Patients with allergic asthma have lower risk of severe COVID-19 outcomes than patients with nonallergic asthma.

BACKGROUND: Although asthma does not appear to be a risk factor for severe coronavirus disease 2019 (COVID-19), outcomes could vary for patients with different asthma subtypes. The objective of this analysis was to compare COVID-19 outcomes in real-world cohorts in the United States among patients with asthma, with or without evidence of allergy. METHODS: In a retrospective analysis of the COVID-19 Optum electronic health record dataset (February 20, 2020-January 28, 2021), patients diagnosed with COVID-19 with a history of moderate-to-severe asthma were divided into 2 cohorts: those with evidence of allergic asthma and those without (nonallergic asthma). After 1:1 propensity score matching, in which covariates were balanced and potential bias was removed, COVID-19 outcomes were compared between cohorts. RESULTS: From a COVID-19 population of 591,198 patients, 1595 patients with allergic asthma and 8204 patients with nonallergic asthma were identified. After propensity score matching (n = 1578 per cohort), risk of death from any cause after COVID-19 diagnosis was significantly lower for patients with allergic vs nonallergic asthma (hazard ratio, 0.48; 95% CI 0.28-0.83; P = 0.0087), and a smaller proportion of patients with allergic vs nonallergic asthma was hospitalized within - 7 to + 30 days of COVID-19 diagnosis (13.8% [n = 217] vs 18.3% [n = 289]; P = 0.0005). Among hospitalized patients, there were no significant differences between patients with allergic or nonallergic asthma in need for intensive care unit admission, respiratory support, or COVID-19 treatment. CONCLUSIONS: Asthma subtype may influence outcomes after COVID-19; patients with allergic asthma are at lower risk for hospitalization/death than those with nonallergic asthma.

Health care utilization and expenditures of parents of children with and without hemophilia A.

BACKGROUND: Caring for children with hemophilia A (HA) impacts many aspects of parents' lives. How this translates to caregivers' utilization of health services is unknown, and its elicitation can inform future evaluations of interventions that address caregiver burden for HA. OBJECTIVE: To understand the impact of caring for children with HA on parents' utilization of nonmental and mental health services by comparing 1-year costs and number of claims with parents of children without HA. METHODS: Retrospective matched cohort study using MarketScan commercial medical and pharmacy claims from 2011 to 2019. Children with HA were male sex, aged younger than 18 years, dependent policyholders, and had at least 1 HA-related medical claim from 2011 to 2018 and either an HA-related procedure or drug claim. Parents of children with HA (PCH) were primary or secondary policyholders, shared the same family ID as children with HA, and were continuously enrolled for 1-year post-index. PCH were matched (1:2) with parents of children without HA on age, sex, beneficiary type, child's age, number of children, index month and year, health plan type, employment status, and region. Primary outcomes were nonmental and mental health care costs (2020 US dollars). Secondary outcomes were number of nonmental health outpatient claims and utilization of mental health outpatient or drug claim. Subgroup analyses excluding parents with HA were also conducted. Productivity loss was also explored. Outcomes were compared using 2-sided, paired t-tests, and McNemar test. RESULTS: 1,068 PCH met inclusion criteria and were matched to 2,122 control parents. Mean 1-year cost for PCH was higher for nonmental health (mean difference $1,826 [95% CI = -1,000 to 4,652; P = 0.20]) and similar for mental health services (mean difference $14 [95% CI = -77 to 105; P = 0.76]). When parents with HA were excluded in the subgroup analyses, mental health cost was significantly higher for PCH (mean difference $676 [95% CI = 399 to 953; P < 0.001]). PCH had more nonmental health outpatient claims compared with parents of children without HA (mean difference 1.9 [95% CI = -1.1 to 4.9; P = 0.21]) and were 1.2 times (95% CI = 0.99 to 1.45; P = 0.07) more likely to have a mental health outpatient or drug claim. CONCLUSIONS: PCH had moderately higher health care costs and utilization compared with parents of children without HA; however, these results were not statistically significant. Future studies to better characterize HA disease severity and assess its impact on caregiver burden or to expand caregivers to spouses of adult patients with HA may be warranted. Limitations include inability to ascertain severity of HA in children and the use of claims data to capture complex effects on health care utilization. DISCLOSURES: Dr. Kim's postdoctoral fellowship is supported by Genentech, Inc. Dr. Raimundo is an employee of Genentech, Inc.

