Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Disease Burden, Treatment Patterns, and Economic Impact of Rectovaginal Fistulas in Patients with Crohn's Disease: Findings from a Retrospective, Observational, Longitudinal Study Based on US Claims Databases.

BACKGROUND: Crohn's-related rectovaginal fistulas (RVF) greatly impact quality of life and are notoriously difficult to treat. The aim of this study was to assess the burden of recurrent episodes of care for RVF and its economic impact. METHODS: A retrospective observational cohort study of administrative US claims databases was conducted. Eligible patients were female adults, with a diagnosis code for Crohn's disease with or without a diagnosis/procedural code for RVF. For the RVF cohort, rates of recurrence of RVF episodes of care were estimated using Kaplan-Meier analyses. Healthcare resource utilization (HCRU) and direct healthcare costs were compared between the RVF cohort and RVF-free cohort. RESULTS: Mean ages in the RVF cohort (n = 963) and RVF-free cohort (n = 56,564) were 47.2 and 50.8 years, with a mean follow-up period of 58.7 and 49.8 months, respectively. For the RVF cohort, the probability of having a second RVF episode of care within 2 years of the first one was estimated to be 35.9% and of having a third episode within 2 years of the second was 47.8%. During the first 2 years, the RVF cohort had 67% more inpatient admissions than the RVF-free cohort with each RVF episode of care being associated with 16% more admissions. The estimated incremental cost associated with having RVF was US$17,561, with an incremental cost of US$11,607 for each additional RVF episode of care. CONCLUSIONS: This real-world study highlights the significant impact of RVF in patients with Crohn's disease with regard to repeat interventions and associated HCRU and direct healthcare costs, suggesting novel therapeutics are needed in this patient population.

Real-world experience of pediatric patients treated with peanut (Arachis hypogaea) allergen powder-dnfp.

BACKGROUND: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) is the first oral immunotherapy indicated for children aged 4 to 17 years with peanut allergy. There are limited real-world data on patients treated with PTAH. OBJECTIVE: To characterize pediatric patients treated with PTAH and associated treatment patterns in US clinical practice. METHODS: US-based physicians with allergy and immunology training treating patients with peanut allergy aged 4 to 17 years with PTAH were recruited from an existing physician panel and completed an online case report form (October to December 2021) with data abstracted from patient medical charts. Physician practice circumstances, patient characteristics, and PTAH treatment patterns were reported. Time to reach the 300-mg dose and treatment persistence were assessed using Kaplan-Meier analysis. RESULTS: A geographically balanced sample of 43 physicians contributed data for 118 demographically diverse pediatric patients. Patients had heterogeneous diagnostic test results, with a wide range of peanut-specific immunoglobulin E levels; 6.8% received an oral food challenge. During the updosing phase, there were no temporary interruptions and 5.1% of the patients required downdosing. Patients reached the 300-mg dose at a median of 21.3 weeks post-initiation. The rate of PTAH persistence at 24 weeks was 93.4%. Only 1 patient discontinued treatment because of treatment-related systemic allergic symptoms, and the remaining discontinuations were for reasons other than treatment-related symptoms. Prophylactic antihistamines were used by 33.9% of the patients to prevent PTAH adverse effects. CONCLUSION: PTAH was prescribed in demographically diverse patients with a wide range of peanut-specific immunoglobulin E levels. Treatment persistence with PTAH was high in this study population, with a small number of patients experiencing treatment modification.

Treatment and comorbidity burden among people living with HIV: a review of systematic literature reviews.

Background: As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV. Objective: To better understand the current treatment and comorbidity burden in people living with HIV (PLWH). Methods: Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies. Results: Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times. Conclusions: There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.

Management of Patients with Metastatic Castration-Sensitive Prostate Cancer in the Real-World Setting in the United States.

