Patient Characteristics, Treatment Patterns, and Outcomes for Patients With Renal Cell Carcinoma in England: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVE: Considering the rapidly evolving treatment landscape of renal cell carcinoma (RCC), recent descriptions of the RCC population in the UK are lacking, as are real-world data on treatment and patient outcomes. To analyse the demographic and clinical characteristics, treatment patterns, and overall survival of patients with RCC using national data sets in England. PATIENTS AND METHODS: This was a retrospective cohort study of patients diagnosed with RCC (all stages) between 2014-2018 using demographic, clinical, cancer registration, and treatment data. Patients were followed until death or study end (December 31, 2020). Treatments administered in each line were described to understand treatment sequencing. Kaplan-Meier methods were used for time-to-event analyses. Factors associated with discontinuation and survival were identified using Cox proportional hazard models. RESULTS AND LIMITATIONS: Among 32,577 included patients, the median age at diagnosis was 66 years, 63.4% were male, and 6,786 (20.8%) had metastatic RCC at diagnosis. Tyrosine kinase inhibitor (TKI) monotherapy was the most common treatment class across lines. Over three quarters of patients (78.5% [95% CI: 78.0-78.9]) were alive one year after diagnosis (93.2% in the non-metastatic at diagnosis subgroup and 37.1% among patients with metastases at diagnosis). At three years post initial diagnosis, 18.0% patients were alive in the metastatic at diagnosis subgroup. Rapid evolution of the treatment landscape limits the results regarding lines of therapy. CONCLUSION: This large-scale study provides insight on characteristics of patients with RCC, and it highlights the need for better treatment options to improve survival.

Risk of venous thromboembolism among women receiving ospemifene: a comparative observational study.

Introduction: The primary aim of this study was to compare the incidence of venous thromboembolism (VTE) among women initiating ospemifene vs other selective estrogen receptor modulator (SERM) therapies for estrogen-deficiency conditions or breast cancer prevention, and vs women with untreated vulvar and vaginal atrophy (VVA). The secondary objective examined numerous additional safety outcomes. Methods: This was a retrospective cohort study using the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for incident adverse outcomes. The primary outcome was the first occurrence of VTE following cohort entry; secondary outcomes included cerebrovascular events and other adverse events potentially associated with SERM use. Cox models compared the risk of VTE between ospemifene and comparators, using a variety of approaches to control for confounding. Results: The incidence of VTE during the first continuous treatment episode was 3.39 (95% confidence interval [CI]: 1.55-6.43) events per 1,000 person-years (PY) for ospemifene (N = 8977), 11.30 (95% CI: 8.81-14.28) events per 1,000 PY for comparator SERM (N = 12,621), and 10.92 (95% CI: 10.49-11.37) events per 1,000 PY for untreated VVA (N = 242,488). Cox models indicated no increase in risk of VTE for ospemifene vs other SERMs (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.82), and vs untreated VVA (HR: 0.47, 95% CI: 0.24-0.91). Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women. Plain Language Summary: Introduction: This study assessed the risk of venous thromboembolism (VTE) among women treated with ospemifene or another selective estrogen receptor modulator (SERM) therapy and women with untreated vulvar and vaginal atrophy (VVA). Numerous additional safety outcomes were examined.Methods: This study was conducted in the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for adverse outcomes, including VTE, cerebrovascular events (such as stroke), and other outcomes that might occur with use of a SERM. The analyses compared the risk of VTE between ospemifene and the other two groups, using methods that accounted for differences in patient characteristics between the groups. Because few women over 72 years old used ospemifene, the main analyses examined women aged 54-72 years.Results: The analyses included 8,977 ospemifene users, 12,621 other SERM users, and 242,488 women with untreated VVA. Among women aged 54-72 years, only 9 experienced a VTE during ospemifene treatment, while 55 other SERM users and 1,788 women with untreated VVA had a VTE. The analyses that accounted for differences between the groups confirmed that the risk of VTE was no higher in ospemifene users than in either comparison group.Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women.

Treatment patterns and outcomes following disease progression on anti-PD-1 therapies for advanced melanoma.

Background: Anti-PD-1-based therapies prolong survival in advanced melanoma, but disease progression is common. This study evaluated treatment patterns and overall survival (OS) after anti-PD-1 progression. Methods: Retrospective data from patients with advanced melanoma and progression on anti-PD-1 treatment between 2014 and 2019 were taken from Flatiron Health, which reflects largely community practice. Treatment patterns and OS were analyzed for BRAF mutant (mt) and wild-type (wt) subgroups; OS was also examined across all patients. Results: Progression following anti-PD-1 was recorded for 679 patients. Median OS ranged from 5.0 to 11.3 months. Of 275 BRAFmt and 374 BRAFwt patients, 113 (41.1%) and 228 (61.0%) received no subsequent therapy, respectively. However, 48.4% of BRAFmt and 57.8% of BRAFwt patients continued anti-PD-1 treatment beyond progression. Conclusion: This real-world study underscores the need for effective treatments for advanced melanoma post-progression on anti-PD-1 therapy.

