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      Patterns and Economic Burden of Hospitalizations and Exacerbations Among Patients Diagnosed with Idiopathic Pulmonary Fibrosis

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          Abstract

          BACKGROUND:

          Idiopathic pulmonary fibrosis (IPF) is a rare and fatal restrictive respiratory disease under the idiopathic lung disease (ILD) class. IPF is a form of chronic, progressive fibrosing interstitial pneumonia and has more scarring, less inflammation, and poorer prognosis than most other ILD forms. Exacerbation of IPF is rapid, with unpredictable deterioration of lung function, and is associated with short-term mortality. The American Thoracic Society (ATS) evidence-based guidelines for diagnosis and management of IPF reports that the incidence of acute exacerbations is between 5%-10%. Limited real-world evidence has been identified in the United States that assesses patterns of hospitalization, exacerbation of IPF, and the associated economic burden.

          OBJECTIVES:

          To (a) characterize patients newly diagnosed with IPF and (b) examine incidence rates and costs of all-cause hospitalizations, IPF-related hospitalizations, and exacerbations.

          METHODS:

          A retrospective analysis was performed with a national commercial claims database from calendar years 2006 to 2011. Newly diagnosed IPF patients were identified with either ≥ 2 claims for idiopathic fibrosing alveolitis (IFA) or ≥ 1 claim for IFA and ≥ 1 claim for postinflam-matory pulmonary fibrosis and a lung biopsy or thoracic high-resolution computed tomography within 90 days of the first claim for IFA (index date). IPF-related hospitalizations and possible IPF exacerbations were defined based on diagnoses recorded on event claims. Frequency, incidence rate, duration of events, and associated costs from the third-party payer’s perspective were estimated.

          RESULTS:

          Among 1,735 identified IPF patients, 38.6% had at least 1 all-cause hospitalization; 10.8% had IPF-related hospitalizations; 4.6% had suspected IPF exacerbations leading to hospitalization; and 72.1% had suspected IPF exacerbations leading to urgent outpatient visits during the 1-year post-index period. Incident rates for these 4 events were 83 (95% CI = 79-88), 17 (95% CI = 14-19), 7 (95% CI = 6-9), and 277 (95% CI = 269-286) per 100 person-years, respectively. Average costs per event were $13,987 (SD = $41,988), $16,812 (SD = $66,399), $14,731 (SD = $85,468), and $444 (SD = $1,481), respectively.

          CONCLUSIONS:

          Hospitalizations and possible exacerbations among patients with IPF were costly. Appropriate management of IPF needs to be considered to help slow IPF disease progression.

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          Most cited references28

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          An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management

          American Journal of Respiratory and Critical Care Medicine, 183(6), 788-824
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            Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases

            R Deyo (1992)
            Administrative databases are increasingly used for studying outcomes of medical care. Valid inferences from such data require the ability to account for disease severity and comorbid conditions. We adapted a clinical comorbidity index, designed for use with medical records, for research relying on International Classification of Diseases (ICD-9-CM) diagnosis and procedure codes. The association of this adapted index with health outcomes and resource use was then examined with a sample of Medicare beneficiaries who underwent lumbar spine surgery in 1985 (n = 27,111). The index was associated in the expected direction with postoperative complications, mortality, blood transfusion, discharge to nursing home, length of hospital stay, and hospital charges. These associations were observed whether the index incorporated data from multiple hospitalizations over a year's time, or just from the index surgical admission. They also persisted after controlling for patient age. We conclude that the adapted comorbidity index will be useful in studies of disease outcome and resource use employing administrative databases.
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              Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.

              Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period. A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. (Funded by Boehringer Ingelheim; INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.).
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                Author and article information

                Journal
                J Manag Care Spec Pharm
                J Manag Care Spec Pharm
                jmcsp
                Journal of Managed Care & Specialty Pharmacy
                Academy of Managed Care Pharmacy
                2376-0540
                2376-1032
                April 2016
                : 22
                : 4
                : 10.18553/jmcp.2016.22.4.414
                Affiliations
                [1 ]Product Director, Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut.
                [2 ]HEOR Contractor, Biogen, Cambridge, Massachusetts.
                [3 ]Senior Manager, Sunovion Pharmaceuticals, Marlborough, Massachusetts.
                [4 ]Research Associate, Consultant, Evidera, Lexington, Massachusetts.
                [5 ]Research Scientist, Consultant, Evidera, Lexington, Massachusetts.
                [6 ]Consultant, Evidera, Lexington, Massachusetts.
                [7 ]Senior Director, Shire Pharmaceuticals, Lexington, Massachusetts.
                [8 ]Chief of Staff, Veterans Affairs Portland Health Care System, Portland, Oregon.
                Author notes
                [* ]AUTHOR CORRESPONDENCE: Xiaoyun Pan, MS, PhD, Research Scientist, Evidera, 430 Bedford St., Ste. 300, Lexington, MA 02420. Tel.: 781.960.0317; E-mail: lucy.pan@evidera.com.

                Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) provided funding for this study. Yu and Devercelli are currently salaried employees of BIPI. Wu, Chuang, Wang, Pan, and Benjamin are currently employees of Evidera, which provides consulting and other research services to pharmaceutical, device, government, and nongovernment organizations. In their salaried positions, they work with a variety of companies and organizations and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from BIPI to conduct the analysis. Coultas was previously a paid consultant of BIPI. The contents do not represent the views of the Department of Veterans Affairs or the U.S. government.

                This manuscript does not contain clinical studies or patient data. The authors have full control of all primary data, and they agree to allow the journal to review their data if requested.

                All authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors, and they are fully responsible for all content and editorial decisions and were involved at all stages of manuscript development.

                The manuscript was drafted by Benjamin, Wu, and Yu and revised by Wang, Pan, Yu, Coultas, and Devercelli. The study was designed by Yu, Wu, Chuang, Wang, Benjamin, and Coultas. Statistical analysis was conducted by Wu, Chuang, and Wang. Senior review was provided by Coultas and Devercelli.

                Article
                10.18553/jmcp.2016.22.4.414
                10398274
                27023695
                b5920683-5991-43fb-8220-7e9ee9da3d60
                © 2016, Academy of Managed Care Pharmacy. All rights reserved.

                This article is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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