study, increased SABA fills and occurrence of exacerbations were correlated and associated with higher all-cause and asthma-related costs across all severities. New treatment paradigms, particularly for rescue therapies, are warranted to improve clinical and cost outcomes in these patients. DISCLOSURES: This analysis was funded by AstraZeneca. Michael Pollack, Hitesh Gandhi, and Ileen Gilbert are employees and stockholders of AstraZeneca and contributed to the design and conduct of the study. AstraZeneca was given an opportunity to review the final version of the manuscript. At the time of the study, Joseph Tkacz was an employee of IBM Watson Health, which received funding from AstraZeneca to conduct this study. Miguel Lanz has received research funding from AstraZeneca, Optinose, and Regeneron and consulting fees and honoraria from ALK, Amgen, AstraZeneca, Novartis, Sanofi, and Regeneron. Njira Lugogo received consulting fees for advisory board participation from Amgen, AstraZeneca, Genentech, GlaxoSmith-Kline, Novartis, Regeneron, Sanofi, and Teva; honoraria for nonspeaker's bureau presentations from GlaxoSmithKline and AstraZeneca; and travel support from AstraZeneca. Her institution received research support from Amgen, AstraZeneca, Avillion, Gossamer Bio, Genentech, GlaxoSmithKline, Regeneron, Sanofi, and Teva.

Suboptimal Control of Asthma Among Diverse Patients: A US Mixed Methods Focus Group Study.

Purpose: The US National Asthma Education and Prevention Program updates and Global Initiative for Asthma report encourage considering the patient perspective to improve asthma control. The objective of the present study was to collect data about the perceptions, experiences, and concerns of adult patients and caregivers of children with asthma regarding rescue, maintenance, and oral corticosteroid treatments. Patients and Methods: In-person focus groups were conducted in three cities across the US. Participants also completed patient-reported outcome measures assessing asthma control and experiences. Results: Focus groups were conducted in demographically and clinically diverse adults with asthma (five groups, n=34), caregivers of children with asthma (five groups, n=35), and adults with a dual diagnosis of asthma and chronic obstructive pulmonary disease (one group, n=5). Only 28% of patients were well-controlled by Asthma Control Test/Asthma Control Test-Caregiver Report and 18% by Asthma Impairment and Risk Questionnaire. Forty-four percent of participants reported not following their prescribed medical plan. Four key themes emerged from the focus groups: (1) asthma symptom control and monitoring are often inadequate; (2) treatments are often used incorrectly; (3) communication between health care professionals and patients or caregivers is often ineffective; and (4) concerns related to treatment and desires to improve treatment. Conclusion: Control of asthma symptoms is suboptimal in the vast majority of patients and both patients and caregivers do not feel sufficiently informed about asthma. Health care providers should be encouraged to engage patients and caregivers in shared decision making for managing asthma and selecting treatments that integrate patient values, preferences, and lifestyles.

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America.

BACKGROUND: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. OBJECTIVE: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. METHODS: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. RESULTS: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. CONCLUSIONS: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

The Asthma Impairment and Risk Questionnaire (AIRQ) Control Level Predicts Future Risk of Asthma Exacerbations.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, equally weighted, yes/no control tool validated in patients with asthma aged 12 years and older. OBJECTIVE: To evaluate AIRQ's ability to predict patient-reported exacerbations over 12 months. METHODS: Patients completed a baseline AIRQ during an in-person enrollment visit and reported exacerbations (ie, asthma-related courses of oral corticosteroids, emergency department/urgent care visits, and hospitalizations) via monthly online surveys. Logistic regressions were performed using AIRQ control level (well-controlled [WC], not well-controlled [NWC], very poorly controlled [VPC]), age, sex, race, and body mass index as covariates and 1 or more and 2 or more exacerbations as the dependent variables (adjusted odds ratios [OR] and 95% Wald CIs). Kaplan-Meier analyses of time to first exacerbation by AIRQ control level were performed. RESULTS: A total of 1,112 patients were enrolled; 1,070 completed 1 or more surveys over 12 months (mean ± SD 10.5 ± 2.8 months); 70.5% female; age 43.9 ± 19.3 years; 20.4% non-White; body mass index 30.6 ± 8.7 kg/m2; AIRQ: WC 35.2%, NWC 38.1%, VPC 26.6%. A total of 45.7% of patients reported 1 or more exacerbations and 26.7% 2 or more exacerbations (WC 28.4% ≥ 1, 11.1% ≥ 2; NWC 46.3% ≥ 1, 27.9% ≥ 2; VPC 67.7% ≥ 1, 45.6% ≥ 2). The ORs for 1 or more exacerbations NWC versus WC were 2.1 (CI 1.6-2.9), and VPC versus WC were 4.6 (CI 3.3-6.5). The ORs for 2 or more exacerbations NWC versus WC were 3.1 (CI 2.1-4.6), and VPC versus WC were 6.1 (CI 4.0-9.1). Kaplan-Meier curves demonstrated clear differentiation of time to first exacerbation by AIRQ control level (P < .001). CONCLUSIONS: The AIRQ control level predicts exacerbation risk over 12 months and probability of time to first exacerbation.

