Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within breast cancer subtypes and stages among older women: a SEER-Medicare analysis.

BACKGROUND: This study aimed to compare survival outcomes of neoadjuvant (NAC) and adjuvant chemotherapy (AdC) within each breast cancer subtype and stage among older women. METHODS: Older (≥ 66 years) women newly diagnosed with stage I-III invasive ductal breast cancer during 2010-2017 and treated with both chemotherapy and surgery within one year were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Analyses were performed within each of six groups, jointly defined based on subtype (hormone receptor [HR]-positive/human epidermal growth factor receptor 2 [HER2]-negative, HER2 + , and triple-negative) and stage (I-II and III). Kaplan-Meier curves and multivariable Cox models were used to compare overall and recurrence-free survival between NAC and AdC, with optimal full matching performed for confounding adjustment. RESULTS: Among 8,495 included patients, 8,329 (20.6% received NAC) remained after matching. Before multiple testing adjustment, Cox models showed that NAC was associated with a lower hazard for death among stage III HER2 + patients (hazard ratio = 0.347, 95% confidence interval CI 0.161-0.745) but a higher hazard for death among triple-negative patients (stage I-II: hazard ratio = 1.558, 95% CI 1.024-2.370; stage III: hazard ratio = 2.453; 95% CI 1.254-4.797). A higher hazard for death/recurrence was associated with NAC among stage I-II HR + /HER2- patients (hazard ratio = 1.305, 95% CI 1.007-1.693). No significant difference remained after multiple testing adjustment. CONCLUSIONS: The opposite trends (before multiple testing adjustment) of survival comparisons for advanced HER2 + and triple-negative disease warrant further research. Caution is needed due to study limitations such as cancer stage validity.

Real-world opioid use among patients with migraine enrolled in US commercial insurance and risk factors associated with migraine progression.

BACKGROUND: Migraineurs may be categorized as having episodic migraine (EM: < 15 headache days/month) or chronic migraine (CM: ≥ 15 days/month for > 3 months with ≥ 8 days/month having features of migraine). Opioid use has been linked to progression from EM to CM. OBJECTIVE: To describe the utilization of opioid prescriptions among patients with migraine, to determine the association between opioid use and migraine progression, and to explore demographic and clinical risk factors for migraine progression. METHODS: This retrospective cohort study used Optum's deidentified Clinformatics Data Mart Database from January 2015 to December 2018. Adult patients with a migraine diagnosis and continuous health plan enrollment were included. Opioid use was measured by average daily morphine equivalent dose, also known as morphine milligram equivalent (MME). Descriptive statistics were used to summarize the opioid use by patient demographic and clinical characteristics. A Cox proportional hazards model with stepwise selection was used to determine the risk factors of new-onset CM. RESULTS: Overall, 35% of patients with migraine (27,331 of 78,134) received prescription opioids (> 0 MME/day) during the 12-month follow-up period. Higher opioid dosage was found in patients who had CM and comorbidities of interest. Compared with patients with EM, patients with CM were twice as likely to receive at least 20 MME/day (CM 3.8% vs EM 1.9%) and had a higher median opioid day supply (CM 20 vs EM 10) during follow-up. About 7% of patients with CM with at least 1 opioid prescription had at least 50 MME/day in any 90-day period during follow-up. A significant association was found between MME level and the likelihood of new-onset CM. Additional significant risk factors of migraine progression included younger age, female sex, South and West regions, and having a diagnosis of medication overuse headache, depression, back pain, or fibromyalgia (all P < 0.05). CONCLUSIONS: Despite guidelines and the availability of more migraine-specific treatments, opioids are still commonly prescribed to patients with migraines in real-world practice, especially for those with CM. In this study population, a higher risk of new-onset CM was associated with receiving higher opioid doses.

Neoadjuvant chemotherapy use trends among older women with breast cancer: 2010-2017.

PURPOSE: This study assessed chemotherapy use trends before (neoadjuvant chemotherapy [NAC]) or after surgery (adjuvant chemotherapy [AdC]) among older women with breast cancer and examined factors related to NAC receipt. METHODS: Women (> 65 years) diagnosed with stage I-III breast cancer during 2010-2017 who received NAC or AdC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. All patients were stratified into six strata based on subtype (hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR + /HER2-], HER2 + , and triple-negative breast cancer [TNBC]) and stage (I-II and III). Cochran-Armitage tests were performed to test temporal trends of NAC use in each stratum. Multivariable logistic regression analyses were performed to identify factors (sociodemographic and clinical) related to NAC use. RESULTS: Among included older (mean ± standard deviation: 72.3 ± 5.2 years) women (N = 8,495) with stage I-III breast cancer, NAC use increased from 11.7% (2010) to 32.6% (2017). Significant increases in NAC were found in all strata (p < .0001) with more substantial increases in HER2 + disease and TNBC compared to HR + /HER2- disease. Multivariable logistic regressions identified the youngest age category (66-69 years) and later stage as significant (p < 0.05) predictors of NAC receipt in most strata, in addition to diagnosis year. CONCLUSION: Similar to the overall breast cancer population, NAC use increased among a population of older women. NAC was received by most patients with stage III HER2 + disease or TNBC in more recent years and was more common among younger elderly women and those in stage III.

Economic Burden of Chronic Comorbidities Among Community-Dwelling Older Adults With Dementia: A Propensity Score Matched National-Level Study.

