Claims-based Prevalence of Disease Progression among Patients with Fibrosing Interstitial Lung Disease Other than Idiopathic Pulmonary Fibrosis in the United States.

Rationale: Chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype is a clinical concept describing the broad group of ILDs characterized by progressive pulmonary fibrosis. The prevalence of progressive fibrotic ILDs other than idiopathic pulmonary fibrosis (IPF) is not well understood. Objectives: We used a novel algorithm to estimate the prevalence range of disease progression among patients with non-IPF fibrotic ILD in a U.S. claims database. Methods: This was a retrospective study including adults with commercial or Medicare Advantage with Part D (MAPD) insurance using administrative claims data from October 2015 to September 2019. Patients likely to have non-IPF fibrosing ILD with a progressive phenotype were identified via an algorithm that incorporated ILD-related diagnosis codes (excluding IPF) and claims-based proxies for fibrotic ILD progression, including pulmonary function tests, chest imaging, oral corticosteroid (OCS) medications, immunosuppressive medications, lung transplant, oxygen therapy, palliative care, and respiratory hospitalization. The prevalence range of non-IPF fibrotic ILD with progressive disease behavior was calculated using strict and lenient case definitions to account for potential imprecision in the progression proxies. Results: Of nearly 9 million study-eligible patients, 17,136 were identified with non-IPF fibrosing ILD. The prevalence of disease progression per 10,000 (95% confidence interval) ranged from 12.14 (11.74-12.54) to 29.05 (28.43-29.67) over a mean observation time of 1.44 years for MAPD enrollees (n = 14,686), and from 0.89 (0.81-0.97) to 2.36 (2.24-2.48) over a mean observation time of 1.29 years for commercial enrollees (n = 2,450). Prevalence estimates increased with age for both insurance types. Among patients with progression, 4,097 met at least two progression proxies not considering OCS (strict case definition) and 9,946 met at least one progression proxy (lenient case definition). The mean (standard deviation) number of proxies met was 2.1 (1.3), and the most common individual proxies met (alone or in combination with other proxies) were OCS use (48.9%), respiratory hospitalization (44.2%), and oxygen therapy (44.1%). Conclusions: This is among the first claims-based estimates of the prevalence of non-IPF chronic fibrosing ILD with a progressive phenotype. Our analysis indicates that this phenotype is rare in the overall population but increases substantially with increasing age.

Impact of timing of nintedanib initiation among patients newly diagnosed with idiopathic pulmonary fibrosis.

AIMS: While nintedanib treatment has been shown to slow the progression of idiopathic pulmonary fibrosis (IPF) in patients across varying levels of lung function, the effect of treatment timing on outcomes has not been examined. We assessed hospitalization risk and medical costs among patients with IPF based on the timing of nintedanib initiation after IPF diagnosis. MATERIALS AND METHODS: This retrospective administrative claims study included data from 04/01/2014-09/30/2019 for patients aged ≥40 years who initiated nintedanib within 1 year of IPF diagnosis. Patients were assigned to study cohorts based on the time from IPF diagnosis to nintedanib initiation. All-cause hospitalization and all-cause medical costs were modeled using marginal structural models including inverse probability weights to adjust for both baseline and time-varying characteristics. RESULTS: Of 11,195 patients diagnosed with IPF during the identification period, 449 met the study selection criteria (mean age 72.3 years, 68% male, mean follow-up time 13.3 months). Adjusted hospitalization risk and medical costs both varied significantly by the timing of nintedanib initiation (p < .001 and p = .020, respectively). Adjusted weighted hospitalization risk was higher among untreated vs. treated patients in months 2-3, months 4-6, and months 7-12 after diagnosis (hazard ratio [95% CI] 1.97 [1.09-3.56], p = .026; 2.62 [1.22-5.63], p = .014; and 5.57 [2.31-13.45], p < .001, respectively). Medical costs were 69% higher for patients initiating treatment in months 2-3 vs. month 1 (cost ratio [95% CI] 1.69 [1.20-2.38], p = .003). LIMITATIONS: Disease severity could not be assessed because clinical data were unavailable; however, proxies such as oxygen use were included to adjust for between-cohort differences in disease severity. CONCLUSIONS: Patients who initiate nintedanib promptly after IPF diagnosis may have reduced hospitalization risk and medical costs compared with those who start treatment later. Additional studies are warranted to improve understanding of the impact of prompt antifibrotic therapy on patient outcomes.

Burden of illness in progressive fibrosing interstitial lung disease.