PURPOSE: This study provides a contemporary assessment of the treatment patterns, health care resource utilization (HRU) and costs among metastatic castration-sensitive prostate cancer (mCSPC) patients in the U.S. MATERIALS AND METHODS: Adults with mCSPC were selected from Optum's de-identified Clinformatics® Data Mart Database (Commercial insurance/Medicare Advantage [COM/MA]; January 1, 2014-July 31, 2019) or Medicare Fee-for-Service (FFS; January 1, 2014-December 31, 2017). The index date was the first metastatic disease diagnosis date on/after the first prostate cancer diagnosis (without prior evidence of castration resistance). Patients were observed for 12 months pre-index (baseline) through their mCSPC period (from index until castration resistance or followup end). First-line (1L) mCSPC therapy was assessed during the mCSPC period; all-cause HRU and health plan-paid costs per-patient-per-year (PPPY) were measured during baseline and mCSPC periods. RESULTS: Among 6,517 COM/MA and 13,324 Medicare-FFS mCSPC patients over ∼10 months (median mCSPC period), 38% and 48% remained untreated/deferred treatment, and 45% and 46% received 1L androgen deprivation therapy (ADT) monotherapy, respectively. 1L abiraterone acetate and docetaxel were used among 7% and 6% of COM/MA and 1% and 2% of Medicare-FFS patients, respectively. HRU increased from baseline to mCSPC period, resulting in increased health plan-paid costs from $21,201 to $108,767 in COM/MA and from $16,819 to $69,639 PPPY in Medicare-FFS. CONCLUSIONS: This study highlights the limited use of newer therapies that improve survival in men with mCSPC in the U.S. HRU and costs increased substantially after onset of metastasis. Given the emergence of newer effective mCSPC therapies, further evaluation of future real-world mCSPC treatment patterns and outcomes is warranted.

Real-World Utilization and Safety of Daratumumab IV Rapid Infusions Administered in a Community Setting: A Retrospective Observational Study.

BACKGROUND: Some institutions have implemented a daratumumab intravenous rapid-infusion protocol in which patients with multiple myeloma (MM) receive their third and subsequent infusions within ~ 90 min instead of ≥ 3 h. OBJECTIVE: This study sought to understand the utilization, effectiveness, and infusion reactions (IRs) observed in patients with MM who received daratumumab rapid infusions. METHODS: Electronic medical records from Florida Cancer Specialists & Research Institute were used. Adult patients with MM who received one or more rapid daratumumab infusion (full dose in ≤ 110 min) at their third or later infusion of the first daratumumab-containing regimen (index date: 16 November 2015 to 15 March 2019) were included. IRs included events that (1) occurred ≤ 24 h post-daratumumab infusion or (2) were stated as an IR in the patient charts. Non-IR adverse events (AEs) were events attributed to daratumumab in patient charts that did not meet the IR definition. RESULTS: In total, 147 patients received one or more rapid infusion in their first daratumumab-containing regimen. Median time from initial MM diagnosis to index date was 2.5 years. Non-IR AEs occurred in 10.2% of patients during treatment, and 36.7% experienced one or more IR after receiving a daratumumab infusion. No IRs occurred after a rapid infusion. The overall response rate was 91.1% (after rapid infusions only: 71.3%). CONCLUSIONS: This study provides real-world evidence on the practice patterns of daratumumab rapid infusions in a large community-based oncology clinic system. These results suggest that treatment regimens including daratumumab rapid infusions at the third infusion or later were well-tolerated, and their effectiveness was comparable to that observed in clinical trials.

Disease Management and Outcomes in Patients Hospitalized for Acute Heart Failure in Japan.