Real-world treatment, clinical outcomes and healthcare resource utilization among persons with hemophilia A by age.

Aim: Examine real-world characteristics, treatment patterns, and outcomes among treated persons with hemophilia A (PwHA) stratified by age. Patients & methods: This study utilized US claims data from 1 January 2007-31 July 2018 from the Humana Research Database. Unadjusted comparisons were conducted across PwHA (<18, 18-55, 56-89 years) enrolled in commercial or Medicare Advantage Prescription Drug plans. Results: A total of 294 PwHA were identified; 21.1% experienced ≥1 bleeding event, and 41.2 and 53.1% had evidence of arthropathy or related disorders, and pain, respectively. Along with all-cause and hemophilia-related healthcare resource utilization (HCRU), these were highest among PwHA aged 56-89 years. Conclusion: Insights into treatment, outcomes and HCRU may identify opportunities for enhanced disease management, particularly in older PwHA.

Development and Initial Validation Analyses of the Living with Idiopathic Pulmonary Fibrosis Questionnaire.

Rationale: Several new drugs for idiopathic pulmonary fibrosis (IPF) are in development. Tools are needed to assess whether these drugs benefit patients on outcomes that matter most to them. Health-related quality of life (HRQL) is one such outcome. It is influenced by many factors, but symptoms and their impacts are two strong drivers.Objectives: To develop a questionnaire to assess symptoms, disease impacts, and HRQL specifically for patients with IPF.Methods: Working with the U.S. Food and Drug Administration through the Drug Development Tool Qualification process, focus groups, concept elicitation, and cognitive debriefing interviews were conducted to inform the development of a 44-item pilot questionnaire. The pilot paper-and-pen questionnaire was migrated to an equivalent electronic version and field-tested in a 14-day study. Response data were subjected to psychometric testing, including exploratory factor analysis, item calibration using item response theory models, test-retest reliability, and validity testing.Measurements and Main Results: A total of 125 patients with IPF (62.4% men) completed the longitudinal study. The mean ± SD age of the cohort was 69 ± 7.60 years, and the mean FVC% predicted was 71 ± 20.0. After factor and item analyses, 35 items were retained, and these comprise the two modules (symptoms and impacts) of the Living with IPF (L-IPF) questionnaire. The L-IPF yields five scales demonstrating good psychometric properties, including correlation with concurrently collected FVC% predicted and the ability to discriminate between patients with differing levels of IPF severity.Conclusions: The L-IPF is a new questionnaire that assesses symptoms, disease impacts, and HRQL in patients with IPF.

Model of Short- and Long-Term Outcomes of Emicizumab Prophylaxis Treatment for Persons with Hemophilia A.

