Disparities in Antifibrotic Medication Utilization Among Veterans With Idiopathic Pulmonary Fibrosis.

BACKGROUND: Two antifibrotic medications, pirfenidone and nintedanib, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Little is known about their real-world adoption. RESEARCH QUESTION: What are the real-world antifibrotic utilization rates and factors associated with uptake among a national cohort of veterans with IPF? STUDY DESIGN AND METHODS: This study identified veterans with IPF who received care either provided by the Veterans Affairs (VA) Healthcare System or non-VA care paid for by the VA. Patients who had filled at least one antifibrotic prescription through the VA pharmacy or Medicare Part D between October 15, 2014, and December 31, 2019, were identified. Hierarchical logistic regression models were used to examine factors associated with antifibrotic uptake, accounting for comorbidities, facility clustering, and follow-up time. Fine-Gray models were used to evaluate antifibrotic use by demographic factors, accounting for the competing risk of death. RESULTS: Among 14,792 veterans with IPF, 17% received antifibrotics. There were significant disparities in adoption, with lower uptake associated with female sex (adjusted OR, 0.41; 95% CI, 0.27-0.63; P < .001), Black race (adjusted OR, 0.60; 95% CI, 0.49-0.73; P < .001), and rural residence (adjusted OR, 0.88; 95% CI, 0.80-0.97; P = .012). Veterans who received their index diagnosis of IPF outside the VA were less likely to receive antifibrotic therapy (adjusted OR, 0.15; 95% CI, 0.10-0.22; P < .001). INTERPRETATION: This study is the first to evaluate the real-world adoption of antifibrotic medications among veterans with IPF. Overall uptake was low, and there were significant disparities in use. Interventions to address these issues deserve further investigation.

A Systematically Derived Exposure Assessment Instrument for Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis. METHODS: A list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, interquartile range = 0 on a 5-point Likert scale (1, strongly agree; 2, tend to agree; 3, neither agree nor disagree; 4, disagree; 5, strongly disagree). RESULTS: In two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by patients with ILD for readability and usability. CONCLUSIONS: This Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.

Prognostic and predictive biomarkers for patients with idiopathic pulmonary fibrosis treated with pirfenidone: post-hoc assessment of the CAPACITY and ASCEND trials.

BACKGROUND: Heterogeneity in the progression of idiopathic pulmonary fibrosis (IPF) might reflect diversity in underlying pathobiology, and represents a major challenge in the prediction of clinical progression and treatment benefit. Previous studies have found peripheral blood concentrations of several protein biomarkers to be prognostic for overall survival duration in patients with IPF, but these findings have generally not been directly compared and replicated between cohorts. We aimed to use the pivotal trials for pirfenidone to evaluate prognostic and predictive properties of biomarkers across multiple endpoints, and whether they are modulated by pirfenidone treatment. METHODS: We did post-hoc analyses of test and replication cohorts from CAPACITY 004 (NCT00287716), CAPACITY 006 (NCT00287729), and ASCEND (NCT01366209) trials for the plasma proteins CCL13, CCL17, CCL18, CXCL13, CXCL14, COMP, interleukin 13, MMP3, MMP7, osteopontin, periostin, and YKL40. Eligible participants had IPF and received pirfenidone 2403 mg/day or placebo in CAPACITY (test cohort) or ASCEND (replication cohort), were aged 40-80 years, and without missing biomarker data at baseline. To identify biomarkers that were consistently prognostic for clinical outcome measures, the primary analysis was the association between biomarker concentrations at baseline and absolute change in percentage of predicted forced vital capacity (FVC%pred) at 12 months (CAPACITY week 48, ASCEND week 52) in the placebo group. Biomarkers within the test cohort that met predefined success criteria of a prognostic p value less than 0·10 from multivariate analysis were further assessed in the replication cohort. Furthermore, the predictive effect size (ie, biomarkers that were predictive for benefit from pirfenidone) was calculated as the difference in FVC%pred treatment effect (pirfenidone in relation to placebo) between high versus low biomarker subgroups at week 48 (test cohort) or week 52 (replication cohort). FINDINGS: Several baseline biomarkers (CCL13, CCL18, COMP, CXCL13, CXCL14, periostin, and YKL40) were prognostic for progression outcomes in the placebo groups of the test cohort. However, only CCL18 was consistently prognostic for absolute change in percentage of FVC%pred in both the test (p=0·032) and replication (p=0·004) cohorts. Pirfenidone treatment benefit was consistent regardless of baseline biomarker concentration. INTERPRETATION: Blood CCL18 concentrations were the most consistent predictor of disease progression across IPF cohorts with potential to inform new target discovery and clinical trial design. Future validation of these findings in prospective studies is warranted. FUNDING: Genentech Inc.