Individualized HbA1c target selection and achievement in the Multinational Observational Study Assessing Insulin Use (MOSA1c) type 2 diabetes study.

AIM: To identify which individual-, physician-, and the healthcare system-related factors can predict individualized hemoglobin A1c (HbA1c) targets and the likelihood of reaching those targets after initial insulin therapy over a two-year follow-up period. METHODS: Real-world data, including baseline characteristics of people with type 2 diabetes mellitus (T2DM), psychosocial data, and diabetes medication use, collected from the Multinational Observational Study Assessing Insulin Use (MOSA1c) study in 18 countries were analyzed. RESULTS: Overall, 225 of 1194 people with T2DM (18.8%) who received initial insulin therapy for ≥3 months reached HbA1c targets at two-year follow-up; most were likely to be White (64.9%) and perceptions of their relationship with physicians were less positive than those who did not reach HbA1c targets. Higher baseline HbA1c (>8%) was the strongest predictor of being assigned an HbA1c target >7% (odds ratio [OR] 6.06, 95% confidence interval [CI] 3.97, 9.26). A smaller difference between baseline and target HbA1c levels was the strongest predictor of reaching an HbA1c target at two-year follow-up (large vs small difference, OR 0.28, 95% CI 0.17, 0.47). CONCLUSIONS: Several factors were significantly associated with establishing individualized HbA1c targets and reaching these targets. A small proportion of people with T2DM on insulin therapy reached their HbA1c target. Personalized management of glycemic targets necessitates the adoption of multi-factorial strategies, as several factors could influence an individual's glycemic outcome. CLINICALTRIALS. GOV IDENTIFIER: NCT01400971.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

Burden of illness associated with eosinophilic granulomatosis with polyangiitis: a systematic literature review and meta-analysis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease associated with vascular inflammation and multisystem organ damage. The literature reporting EGPA incidence or prevalence is limited. We performed a systematic literature review and meta-analysis to describe the incidence, prevalence, and disease burden associated with EGPA. Real-world, observational, English-language studies in MEDLINE, MEDLINE In-Process, and Embase up to 6 June, 2019, were included. A single investigator screened all identified titles/abstracts and extracted data; an additional, independent investigator repeated the screening and validated the extracted data. A random-effects meta-analysis was conducted to generate pooled estimates for EGPA incidence and prevalence. Data from 100 eligible publications were extracted (32 with incidence/prevalence data, 65 with morbidity/healthcare resource data; 3 with both types of data). Significant evidence of between-study heterogeneity for reported incidence (p = 0.0013-0.0016) and prevalence (p = 0.0001-0.0006) estimates was observed. Global and European pooled estimates (95% confidence interval) of EGPA incidence were 1.22 (0.93, 1.60) and 1.07 (0.94, 1.35) cases per million person-years, respectively; global and European pooled estimates (95% confidence interval) for EGPA prevalence were 15.27 (11.89, 19.61) and 12.13 (6.98, 21.06) cases per million individuals, respectively. The proportions of patients experiencing relapses, or who had nasal polyps or severe asthma, varied considerably across studies. EGPA healthcare resource use was high, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Our results indicate that although global and European EGPA incidence and prevalence is low, the associated disease burden is substantial. Key points • We performed a systematic literature review and meta-analysis of real-world, observational studies describing the incidence, prevalence, and disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA). • Based on meta-analysis data from 35 eligible studies reporting incidence and prevalence, the incidence and prevalence of EGPA were low (globally 1.22 cases per million person-years and 15.27 cases per million individuals, respectively). • Among the 49 studies with morbidity and/or healthcare resource data, most reported a large proportion of patients with EGPA relapses and comorbidities of nasal polyps and severe asthma. • Healthcare resource use was also high among patients with EGPA in these studies, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Taken together, these data indicate the substantial disease burden associated with EGPA.

STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world.

BACKGROUND: Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. METHODS: This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). RESULTS: Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9-2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3-2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2-1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. CONCLUSIONS: This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.

Real-World Treatment Patterns and Progression-Free Survival Associated with Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer.