INTRODUCTION: This study described patients hospitalized for acute heart failure (AHF) in Japan who received intravenous (IV) diuretics and/or vasodilators as the initial therapy. METHODS: The Japan Medical Data Vision database was used to identify adult patients hospitalized for AHF during 2013-2017, who were hemodynamically stable at presentation and treated with IV diuretics and/or IV vasodilators as initial therapy. Treatment patterns and use of cardiac rehabilitation, as well as outcomes (e.g., length of stay [LOS], in-hospital mortality, HF-readmission) were reported overall and by year of AHF hospitalization. RESULTS: Of 30,360 patients (mean age = 80.0 years; 52.2% male), 87.0% were treated during the hospitalization with IV diuretics, 63.9% with IV vasodilators, and 13.8% with intensified therapies. On average, the duration of IV therapy was 10.6 days. In-hospital cardiac rehabilitation was utilized by 51.7% of the patients for 11.7 days on average. Mean LOS was 23.3 days, while in-hospital mortality and 30-day HF readmission post-discharge were 13.2 and 9.5%, respectively. Hospitalization outcomes remained stable between 2013 and 2017 despite important changes in AHF management such as a decrease in carperitide use (55.9-40.0% in 2017), and increases in use of tolvaptan (from 14.2% in 2013 to 31.3% in 2017) and of cardiac rehabilitation (from 43.2% in 2013 to 56.1% in 2017). Patients with intensified therapies had the longest IV therapy duration (mean 23.8 days vs. 5.5-9.9 days), the highest cardiac rehabilitation services use (60.2 vs. 38.3-57.0%), the longest LOS (mean 36.7 vs. 16.3-22.2 days), and the highest in-hospital mortality (37.4 vs. 3.1-12.4%) compared to the other treatment groups. CONCLUSIONS: Contemporary treatment for AHF hospitalization in Japan comprises a long duration of IV therapy followed by extended use of oral medications and in-hospital cardiac rehabilitation prior to discharge. Patients requiring intensified therapies had much longer LOS and higher in-hospital mortality.

Identification of patients with metastatic castration-sensitive or metastatic castration-resistant prostate cancer using administrative health claims and laboratory data.

OBJECTIVE: To develop algorithms to identify metastatic castration-sensitive prostate cancer (mCSPC) patients and castration-resistant prostate cancer (mCRPC) patients, using health claims data and laboratory test results. METHODS: A targeted literature review summarized mCSPC and mCRPC patient selection criteria previously used in real-world retrospective studies. Novel algorithms to identify mCSPC and mCRPC were developed based on diagnosis codes indicating hormone sensitivity/resistance, prostate-specific antigen (PSA) test results, and claims for castration and mCRPC-specific treatments. These algorithms were applied to claims data from Optum Clinformatics Extended DataMart (Date of Death) Databases (commercial insurance/Medicare Advantage [COM/MA]; 01 January 2014-31 July 2019) and Medicare Fee-for-Service (Medicare-FFS; 01 January 2014-31 December 2017). RESULTS: Previous real-world studies identified mCSPC primarily based on metastasis diagnosis codes, and mCRPC based on mCRPC-specific drugs. Using the current study's algorithms, 7034 COM/MA and 19,981 Medicare-FFS patients were identified as having mCSPC, and 2578 COM/MA and 11,554 Medicare-FFS as having mCRPC. Most mCSPC patients were identified based on evidence of being hormone/castration-naive. Patients were identified as having mCRPC most commonly based on rising PSA (COM/MA), or at the metastasis diagnosis date if it occurred after castration (Medicare-FFS). Among patients with mCSPC, 14-17% had evidence of progression to castration resistance during a median 1-year follow-up period, mostly based on use of mCRPC-specific drugs. CONCLUSIONS: Comprehensive algorithms based on claims and laboratory data were developed to identify and distinguish patients with mCSPC and mCRPC. This will facilitate appropriate identification of mCSPC and mCRPC patients based on health claims data and better understanding of patient unmet needs in real-world settings.

Long-Term Benefits of Rapid Antiretroviral Therapy Initiation in Reducing Medical and Overall Health Care Costs Among Medicaid-Covered Patients with Human Immunodeficiency Virus.

