Evaluation of Treatment Patterns and Maintenance Dose Titration Among Patients With Crohn's Disease Initiating Biologics With 3 Years of Follow-Up.

Background: There is limited real-world evidence on treatment patterns of patients with Crohn's disease (CD) initiating biologics with an extensive follow-up period. This study describes persistence and dose titration among CD patients with 3 years of follow-up. Methods: This retrospective observational study was conducted using the STATinMED RWD Insights all-payer medical and pharmacy data. Adult patients with at least 1 CD medical claim and at least 1 medical/pharmacy claim for a biologic (adalimumab [ADA], certolizumab pegol (CZP), infliximab [IFX] and its biosimilar products [IFX-BS], ustekinumab [UST], and vedolizumab [VDZ]) between September 2016 and October 2018 were identified. Commercially insured patients with continuous capture for at least 12 months before and at least 36 months after biologics initiation were selected. Confirmed CD patients were included in the final cohort. Baseline patient characteristics and treatment patterns over the 3-year follow-up period were evaluated. Results were summarized using means and SD or counts and percentages. Results: A total of 2309 confirmed patients with CD were identified (847 [36.7%] IFX, 534 [23.1%] ADA, 486 [21.1%] VDZ, 394 [17.1%] UST, 85 [3.7%] CZP, and 72 [3.1%] IFX-BS). CZP and IFX-BS were excluded due to small sample sizes. Approximately half of CD patients were between ages 35 and 54. Patients on UST had a higher Charlson Comorbidity Index score. Common comorbidities (>10%) included anemia, anxiety, depression, and hypertension. Persistence over 3 years' follow-up was highest for UST (61.4%) patients, followed by VDZ (58.0% ), ADA (52.1% , and IFX (48.1%). The discontinuation rate without switch or restart was highest for ADA (37.3%), followed by UST (30.7%), IFX (28.1%), and VDZ (25.3%). Over the 3 years of follow-up, the dose titration rate was highest for IFX (76.5%) and lowest for UST (50.8%). In particular, UST had the lowest dose escalation rate (35.5%) and highest dose-reduction rate (16.5%). Conclusions: Patients with CD on UST had the highest persistence and lowest dose escalation across different biologic users over the 3-year follow-up period, possibly suggesting a better clinical response of UST. Future studies with longer follow-up adjusting for confounders are needed to better understand treatment patterns among biologics users.

Assessment of Evidence-Based Standards in the Treatment of Advanced Prostate Cancer in a Community Practice.

INTRODUCTION: Although the monitoring of patients with advanced prostate cancer is essential to optimize treatment, little is known about adherence to guidelines. In this study we compared testing practices at an integrated urology/radiation oncology group practice with evidence-based guidelines and best practices. METHODS: Electronic medical records up to December 2014 from the integrated urology/radiation oncology group practice were queried to identify patients who received androgen deprivation therapy and in whom advanced disease was staged as androgen deprivation therapy sensitive, subcastration resistant (incompletely defined probable castration resistant prostate cancer) or castration resistant after April 2011 and for 6 months or more. Frequency of prostate specific antigen and testosterone level testing as well as imaging (magnetic resonance imaging, computerized tomography, positron emission tomography/computerized tomography, bone scan or x-ray) was evaluated, and compared to national guidelines and best practices. RESULTS: Overall 346 patients with androgen deprivation therapy sensitive prostate cancer, 90 with subcastration resistant prostate cancer and 102 with castration resistant prostate cancer met the study inclusion criteria. On average, prostate specific antigen was tested every 4.7, 3.7 and 3.3 months for patients with androgen deprivation therapy sensitive disease, subcastration resistant prostate cancer and castration resistant prostate cancer, respectively, compared with the 3 to 12 months and 3 months recommendations of the National Comprehensive Cancer Network and RADAR (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence) for patients with androgen deprivation therapy sensitive disease and nonmetastatic castration resistant prostate cancer, respectively. Testosterone levels were assessed within 6 months of classification for 23% and 46% of patients with subcastration resistant prostate cancer and castration resistant prostate cancer, respectively. Finally, 28% and 46% of patients with subcastration resistant prostate cancer and castration resistant prostate cancer, respectively, underwent some type of imaging within 6 months. CONCLUSIONS: This retrospective study of patients receiving androgen deprivation therapy at a particular integrated urology/radiation oncology group practice demonstrated adherence to prostate specific antigen best practices. However, there was some room for improvement in terms of testosterone testing and imaging.

Burden of systemic glucocorticoid-related complications in severe asthma.