OBJECTIVE: This study examined the extent to which chronic comorbidities contribute to excess health care expenditures between older adults with dementia and propensity score (PS)-matched nondementia controls. METHODS: This was a retrospective, cross-sectional, PS-matched case (dementia): control (nondementia) study of older adults (65 y or above) using alternative years data from pooled 2005 to 2015 Medical Expenditure Panel Surveys (MEPS). Chronic comorbidities were identified based on Clinical Classifications System or ICD-9-CM codes. Ordinary least squares regression was utilized to quantify the impact of chronic comorbidities on the excess expenditures with logarithmic transformation. Expenditures were expressed as 2019 US dollars. All analyses accounted for the complex survey design of MEPS. RESULTS: The mean yearly home health care expenditures were particularly higher among older adults with dementia and co-occurring anemia, eye disorders, hyperlipidemia, and hypertension compared with PS-matched controls. Ordinary least squares regression models revealed that home health care expenditures were 131% higher (ß=0.837, P <0.001) among older adults with dementia compared with matched nondementia controls before adjusting for chronic comorbidities. When additionally adjusting for chronic comorbidities, the percentage increase, while still significant ( P <0.001) decreased from 131% to 102%. CONCLUSIONS: The excess home health care expenditures were partially explained by chronic comorbidities among community-dwelling older adults with dementia.

Improving Asthma Management: Patient-Pharmacist Partnership Program in Enhancing Therapy Adherence.

Community pharmacist interventions can assist in improving adherence in patients with asthma. The objective of the study was to assess the feasibility of patient-centered counseling using the developed asthma-specific tools to identify barriers to adherence and identify their preliminary effect on adherence barrier score and asthma control. Adult patients with persistent asthma were invited to participate in a 3-month pre-post intervention study involving community pharmacist-provided patient-centered counseling. Bivariate analyses were conducted to determine whether there were changes in outcomes from the pre to post period. Of 36 recruited patients, 17 completed both pre and post surveys. At baseline, patients had a mean ACT score of 15.1 ± 3.5, with 94% having uncontrolled asthma, and an average of 4.2 ± 2.5 reported barriers. The following barriers were most common: not having an Asthma Action Plan (52.9%), use of inhaler more or less often than prescribed (47.1%) and forgetfulness (41.2%). The ACT score increased by 2.7 ± 5.4, which was not statistically significant; however, it might be clinically significant. Two barrier scores improved as a result of the intervention. Preliminary evidence on the feasibility of identifying and addressing patient-specific barriers to adherence delivered by pharmacists showed that it has the potential to resolve barriers and improve asthma outcomes.

Healthcare utilization and costs among patients with chronic migraine, episodic migraine, and tension-type headache enrolled in commercial insurance plans.

OBJECTIVE: To quantify and compare healthcare utilization and costs for patients with chronic migraine (CM), episodic migraine (EM), and tension-type headache (TTH) enrolled in US commercial health plans. METHODS: This retrospective cohort study used the Optum Clinformatics® Data Mart database from January 2015 to December 2018. Adult patients with a diagnosis of EM, CM or TTH and at least 12 months of continuous enrollment before and after diagnosis were included. Inverse probability of treatment weighting was used to adjust for baseline differences among the three groups. Patient demographic and clinical characteristics at baseline, and healthcare utilization and costs during follow-up, were described and compared between the three groups. RESULTS: A total of 45,849 patients were included: 8955 with CM, 31,961 with EM, and 4933 with TTH. The total all-cause annual direct medical costs of patients with CM ($17,878) were 1.38 times higher (95% CI: 1.31-1.44) than those with EM ($12,986), and 2.26 times higher (95% CI: 2.08-2.47) than those with TTH ($7902). The annual migraine/TTH-related costs of patients with CM ($1869) were 4.19 times higher (95% CI: 3.92-4.48) than those with EM ($446), and 11.90 times (95% CI: 10.59-13.52) higher than those with TTH ($157). In the adjusted analyses, for all service categories (emergency department, inpatient, outpatient, and prescriptions), the expected costs in the migraine groups were higher than in the TTH group (all p < 0.001), while controlling for covariates. Main findings were consistent in both weighted and unweighted samples, and with both unadjusted and adjusted analyses. CONCLUSION: This study provides an updated assessment of healthcare utilization and expenditures for adult patients with primary headache disorders. Compared to TTH, migraine is associated with higher resource use and direct medical costs, especially for those with a chronic condition. Future studies are needed to understand the indirect medical costs (productivity loss) and humanistic burden (quality of life) between migraine and TTH.

Healthcare Utilization, Costs, and Adverse Events of Real-Time Continuous Glucose Monitoring versus Traditional Blood Glucose Monitoring Among US Adults with Type 1 Diabetes.