BACKGROUND: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody. OBJECTIVE: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States. METHODS: A Markov model was developed to compare clinical outcomes and costs of emicizumab versus FVIII prophylaxis among persons with severe HA from U.S. payer and societal perspectives. Patients started prophylaxis at age 1 year in the base case. Mutually exclusive health states considered were "no arthropathy," "arthropathy," "surgery," and "death." Serious adverse events, breakthrough bleeds, and inhibitor development were simulated throughout the modeled time horizon. In addition to the prophylaxis drug costs, patients could incur other direct costs related to breakthrough bleeds treatment, serious adverse events, development of inhibitors, arthropathy, and orthopedic surgery. Indirect costs associated with productivity loss (i.e., missed work or disabilities) were applied for adults. Model inputs were obtained from the HAVEN 3 trial, published literature, and expert opinion. The model used a lifetime horizon, and results for 1 year and 5 years were also reported. Deterministic sensitivity analyses and scenario analyses were conducted to assess robustness of the model. RESULTS: Over a lifetime horizon, the cumulative number of all treated bleeds and joint bleeds avoided on emicizumab versus FVIII prophylaxis were 278.2 and 151.7, respectively. Correspondingly, arthropathy (mean age at onset: 12.9 vs. 5.4 years) and FVIII inhibitor development (mean age at development: 13.9 vs. 1.1 years) were delayed. Total direct and indirect costs were lower for emicizumab versus FVIII prophylaxis for all modeled time horizons ($97,159 vs. $331,610 at 1 year; $603,146 vs. $1,459,496 at 5 years; and $15,238,072 vs. $22,820,281 over a lifetime horizon). The sensitivity analyses indicated that clinical outcomes were sensitive to efficacy inputs, while economic outcomes were driven by the discount rate, dosing schedules, and treatments after inhibitor development. Results for moderate to severe patients were consistent with findings in the severe HA population. CONCLUSIONS: The model suggests that emicizumab prophylaxis confers additional clinical benefits, resulting in a lower number of bleeding events and delayed onset of arthropathy and inhibitor development across all time assessment horizons. Compared with short-acting recombinant FVIII, emicizumab prophylaxis leads to superior patient outcomes and cost savings from U.S. payer and societal perspectives. DISCLOSURES: Funding for this study was provided by Genentech. Raimundo and Patel are employees of Genentech and own stock or stock options. Zhou, Han, Ji, Fang, Zhong, and Betts are employees of Analysis Group, which received consultancy fees from Genentech for conducting this study. Mahajerin received consultancy fees from Genentech for work on this study. Portions of this research were presented as a poster at the 2018 American Society of Hematology Conference; December 1-4, 2018; San Diego, CA.

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry.

BACKGROUND: Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection. METHODS: Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation. RESULTS: 703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent. CONCLUSIONS: This analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.

Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events.

Aims: Cumulative exogenous factor VIII (FVIII) exposure is an important predictor of developing neutralizing antibodies (inhibitors) to FVIII in patients with persons with hemophilia A (PwHA). The aim of this study was to model the costs of emicizumab versus FVIII prophylaxis and total treatment costs for patients with severe HA.Materials and Methods: An Excel-based decision model was developed to calculate cumulative costs in PwHA over a 20-year time horizon from the US payer perspective. The model considered persons with severe HA beginning at age 12 months with no prior FVIII exposure and initiating prophylaxis with emicizumab or FVIII. PwHA could develop inhibitors on accumulation of 20 FVIII exposure days. PwHA with inhibitors replaced FVIII with bypassing agents until inhibitors resolved spontaneously, following immune tolerance induction (ITI), or at the end of the time horizon. The primary model outcome was the difference in emicizumab versus FVIII treatment costs in 2019 USD. Sensitivity analyses were performed to test the robustness of results.Results: Total incremental cost over 20 years was -$1,945,480 (emicizumab arm, $4,919,058; FVIII arm, $6,864,538). Prophylaxis costs (emicizumab arm, $4,096,105; FVIII arm, $6,290,919) comprised the majority of costs in both groups, followed by breakthrough bleed treatment for the FVIII arm ($342,652) and ITI costs for the emicizumab arm ($733,671). Higher costs in the FVIII group reflected earlier inhibitor development (FVIII, 4 months; emicizumab, 162 months) and switch to bypassing agents.Limitations: The model design reflects a simplified treatment pathway for patients with severe HA who initiate FVIII or emicizumab prophylaxis. In the absence of clinical data, a key conservative assumption of the model is that patients receiving emicizumab and FVIII prophylaxis have the same risk of developing inhibitors.Conclusions: This study suggests that prophylaxis with emicizumab results in cost savings compared to FVIII prophylaxis in HA.

Rheumatoid Arthritis-Interstitial Lung Disease in the United States: Prevalence, Incidence, and Healthcare Costs and Mortality.