BACKGROUND: New guidelines for the treatment of human immunodeficiency virus (HIV) suggest that morbidity and mortality could be reduced if antiretroviral therapy (ART) was initiated immediately after diagnosis, regardless of CD4 cell count. OBJECTIVE: To assess real-world time to ART initiation and describe medical, pharmacy, and total health care costs in the 6-, 12-, 24-, and 36-month periods after HIV diagnosis based on time to ART initiation among Medicaid-covered patients. METHODS: Multistate Medicaid data (January 2012-March 2017) was used to identify adults with HIV-1 initiating ART ≤ 360 days of initial HIV-1 diagnosis. People living with HIV (PLWH) were sorted into mutually exclusive cohorts based on time from diagnosis to ART initiation (≤ 14 days, > 14 to ≤ 60 days, > 60 to ≤ 180 days, and > 180 to ≤ 360 days). ART regimen had to include a protease inhibitor, an integrase strand transfer inhibitor, or a non-nucleoside reverse transcriptase inhibitor, with ≥ 2 nucleoside reverse transcriptase inhibitors. Medical, pharmacy, and total health care costs in the 6, 12, 24, and 36 months following HIV diagnosis were stratified by timeliness of ART initiation. RESULTS: Of 974 patients, 347 (35.6%) initiated ART > 360 days after diagnosis and were excluded. Among the remaining 627 eligible patients, mean age was 39.9 years, 42.7% were female, and 53.9% were black. Among them, 128 (20.4%) were treated ≤ 14 days, 228 (36.4%) between > 14 and ≤ 60 days, 163 (26.0%) between > 60 and ≤ 180 days, and 108 (17.2%) between > 180 and ≤ 360 days. Among patients treated ≤ 180 days, 4.6% had ≥ 1 opportunistic infection in the 6-month period before ART initiation; this proportion reached 5.6% for patients treated >180 and ≤ 360 days. Over the 6-, 12-, 24-, and 36-month periods after diagnosis, per-patient-per-month (PPPM) medical costs were lower for patients who initiated ART ≤ 14 days than for those who initiated > 180 and ≤ 360 days after diagnosis (6 months: $1,611 [≤ 14 days] vs. $3,008 [> 180 and ≤ 360 days]; 12 months: $1,188 vs. $2,110; 24 months: $754 vs. $1,368; 36 months: $651 vs. $1,196). Over the same periods, medical costs generally accounted for > 50% of total health care costs for patients who initiated ART between > 60 and ≤ 180 days and > 180 and ≤ 360 days and for 30%-40% of total health care costs for patients treated ≤ 14 days and between > 14 and ≤ 60 days. Total PPPM health care costs increased with delay of ART initiation in the 36-month period after diagnosis ($2,058 [treated ≤ 14 days] vs. $2,310 [treated between > 180 and ≤ 360 days]). CONCLUSIONS: In this study from 2012 to 2017 of Medicaid PLWH treated with ART, 20.4% initiated ART ≤14 days of HIV diagnosis. Patients with delayed ART initiation accumulated more total health care costs in the 36-month period after HIV diagnosis than those initiated within 14 days, highlighting the long-term benefit of rapid ART initiation. An important opportunity remains to engage PLWH in care more rapidly. DISCLOSURES: This study was supported by Janssen Scientific Affairs, which was involved in the study design, interpretation of results, manuscript preparation, and publication decisions. Emond, Romdhani, Lefebvre, and Côté-Sergent are employees of Analysis Group, a consulting company that was contracted by Janssen Scientific Affairs to conduct this study and develop the manuscript. Shohoudi was an employee of Analysis Group at the time the study was conducted. Benson, Tandon, Chow, and Dunn are employees and stockholders of Johnson & Johnson. Parts of the material in this study have been presented at the HIV Drug Therapy Meeting; October 28-31, 2018; Glasgow, UK, and the AMCP Annual Meeting; March 25-28, 2019; San Diego, CA.

Comparison of Time to Next Treatment, Health Care Resource Utilization, and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy.

BACKGROUND: Studies assessing ibrutinib's economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT. MATERIALS AND METHODS: Optum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted. RESULTS: TTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib's higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = -$10,615; P < .0001), yielding net savings (MMCD = -$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = -$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy. CONCLUSION: During front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.

Adherence, Healthcare Resource Utilization, and Costs in Medicaid Beneficiaries with Schizophrenia Transitioning from Once-Monthly to Once-Every-3-Months Paliperidone Palmitate.