Association of Nonmedical Switches in Inhaled Respiratory Medications with Disruptions in Care: A Retrospective Prescription Claims Database Analysis.

INTRODUCTION: There are limited data on the effects of forced medication switching for a nonmedical reason in patients with obstructive airway conditions. This study evaluated disruption in care resulting from a nonmedical medication switch for patients with asthma and/or chronic obstructive pulmonary disease who previously received the inhaled corticosteroid/long-acting ß2-agonist budesonide/formoterol. METHODS: This retrospective pharmacy benefit prescription claims analysis evaluated Medicare Part D patients who filled a prescription for budesonide/formoterol as their last inhaled corticosteroid/long-acting ß2-agonist in 2016 and were affected by a formulary block of budesonide/formoterol in 2017. Changes to respiratory maintenance therapy, length of gaps in care during which a patient was not in possession of a respiratory controller medication, acute medication use indicative of disease exacerbations, and medication adherence were assessed. RESULTS: A total of 42,553 patients were included in the analysis. Following the formulary block, 30,016 patients (71%) switched to another controller; 20,628 of these patients (69%) switched to a new inhaled corticosteroid/long-acting ß2-agonist, 7081 (23%) stepped down to a monotherapy, and 2307 (8%) switched to a non-inhaled corticosteroid-containing controller. Despite the formulary block, 22,903 patients (54%) attempted to fill budesonide/formoterol as their first postblock controller, and 6624 patients (16%) attempted to return to budesonide/formoterol after switching to another controller. On average, patients experienced a gap in care of approximately 4 months without a controller medication. Also, 9674 (23%) did not fill any controller over the 1-year postblock period. Of those patients who experienced a gap in care, 14,926 (47%) filled a prescription indicative of a possible exacerbation during the gap period (i.e., oral corticosteroids for patients with asthma and oral corticosteroids and/or antibiotics for patients with chronic obstructive pulmonary disease). CONCLUSIONS: The Medicare Part D formulary block was associated with disruption in the management of patients' respiratory conditions and may have adversely impacted disease control.

Dual-combination maintenance inhaler preferences in asthma and chronic obstructive pulmonary disease: A patient-centered benefit-risk assessment.

BACKGROUND: A variety of dual-combination maintenance inhalers are used to treat asthma and chronic obstructive pulmonary disease (COPD). Understanding patient preferences for treatment attributes may help select an optimal treatment from the patient perspective. METHODS: Patient preferences for maintenance inhaler device and medication attributes were elicited through a discrete choice experiment and used in benefit-risk assessments to calculate predicted choice probabilities (PrCPs) for 14 dual-combination maintenance inhalers in four treatment classes: lower- and higher-dose inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) inhalers for asthma, and ICS/LABA and long-acting muscarinic antagonist (LAMA)/LABA inhalers for COPD. RESULTS: For all treatment classes, reduced exacerbations and faster onset of action were the most important attributes. For all classes, patients were willing to tolerate an extra yearly exacerbation to decrease the medication's onset of action from 30 to 5 min. For patients with asthma using lower-dose ICS/LABA (n = 497), budesonide/formoterol fumarate dihydrate (80 µg/4.5 µg) pressurized metered-dose inhaler (pMDI) had the highest PrCP (28.4%), and for those using a higher-dose ICS/LABA (n = 285), PrCPs were highest for mometasone furoate/formoterol fumarate dihydrate (200 µg/5 µg) pMDI (27.0%) and budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI (26.9%). For patients with COPD using an ICS/LABA (n = 574), budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI had the highest PrCP (56.6%), and for those using a LAMA/LABA inhaler (n = 217), tiotropium/olodaterol (2.5 µg/2.5 µg) soft mist inhaler had the highest PrCP (42.3%). CONCLUSIONS: Patient preference data for maintenance inhaler attributes can be used to identify a preference order of inhalers in different treatment classes.