OBJECTIVE: Interstitial lung disease (ILD) is commonly associated with rheumatoid arthritis (RA) and can have significant morbidity and mortality. The objective of this study was to calculate the prevalence, incidence, healthcare costs, and mortality of RA-related ILD (RA-ILD) in the United States. METHODS: This retrospective cohort analysis used the Truven Health MarketScan Commercial and Medicare Supplemental health insurance databases from 2003 to 2014 and the Social Security Administration death database. Patients with RA-ILD were selected based on diagnoses on medical claims. Outcomes were 1-year prevalence and incidence of RA-ILD among the general enrollee population, all-cause and respiratory-related healthcare costs (2014 US$), and all-cause survival for a subset of newly diagnosed patients with vital status information. This analysis was descriptive. No statistical testing was conducted. RESULTS: Prevalence of RA-ILD ranged from 3.2 to 6.0 cases per 100,000 people across the 10-year period and incidence ranged from 2.7 to 3.8 cases per 100,000 people. There were 750 incident patients with 5 years of followup data. Over that time, 72% had an inpatient admission and 76% had an emergency room visit. Mean total 5-year costs were US$173,405 per patient (SD $158,837). Annual per-patient costs were highest in years 1 and 5. At 5 years after first diagnosis in the data, 35.9% of patients had died. CONCLUSION: Prevalence of RA-ILD increased over time. For patients who could be followed over a 5-year period, healthcare use and costs were somewhat stable over time, but were substantial. RA-ILD is associated with decreased survival.

Real-World Practice Patterns for Prevention and Management of Potential Adverse Events with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Pirfenidone is an oral antifibrotic agent approved for idiopathic pulmonary fibrosis (IPF). Real-world data on adverse event (AE) management for pirfenidone are limited. Strategies for managing potential antifibrotic therapy AEs were examined in a sample of US pulmonologists. METHODS: An online, self-administered survey was fielded to pulmonologists between April 10 and May 17, 2017. Pulmonologists were included if they spent > 20% of their time in direct patient care and had ≥ 5 patients with IPF on antifibrotic therapy. Participants answered questions regarding initiation of pirfenidone, dose titration, and management of potential AEs. RESULTS: A total of 169 pulmonologists participated. Gastrointestinal (GI) intolerance was the most important factor in implementing alternative titration schedules for pirfenidone. Approximately three-quarters of pulmonologists recommended the standard titration scheme for starting treatment; however, a range of titration schedules up to 8 weeks were described, with a 4-week schedule being most common. Pulmonologists reported that most patients treated with alternative titration schedules could achieve the full dose of pirfenidone. Pulmonologists who were most effective at mitigating pirfenidone-related GI AEs by advising dosing at mealtimes more frequently recommended taking pirfenidone during a substantial meal than pulmonologists who were less effective. For photosensitivity AEs, pulmonologists recommended sunscreen use, sun avoidance, wearing a hat, and ultraviolet protection factor clothing. CONCLUSIONS: Pulmonologists reported that alternative titration schedules for initiating pirfenidone were common and can aid in maintaining the full dose. Proposed strategies to ameliorate pirfenidone-related GI and photosensitivity AEs included taking pirfenidone during a substantial meal and minimizing sun exposure, respectively. FUNDING: F. Hoffmann-La Roche Ltd./Genentech, Inc. Plain language summary available for this article.

Epidemiology of Hypersensitivity Pneumonitis among an Insured Population in the United States: A Claims-based Cohort Analysis.