OBJECTIVE: To compare healthcare utilization, costs, and incidence of diabetes-specific adverse events (ie, hyperglycemia, diabetic ketoacidosis, and hypoglycemia) in type 1 diabetes adult patients using real-time continuous glucose monitoring (rtCGM) versus traditional blood glucose monitoring (BG). METHODS: Adult patients (≥18 years old) with type 1 diabetes in a large national administrative claims database between 2013 and 2015 were identified. rtCGM patients with 6-month continuous health plan enrollment and ≥1 pharmacy claim for insulin during pre-index and post-index periods were propensity-score matched with BG patients. Healthcare utilization associated with diabetic adverse events were examined. A difference-in-difference (DID) method was used to compare the change in costs between rtCGM and BG cohorts. RESULTS: Six-month medical costs for rtCGM patients (N = 153) increased from pre- to post-index period, while they decreased for matched BG patients (N = 153). DID analysis indicated a $2,807 (P = .062) higher post-index difference in total medical costs for rtCGM patients. Pharmacy costs for both cohorts increased. DID analysis indicated a $1,775 (P < .001) higher post-index difference in pharmacy costs for rtCGM patients. The incidence of hyperglycemia for both cohorts increased minimally from pre- to post-index period. The incidence of hypoglycemia for rtCGM patients decreased, while it increased marginally for BG patients. Inpatient hospitalizations for rtCGM and BG patients increased and decreased marginally, respectively. CONCLUSIONS: rtCGM users had non-significantly higher pre-post differences in medical costs but significantly higher pre-post differences in pharmacy costs (mostly due to the rtCGM costs themselves) compared to BG users. Changes in adverse events were minimal.

Age-related prescription medication utilization for the -management of sickle cell disease among Texas Medicaid patients.

INTRODUCTION: Sickle cell disease (SCD) is associated with recurrent complications and healthcare burden. Although SCD management guidelines differ based on age groups, little is known regarding actual utilization of preventative (hydroxyurea) and palliative therapies (opioid and nonopioid analgesics) to manage complications. This study assessed whether there were agerelated differences in SCD index therapy type and SCD-related medication utilization. DESIGN AND PATIENTS: Texas Medicaid prescription claims from September 1, 2011 to August 31, 2016 were retrospectively analyzed for SCD patients aged 2-63 years who received one or more SCD-related medications (hydroxyurea, opioid, or nonopioid analgesics). OUTCOME MEASURES: The primary outcomes were SCD index drug type and medication utilization: hydroxyurea adherence, and days' supply of opioid, and nonopioid analgesics. Chi-square, analysis of variance, and Kruskal-Wallis tests were used. RESULTS: Index therapy percentages for included patients (N = 2,339) were the following: opioids (45.7 percent), nonopioids (36.6 percent), dual therapy-opioids and nonopioids (11.2 percent), and hydroxyurea (6.5 percent), and they differed by age-groups (χ2 = 243.0, p < 0.0001). Hydroxyurea as index therapy was higher among children (2-12:9.1 percent) compared to adults (26-40:3.7 percent; 41-63:2.9 percent). Opioids as index therapy were higher among adults (18-25:48.0 percent; 26-40:54.9 percent; 41-63:65.2 percent) compared to children (2-12:36.6 percent). Mean hydroxyurea adherence was higher (p < 0.0001) for younger ages, and opioid days' supply was higher for older ages. CONCLUSIONS: Texas Medicaid SCD patients had low hydroxyurea utilization and adherence across all age groups. Interventions to increase the use of hydroxyurea and newer preventative therapies could result in better management of SCD-related complications and reduce the frequency of pain crises, which may reduce the need for opioid use.

Utilization, adherence, and outcomes of 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention.

OBJECTIVE: To describe the use of and adherence to 17-alpha hydroxyprogesterone caproate (17-OHPC), explore factors associated with its utilization and adherence, and to investigate the outcomes of 17-OHPC in a real-world setting. METHODS: The Decision Resources Group (DRG) database (1 January 2012-31 December 2017) was used to identify women with diagnosis of "history of preterm labor", aged 16-50 years old, had a singleton gestation, were continuously enrolled for at least 6 months and 9 months before and after the index date, respectively, and had a delivery outcome recorded. Adequate adherence was defined and compared using two approaches: (1) patients receiving at least 10 injections of 17-OHPC; (2) number of received injections/eligible number of injections ≥0.7. The outcome of 17-OHPC was evaluated by the incidence rate of preterm birth (PTB). Bivariate tests compared patients' characteristics with their use of and adherence to 17-OHPC, and examined the associations between 17-OHPC utilization and incidence of diabetes or hypertension. Stepwise logistic regression was conducted to assess the effect of adherence on the delivery outcome. RESULTS: Of 28,339 patients meeting study criteria, 2585 (9.1%) had ≥1 claim for 17-OHPC. An increasing trend of utilization was observed from 2012 to 2017 (7.6-13.1%). The utilization rate was highest in the Southwest US (13.8%) (p < .001). Commercial insurance patients (9.6%) were more likely to use 17-OHPC than Medicaid patients (7.9%) (p < .001). Patients with higher Charlson Comorbidity Index (CCI) scores were less likely to use 17-OHPC. Of women prescribed 17-OHPC, 792 (30.6%) and 424 (16.4%) were adherent using two definitions, respectively. No difference in PTB rate was observed between adherers and non-adherers (definition 1: aOR = 0.97, 95% CI = 0.81-1.16; definition 2: aOR = 1.18, 95% CI = 0.95-1.48). No association was found between 17-OHPC and incidence of diabetes (p = .96); however, use of 17-OHPC was associated with a lower incidence rate of hypertension (p = .002). CONCLUSIONS: 17-OHPC utilization and adherence rates remain low. Insurance type and geographic region were associated with both utilization and adherence. There was no association between 17-OHPC adherence and effectiveness. More evidence is needed to determine if the use of 17-OHPC is advantageous in a sub-group of patients.

Impact of emergency department opioid use on future health resource utilization among patients with migraine.