BACKGROUND: Little is known about real-world treatment and outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This retrospective study of the Flatiron Health EHR-derived deidentified database included patients with a lung cancer diagnosis and confirmed advanced NSCLC who received ALK tyrosine kinase inhibitor (TKI) therapy (January 1, 2011, through June 30, 2018). Patient characteristics and treatment patterns were characterized. Real-world progression-free survival (rwPFS) and time to discontinuation were calculated using the Kaplan-Meier method. RESULTS: First-line ALK TKI therapy was administered to 581 patients (27.5% had brain metastasis on or prior to initiation) and second-line ALK TKI therapy to 254 patients post crizotinib (45.7% had brain metastasis on or prior to second-line ALK TKI initiation). Crizotinib (84.6%; n = 492) was the most commonly administered first-line ALK TKI therapy. For second-line ALK TKI post crizotinib (n = 254), 49.6% received ceritinib, 41.7% received alectinib, 5.9% received crizotinib retreatment, and 2.8% received brigatinib. Median (95% confidence interval [CI]) rwPFS was 7.47 (6.48-8.32) months for first-line and 7.30 (5.72-8.42) months for second-line ALK TKI. Median (95% CI) rwPFS was significantly longer among first-line ALK TKI patients without than with brain metastasis (8.52 [7.57-10.59] vs. 4.97 [3.75-5.99] months; p < .0001) and patients with brain metastasis on or prior to first-line ALK TKI therapy had a significantly increased risk of progression (hazard ratio ± SE, 1.976 ± 0.112; p < .0001). CONCLUSION: Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first- and second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population. IMPLICATIONS FOR PRACTICE: Results presented herein describe real-world treatment of advanced ALK+ NSCLC with ALK TKI therapies from January 2011 through June 2018. Crizotinib was the most commonly prescribed first-line ALK TKI therapy in this patient population, but the majority of data analyzed were obtained prior to Food and Drug Administration approval of alectinib and ceritinib in the first-line ALK TKI setting. Physicians should monitor patients closely to help identify when a change in treatment should occur.

Incidence of venous thromboembolism among postmenopausal women prescribed ospemifene, selective estrogen receptor modulators for noncancer indications, or untreated vulvar and vaginal atrophy.

OBJECTIVE: Ospemifene is a nonsteroidal selective estrogen receptor modulator (SERM) for the treatment of moderate symptomatic vulvar and vaginal atrophy (VVA) due to menopause. A postauthorization safety study is currently examining the incidence of venous thromboembolism (VTE) among postmenopausal women receiving ospemifene or other SERM (raloxifene, bazedoxifene, or tamoxifen, for noncancer indications), or with untreated VVA. METHODS: This interim analysis used the US MarketScan Commercial and Medicare Supplemental claims database from 2013 to 2017 to identify incident VTE. The incidence rate and 95% confidence interval of VTE during the first continuous course of treatment (or continuous untreated time for the untreated cohort) were calculated for each cohort overall and by age group, with sensitivity analyses examining incidence in the short term (up to 90 days) and long term (all available follow-up, regardless of treatment changes). RESULTS: Analyses included 8,188 ospemifene users, 11,777 other SERM users, and 220,242 women with untreated VVA. The incidence per 1,000 person-years and 95% confidence interval of VTE were 3.7 (1.7-7.1) for ospemifene, 11.5 (8.9-14.6) for other SERM, and 11.3 (10.8-11.7) for untreated VVA. Stratification by age and altering the time frame for analysis produced results with similar patterns to the primary analysis. CONCLUSIONS: This interim analysis of an ongoing study suggests a favorable safety profile for ospemifene with respect to VTE. Comparative analyses with covariate adjustment will be performed when data accrual is complete.

Burden of asthma exacerbations and health care utilization in pediatric patients with asthma in the US and England.

BACKGROUND: Data on asthma burden in pediatric patients are limited; this real-world study investigated exacerbation frequency and health care resource utilization (HCRU) in pediatric asthma patients from the US and England. METHODS: Data from pediatric patients (aged 6-17 years) in the Optum claims database (US) or Clinical Practice Research Datalink with linkage to Hospital Episode Statistics (England) were analyzed. Patients were categorized into four hierarchical groups: treated asthma (patients with ≥1 baseline asthma medication), severe asthma (plus Global Initiative for Asthma Step 4/5), severe refractory asthma ([SRA] plus ≥2 baseline severe asthma exacerbations), and eosinophilic SRA (SRA plus blood eosinophil count ≥150 cells/µL). Exacerbation frequency and HCRU during the 12 months postindex were described. RESULTS: Of 151 549 treated asthma patients in the US, 18 086 had severe asthma, 2099 SRA, and 109 eosinophilic SRA. There were 32 893 treated asthma patients in England, of whom 2711 had severe asthma, 265 SRA, and 8 eosinophilic SRA. In the 12 months postindex, ≥1 exacerbation occurred in 12.4% and 10.8% of patients with severe asthma, and 32.6% and 42.6% with SRA in the US and England, respectively. The proportions of patients with ≥1 asthma hospitalization in the 30 days after the first asthma exacerbation were 2.7% and 4.4% (treated), 3.5% and 8.2% (severe asthma), and 6.0% and 16.8% (SRA) in the US and England, respectively. CONCLUSION: This study provides insights into current asthma management practices in the US and England and indicates that some patients with severe disease have an unmet need for effective management.

