Healthcare Resource Utilization and Related Costs in Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype: A US Claims Database Analysis.

INTRODUCTION: We aimed to describe healthcare resource utilization (HCRU) patterns and costs in patients with fibrosing interstitial lung disease (ILD) and those with a progressive phenotype of fibrosing ILD in a US claims database. METHODS: Data from the IBM® MarketScan® databases (1 October 2011-30 September 2015) were used. Diagnosis codes documented on medical claims on two occasions (without any claims during the 12 months prior) identified patients with incident fibrosing ILD. Patients with chronic fibrosing ILD with a progressive phenotype were identified by proxies for progression. Patients aged ≥ 18 years with 365 days of continuous coverage before the index date were eligible for inclusion. Data were analyzed for 12 months prior to identification of fibrosing ILD/progressive phenotype (baseline) and 12 months after (follow-up). Outcomes included treatment patterns, outpatient and inpatient claims, and costs. RESULTS: We identified 23,577 patients with incident fibrosing ILD and 14,722 with the progressive phenotype. Follow-up data were available for 9986 and 5840 patients, respectively. The most frequent ILD-related medications during baseline were corticosteroids (49.4% and 56.6%). Mean (± standard deviation [SD]) annualized number of outpatient claims was 30.0 (± 26.4) and 34.1 (± 27.7) in the baseline period and 36.2 (± 28.6) and 41.9 (± 30.2) in the follow-up in fibrosing ILD and with a progressive phenotype, respectively. Mean (SD) number of all-cause hospitalizations was 0.5 (± 1.1) and 0.7 (± 1.2) during baseline and 0.6 (± 1.1) and 0.7 (± 1.2) during follow-up. Mean (SD) total costs were $40,907 (± 92,496) and $49,561 (± 98,647) during baseline and $46,157 (± 102,858) and $54,215 (± 116,833) during follow-up. Inpatient mortality during follow-up was 53.50 and 77.44 per 1000 patient-years. CONCLUSION: HCRU and costs were high in patients with chronic fibrosing ILD with a progressive phenotype, likely reflecting the disease severity and the need for close monitoring and acute care. Outpatient claims accounted for a substantial proportion of the total costs.

Some patients with lung diseases have inflammation or scarring of the lung tissues (interstitial lung diseases, or ILDs). In some patients with lung scarring, the scarring may become progressive (i.e., it worsens over time). In this study, we looked at these patients identified in US health insurance records. We counted how many times patients visited a doctor, were admitted to hospital, or needed medications or tests. We also looked at the total cost of all this medical care. Overall, we concluded that patients with ILDs with progressive lung scarring had a high number of visits to the doctor, and the total costs of their medical care were high.

Stimulation of a subset of natural killer T cells by CD103+ DC is required for GM-CSF and protection from pneumococcal infection.

Innate-like T cells, including invariant natural killer T cells, mucosal-associated invariant T cells, and γδ T cells, are present in various barrier tissues, including the lung, where they carry out protective responses during infections. Here, we investigate their roles during pulmonary pneumococcal infection. Following infection, innate-like T cells rapidly increase in lung tissue, in part through recruitment, but T cell antigen receptor activation and cytokine production occur mostly in interleukin-17-producing NKT17 and γδ T cells. NKT17 cells are preferentially located within lung tissue prior to infection, as are CD103+ dendritic cells, which are important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas interleukin-17-producing γδ T cells are numerous, granulocyte-macrophage colony-stimulating factor is exclusive to NKT17 cells and is required for optimal protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.

Prevalence and Incidence of Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype in the United States Estimated in a Large Claims Database Analysis.

