Change in forced vital capacity and associated subsequent outcomes in patients with newly diagnosed idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare and serious disease characterized by progressive lung-function loss. Limited evidence has been published on the impact of lung-function loss on subsequent patient outcomes. This study examined change in forced vital capacity (FVC) across IPF patients in the 6 months after diagnosis and its association with clinical and healthcare resource utilization (HRU) outcomes in a real-world setting in the U.S. METHODS: A retrospective chart review was conducted of patients diagnosed with IPF by U.S. pulmonologists. Patient eligibility criteria included: 1) 40 years or older with a confirmed date of first IPF diagnosis with high-resolution computed tomography and/or lung biopsy between 01/2011 and 06/2013; 2) FVC results recorded at first diagnosis (±1 month) and at 6 months (±3 months) following diagnosis. Based on relative change in FVC percent predicted (FVC%), patients were categorized as stable (decline <5%), marginal decline (decline ≥5% and <10%), or significant decline (decline ≥10%). Physician-reported clinical and HRU outcomes were assessed from ~6 months post-diagnosis until the last contact date with the physician and compared between FVC% change groups. Multivariable Cox proportional-hazards models were constructed to assess risk of mortality, suspected acute exacerbation (AEx), and hospitalization post-FVC% change. Generalized estimating equations were used to account for multiple patients contributed by individual physicians. RESULTS: The sample included 490 IPF patients contributed by 168 pulmonologists. The mean (SD) age was 61 (11) years, 68% were male, and the mean (SD) baseline FVC% was 60% (26%). 250 (51%) patients were categorized as stable, 98 (20%) as marginal decline, and 142 (29%) as significant decline. The mean (SD) observation time was 583 (287) days. In both unadjusted analysis and multivariable models, significantly worse clinical outcomes and increased HRU were observed with greater lung-function decline. CONCLUSIONS: These findings suggest that nearly half of IPF patients experienced decline in FVC% within ~6 months following IPF diagnosis. Greater FVC% decline was associated with an increased risk of further IPF progression, suspected AEx, mortality, and higher rate of HRU. Management options that slow FVC decline may help improve future health outcomes in IPF.

Stroke and transient ischemic attack in the long-term care setting: patient characteristics, medication treatment, and length of stay.

OBJECTIVE: To examine the percentage of patients treated with antiplatelet or anticoagulant therapy among patients with stroke or transient ischemic attack (TIA) in the long-term care setting. DESIGN: Data were taken from the Minimum Data Set. Information regarding medications was derived from a linked pharmacy-claims database. SETTING: Long-term care facilities. PATIENTS, PARTICIPANTS: Residents of long-term care facilities with stroke or TIA as indicated in the database between January 1, 2007, and December 31, 2008, were selected; 14,469 patients with stroke and 833 patients with TIA were identified. INTERVENTIONS: None. MAIN STUDY VARIABLES: Demographics, admission and payer source, residential history, quality measures, comorbidities, and antiplatelet and anticoagulant therapies received. RESULTS: Approximately 48% of stroke patients and 53% of TIA patients received any antiplatelet or anticoagulant medication. Stroke patients had a mean (standard deviation [SD]) of 19.5 (73.2) days from their first assessment to their first medication, and they received therapy for a mean (SD) of 112.3 (258.3) days. TIA patients had a mean (SD) of 13.7 (54.9) days from their first assessment to their first medication, and they received therapy for a mean (SD) of 67.0 (165.7) days. In both cohorts, clopidogrel was the most common therapy received (22.5% of stroke patients and 24.6% of TIA patients). CONCLUSIONS: Health care providers treating patients in the long-term care setting should be aware of the population characteristics and high rate of undertreatment observed in this analysis. This study may help inform optimal decision-making by physicians and other health care practitioners.

Estimating the effect of medication adherence on health outcomes among patients with type 2 diabetes--an application of marginal structural models.

OBJECTIVE: We applied marginal structural models (MSMs) to estimate the effects of medication adherence with hypoglycemics on reducing the risk of microvascular complications in type 2 diabetic patients. METHODS: A retrospective longitudinal cohort study for type 2 diabetes patients was conducted using the California Medicaid claims database (1995-2002). Medication adherence and multiple time-varying confounders were measured quarterly over a maximum of 7.5 years follow-up. Cox regression models and MSMs results on the effect of compliance were compared. RESULTS: Of 4708 eligible patients, 2644 (56.2%) experienced microvascular complications during the follow-up period. After controlling for baseline covariates, standard Cox models estimated that adherence was associated with increased risk of complication with hazard ratio (HR) of 1.09 (95% confidence interval (CI): 1.00, 1.18). With adjustment of time-varying confounders as exogenous variables, the HR was 0.96 (0.88, 1.04). Using the MSM technique, the HR was 0.76 (95% bootstrap CI: 0.60, 0.92), indicating a significant benefit of medication adherence with hypoglycemics on the reduction of microvascular complications. This result contrasts with the negative results obtained in the hazard model, and is more consistent with prior clinical trial results CONCLUSION: Unlike conventional models, MSMs estimated that higher medication adherence may result in reduced risk of microvascular complications among patients with type 2 diabetes.