OBJECTIVES: The aim was to compare adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs before and after once-every-3-months paliperidone palmitate (PP3M) initiation in patients with schizophrenia. METHODS: Medicaid data (Iowa, Kansas, and Missouri; 1/2014-3/2017) were used to identify adults with at least one PP3M claim, ≥ 12 months of pre-index enrollment, and at least two schizophrenia diagnoses. Adequate treatment with once-monthly paliperidone palmitate (PP1M) was required pre-PP3M transition. Generalized estimating equations were used to assess linear trends in adherence to APs, HRU, and costs over the four quarters pre-PP3M transition, and to compare monthly HRU and costs 6 months pre- and 12 months post-PP3M transition as well as adherence to APs 12 months pre- and post-PP3M transition. RESULTS: Among 324 patients initiated on PP3M, the mean age was 41.4 years and 36.1% were females. Over the four quarters pre-PP3M transition, the monthly number of emergency room visits, medical costs, and inpatient costs decreased, while pharmacy costs and adherence to APs increased. For patients with ≥ 12 months of follow-up (n = 151), adherence to APs (66.2 vs. 70.2%, p = 0.3758), total (US$3371 vs. US$3456; p = 0.7000), pharmacy (US$1805 vs. US$1870; p = 0.2960), and medical costs (US$1565 vs. US$1586; p = 0.9040) remained similar pre- and post-PP3M transition, while mean monthly number of 1-day mental institute visits (1.71 vs. 1.51; p < 0.01) and associated costs (US$260 vs. US$232, p = 0.01) decreased. CONCLUSIONS: Adherence to APs, HRU, and costs were similar pre- and post-PP3M transition, suggesting that PP3M has no impact on monthly costs for patients adequately treated with PP1M, with the added flexibility of once-every-3-months dosing.

Monitoring of Hematologic, Cardiac, and Hepatic Function in Post-Menopausal Women with HR+/HER2- Metastatic Breast Cancer.

INTRODUCTION: In the treatment of metastatic breast cancer (mBC), regular monitoring is key in helping physicians to make informed clinical decisions, managing treatment side effects, and maintaining patients' quality of life. Therefore, we investigated the monitoring frequency in post-menopausal women with HR+/HER2- mBC stratified by first-line regimen. METHODS: Treatment monitoring was assessed using two complementary data sources: a medical chart review (chart review analysis) and a commercial claims database (claims analysis). Women with post-menopausal HR+/HER2- mBC who initiated first-line therapy for mBC were selected and classified under three cohorts, based on treatment received: cyclin-dependent kinase 4/6 (CDK4/6) inhibitor (i.e., palbociclib-the only CDK4/6 approved at the time of the study), endocrine therapy (ET), and chemotherapy. Frequency of monitoring [complete blood count (CBC), electrocardiogram (EKG), and liver function test (LFT)] and laboratory abnormalities detected during the first line of therapy were analyzed. RESULTS: In the chart review analysis, 64 US oncologists abstracted medical information on 401 eligible patients, including 210 CDK4/6 users, 121 ET users, 51 chemotherapy users; 19 patients used other regimens. All patients had ≥ 1 CBC; between 8.3% (ET users) and 39.5% (CDK4/6 users) had ≥ 1 EKG; and over 98% of patients had ≥ 1 LFT across all three cohorts. Among monitored patients, 64.6% had a CBC abnormality, with anemia (39.9%), leukopenia (27.4%), and neutropenia (26.7%) being the most common. Abnormal EKG readings were detected in 8.4, 0.0%, and 7.7% of CDK4/6, ET, and chemotherapy users, respectively. LFT abnormalities were detected in 14.1-26.0% of CDK4/6 and chemotherapy users, respectively. Similar frequency of monitoring was observed in the claims analysis, with the exception of EKG monitoring, for which the proportion of patients tested was higher. CONCLUSION: Post-menopausal women with HR+/HER2- mBC receiving first-line therapy with CDK4/6, ET, or chemotherapy were regularly monitored regardless of the first-line regimen received. FUNDING: Novartis Pharmaceuticals Corporation.

Risk Factors, Health Care Resource Utilization, and Costs Associated with Nonadherence to Antiretrovirals in Medicaid-Insured Patients with HIV.