INTRODUCTION: Many fibrosing interstitial lung diseases (ILDs) develop a chronic progressive phenotype. While idiopathic pulmonary fibrosis, which is always progressive, is well characterized with established treatment options, the epidemiology of other chronic fibrosing ILDs with a progressive phenotype has not been widely investigated. Treatment options are limited, with a high unmet need. This claims database study estimates the incidence and prevalence of these diseases in the USA. METHODS: Diagnosis, procedure and resource utilization codes from insurance claims were used to identify patients with fibrosing ILD and those with a chronic progressive phenotype among 37,565,644 adult patients in the IBM® MarketScan® Research Database 2012-2015. Two eligible ILD claims were required for a fibrosing ILD diagnosis. Progression was defined using a novel algorithm constituted by criteria considered proxies for progression. Patients were defined as having incident (new) or existing diagnoses based on claims during a 365-day period before study entry. RESULTS: The estimated age- and sex-adjusted prevalence per 100,000 persons of fibrosing ILD (95% confidence interval) was 117.82 (116.56, 119.08) and of chronic fibrosing ILDs with a progressive phenotype was 70.30 (69.32, 71.27). The estimated adjusted incidence per 100,000 patient-years of fibrosing ILD was 51.56 (50.88, 52.24) and of chronic fibrosing ILDs with a progressive phenotype was 32.55 (32.01, 33.09). Among incident fibrosing ILD patients, 57.3% experienced progression over a median of 117 days (interquartile range 63-224), with largely comparable rates of progression among different diseases. CONCLUSIONS: Chronic fibrosing ILDs with a progressive phenotype comprise a relatively new disease construct requiring varied approaches to obtain reliable estimates of prevalence and incidence. This is the first large claims database study using real-world data to provide estimates of the prevalence and incidence of these diseases among a very large segment of the US population and could form the groundwork for future studies.

Progressive lung fibrosis occurs in idiopathic pulmonary fibrosis; however, interstitial lung fibrosis may occur in other diseases such as rheumatoid arthritis, chronic hypersensitivity pneumonitis and sarcoidosis, and may or may not be progressive in these diseases. Little is known about the frequency of lung fibrosis among patients with these diseases or how often such fibrosis is progressive. This study used information from a large insurance claims database (IBM^® MarketScan^®) to estimate the frequency and progression of lung fibrosis associated with different diseases.

Metabolic activation and colitis pathogenesis is prevented by lymphotoxin ß receptor expression in neutrophils.

Inflammatory bowel disease is characterized by an exacerbated intestinal immune response, but the critical mechanisms regulating immune activation remain incompletely understood. We previously reported that the TNF-superfamily molecule TNFSF14 (LIGHT) is required for preventing severe disease in mouse models of colitis. In addition, deletion of lymphotoxin beta receptor (LTßR), which binds LIGHT, also led to aggravated colitis pathogenesis. Here, we aimed to determine the cell type(s) requiring LTßR and the mechanism critical for exacerbation of colitis. Specific deletion of LTßR in neutrophils (LTßRΔN), but not in several other cell types, was sufficient to induce aggravated colitis and colonic neutrophil accumulation. Mechanistically, RNA-Seq analysis revealed LIGHT-induced suppression of cellular metabolism, and mitochondrial function, that was dependent on LTßR. Functional studies confirmed increased mitochondrial mass and activity, associated with excessive mitochondrial ROS production and elevated glycolysis at steady-state and during colitis. Targeting these metabolic changes rescued exacerbated disease severity. Our results demonstrate that LIGHT signals to LTßR on neutrophils to suppress metabolic activation and thereby prevents exacerbated immune pathogenesis during colitis.

Antifibrotic Drug Use in Patients with Idiopathic Pulmonary Fibrosis. Data from the IPF-PRO Registry.