OBJECTIVES: Although systemic glucocorticoids (SGCs) are efficacious, their chronic use is associated with a range of complications. Yet limited data are available about the risks following chronic use in patients with severe asthma, who are at risk of long-term SGC-related complications. This study was carried out to investigate the risks of developing SGC-related complications, and to quantify the associated healthcare resource utilization and costs for patients with severe asthma in the United States. METHODS: This was a longitudinal, open-cohort, observational study. Medicaid claims data (1997-2013) for patients ≥12 years old with ≥2 asthma diagnoses were used. A total of 26,987 SGC non-users were identified for inclusion in the study, alongside 3628 SGC users with ≥6 months' continuous SGC use. RESULTS: Multivariate generalized estimating equation models were used to estimate the adjusted risk of developing SGC-related complications, and to quantify the associated healthcare resource utilization and costs. This analysis compared SGC users with SGC non-users, and found that SGC users had an increased likelihood of developing complications. A significant dose-response relationship was demonstrated between chronic SGC use and risk of developing any complications (odds ratios for low, medium, and high SGC exposure were 2.03 [p = .0511], 2.85 [p < .0001], and 3.64 [p < .0001], respectively, vs. SGC non-users). The increased likelihood of SGC-related complications translated into estimated annual healthcare costs for SGC users of $2712 to $8560 above those of SGC non-users. A key limitation of this study is the disparity in age between the SGC users and the SGC non-users; however, age was included as a confounding factor in the analysis. CONCLUSIONS: These findings confirm the risk associated with chronic use of SGCs, irrespective of dose level, and highlight the need for new SGC-sparing treatment strategies for patients with severe asthma.

Retrospective analysis of the impact of increasing access to long acting reversible contraceptives in a commercially insured population.

BACKGROUND: Unintended pregnancies have been shown to be associated with high costs for the healthcare system, among other adverse impacts, but could still account for up to 51 % of pregnancies in the US. Improvements in contraception among women are needed. Long acting reversible contraceptives (LARCs), which have proved their safety and efficacy, have been found to significantly decrease the risk of unintended pregnancy. Yet they are still marginally employed. This study aims at investigating the evolution of LARC use over 15 years and at assessing the impact of the introduction of newer LARCs on LARC use relative to all contraceptive use. METHODS: This retrospective study identified women with LARC or short acting reversible contraceptive (SARC) claims from a US insurance claims database (01/1999-03/2014). Yearly proportions of LARC users relative to all contraceptive users were reported. Generalized estimating equation models were used to assess the impact of user characteristics, such as age group (15-17, 18-24, 25-34, and 35-44), and of time periods related to the introduction of new LARCs (01/2001: Mirena, 07/2006: Implanon, 01/2013: Skyla) on LARC use. RESULTS: A total of 1,040,978 women were selected. LARC use increased yearly from 0.6 % (1999) to 16.6 % (2013) among contraceptive users. Time periods associated with the introduction of a newer LARC were significant predictors of LARC use; women in 2006-2012 and 2013-2014 were respectively 3.7-fold (95 % CI:3.57-3.74) and 6.6-fold (95 % CI:6.43-6.80) more likely to use LARCs over SARCs relative to women in 2001-2006. The increase in LARC use was especially pronounced in young women. Compared to women aged 18-24 in 2001-2006, women aged 18-24 in 2006-2012 and 2013-2014 were respectively 6.4-fold (95 % CI:5.91-6.86) and 14.7-fold (95 % CI:13.59-15.89) more likely to use LARCs over SARCs. CONCLUSIONS: This broadly representative commercial claim-based study showed that the proportion of privately insured women of childbearing age using LARCs increased over time and that the introduction of newer LARCs corresponded with significant increases in overall LARC use. Future research is needed to assess LARC use in uninsured or publicly-insured populations.

Dose-Response Relationship Between Long-Term Systemic Corticosteroid Use and Related Complications in Patients with Severe Asthma.

BACKGROUND: Systemic corticosteroids are a leading cause of drug-related complications, yet little has been done to quantify the dose-response relationship between systemic corticosteroid exposure and complications in patients with severe asthma. OBJECTIVES: To (a) evaluate the risk of developing systemic corticosteroid-related complications by corticosteroid exposure in severe asthma and (b) quantify the associated health care resource utilization and costs. METHODS: This is a retrospective study using administrative claims data from a large commercial database between 2003 and 2014. Multivariate generalized estimating equation models were used to compare corticosteroid-related complications in patients continuously exposed to at least 5 mg of prednisone or equivalent for ≥ 6 months with a 1:1 ratio of propensity score-matched patients with asthma who did not use corticosteroids. RESULTS: A total of 12,697 corticosteroid users and as many matched nonusers were identified. The odds of developing associated complications increased significantly in a dose-dependent manner with systemic corticosteroid exposure: odds ratios were 2.50, 2.95, and 3.32 (P values <0.05) for low (defined as < 5 mg/day), medium (≥ 5-10 mg/day), and high (>10 mg/day) exposure, respectively, relative to no exposure. Health care resource utilization increased significantly with levels of systemic corticosteroid exposure. Hence, incidence rate ratios for inpatient visits with low, medium, and high exposure relative to none were estimated to be 1.86, 2.40, and 3.37, respectively (P < 0.05). CONCLUSIONS: A significant dose-response relationship was found between the long-term use of systemic corticosteroids and the risk of developing systemic corticosteroid-related complications in patients with severe asthma, resulting in increased burden and costs on the health care system that intensified with systemic corticosteroid exposure. DISCLOSURES: Funding for this study was provided by GlaxoSmithKline, Study number H0-15-15930, to Analysis Group for the conduct of this study. Lefebvre, Duh, and Gozalo are employees of Analysis Group, a contract research organization that has received research grants from GlaxoSmithKline. Robitaille was employed by Analysis Group at the time of this study. Yancey, Forshag, Lin, and Albers are employees of GlaxoSmithKline and own company stock. Dalal and Ortega were employed by GlaxoSmithKline at the time of this study. Lefebvre had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Additionally, all listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Study concept and design were contributed by Dalal, Duh, Albers, Yancey, Ortega, Forshag, and Lefebvre. Data acquisition was by Dalal, Gozalo, Robitaille, Forshag, and Lefebvre and was analyzed and interpreted by Dalal, Gozalo, Robitaille, Albers, Yancey, Ortega, Forshag, and Lefebvre. The manuscript was drafted and approved by Dalal, Duh, Gozalo, Robitaille, Albers, Yancey, Ortega, Forshag, Lin, and Lefebvre.