Correction to: Real-World Predictors of Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Chronic Coronary Artery Disease and/or Peripheral Arterial Disease.

In the original article. The third author name is incorrect. The correct name is Nicholas J. Leeper.

Effectiveness of durvalumab versus chemotherapy in metastatic urothelial cancer: an observational, indirect comparison.

Aim: To compare the overall survival of patients with metastatic urothelial carcinoma (mUC) who failed platinum-based chemotherapy and received durvalumab or chemotherapy. Patients & methods: In an indirect comparison of patients with mUC who failed platinum-based chemotherapy, those who received durvalumab in a single-arm study were matched to patients from the Flatiron oncology electronic medical record database who received chemotherapy (n = 158 for each cohort). Matching was based on propensity scores. Kaplan-Meier methods and Cox regression models were utilized. Results: Median overall survival was 11.2 months (95% CI: 7.2-16.9) for durvalumab versus 8.2 months (95% CI: 6.7-9.8) for chemotherapy (hazard ratio: 0.63; 95% CI: 0.48-0.84). Conclusion: As a second-line therapy for mUC, durvalumab was associated with longer overall survival than chemotherapy.

Real-World Predictors of Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Chronic Coronary Artery Disease and/or Peripheral Arterial Disease.

INTRODUCTION: Collectively, coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent and are associated with increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Improved ability to identify those at highest risk of these events may help optimize secondary prevention efforts in this population. METHODS: Using the Optum Integrated Database, a healthcare claims database linked to electronic medical records (EMR), we identified patients with CAD and/or PAD between January 1, 2009, and September 30, 2016. Index date was the earliest date on which chronic and stable disease was established. Follow-up ran from index date until earliest of patient death, plan disenrollment, or end of study. We developed multivariate Cox proportional hazards models to identify predictors of MACE and/or MALE, limited to measures presumed available to clinicians during patient encounters (e.g., age, presence of selected comorbidities). RESULTS: A total of 20,932 patients met all selection criteria; 86.9% had CAD and 26.1% had PAD; 13% (n = 2753) experienced MACE and/or MALE during a mean follow-up of 2.3 years, for a rate of 7.1 events per 100 person-years (PYs). We identified 11 predictors of MACE and/or MALE. Most (95.1%) patients had ≥ 1 predictors; 34.0% and 6.9% had ≥ 4 and ≥ 6, respectively. Incidence of MACE and/or MALE was strongly correlated with number of predictors (r2 = 0.98), ranging from 2.3 per 100 PYs among those without predictors (4.9% of patients) to 18.7 per 100 PYs among those with ≥ 6 (6.9%). Patients with ≥ 1 predictor experienced 7.4 MACE and/or MALE per 100 PYs. CONCLUSION: Readily identifiable predictors can be used to identify subgroups with chronic CAD and/or PAD at elevated risk of MACE and/or MALE. Further research is required to understand the degree to which these subgroups may benefit from early identification and treatment with secondary prevention therapies. FUNDING: Janssen Pharmaceuticals.

Treatment patterns and overall survival in metastatic non-small-cell lung cancer in a real-world, US setting.

Aim: To conduct a retrospective analysis of electronic medical record data to understand real-world treatment patterns and overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC). Materials & methods: We included n = 9656 adults (≥18 years) with metastatic NSCLC and no prior therapy. Data from 1 January 2013 to 31 January 2017 were analyzed. Results: Carboplatin plus paclitaxel was the most common first-line therapy (18.6%), and nivolumab was the most common second- (31.0%) and third-line (38.4%) therapy; 26.7% of all patients were untreated. Median OS from initial metastatic diagnosis was 11.1 months (95% CI: 10.8-11.5). Second-line immunotherapy extended OS by over 3 months versus second-line chemotherapy. Conclusion: Platinum-based therapy was the most common first-line therapy, and immunotherapy was the most common second- and third-line therapy. Median OS of patients with metastatic NSCLC was <1 year.

Commonly used definitions in real-world studies may underestimate the prevalence of renal disease among nonvalvular atrial fibrillation patients.