Delay in filling the initial prescription for a statin: a potential early indicator of medication nonpersistence.

BACKGROUND: Identification of early predictors of medication nonpersistence may allow timely adherence-promoting interventions and potentially reduce the risk of negative health outcomes. OBJECTIVE: This study was conducted to determine whether delay in filling an initial statin prescription predicts subsequent nonpersistence with medication. METHODS: This observational study of a cohort of adult patients (>18 years) who newly initiated statin therapy between December 1997 and June 2000 employed data from the administrative claims database of a large US managed care organization. Patients initiating statin therapy had to have at least 18 months of continuous eligibility and no statin use in the 6-month period before the index prescription. A new measure, dispensation delay, was measured as the gap between the most recent physician or hospital visit and the fill date of the index prescription. Five categories of dispensation delay were created--no delay, 1 to 7 days, 8 to 30 days, 31 to 183 days, and >183 days. Nonpersistence was defined as a gap of >or=30 days in the statin prescription supply during the follow-up period. Cox proportional hazards regression was used to model the risk of the initial dispensation delay on the time to discontinuation, controlling for such variables as demographic characteristics, comorbidities, physician specialty, and previous health care utilization. RESULTS: The final sample included 19,038 patients. Among all variables studied, the dispensation-delay variables were the most significant predictors of non-persistence, with a longer delay predicting a higher risk of early discontinuation. Patients with delays in filling the initial prescription of >30 days but <183 days were 30% more likely to discontinue therapy than those without delays (hazard ratio=1.30; 95% CI=1.20-1.40). CONCLUSIONS: The delay in filling the first statin prescription significantly predicted future non-persistence. Use of this measure may allow early identification of patients at high risk for early discontinuation.

Comparison of costs associated with the use of etanercept, infliximab, and adalimumab for the treatment of rheumatoid arthritis.

A retrospective study of health plan costs related to rheumatoid arthritis (RA) revealed that etanercept was associated with the lowest drug and outpatient costs to the health plan than infliximab and adalimumab. Compared with etanercept, infliximab was related to 55% higher postindex RA-related monthly total health care costs paid by the health plan, based on adjusted analyses (95% confidence interval, 1.47-1.64). Patients receiving adalimumab had 12% higher costs (95% confidence interval, 1.04-1.21). The study showed the average dispensing dose increase was greatest for infliximab (17.4%) and least for etanercept (4.1%).

Association of Part D coverage gap with COPD medication adherence.

OBJECTIVES: This study assessed the association of the Medicare Part D coverage gap with medication adherence among beneficiaries with chronic obstructive pulmonary disease (COPD). STUDY DESIGN: Retrospective observational study based on Medicare claims data. METHODS: A 5% random sample of Medicare claims data (2006-2010) was used in this study. Beneficiaries diagnosed with COPD and treated with long-acting bronchodilators (LABDs) were assigned to an exposure cohort (at risk of the coverage gap) or a control cohort (otherwise). The exposure and control cohorts were matched using high-dimensional propensity scores. Adherence was defined as ≥80% of the proportion of days covered by LABDs. Logistic regressions controlling for unbalanced covariates post matching were applied to assess the association of the coverage gap with adherence. RESULTS: The final matched exposure and control cohorts each included 4147 patient-year observations with about 42% and 46% of them adherent to LABDs, respectively. About 17% of the exposure cohort hit the coverage gap after October 31. Logistic regression showed that, compared with the control cohort, the beneficiaries in the exposure cohort had a significantly lower likelihood of being adherent if they hit the coverage gap later in the year (odds ratio [OR], 0.603; 95% CI, 0.493-0.738), or had a lower likelihood without statistical significance if otherwise (OR, 0.931; 95% CI, 0.846-1.024). CONCLUSIONS: The findings suggest that the Part D coverage gap was associated with lower adherence in patients with COPD, which may serve as evidentiary support for phasing out the coverage gap by 2020.

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

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 postinflammatory 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. DISCLOSURES: 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.