Health care utilization and costs of idiopathic pulmonary fibrosis in U.S. Medicare beneficiaries aged 65 years and older.

RATIONALE: Management of idiopathic pulmonary fibrosis (IPF) is resource-intensive. Because an increasing prevalence of IPF was found among the elderly in the United States, it is important to understand the economic burden associated with the disease in this population. OBJECTIVES: To compare health care resource utilization and costs between patients with IPF and matched control subjects without IPF in Medicare, the largest U.S. payer covering the elderly. METHODS: Administrative claims from a 5% random sample of Medicare beneficiaries (aged 65+) from years 2000 to 2011 were analyzed. Incident patients with IPF were identified on the basis of International Classification of Diseases, ninth revision, Clinical Modification diagnosis codes, with at least 1 year of enrollment before (preindex) and after (postindex) the first diagnosis (index date). Up to five beneficiaries without IPF were matched to each patient with IPF, based on age, sex, race, and region. Annual health care resource utilization and medical costs (excluding outpatient drug costs) during the preindex and postindex periods were compared between patients with IPF and matched control subjects. MEASUREMENTS AND MAIN RESULTS: A total of 7,855 patients with IPF were matched to 38,856 control subjects. Compared with matched control subjects during the preindex period, patients with IPF had an 82% higher risk of hospitalization (28.8 vs. 15.8%), and 72% higher total medical costs ($10,124 vs. $5,888). Compared with matched control subjects during the postindex period, patients with IPF had a 134% higher risk of hospitalization (48.7 vs. 20.8%), similar increased risk of emergency room visits (39.6 vs. 17.5%), and 134% higher total medical costs ($20,887 vs. $8,932). CONCLUSIONS: In the U.S. Medicare population, patients with IPF incurred substantial health care resource utilization. The annual IPF-attributable medical cost to the U.S. health care system, excluding medication costs, is estimated at close to $2 billion.

Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001-11.

BACKGROUND: Published data for the epidemiology of idiopathic pulmonary fibrosis in the USA are scarce. We sought to estimate the incidence, prevalence, and mortality risk of idiopathic pulmonary fibrosis among US Medicare beneficiaries. METHODS: We used administrative claims from a 5% random sample of Medicare beneficiaries (aged 65 years and older) from the years 2000-11 as a data source. Idiopathic pulmonary fibrosis was defined by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. We estimated annual incidence and cumulative prevalence of idiopathic pulmonary fibrosis, median survival time of patients, and potential risk factors for diagnosis of idiopathic pulmonary fibrosis and death between 2001 and 2011. We also estimated incidence and prevalence using more restrictive algorithms for diagnosis. FINDINGS: The annual incidence of idiopathic pulmonary fibrosis in the Medicare population remained stable between 2001 and 2011, with an overall estimate of 93.7 cases per 100000 person-years (95% CI 91.9-95.4) across the study period. The annual cumulative prevalence increased steadily from 202.2 cases per 100000 people in 2001 to 494.5 cases per 100000 people in 2011. Among newly diagnosed patients with Medicare (mean age 79.4 years [SD 7.2], 54% female, 91% white), the median survival time was 3.8 years (95% CI 3.5-3.8). Older age and male sex were associated with a higher incidence of disease and shorter survival time after diagnosis. Mortality risk was lower in patients diagnosed in more recent years (median survival time 3.3 years [95% CI 3.0-3.8] in 2001 vs 4.0 years [3.8-4.5] in 2007). INTERPRETATION: The incidence and prevalence of idiopathic pulmonary fibrosis in people aged 65 years and older in the USA are substantially higher than previously reported, and prevalence is increasing annually, even in the subgroups based on more restrictive algorithms for diagnosis. Patients with idiopathic pulmonary fibrosis aged 65 years and older were living longer in 2011 than they were 10 years before, which could partly account for the steady increase in prevalence. FUNDING: Biogen Idec.