OBJECTIVE: The purpose of this study was to evaluate the subsequent health resource utilization (HRU) between patients with migraine who received opioid medications at their emergency department (ED) visits ("opioid recipients") versus patients with migraine who did not receive opioid medications at their ED visits ("non-recipients"). BACKGROUND: Previous studies have found that opioid use is common among patients with migraine at emergency settings. Medication overuse, especially the use of opioids, is associated with migraine progression, which can ultimately lead to substantial health resource use and costs. There is limited evidence on opioid use specifically in emergency settings and its impact on future HRU among people with migraine. METHOD: This retrospective cohort study used electronic health record data from the Baylor Scott & White Health between December 2013 and April 2017. Adult patients who had at least 6 months of continuous enrollment before (baseline or pre-index) and after (follow-up) the first date they had an ED visit with a diagnosis of migraine (defined as index date) were enrolled in the study. Opioid use and HRU during follow-up period between opioid recipients and non-recipients were summarized and compared. RESULTS: A total of 788 patients met the eligibility criteria and were included in this study. During the 6-month follow-up period, compared to patients with migraine who were non-recipients at their index ED visits, opioid recipients had significantly more all-cause (3.6 [SD = 6.3] vs. 1.9 [SD = 4.8], p < 0.0001) and migraine-related (1.6 [SD = 4.2] vs. 0.6 [SD = 2.1], p < 0.0001) opioid prescriptions (RXs), and more all-cause (2.6 [SD = 4.3] vs. 1.6 [SD = 2.6], p = 0.002) and migraine-related (0.6 [SD = 1.4] vs. 0.3 [SD = 0.8], p = 0.001) ED visits. In addition, opioid recipients had higher risk of future migraine-related ED visits controlling for covariates (HR = 1.49, 95% CI = 1.09-2.03, p = 0.013). Factors that were significantly (p < 0.05) related to future migraine-related ED visits include previous opioid use (HR = 2.12, 95% CI = 1.24-3.65, p = 0.007), previous ED visits (HR = 2.38, 95% CI = 1.23-4.58, p = 0.010), hypertension (HR = 1.46, 95% CI = 1.07-2.00, p = 0.017), age between 45 and 64 years (HR = 0.68, 95% CI = 0.48-0.97, p = 0.033), female sex (HR = 1.82, 95% CI = 1.12-2.86, p = 0.015), and tobacco use disorder (HR = 1.45, 95% CI = 1.07-1.97, p = 0.017). Sub-analyses were restricted to the group of patients who were opioid naïve at baseline (n = 274, defined as having ≤1 opioid RXs during the 6-month pre-index period). Patients who were baseline opioid naïve but received opioids during their index ED visits were more likely to have future migraine-related ED visits compared to patients who were baseline opioid naïve and did not receive any opioids during their index ED visits, controlling for covariates (HR = 2.90, 95% CI = 1.54-5.46, p = 0.001). CONCLUSION: Opioid use among patients with migraine presenting to the ED is associated with increased future HRU, which highlights the need for optimizing migraine management in emergency settings.

Prevalence of and Factors Associated with Gabapentinoid Use and Misuse Among Texas Medicaid Recipients.

BACKGROUND AND OBJECTIVES: Gabapentin and pregabalin have been considered relatively safe opioid-sparing adjuncts for pain management. However, rising prescribing trends, presence of gabapentinoids in opioid-related overdoses, and the growing body of evidence regarding gabapentinoid misuse and abuse, have caused gabapentinoids to emerge as a drug class of public health concern. This study aimed to assess the prevalence of, and factors associated with gabapentinoid use and misuse. METHODS: This retrospective study of Texas Medicaid data from 1/1/2012 to 30/8/2016 included patients aged 18-63 years at index date, with ≥ 1 gabapentinoid prescription, and continuously enrolled 6 months pre-index and 12 months post-index. Gabapentinoid misuse was defined as ≥ 3 claims exceeding daily doses of 3600 mg for gabapentin and 600 mg for pregabalin. Age, gender, concurrent opioid use, neuropathic pain diagnoses and gabapentinoid type were independent variables. Descriptive and inferential statistics were used. RESULTS: Of included subjects (N = 39,000), 0.2% (N = 81) met study criteria for gabapentinoid misuse. Overall, the majority (76.4%) of gabapentinoid users were aged 41-63 years with a mean ± SD age of 48.2 ± 10.7 years. Those patients meeting the study criteria for gabapentinoid misuse were significantly younger (45.1 ± 11.0 vs 48.2 ± 10.7, p = 0.0084). Majority of the study sample was female (68.1%). However, a significantly higher proportion of males met the study criteria for gabapentinoid misuse compared to females (0.3% vs 0.2%, p = 0.0079). Approximately one-half (51.9%) of the study sample had neuropathic pain, and gabapentinoid misuse was significantly higher in neuropathic pain patients compared to those without neuropathic pain (0.3% vs 0.1%, p = 0.0078). Over three-quarters (77.4%) of patients were using gabapentin; however, gabapentinoid misuse was significantly higher among pregabalin users (0.4% vs 0.2%, p = 0.0003). Approximately 20% (17.3%) of gabapentinoid users had ≥ 90 days of concurrent opioid use. However, there was no significant difference in gabapentinoid misuse among patients with concurrent opioid use compared to patients without (0.3% vs 0.2%, p = 0.1440). Factors significantly associated with misuse included: male sex (odds ratio [OR] 0.486; 95% confidence interval [CI] 0.313-0.756; p = 0.0013); neuropathic pain (OR 2.065; 95% CI 1.289-3.308; p = 0.0026); and pregabalin versus gabapentin use (OR 2.337, 95% CI 1.492-3.661; p = 0.0002). Concurrent opioid use was not significantly associated with gabapentinoid misuse (OR 1.542, 95% CI 0.920-2.586; p = 0.1006). CONCLUSION: Prevalence of gabapentinoid misuse was low (0.2%) among Texas Medicaid recipients. Younger age, male gender, neuropathic pain diagnosis and pregabalin use were significantly associated with higher levels of gabapentinoid misuse.