Association of early suspected acute exacerbations of idiopathic pulmonary fibrosis with subsequent clinical outcomes and healthcare resource utilization.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) may be complicated by episodes of acute exacerbation. This study quantified the association between occurrence of suspected acute exacerbations of IPF (AEx-IPF) in the 6 months post-IPF diagnosis with clinical outcomes and IPF-related healthcare resource utilization (HRU). METHODS: U.S. pulmonologists participated in a retrospective chart review of IPF patients. Patient eligibility criteria included: 1) ≥40 years of age and a confirmed date of first IPF diagnosis with HRCT and/or lung biopsy between January 2011-June 2013; 2) 2 separate FVC results recorded around first diagnosis and 6 months post-diagnosis. Patients with a suspected AEx-IPF within 6 months post-diagnosis were categorized as "early AEx-IPF." Subsequent clinical outcomes and IPF-related HRU were assessed from 6 months post-diagnosis until the latest physician contact date. RESULTS: The sample included 490 IPF patients from 168 pulmonologists; 72 (15%) patients had a suspected early AEx-IPF. At IPF diagnosis, the mean (SD) age was 61 (11) years, 68% were male, and the mean FVC percent predicted was 60% (26%). Compared to patients without a suspected early AEx-IPF, patients with an early AEx-IPF had higher mortality risk (HR = 2.87, p < 0.001) and higher rates of subsequent suspected AEx-IPF (IRR = 3.87, p < 0.001), outpatient visits (IRR = 1.46, p < 0.001), ER visits (IRR = 4.39, p < 0.001), hospitalizations (IRR = 7.96, p < 0.001), and ICU stays (IRR = 9.74, p < 0.001). CONCLUSIONS: Using a large sample of IPF patients from varied practice settings, we found a strong relationship between suspected early AEx-IPF and worse subsequent clinical outcomes and increased IPF-related HRU. This relationship was particularly pronounced for acute resource use.

Healthcare resource utilization among patients diagnosed with idiopathic pulmonary fibrosis in the United States.

OBJECTIVES: Few studies have characterized healthcare resource utilization among patients with idiopathic pulmonary fibrosis. The objective of this study is to assess healthcare resource utilization among patients with idiopathic pulmonary fibrosis as compared to members without this condition. METHODS: Patients newly diagnosed with idiopathic pulmonary fibrosis were identified from a national administrative claims database (2006-2011) as having ≥ 2 claims with idiopathic fibrosing alveolitis, or ≥ 1 claim with idiopathic fibrosing alveolitis and ≥ 1 claim with post-inflammatory pulmonary fibrosis (earliest claim with idiopathic fibrosing alveolitis denoted the index date), a procedure of lung biopsy or high-resolution computed tomography within ± 90 days of the index date, 12-month pre-index continuous enrollment, plus ≥ 2 confirmatory idiopathic fibrosing alveolitis diagnoses after the procedure. For each idiopathic pulmonary fibrosis patient, three members without the condition were matched by age/gender/region/payer type. Demographic/clinical characteristics were measured during the 1-year pre-index period. Healthcare resource utilization was assessed by quarter during 1-year pre- and post-index periods. Generalized estimating equation models controlling for patient characteristics were constructed to estimate adjusted post-index healthcare resource utilization. RESULTS: In total, 1735 patients with idiopathic pulmonary fibrosis and 5205 without (mean age = 71.5 years; 46.1% female) were included. Adjusted results revealed idiopathic pulmonary fibrosis patients were more likely to use healthcare resources than members without the condition 1-year post-index (number of hospitalizations, emergency room visits, and outpatients visits: 0.63 vs 0.31, 0.62 vs 0.48, and 5.7 vs 3.1 per person-year, respectively). CONCLUSIONS: Healthcare resource utilization is considerably higher among patients with idiopathic pulmonary fibrosis than members without the condition. Effective treatments for patients with idiopathic pulmonary fibrosis are needed to help reduce burden of healthcare resource use.

Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the california medicaid program.

OBJECTIVES: To investigate persistence and adherence of medication treatment in chronic overactive bladder/urinary incontinence (OAB/UI) patients, and to evaluate OAB/UI-related comorbidity events associated with persistence. METHODS: Pharmaceutical outcomes research with a health-care provider perspective was conducted on a California Medicaid (Medi-Cal) chronic OAB/UI population. The primary end point was medication possession ratio (MPR), which was used to measure refill adherence. Secondary end points measuring persistence patterns included discontinuation of OAB drug therapy (medication-uncovered interval > 30 days) and time to discontinuation (period from the index date until the first discontinuation date). Significant factors on nonpersistence were found by using a Cox Proportional Hazards model. Factors contributing to nonadherence (MPR < 0.8) and the relationship between OAB/UI comorbidity events and persistence were examined by logistic regressions. RESULTS: Of 2496 eligible patients, 36.9% had only one OAB/UI prescription. The mean MPR was 0.34 (SD 0.21) and the median was 0.3, indicating that on average only about one-third of period of time since medication initiation was covered by the therapy. Only 122 patients exhibited > 80% adherence during the 6-month follow-up-period. Significant predictors of higher persistence included: white ethnicity, previous hospitalization length, starting with tolterodine or oxybutynin extended-release, and previous use of topical drugs or antipsychotics. Nevertheless, previous depression or urinary tract infection (UTI) diagnosis, polypharmacy, significantly increased the odds of early discontinuation. Treatment discontinuation increased the risk of UTI diagnosis by 37% in the post-treatment period (P = 0.03; OR 1.37; 95% CI 1.03-1.84), but had no significant effect on other OAB/UI-related comorbidities. CONCLUSIONS: For chronic OAB/UI patients identified in this study, both persistence and adherence with medication treatment were suboptimal. These results suggest that persistence and treatment discontinuation remains problematic for the OAB/UI population.