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is a relatively new clinical concept describing a variety of ILDs characterized by progressive pulmonary fibrosis with associated lung function decline and worsening chest imaging. Little is known about health care resource utilization (HCRU) and costs associated with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF). This study analyzed the adjusted HCRU and cost burden among patients with incident non-IPF progressive fibrosing ILD vs matched patients with incident fibrosing ILD that had not yet progressed. METHODS: This was a retrospective study of insured US adults newly diagnosed with non-IPF fibrosing ILD from October 2016 to June 2019, conducted using administrative claims data from the Optum Research Database. Progressive disease was identified using claims-based proxies comprising health care utilization associated with management of progressive fibrosing ILD. Patients in the progressive population were 1:1 propensity score matched to not-yet-progressed patients on the basis of baseline demographic and clinical characteristics. All-cause HCRU and health care costs were presented as weighted per-patient-per-month (PPPM) measures to account for variable follow-up. Differences in study outcomes between matched cohorts were evaluated using Z-tests for continuous measures and Rao-Scott tests for binary measures. RESULTS: The postmatch cohorts comprised 11,025 patients with evidence of progression matched to 11,025 patients with not-yet-progressed fibrosing ILD. Mean (SD) weighted PPPM counts of follow-up health care encounters were significantly higher for the progressive vs not-yet-progressed cohort: ambulatory visits, 4.2 (3.6) vs 3.1 (3.3); emergency department visits, 0.3 (0.5) vs 0.1 (0.3); and inpatient (IP) stays, 0.1 (0.2) vs 0.0 (0.1) (P < 0.001 for all). Among patients with an IP stay, those with progressive disease had more inpatient days than those with not-yet-progressed disease (mean [SD] 1.6 [2.4] days vs 1.0 [1.3] days, P < 0.001). Mean weighted PPPM (SD) all-cause health care costs were also significantly higher for progressive vs not-yet-progressed patients, including total costs ($4,382 [$9,597] vs $2,243 [$4,162], P < 0.001), medical costs ($3,662 [$9,150] vs $1,627 [$3,524], P < 0.001), and pharmacy costs ($720 [$2,097] vs $616 [$2,070], P = 0.002). The difference in medical costs between cohorts was driven primarily by higher inpatient costs for progressive vs not-yet-progressed patients ($1,729 [$7,557] vs $523 [$2,118], P < 0.001). CONCLUSIONS: Progressive fibrosing ILD carries a substantial economic and health care burden. Among patients with incident non-IPF fibrosing ILD, all-cause HCRU and costs were significantly higher for those with a progressive phenotype than for matched patients whose disease had not yet progressed. The cost differential was driven primarily by hospitalizations, which were longer and more frequent for the progressive cohort. Disclosures: This work was funded by Boehringer Ingelheim Pharmaceuticals, Inc. Drs Conoscenti and Shetty are employees of Boehringer Ingelheim (BI). Dr Singer was an employee of BI at the time the study was conducted. Dr Brown was a paid consultant for BI for this study. Dr Bengtson, Ms Anderson, and Dr Brekke are employees of Optum, which was contracted by BI to conduct the study. Medical writing assistance was provided by Yvette Edmonds, PhD (Optum), and was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc.

Quantifying the Risk Continuum for Cardiovascular Death in Adults with Type 2 Diabetes.

OBJECTIVES: In type 2 diabetes (T2D), the most common causes of death are cardiovascular (CV) related, accounting for >50% of deaths in some reports. As novel diabetes therapies reduce CV death risk, identifying patients with T2D at highest CV death risk allows for cost-effective prioritization of these therapies. Accordingly, the primary goal of this study was to quantify the risk continuum for CV death in a real-world T2D population as a means to identify patients with the greatest expected benefit from cardioprotective antidiabetes therapies. METHODS: This retrospective study included patients with T2D receiving services through an integrated health-care system and used data generated through electronic medical records (EMRs). Quantifying the risk continuum entailed developing a prediction model for CV death, creating an integer risk score based on the final prediction model and estimating future CV death risk according to risk score ranking. RESULTS: Among 59,180 patients with T2D followed for an average of 7.5 years, 15,691 deaths occurred, 6,033 (38%) of which were CV related. The EMR-based prediction model included age, established CV disease and risk factors and glycemic indices (c statistic = 0.819). The 10% highest-risk patients according to prediction model elements had an annual CV death risk of ∼5%; the 25% highest-risk patients had an annual risk of ∼2%. CONCLUSIONS: This study incorporated a prediction modelling approach to quantify the risk continuum for CV death in T2D. Prospective application allows us to rank individuals with T2D according to their CV death risk, and may guide prioritization of novel diabetes therapies with cardioprotective properties.

A risk prediction model for heart failure hospitalization in type 2 diabetes mellitus.

BACKGROUND: Antidiabetic therapies have shown disparate effects on hospitalization for heart failure (HHF) in clinical trials. This study developed a prediction model for HHF in type 2 diabetes mellitus (T2DM) using real world data to identify patients at high risk for HHF. HYPOTHESIS: Type 2 diabetics at high risk for HHF can be identified using information generated during usual clinical care. METHODS: This electronic medical record- (EMR-) based retrospective cohort study included patients with T2DM free of HF receiving healthcare through a single, large integrated healthcare system. The primary endpoint was HHF, defined as a hospital admission with HF as the primary diagnosis. Cox regression identified the strongest predictors of HHF from 80 candidate predictors derived from EMRs. High risk patients were defined according to the 90th percentile of estimated risk. RESULTS: Among 54,452 T2DM patients followed on average 6.6 years, estimated HHF rates at 1, 3, and 5 years were 0.3%, 1.1%, and 2.0%. The final 9-variable model included: age, coronary artery disease, blood urea nitrogen, atrial fibrillation, hemoglobin A1c, blood albumin, systolic blood pressure, chronic kidney disease, and smoking history (c = 0.782). High risk patients identified by the model had a >5% probability of HHF within 5 years. CONCLUSIONS: The proposed model for HHF among T2DM demonstrated strong predictive capacity and may help guide therapeutic decisions.