Use of a claims-based algorithm to estimate disease severity in the multiple sclerosis Medicare population.

BACKGROUND/OBJECTIVE: To compare algorithm determined disease severity, risk of multiple sclerosis (MS) relapse, and MS-related hospitalization between the age-eligible and disability-eligible MS Medicare populations. METHODS: Using the Humana claims dataset (2013 - 2015), patients were divided into Medicare age-eligible and disability-eligible groups. A previously developed algorithm, which used MS symptoms and healthcare utilization to categorize MS disease severity into three groups (low, moderate, high) at baseline was employed. Flexible parametric and Cox proportional hazard models were used to estimate the risk for MS relapses and MS-related hospitalizations among the MS disease severity groups and the two eligibility cohorts in the follow-up period. RESULTS: Of the overall sample (N = 6,559), the majority (N = 4,813, 73.4%) were disability-eligible and in the low disease severity group (N = 4,468, 68.1%). In 10 of 16 disease severity algorithm predictors, the prevalence of these predictors was significantly (p<0.001) higher in the disability-eligible group compared to the age-eligible group. Survival analyses revealed that the disability-eligible group had a significantly higher risk for follow-up MS relapses and follow-up MS-related hospitalizations (HR = 1.79 [CI 1.54 - 2.08] and HR = 1.38 [CI 1.11-1.72], respectively) compared to those in the age-eligible group. When both eligibility and disease severity were considered in the model increases in hazard ratios corresponded generally to increases in disease severity. However, the type of Medicare eligibility does not appear to have a clear pattern across MS disease severity groups for either MS relapse or hospitalizations, CONCLUSION: The disability-eligible Medicare population had a significantly higher prevalence of MS comorbidities and higher MS severity scores at baseline. In addition, they had a higher risk for MS-related relapses and MS-related hospitalizations in the follow-up period. It is important to account for disability status when assessing disease severity and healthcare utilization.

A network meta-analysis of efficacy and safety of first-line and second-line therapies for the management of metastatic renal cell carcinoma.

WHAT IS KNOWN AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) is the most common type of kidney cancers. Disease-specific survival for mRCC has been significantly improved with the introduction of new targeted agents since 2005. However, there is a lack of head-to-head clinical trials comparing the efficacy between therapies. This study compared indirectly progression-free survival (PFS) and overall survival (OS) among first-line and second-line therapies in patients with mRCC using network meta-analysis (NMA). METHODS: The PubMed, MEDLINE, Cochrane Library and Web of Science were searched to identify phase II or phase III randomized controlled trials (RCTs) of targeted and biological therapies in patients with mRCC published between January 2000 and June 2020. The Bayesian fixed-effect NMA was performed to evaluate relative PFS and OS of first-line and second-line therapies of axitinib, bevacizumab, cabozantinib, everolimus, lenvatinib, nivolumab, ipilimumab, pazopanib, sorafenib, sunitinib, temsirolimus, tivozanib, avelumab and pembrolizumab, which were approved by the Food and Drug Administration or European Medicines Agency. End points were compared using hazard ratio (HR) and 95% credible interval (CrI). The surface under the cumulative ranking curve (SUCRA) was estimated to assess the probability of being the best treatment. RESULTS AND DISCUSSION: A total of 26 RCTs (first line: 19, second line: 9) with 13 893 patients were included in the NMA. For the first-line therapy, cabozantinib was associated with the highest improved PFS (HR = 0.26, 95% CrI = 0.14-0.44) followed by avelumab + axitinib and pembrolizumab + axitinib (HR = 0.27, SUCRA = 90%). Pembrolizumab + axitinib had a high likelihood of being the preferred treatment when using OS as the outcome measure (HR = 0.41, 95% CrI = 0.16-0.85). Avelumab + axitinib had the lowest HR compared with placebo + interferon on discontinuations due to AE (HR = 1.04, 95% CrI = 0.54-1.86). For second-line therapy, cabozantinib was identified as the most effective treatment option when assessing PFS (HR = 0.17, 95% CrI = 0.12-0.24). Axitinib had the lowest HR of OS and discontinuation due to AE (HR = 0.54, 95% CrI = 0.40-0.71; HR = 0.98, 95% CrI = 0.42-1.97, respectively). Pazopanib was the second choice in terms of OS (HR = 0.56, 95% CrI = 0.28-1.00; SUCRA = 76%) compared with placebo. WHAT IS NEW AND CONCLUSION: With respect to PFS and OS improvement, cabozantinib, avelumab + axitinib and pembrolizumab + axitinib are likely to be the preferred options for the first-line therapy and cabozantinib and axitinib for the second-line therapy in the management of mRCC. Regarding safety, avelumab + axitinib and temsirolimus were considered preferred treatment options in first-line and second-line therapies. More future research is needed to establish subgroup analyses, allowing evaluation of the impact of some of the differences in patient characteristics, including treatment effect modifiers.