RATIONALE: Hypersensitivity pneumonitis is a complex lung disease resulting from repeated inhalation of a variety of antigens. Limited data exist regarding its epidemiology. OBJECTIVES: To describe the trends in the annual incidence and prevalence of hypersensitivity pneumonitis in the United States. METHODS: We developed novel claims-based coding algorithms to identify hypersensitivity pneumonitis, chronic hypersensitivity pneumonitis, and fibrotic hypersensitivity pneumonitis cases using the 2004 to 2013 MarketScan Commercial and Medicare Supplemental healthcare claims databases. Algorithm validity and reliability were assessed with clinical data from National Jewish Health. We calculated yearly cumulative incidence and prevalence overall and by age. For the subgroup with vital status, Kaplan-Meier methods were used to analyze survival stratified by evidence of fibrosis. RESULTS: We identified 7,498 cases that met our hypersensitivity pneumonitis definition over the 10-year study period, including 3,902 with chronic hypersensitivity pneumonitis and 1,852 with fibrotic hypersensitivity pneumonitis. On the basis of the clinical-radiological adjudication of the validation sample, 38 cases (95%) were confirmed as hypersensitivity pneumonitis. The mean age was 52 years, and 58% were women. The 1-year prevalence rates for hypersensitivity pneumonitis ranged from 1.67 to 2.71 per 100,000 persons, and 1-year cumulative incidence rates ranged from 1.28 to 1.94 per 100,000 persons. The prevalence increased with age, ranging from 0.95 per 100,000 among 0- to 9-year-olds to 11.2 per 100,000 among those aged 65 years and older. Between 56 and 68% of hypersensitivity pneumonitis cases in each year were classified as chronic hypersensitivity pneumonitis (prevalence, 0.91-1.70 per 100,000 persons; cumulative incidence, 0.63-1.08 per 100,000 persons). Fewer had fibrotic hypersensitivity pneumonitis (prevalence, 0.41-0.80 per 100,000 persons; cumulative incidence: 0.29-0.43 per 100,000 persons). Most cases (74%) were classified as unspecified hypersensitivity pneumonitis. Older age, male sex, and fibrosis were associated with higher mortality rates in unadjusted analyses. CONCLUSIONS: Using U.S. administrative claims-based data, we developed an algorithm with a high sensitivity and specificity for hypersensitivity pneumonitis. Between 2004 and 2013, hypersensitivity pneumonitis was more common among women and those older than 65 years. Most cases were classified as chronic hypersensitivity pneumonitis. Approximately one-fourth met our criteria for fibrotic hypersensitivity pneumonitis, which was associated with a higher mortality rate.

All-cause Healthcare Costs and Mortality in Patients with Systemic Sclerosis with Lung Involvement.

OBJECTIVE: Patients with systemic sclerosis (SSc) often develop interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). The effect of ILD and PAH on healthcare costs among patients with SSc is not well described. The objective of this analysis was to describe healthcare costs in patients with newly diagnosed SSc and SSc patients newly diagnosed with ILD and/or PAH in the United States. METHODS: This retrospective cohort analysis was conducted in the Truven Health MarketScan Commercial and Medicare Supplemental healthcare claims databases from 2003 to 2014. Based on International Classification of Diseases-9-Clinical Modification diagnosis codes on medical claims, patients were classified into 3 groups: incident SSc, SSc with incident ILD (SSc-ILD), and SSc with incident PAH (SSc-PAH). Patients were required to have continuous enrollment for 5 years to measure all-cause healthcare costs. Costs (adjusted to US$) were reported overall and by service type and year following diagnosis. Because of the overlap between groups, statistical comparisons were not conducted. RESULTS: There were 1957 patients with incident SSc, 219 with incident SSc-ILD, and 108 patients with incident SSc-PAH. Average (mean ± SD) all-cause healthcare costs over followup were higher for patients with incident SSc-ILD ($191,107 ± $322,193) or patients with incident SSc-PAH ($254,425 ± $240,497), compared to patients with incident SSc ($101,839 ± $167,155). Average annual costs over the 5-year period ranged from $18,513 to $23,268 for patients with incident SSc, from $31,285 to $55,446 for patients with incident SSc-ILD, and from $44,454 to $63,320 for patients with incident SSc-PAH. Costs tended to be the highest in the fifth year of followup. CONCLUSION: Among patients with SSc, ILD and PAH can result in substantial increases in healthcare costs.

Patient Outcomes, Health Care Resource Use, and Costs Associated with High Versus Low HEDIS Asthma Medication Ratio.