Acute and chronic systemic corticosteroid-related complications in patients with severe asthma.

BACKGROUND: Many patients with severe asthma require maintenance treatment with systemic corticosteroids (SCSs) to control daily symptoms and prevent serious acute exacerbations, but chronic SCS use is associated with complications. OBJECTIVE: We sought to evaluate the risk of SCS-related complications by SCS exposure and quantify the associated health care costs and resource use in patients with severe asthma. METHODS: We performed a longitudinal, open-cohort, observational study using health insurance claims data (1997-2013: Medicaid) from Florida, Iowa, Kansas, Missouri, Mississippi, and New Jersey. Eligible patients were 12 years old or older with 2 or more asthma diagnoses and had more than 6 months of continuous SCS use. An open-cohort approach was used to classify patients' follow-up into low, medium, and high SCS exposure (≤ 6, >6-12, and >12 mg/d, respectively). Multivariate generalized estimating equation models were used to estimate the adjusted risk of SCS-related complications for patients with medium and high exposure compared with patients with low exposure and quantify the resulting health care resource use and costs. RESULTS: The study included 3628 patients (mean age, 57.6 years; 68% female). Patients with medium and high SCS exposure had significantly higher risks of SCS-related complications, including infections and cardiovascular, metabolic, psychiatric, ocular, gastrointestinal, and bone-related complications (odds ratio, 1.23-2.12 by complication; P < .05 for all but one) versus those with low (reference group) SCS exposure. Medium and high SCS exposure were also associated with significantly more emergency department visits (incidence rate ratios, 1.31 [P = .0004] and 1.78 [P < .0001]) and inpatient visits (incidence rate ratios, 1.25 [P < .0001] and 1.59 [P < .0001]) versus low SCS exposure. CONCLUSIONS: A significant dose-response relationship was demonstrated between chronic SCS use and risk of SCS-related complications in patients with severe asthma. Effective SCS-sparing strategies might reduce the burden associated with SCS-related complications in patients with severe asthma.

Treatment Sequences and Pharmacy Costs of 2 New Therapies for Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The approval of new therapies for metastatic castration-resistant prostate cancer (mCRPC), including the oral agents abiraterone acetate and enzalutamide, has altered the standard of care for patients with mCRPC. Little information exists regarding the sequences in which new therapies for mCRPC with evidence of survival benefits are used. OBJECTIVE: To describe the sequence of medication use for patients with mCRPC as observed in 3 healthcare data sets. METHODS: Three healthcare claims data sets were used to identify patients with mCRPC who had no previous use of and were newly initiating 1 of the 2 oral study drugs (ie, abiraterone acetate or enzalutamide). The index date was the first study drug claim after September 1, 2012. Patients were followed until the data cutoff or until being lost to follow-up. Descriptive statistics summarized the proportion of patients receiving 1 line of therapy versus ≥2 lines of therapy. The use of a corticosteroid and the mean monthly pharmacy costs of abiraterone acetate or enzalutamide during the follow-up period were compared between the cohorts. RESULTS: A total of 3525 patients with mCRPC were identified from data set 1, 499 patients from data set 2, and 1949 patients from data set 3. The first-line use of abiraterone acetate was observed in 74%, 82%, and 80% of data sets 1, 2, and 3, respectively, and the first-line use of enzalutamide was seen in 26%, 18%, and 20%, respectively, of these same populations. The concomitant use of corticosteroids was observed in patients receiving first-line abiraterone acetate and in patients receiving first-line enzalutamide in all 3 data sets. After September 2012, abiraterone acetate was the most frequently administered therapy for mCRPC among the 2 oral agents, abiraterone acetate and enzalutamide. The monthly pharmacy costs associated with abiraterone acetate were significantly lower than those associated with enzalutamide in all 3 data sets. CONCLUSIONS: Based on the data used in this study, abiraterone acetate was more frequently administered for patients with mCRPC than enzalutamide. The concomitant use of corticosteroids was common in patients receiving first-line abiraterone acetate or first-line enzalutamide therapy. Patients receiving abiraterone acetate had significantly lower monthly pharmacy costs than patients receiving enzalutamide. These findings may facilitate the estimation of the budgetary impact of a treatment mix for population health and for managed care stakeholders.