BACKGROUND: Adherence to antiretrovirals (ARVs) is critical to achieving durable virologic suppression. OBJECTIVE: To investigate risk factors of poor adherence and the effect of suboptimal adherence on health care resource utilization (HCRU) and costs in Medicaid patients. METHODS: A retrospective longitudinal study was conducted using Medicaid data. Adults (aged ≥ 18 years) with human immunodeficiency virus (HIV)-1 initiating selected ARVs (index date) were identified. Adherence was measured using medication possession ratio (MPR) and proportion of days covered (PDC) at 6 and 12 months post-index. Risk factors of poor adherence (PDC < 80%) were assessed using a logistic regression. HCRU and costs were compared between suboptimal (80% ≤ PDC < 95%) and optimal (PDC ≥ 95%) adherence groups using Poisson and ordinary least square models, respectively. RESULTS: In total, 3,477 patients were identified. Using MPR, 1,282 (39.0%) of the evaluable patients had poor adherence; 667 (20.2%) had suboptimal adherence; and 1,342 (40.8%) had optimal adherence versus 1,342 (51.1%), 509 (19.0%), and 804 (30.0%), respectively, using PDC at 6 months. PDC at 12 months was even lower. Younger age (OR = 1.58; 95% CI = 1.18-2.11; P = 0.002), noncapitated coverage (OR = 1.40; 95% CI = 1.16-1.69; P < 0.001), dual Medicaid/Medicare coverage (OR = 5.98; 95% CI = 4.39-8.16; P < 0.001), no baseline ARV treatment (OR = 1.98; 95% CI = 1.62-2.41; P < 0.001), and baseline asymptomatic HIV (OR = 1.37; 95% CI = 1.13-1.68; P = 0.002) were associated with higher risk of poor adherence. Suboptimal adherence patients had higher total number of days spent in a hospital (incidence rate ratio [IRR] = 1.62; 95% CI = 1.13-2.19; P = 0.008), total number of long-term care admissions (IRR = 3.11; 95% CI = 1.26-7.39; P = 0.008), total medical costs (mean monthly cost difference = $339; 95% CI = $153-$536; P < 0.001), and inpatient costs (mean monthly cost difference = $259; 95% CI = $122-$418; P < 0.001) compared with patients with optimal adherence. CONCLUSIONS: Nonadherence to ARVs was observed in 60%-80% of Medicaid patients, depending on the adherence measure used, and was associated with incremental HCRU and costs. Age, insurance type and coverage, previous ARV treatment, and HIV symptoms were predictors of adherence. Treatment options that enhance adherence and prevent developing virologic failure with drug resistance should be considered for HIV patients. DISCLOSURES: This study was supported by Janssen Scientific Affairs, which was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions. Emond, Lafeuille, Romdhani, and Lefebvre are employees of Analysis Group, a consulting company that received research grants from Janssen Scientific Affairs to conduct this study. Dunn, Woodruff, Pesa, and Tandon are current employees and stockholders of Johnson & Johnson, owner of Janssen Scientific Affairs. Jiao was an employee of Janssen at the time of the study. Emond has received grants from Novartis, Regeneron, Aegerion, Lundbeck, Bristol-Myers Squibb, Bayer, Millennium, Allergan, AbbVie, and GlaxoSmithKline unrelated to this study. Part of the material in this study was presented at the Academy of Managed Care Pharmacy 2017 Annual Meeting; March 27-30, 2017; Denver, CO, and at the 9th International AIDS Society Conference; July 23-26, 2017; Paris, France.

Economic burden of treatment failure in chronic lymphocytic leukemia patients.