BACKGROUND: The Healthcare Effectiveness Data and Information Set (HEDIS) quality measures for asthma include the asthma medication ratio (AMR) as a marker of quality of care for patients with asthma. Few data are available to describe the association between health care use and costs in patients with high versus low AMR. OBJECTIVE: To characterize health care use and costs associated with high versus low AMR in patients participating in commercial health plans. METHODS: In a commercial claims database, this study retrospectively identified patients aged 5 to 64 years on December 31, 2011, who met the HEDIS definition of asthma in the premeasurement year (January 1, 2010-December 31, 2010) and the measurement year (January 1, 2011-December 31, 2011). Each patient was classified as having either high or low AMR based on the HEDIS definition. AMR was calculated as the ratio of controller to total asthma medications; high AMR was defined as ≥ 0.5. Annual per-patient health care use and costs were compared in patients with high versus low AMR using (a) multivariable linear regression models to estimate mean annual number of office visits, oral corticosteroids (OCS) bursts (≤ 15-day supply), and costs and (b) negative binomial models to estimate mean annual hospitalization and emergency department (ED) visits. All estimates were adjusted for age, sex, region, and Charlson Comorbidity Index score to control for differences between patients with high versus low AMR. RESULTS: Patients were identified with high (30,575) and low (6,479) AMR. An average patient with high AMR had more all-cause office visits (14.1 vs. 11.0; P < 0.001), fewer all-cause hospitalizations (0.109 vs. 0.215; P < 0.001), fewer all-cause ED visits (0.321 vs. 0.768; P < 0.001), and fewer OCS bursts (0.83 vs. 1.33; P < 0.001) than an average patient with low AMR. An average patient with high AMR had fewer asthma-related hospitalizations (0.024 vs. 0.088; P < 0.001) and ED visits (0.060 vs. 0.304; P < 0.001) than an average patient with low AMR. Numbers of asthma-related annual office visits were similar between the high and low AMR groups (high 2.2 vs. low 2.2; not significant). The rate of poor asthma control events (≥ 6 short-acting beta-agonist dispensing events or ≥ 2 OCS bursts, asthma-related ED visits, or hospitalizations) was greater in patients with low AMR than in patients with high AMR (74.3% vs. 26.9%). An average patient with high AMR had lower annual nonmedication costs than an average patient with low AMR ($5,733 vs. $6,295; P = 0.011). Similar trends emerged for asthma-related costs. A patient with high AMR had higher average total annual health care costs than a patient with low AMR ($9,811 vs. $8,398; P < 0.001). These increased costs primarily resulted from increased medication costs for patients with high versus low AMR ($4,077 vs. $2,103; P < 0.001). CONCLUSIONS: Although patients with high AMR had more office visits and higher medication (which resulted in higher overall health care) costs, their care was marked by fewer OCS bursts (indicating fewer instances of poor asthma control), fewer ED visits, and fewer hospitalizations and lower non-medication costs than those patients with low AMR. These findings support the use of AMR as a care quality measure for patients with persistent asthma. DISCLOSURES: This study was funded by Genentech. Luskin has received consulting and lecture fees, research and travel support, and payment for developing educational presentations from Genentech and has received lecture fees from Merck. Raimundo and Solari are employees of Genentech. Antonova was employed by Genentech at the time of this study. Broder and Chang are employees of Partnership for Health Analytic Research, which received funding from Genentech to conduct this research. Study concept and design were contributed by all authors. Broder and Chang conducted analyses. All authors interpreted the data. Antonova wrote the manuscript with assistance from the other authors. All authors participated in manuscript review and revisions.

Mechanical ventilation in idiopathic pulmonary fibrosis: a nationwide analysis of ventilator use, outcomes, and resource burden.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with increased risk of respiratory-related hospitalizations. Studies suggest mechanical ventilation (MV) use in IPF does not improve outcomes and guidelines recommend against its general use. Our objective was to investigate MV use and association with cost and mortality in IPF. METHODS: This retrospective study, using a nationwide sample, included claims with IPF (ICD-9-CM: 516.3) in 2009-2011 and principal respiratory disease diagnosis (ICD-9-CM: 460-519); excluding lung transplant. Regression models were used to determine predictors of MV and association with cost, LOS, and mortality. Domain analysis was used to account for use of subpopulation. Costs were adjusted to 2011. Data on patient severity not available. RESULTS: Twenty two thousand three hundred fifty non-transplant IPF patients were admitted with principal respiratory disease diagnosis: Mean age 70.0 (SD 13.9), 49.1% female, mean LOS 7.4 (SD 8.2). MV was used in 11.4% of patients with a non-significant decline over time. In regression models, MV was associated with an increased stay of 9.78 days (95% CI 8.38-11.18) and increased cost of $36,583 (95% CI $32,021-41,147). MV users had significantly increased mortality (OR 15.55, 95% CI 12.13-19.95) versus nonusers. CONCLUSIONS: Mechanical ventilation use has not significantly changed over time and is mostly used in younger patients and those admitted for non-IPF respiratory conditions. MV was associated with a 4-fold admission cost increase ($49,924 versus $11,742) and a 7-fold mortality increase (56% versus 7.5%), although patients who receive MV may differ from those who do not. Advances in treatment and decision aids are needed to improve outcomes in IPF.

Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis.

RATIONALE: Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes. OBJECTIVES: To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials. METHODS: Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity. MEASUREMENTS AND MAIN RESULTS: A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up. CONCLUSIONS: In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.

Hospital cost and length of stay in idiopathic pulmonary fibrosis.

OBJECTIVE: To provide a detailed picture of the economic impact of hospitalization in idiopathic pulmonary fibrosis (IPF) and to identify factors associated with cost and length of stay (LOS). METHODS: In this retrospective cross-sectional study using the Nationwide Inpatient Sample (NIS), this study included hospitalizations for IPF (ICD-9-CM 516.3) with a principal diagnosis of respiratory disease (ICD-9-CM 460-519) from 2009-2011; lung transplant admissions were excluded. Total inpatient cost, LOS, in-hospital death, and discharge disposition were reported. Linear regression models were used to determine variables predictive of LOS and cost. RESULTS: From 2009-2011, 22,350 non-transplant IPF patients with a principal diagnosis of respiratory disease were admitted: mean (±SE) age was 70.0 (0.32), and 49.1% were female. While in hospital, 11.4% of patients received mechanical ventilation and 8.9% received non-invasive ventilation. Mean (±SE) LOS was 7.4 (0.15) days overall (p < .001). The mean (±SD) admission cost was $16,042 (±631). Of hospitalized patients, 14.1% died, 20.6% transferred facilities, and 46.4% were routinely discharged. The adjusted LOS (95% CI) for patients with and without mechanical ventilation was 16.1 days (15-17.5) vs. 6.3 (6-6.5); adjusted costs were $48,772 (43,979-53,565) vs. $11,861 (11,292-12,431). LIMITATIONS: The positive predictive value of the algorithm used to identify IPF is not optimal. The NIS database does not follow patients longitudinally, and claims after admission are not available. Claims do not indicate whether listed diagnoses were present on admission or developed during hospitalization. The exclusion of transplant-related expenditures lead to under-estimation of cost. CONCLUSION: Using a nationally-representative database, we found IPF respiratory-related hospitalizations represent a significant economic burden with ∼7,000 non-transplant IPF admissions per year, at a mean cost of $16,000 per admission. Mechanical ventilation is associated with statistically significant increases in LOS and cost. Therapeutic advances that reduce rates and costs of IPF hospitalizations are needed.

Angioedema in the omalizumab chronic idiopathic/spontaneous urticaria pivotal studies.

BACKGROUND: Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life. OBJECTIVE: To describe patient-reported angioedema and its management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL). METHODS: Enrolled patients with CIU/CSU remained symptomatic despite treatment with histamine1 (H1)-antihistamines at licensed doses (ASTERIA I, ASTERIA II) or H1-antihistamines at up to 4 times the approved dose plus H2-antihistamines and/or a leukotriene receptor antagonist (GLACIAL). All studies administered omalizumab (75, 150, or 300 mg in ASTERIA I and ASTERIA II; 300 mg in GLACIAL) or placebo subcutaneously every 4 weeks for at least 12 weeks. Urticaria Patient Daily Diary entries were completed by patients and summarized. RESULTS: At baseline, angioedema prevalence was higher in GLACIAL (53.1%) than in ASTERIA I (47.5%) or ASTERIA II (40.7%). The mean proportion of angioedema-free days during weeks 4 to 12 was greater for patients treated with 300 mg of omalizumab than placebo in ASTERIA I (96.1% vs 88.2%, P < .001), ASTERIA II (95.5% vs 89.2%, P < .001), and GLACIAL (91.0% vs 88.7%, P = .006). Most patient-reported angioedema was managed by low-intensity interventions (doing nothing or taking medication). CONCLUSION: Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).