Rationale: Two antifibrotic medications, nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the United States. Few data have been published on the use of these medications in clinical practice.Objectives: To investigate patterns of use of antifibrotic medications in the United States.Methods: The Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry, a multicenter U.S. registry, has enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Data from patients enrolled from June 5, 2014, to March 4, 2018, were used to determine antifibrotic medication use ("treatment") in the enrollment window and in a follow-up window approximately 6 months later. Associations between patient characteristics and treatment status were tested using logistic regression.Results: Overall, 551 of 782 eligible patients (70.5%) were treated in the enrollment window. Younger age, lower forced vital capacity percentage predicted, oxygen use with activity, worse self-rated health (based on the Short Form 12 or St. George's Respiratory Questionnaire score), referral to the enrolling center by a pulmonologist, use of a lung biopsy in diagnosis, and carrying a diagnosis of IPF to the enrolling center were associated with being treated. Among 534 patients treated at enrollment who had follow-up data, 94.0% remained treated in follow-up. Better self-rated health (based on the Short Form 12 mental component score or EuroQoL score) and not using oxygen with activity at enrollment were associated with continuing treatment in follow-up. Among 172 patients who were untreated at enrollment and had follow-up data, 29.7% started treatment in follow-up. Lower diffusing capacity of the lung for carbon monoxide percentage predicted, a family history of interstitial lung disease, a history of sleep apnea, and a definite diagnosis of IPF at enrollment were associated with starting treatment in follow-up.Conclusions: The majority of patients in the IPF-PRO Registry were receiving an approved medication for IPF at enrollment. Treatment at enrollment was associated with greater disease severity, more compromised quality of life, and the use of oxygen with activity.Clinical trial registered with ClinicalTrials.gov (NCT01915511).

Characterizing Health Outcomes in Idiopathic Pulmonary Fibrosis using US Health Claims Data.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease (ILD). Characterizing health outcomes of IPF patients is challenging due to disease rarity. OBJECTIVE: This study aimed to identify the burden of disease in patients newly diagnosed with IPF. METHODS: Patients with ≥1 claim with an IPF diagnosis were identified from a United States healthcare insurer's database (2000-2013). Patients with other known causes of ILD or aged <40 years were excluded. Subgroups were compared based on the 2011 change in International Classification of Diseases, 9th Revision (ICD-9) definition of IPF and occurrence of IPF testing. The prevalence and incidence of preselected health conditions of clinical interest were estimated. RESULTS: Median age of newly diagnosed patients (n = 7,298) was 62 years (54.0% male). Restricting to patients with IPF diagnostic testing did not substantially affect cohort characteristics, nor did ICD-9 IPF coding change. Mean follow-up was 1.7 years; 16.8% of patients died; and a substantial proportion of patients were censored due to end of health plan enrollment (50.7%) and other causes of ILD (19.6%). The incidence of pulmonary hypertension, lung cancer, and claims-based algorithm proxy for acute respiratory worsening of unknown cause was 22.5, 17.6, and 12.6 per 1,000 person-years, respectively. CONCLUSIONS: Patients with IPF had a high disease burden with a variety of health outcomes observed, including a high rate of mortality. Database censoring due to changes in enrollment or other ILD diagnoses limited follow-up. Altering cohort entry definitions, including IPF testing or ICD-9 IPF coding change, had little impact on cohort baseline characteristics.

Characterizing idiopathic pulmonary fibrosis patients using US Medicare-advantage health plan claims data.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare life-threating interstitial lung disease (ILD). This study characterizes demographics, health care utilization, and comorbidities among elderly IPF patients and estimates prevalence and incidence rates for selected outcomes. METHODS: Cohort study using a large US health insurance database (Optum's Medicare Advantage plan). INCLUSION CRITERIA: ≥ 1 diagnosis code for IPF (2008 - 2014), age ≥65 years, no diagnosis of IPF or other ILD in prior 12 months. Demographics, health care utilization, comorbidities and incidence rates for various outcomes were estimated. Follow-up continued until the earliest of: health plan disenrollment, death, a claim for another known cause of ILD, or end of the study period. RESULTS: 4,716 patients were eligible; 53.4% had IPF diagnostic testing. Median age was 77.5 years, 50.3% were male, median follow-up time was 0.8 years. Incidence rates ranged from 1.0/1,000 person-years (lung transplantation) to 374.3/1,000 person-years (arterial hypertension). Baseline characteristics and incidence rates were similar for cohorts of patients with and without IPF diagnostic testing. CONCLUSIONS: Elderly IPF patients experience a variety of comorbidities before and after IPF diagnosis. Therapies for IPF and for the associated comorbidities may reduce morbidity and associated health care utilization of these patients.