Examination of Barriers to Medication Adherence, Asthma Management, and Control Among Community Pharmacy Patients With Asthma.

OBJECTIVE: To describe the prevalence of common barriers to asthma medication adherence and examine associations between patient-reported asthma controller adherence and asthma control, therapy adherence barriers, and asthma management characteristics. METHODS: Previously developed asthma-specific tool was pilot tested on a convenience sample of adult patients with persistent asthma. The following data were collected via patient survey: demographic characteristics and comorbidities, adherence, asthma control, and asthma management characteristics. Descriptive and inferential statistics were used to address the study objective. RESULTS: The patients (N = 93) were 45.4 (17.2) years of age, and 66.7% were female. The majority had poor (68.8%) adherence, with 61.3% of patients having controlled asthma. There was no significant association between adherence and asthma control. The mean number of barriers for good and poor adherence groups differed significantly: 2.0 ± 1.1 and 5.4 ± 2.4, respectively (P < .0001). Having an asthma action plan (AAP) was the only asthma management characteristic significantly related to adherence. The majority of patients with poor adherence did not have an AAP (76.6%), whereas 81.5% of patients with good adherence did have an AAP (P < 0.0001). CONCLUSIONS: The use of this survey tool confirmed presence of asthma-specific barriers, thus using this specialized approach may lead to more effective, targeted counseling in community pharmacy settings.

Assessment of basal insulin adherence using 2 methodologies among Texas Medicaid enrollees with type 2 diabetes.

BACKGROUND: Basal insulin is often recommended as the initial therapy for patients with type 2 diabetes who require insulin treatment. Adequate adherence is critical to diabetes management, yet suboptimal insulin adherence has been reported. Second-generation long-acting (SGLA) insulin has higher dosing flexibility and lower hypoglycemia risk and may improve adherence. However, little is known regarding adherence to SGLA insulin and how adherence to SGLA insulin compares with intermediate-acting neutral protamine Hagedorn (NPH) and first-generation long-acting (FGLA) insulin. Measurement of insulin adherence is challenging because of the inaccuracies of recorded days supply of insulin, and traditional medication possession ratio (MPR) may be negatively affected. Adjusted MPR (aMPR) has been developed in an effort to address this issue. OBJECTIVE: To examine the unadjusted and adjusted associations between basal insulin type and adherence to basal insulin using MPR and aMPR. METHODS: This retrospective database study used Texas Medicaid prescription claims from January 1, 2014, through June 30, 2017. The index date was the date of the first basal insulin prescription without the same prescription 6 months before (pre-index), and all patients were followed for 12 months (post-index). Patients aged 18-63 years with ≥ 1 pre-index prescription of an oral hypoglycemia agent (OHA) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), without any post-index prescription of premixed insulin or a basal insulin different from index insulin, and with continuous enrollment throughout the pre- and post-index periods, were included. The dependent variable was basal insulin adherence over 12 months, measured using MPR and aMPR. Unadjusted and adjusted adherence comparisons were conducted by basal (background) insulin type (NPH, FGLA, and SGLA). Covariates included age, gender, baseline use of basal insulins and comorbid medications, total number of medications, OHA adherence, post-index number of OHAs, and use of bolus insulins and GLP-1 RAs. Analysis of variance, chi-square tests, and multiple logistic regression analyses were performed. RESULTS: Of the 5,034 patients included, NPH, FGLA, and SGLA insulin users accounted for 3.7%, 89.8%, and 6.5%, respectively. The overall mean (SD) age was 50.9 (9.9) years, and 65.9% were female. In the unadjusted bivariate analyses, SGLA insulin users had significantly higher adherence, using either MPR (SGLA 0.68 [0.25] vs. FGLA 0.59 [0.27] vs. NPH 0.55 [0.27]; P < 0.0001) or aMPR (0.83 [0.23] vs. 0.78 [0.26] vs. 0.73 [0.28]; P = 0.0001). After controlling for covariates, insulin type was not significantly associated with the likelihood of being adherent (MPR or aMPR ≥ 0.8) using either measure. CONCLUSIONS: Adherence to SGLA insulin was not different from adherence to other basal insulins after controlling for patient characteristics. Yet, MPR and aMPR have limitations and warrant further confirmation of the study findings. Before new adherence measures for insulin therapy are developed, MPR and aMPR should be used with caution. DISCLOSURES: No specific funding was received for this manuscript. The authors report no potential conflicts of interest. Part of the data from this study was presented as posters at the American Pharmacists Association 2020 Annual Meeting & Exposition, March 20-23, 2020, in National Harbor, MD, and at the International Society for Pharmacoeconomics and Outcomes Research 2020 Conference, May 16-20, 2020, in Orlando, FL.

Antihypertensive agent utilization patterns among patients with uncontrolled hypertension in the United States.