Burden of illness in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is a life-threatening condition, and few data concerning the impact on healthcare utilization and associated costs are available. The objective of this study was to describe the burden of illness (comorbidity, healthcare resource utilization, and associated costs) in patients with idiopathic pulmonary fibrosis. METHODS: Two cohorts (patients with idiopathic pulmonary fibrosis and matched controls) were retrospectively identified from US claims databases between January 1, 2001 and September 30, 2008. Cases with idiopathic pulmonary fibrosis were defined by age of 55 years or older and either two or more claims with a code for idiopathic fibrosing alveolitis (ICD-9 516.3), or one claim with ICD 516.3 and a subsequent claim with a code for post-inflammatory pulmonary fibrosis (ICD-9 515). The prevalence and incidence of pre-selected comorbidities, healthcare resource utilization (hospital, outpatient, drugs), and direct medical costs were assessed in each cohort. RESULTS: A total of 9286 patients with idiopathic pulmonary fibrosis were identified. When compared with age- and gender-matched controls, these patients were at significantly increased risk for comorbidities including pulmonary hypertension and emphysema. The all-cause hospital admission rate (0.5 per person-year) and the all-cause outpatient visit rate (28.0 per person-year) were both ∼2-fold higher than in controls. Total direct costs for patients with idiopathic pulmonary fibrosis were $26,378 per person-year; the incremental costs over controls were $12,124 (2008 value). CONCLUSIONS: Patients with idiopathic pulmonary fibrosis experience increased comorbidity, healthcare resource utilization, and direct medical costs compared to controls.

Clinical and economic consequences of ventilator-associated pneumonia: a systematic review.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in critically ill patients. The clinical and economic consequences of VAP are unclear, with a broad range of values reported in the literature OBJECTIVE: To perform a systematic review to determine the incidence of VAP and its attributable mortality rate, length of stay, and costs. DATA SOURCE: Computerized PUBMED and MEDLINE search supplemented by manual searches for relevant articles, limited to articles published after 1990. STUDY SELECTION: English-language observational studies and randomized trials that provided data on the incidence of VAP were included. Matched cohort studies were included for calculation of attributable mortality rate and length of stay. DATA EXTRACTION: Data were extracted on patient population, diagnostic criteria for VAP, incidence, outcome, type of intensive care unit, and study design. DATA SYNTHESIS: The cumulative incidence of VAP was calculated by combining the results of several studies using standard formulas for combining proportions, in which the weighted average and variance are calculated. Results from studies comparing intensive care unit and hospital mortality due to VAP, additional length of stay, and additional days of mechanical ventilation were pooled using a random effects model, with assessment of heterogeneity. RESULTS: Our findings indicate a) between 10% and 20% of patients receiving >48 hrs of mechanical ventilation will develop VAP; b) critically ill patients who develop VAP appear to be twice as likely to die compared with similar patients without VAP (pooled odds ratio, 2.03; 95% confidence interval, 1.16-3.56); c) patients with VAP have significantly longer intensive care unit lengths of stay (mean = 6.10 days; 95% confidence interval, 5.32-6.87 days); and d) patients who develop VAP incur > or = USD $10,019 in additional hospital costs. CONCLUSIONS: Ventilator-associated pneumonia occurs in a considerable proportion of patients undergoing mechanical ventilation and is associated with substantial morbidity, a two-fold mortality rate, and excess cost. Given these findings, strategies that effectively prevent VAP are urgently needed.