OBJECTIVE: This study assessed healthcare costs of first-line treatment failure (TF) in patients with chronic lymphocytic leukemia (CLL), a subtype of non-Hodgkin's lymphoma. METHODS: Pre-diagnosis treatment-naïve adults with ≥2 CLL diagnoses initiated on an antineoplastic agent (index date) after their first CLL diagnosis with ≥12 and ≥6 months of continuous observation pre- and post-index, respectively, were selected from the Truven Health MarketScan Research Databases. Patients had no solid malignancies in the pre-index period nor selected blood malignancies at any time. Initial therapy included antineoplastic agents initiated in the first 30 days post-index. TF occurred at the earliest of: initiation of a new antineoplastic agent, treatment resumption following a ≥3 month break, non-chemotherapy intervention (stem cell transplant or radiotherapy), hospice care or hospital mortality. The cost of TF was evaluated as the healthcare cost difference between patients with and without first-line TF using ordinary least square regressions adjusted for baseline characteristics. Non-parametric bootstrap was used to evaluate statistical significance. RESULTS: Among 2226 patients identified (mean age: 68 years; female: 41%), 46% experienced first-line TF. The average TF cost was $3011 per patient per month (p < .001). When stratifying patients by event indicating TF and by most common therapies, non-chemotherapy intervention ($7582 per patient per month; p < .0001) and fludarabine/cyclophosphamide/rituximab ($4758; p < .001) were associated with the highest TF cost, respectively. CONCLUSIONS: The cost of first-line TF is high and varies across first-line therapies. This should be considered when selecting the initial therapy in these patients.

Current Treatment Patterns Among Postmenopausal Women with HR+/HER2- Metastatic Breast Cancer in US Community Oncology Practices: An Observational Study.

INTRODUCTION: Recent approval of novel agents has changed the treatment landscape for post menopausal women with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer (mBC). The objective of this study was to describe contemporary treatment patterns among postmenopausal women with HR+/HER2- mBC in the real-world setting. METHODS: Data were collected from 64 community oncologists in the US between February and June 2017 using an online medical records extraction tool. Physicians reviewed medical records and provided information on patient demographics and disease characteristics, and treatment regimens. Treatment patterns were described overall and separately by line of therapy and type of treatment received. Discontinuation rates were estimated using Kaplan-Meier analyses to account for censoring. RESULTS: Data were collected on 401 patients. Mean age at the time of mBC diagnosis was 67 years. In the first-line setting, 52.4% of patients received a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based regimen, most commonly with an aromatase inhibitor (AI) (39.2%) or fulvestrant (10.0%); 30.2% received endocrine therapy, most commonly an AI (21.4%) or fulvestrant (5.2%) in monotherapy, while 12.7% received a chemotherapy-based regimen. In the second-line setting, 42.9% of patients received a CDK4/6 inhibitor-based regimen, 18.4% received endocrine therapy, and 22.4% received a chemotherapy-based regimen. The 18-month discontinuation rate was 34.5% for patients receiving a CDK4/6 inhibitor-based regimen and 45.8% for patients receiving endocrine monotherapy. CONCLUSION: CDK4/6 inhibitor-based regimens were the most commonly prescribed treatment in both first- and second-line settings. A wide variety of treatment sequences were observed which suggests an absence of a standard of care for postmenopausal women with HR+/HER2- mBC in real-world practice.

Pathway-based association study of multiple candidate genes and multiple traits using structural equation models.

There is increasing interest in the joint analysis of multiple genetic variants from multiple genes and multiple correlated quantitative traits in association studies. The classical approach involves testing univariate associations between genotypes and phenotypes and correcting for multiple testing that results in loss of power to detect associations. In this paper, we propose modeling complex relationships between genetic variants in candidate genes and measured correlated traits using structural equation models (SEM), taking advantage of prior knowledge on clinical and genetic pathways. We adopt generalized structured component analysis (GSCA) as an approach to SEM and develop a single association test between multiple genetic variants in a gene and a set of correlated traits, taking into account all available data from other genes and other traits. The performance of this test is investigated by simulations. We apply the proposed method to the Quebec Child and Adolescent Health and Social Survey (1999) data to investigate genetic associations with cardiovascular disease-related traits.

On the association between variables with lower detection limits.

In this paper, we define a modified version τ(b) of Kendall's tau to measure the association in a pair (X,Y) of random variables subject to fixed left censoring due to known lower detection limits. We provide a nonparametric estimator of τ(b) and investigate its asymptotic properties. We then assume an Archimedean copula for (X,Y) and express τ(b) in terms of the copula parameter α and the censoring fractions. We deduce estimators for α and for the global Kendall's tau. We develop a goodness-of-fit test for the assumed copula. We evaluate the finite-sample performance of the proposed methods by simulations and illustrate their use with a real data set on plasma and saliva viral loads.