Hypertension affects approximately one-third of the US adults. This study investigated antihypertensive utilization patterns among hypertensive patients who were prescribed treatment, yet still experienced uncontrolled hypertension. Data from the Decision Resources Group Real World Evidence Data Repository US database (2015-2016) were used to construct a cohort of uncontrolled hypertension patients to observe antihypertensive utilization patterns. Results for 5059 patients, with an average age of 57.8 (SD = 13.7), who had, on average 2.4 agents prescribed. Approximately half (51.9%) were female, and most were White (86.8%). More than one-third (N = 1877; 37.1%) of patients were diagnosed with diabetes mellitus (DM) or chronic kidney disease (CKD) that could independently contribute to increased cardiovascular complications. Overall, the most common treatments prescribed, as percent of agents and as percent of patients, respectively, were diuretics (24.9%; 59.6%), followed by angiotensin-converting enzyme inhibitors (ACEIs) (23.8%; 56.9%), beta-blockers (BBs) (18.7%; 44.8%), calcium channel blockers (CCBs) (15.4%; 36.8%), and angiotensin II receptor blockers (ARBs) (13.5%; 32.3%). Approximately one-tenth (10.5%) of the prescriptions were written for fixed-dose combination therapies. Among patients diagnosed with DM and CKD (N = 200), the order of the most common agents was the same as the overall cohort. Only 5.6% of prescriptions written for these patients were fixed-dose combination therapy. Based on clinical guidelines, which suggest using ACEIs, ARBs, or CCBs as first-line therapy, and fixed-dose combination therapy to increase adherence, this indicates over-prescribing of BBs and under-prescribing of fixed-dose combination therapy. These findings illustrate the need to further investigate challenges faced by patients and providers in treatment decision-making.

Patterns and predictors of opioid use among migraine patients at emergency departments: A retrospective database analysis.

OBJECTIVES: To compare medication use and health resource utilization between migraineurs with evidence of opioid use at emergency department visit versus no opioid use at emergency department visit, and to examine predictors of opioid use among migraineurs at emergency department visits. METHODS: This was a retrospective study using REACHnet electronic health records (December 2013 to April 2017) from Baylor Scott & White Health Plan. The index date was defined as the first migraine-related emergency department visit after ≥6 months of enrollment. Adult patients with a migraine diagnosis and ≥6 months of continuous enrollment before and after their index dates were included. Descriptive statistics and bivariate analyses were used to compare medication use and health resource utilization between opioid users and non-opioid users. Multivariable logistic regression was used to examine predictors of opioid use at emergency department visits. RESULTS: A total of 788 migraineurs met eligibility criteria. Over one-third (n = 283, 35.9%) received ≥1 opioid medication during their index date emergency department visit. Morphine (n = 103, 13.1%) and hydromorphone (n = 85, 10.8%) were the most frequently used opioids. Opioid users had more hospitalizations and emergency department visits during their pre-index period (both p < 0.05). Significant (p < 0.05) predictors of opioid use at emergency department visits included past migraine-related opioid use (2-4 prescriptions, Odds Ratio = 1.66; 5-9 prescriptions, Odds Ratio = 2.12; ≥10 prescriptions, Odds Ratio = 4.43), past non-migraine-related opioid use (≥10 prescriptions, Odds Ratio = 1.93), past emergency department visits (1-3 visits, Odds Ratio = 1.84), age (45-64 years, Odds Ratio = 1.45), and sleep disorder (Odds Ratio = 1.43), controlling for covariates. CONCLUSION: Opioids were commonly given to migraineurs at emergency departments. Previous opioid use, health resource utilization, age, and specific comorbidities might be used to identify migraineurs with a high risk of opioid use.

Cardiovascular Outcomes Among Patients with Type 2 Diabetes Newly Initiated on Sodium-Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Other Antidiabetic Medications.

BACKGROUND: Cardiovascular disease (CVD) remains the most prevalent cause of morbidity and mortality in patients with type 2 diabetes (T2D) and is a primary driver for health care costs associated with diabetes management. Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant reductions in cardiovascular endpoints in clinical trials compared with placebo. However, it is uncertain whether these findings can be applied to the broader T2D population because these trials specifically included high-risk patients with established CVD. OBJECTIVE: To evaluate and compare cardiovascular outcomes among adults with T2D newly initiated on SGLT-2is, GLP-1 RAs, and other antidiabetic medications (oADMs) in a real-world setting. METHODS: This retrospective new-user cohort study used administrative claims and electronic health record data from an integrated delivery network in Texas. Patients aged ≥18 years with T2D and ≥1 prescription claim for an SGLT-2i, a GLP-1 RA, or an oADM filled between April 2013 and December 2018 were included. Patients were divided into three 1:1 propensity-matched groups according to index medication identified. Primary outcomes were heart failure hospitalization and a composite end-point of myocardial infarction, stroke, unstable angina, or coronary revascularization. Cox proportional hazards regression was used to compare cumulative incidence of all outcome variables. RESULTS: Among 9,477 patients, 1,134 were initiated on SGLT-2is, 1,072 on GLP-1 RAs, and 7,271 on oADMs. Patients initiating SGLT-2is versus oADMs had significantly lower risk of the composite endpoint (HR = 0.64, 95% CI = 0.46-0.90), heart failure hospitalization (HR = 0.56, 95% CI = 0.39-0.81), and unstable angina requiring hospitalization (HR = 0.56, 95% CI = 0.39-0.81). Patients initiating GLP-1 RAs compared with oADMs had significantly lower risk of the composite endpoint (HR = 0.71, 95% CI = 0.52-0.98) and unstable angina requiring hospitalization (HR = 0.60, 95% CI = 0.41-0.86). No differences in cardiovascular outcomes were found between SGLT-2is and GLP-1 RAs. CONCLUSIONS: Both SGLT-2is and GLP-1 RAs showed significant reductions in the composite outcome and unstable angina requiring hospitalization versus oADMs. However, only SGLT-2is were associated with a lower risk for heart failure hospitalizations. Nevertheless, cardiovascular outcomes were similar between SGLT-2is and GLP-1 RAs. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to report.

Predictors of Annual Base Salary for Health Economics, Outcomes Research, and Market Access Professionals in the Biopharmaceutical Industry.

BACKGROUND: Analysis of salary data for health economics, outcomes research, and market access professionals in biopharmaceutical space plays an important role in hiring talent, benchmarking remuneration, and evaluating income discrepancies. OBJECTIVES: To (a) identify predictors of annual base salary (ABS) for health economics, outcomes research, and market access professionals who participated in the 2017 Global Salary Survey by HealthEconomics.Com and (b) evaluate salary-related gender disparity among survey respondents. METHODS: 501 professionals from the HealthEconomics.Com global subscriber list participated in a survey that assessed salary, bonus, benefits, and job satisfaction in June 2017. Two multivariable regression models identified significant predictors of ABS for U.S. and non-U.S. regions separately. Analysis of variance determined interaction effects between gender, organizational size, job title, and people management responsibilities separately. RESULTS: Of the 501 respondents, 385 were included in the analysis because they reported ABS. Median ABS for male (n = 117) and female (n = 111) U.S.-based respondents was $172,500 and $162,500, respectively. For male (n = 75) and female (n = 65) non-U.S.-based respondents, the median was identical at $92,500. Mean (SD) ABS between male ($180,534 [$77,755]) and female ($165,113 [$64,604]; t [226] = 1.62; P = 0.106) U.S. respondents was not significantly different. Mean (SD) ABS for male ($110,900 [$65,898]) and female ($98,039 [$48,639]; t [138] = 1.30; P = 0.196) non-U.S. respondents was not significantly different, as well. Multivariable regression models for U.S. and non-U.S. respondents accounted for 62.7% and 63.9% of variance in ABS (P < 0.001), respectively. In both models, significantly higher salaries were associated with professionals aged > 40 years; biopharmaceutical employment; having a PhD, PharmD, or MD; and having a job title of president or director (all P < 0.05). CONCLUSIONS: After controlling for covariates, gender was not statistically significantly associated with ABS. Age, organization type, terminal degree, and job title were significant predictors of higher salaries inside and outside of the United States. Additional research should be conducted to increase generalizability of results, which were based on a convenience sample. DISCLOSURES: No funding supported this research. Shah and Peeples are employed by HealthEconomics.Com, which administered the survey used in this study. The authors report no other potential conflicts of interest.

Comparison of Prostaglandin Analog Treatment Patterns in Glaucoma and Ocular Hypertension.

BACKGROUND: Prostaglandin analogs (PGAs) are considered an initial therapy to manage increased intraocular pressure (IOP) for patients with glaucoma. When the initial PGA treatment fails to lower IOP adequately, the patient may add or change medications or have surgery/laser treatment. OBJECTIVE: To compare medication adherence, duration of therapy, and treatment patterns among 3 PGAs-latanoprost, travoprost, and bimatoprost-as initial therapies for patients with glaucoma or ocular hypertension. METHODS: This was a retrospective cohort study using administrative claims data. The cohort consisted of patients newly diagnosed with glaucoma or ocular hypertension with at least 1 prescription claim for latanoprost, travoprost, or bimatoprost and enrolled in a Medicare Advantage plan between 2007 and 2012. The 24-month medication possession ratio (MPR) was used to measure medication adherence. Discontinuation of first-line PGA therapy was defined as nonpersistence (90-day gap allowance) of the index PGA or a change in therapy during the 24-month follow-up period. Types of second-line therapy (i.e., switch, addition, and surgery) were identified. The 1:1:1 propensity score matching was used. RESULTS: Patients who met the inclusion criteria were propensity score matched, resulting in 1,296 patients per PGA group. Latanoprost users showed higher adherence (50.1%) than travoprost (48.8%) and bimatoprost (43.0%) users. The latanoprost and travoprost groups had significantly higher MPRs than bimatoprost (P < 0.0001). The latanoprost group showed significantly longer duration of first-line therapy (372 days) than the bimatoprost group (343 days; P = 0.003) but not the travoprost group (361 days). After controlling for demographic and clinical characteristics, a Cox proportional hazards model showed that the travoprost and bimatoprost groups had a higher risk of discontinuation of first-line therapy than the latanoprost group (P < 0.0001). The percentage of patients continuing on the index PGA without treatment pattern change (i.e., switches, additions, and surgery) was higher for latanoprost users (52.9%) compared with travoprost (39.0%) or bimatoprost users (42.1%; P < 0.001). CONCLUSIONS: Patients who used latanoprost as their initial therapy were more likely to adhere and persist to the index PGA compared with bimatoprost users. The latanoprost group demonstrated a lower risk of discontinuing first-line therapy than the travoprost and bimatoprost groups. The results may assist ophthalmologists in determining the optimal management of this patient population with respect to treatment patterns. DISCLOSURES: No outside funding supported this study. All authors except Heo and Nair are employed by The University of Texas at Austin College of Pharmacy. Heo was with the Health Outcomes Division, The University of Texas at Austin College of Pharmacy during a portion of this study and is employed by Genesis Research. Nair is employed by Humana. The authors have no financial relationships relevant to this article to disclose. This study was presented as a poster at the 2016 International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, May 2016, Washington, DC.