Aim: To describe comorbidities among treated nonvalvular atrial fibrillation (NVAF) patients and assess the impact of using different time ('look back' windows) on the prevalence estimates. Patients & methods: We included all adult nonvalvular atrial fibrillation patients newly initiating treatment in the Clinical Practice Research Datalink. Comorbidities included in the Charlson Comorbidity Index were defined using an all available, 3- and 1-year look back window before the start of treatment. Results: The prevalence of comorbidities was high and increased when using longer look back windows; the largest difference was observed for renal disease (+15.6%). Conclusion: Our findings emphasize the importance of using all available data when characterizing chronic conditions and highlights the high comorbidity burden in this population.

Treatment patterns and overall survival in metastatic urothelial carcinoma in a real-world, US setting.

BACKGROUND: Metastatic urothelial carcinoma (mUC) treated with chemotherapy is associated with poor survival; however, as the field of immuno-oncology continues to evolve, new immunotherapies have recently become available. The current study aimed to assess real-world characteristics, treatment patterns, and overall survival (OS) of patients with mUC treated in the United States (US). METHODS: We conducted a retrospective, observational analysis of patients with mUC from the Flatiron Health longitudinal database from 2011 to 2017. Treatment patterns of patients who started systemic first-line therapy (1 L cohort) or second-line therapy following platinum-based first-line therapy (2 L cohort) were described using medication order and administration data. Kaplan-Meier analyses were used to assess OS from the start of first- and second-line therapy in the 1 L and 2 L cohorts, respectively. RESULTS: A total of 1811 patients qualified for the 1 L cohort (median age [range], 72 [32-84] years); 476 met the criteria for the 2 L cohort (median age [range], 71 [40-84] years). The most common first- and second-line therapies were carboplatin + gemcitabine (n = 562 [34.6%]) and atezolizumab (n = 90 [13.1%]), respectively, in the 1 L cohort. Median OS was 12.7 months (95% confidence interval [CI] 11.8, 13.4) in the 1 L cohort and 8.3 months (95% CI 7.2, 8.9) in the 2 L cohort. CONCLUSIONS: Consistent with clinical trial results, survival was poor in this real-world study in patients with mUC, indicating a continued unmet need. As immunotherapy becomes more commonplace in the treatment of mUC, future studies are needed to understand its real-world impact on survival.

Incidence and Cost of Major Adverse Cardiovascular Events and Major Adverse Limb Events in Patients With Chronic Coronary Artery Disease or Peripheral Artery Disease.

Chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are both associated with elevated risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). The frequency of these events in patients with CAD or PAD, and their corresponding costs, are not well understood. Accordingly, we describe the incidence and cost of both MACE and MALE in patients with CAD or PAD. Using a database that included healthcare claims linked to electronic medical records, we identified patients with evidence of chronic CAD and PAD, respectively, between January 1, 2009, and September 30, 2016. We assessed the occurrence of MACE (defined as myocardial infarction, stroke, or cardiovascular-related death) and MALE (critical limb ischemia, amputation, or peripheral artery disease-related revascularization). A total of 99,730 patients met all selection criteria: 86.0% had CAD, 25.8% had PAD, and 11.8% had both. Mean (±standard deviation) age was 67.7 (±11.5) years and 59.8% were male. During follow-up (mean: 1.8 years), 13.6% experienced MACE or MALE (6.3 per 100 person-years [PYs]), predominantly MACE (9.6% [4.3 per 100 PYs]). Adjusted 1-year healthcare costs were $44,495 greater in patients who experienced MACE or MALE (mean [95% confidence interval]: $64,099 [$33,254 to $123,557] vs $19,604 [$10,175 to $37,771]; p < 0.001). In conclusion, approximately 1 in 7 patients with chronic CAD or PAD experiences additional MACE or MALE within approximately 2 years of follow-up; the relatively high risk and cost of these events highlight the need for new secondary prevention therapies that may improve outcomes in these patients.

Discontinuation and primary care visits in nonvalvular atrial fibrillation patients treated with apixaban or warfarin.

AIM: Nonvalvular atrial fibrillation (NVAF) requires long-term anticoagulation treatment, which may necessitate frequent primary care visits. MATERIALS & METHODS: NVAF patients initiating warfarin or apixaban in 2012-2017 were identified from linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. A propensity score matched Cox regression model compared discontinuation risk. Primary care visits were compared via negative binomial regression. RESULTS: A total of 2695 apixaban users were matched to warfarin patients. Discontinuation risk was lower with apixaban than warfarin (hazard ratio: 0.40; 95% CI: 0.35-0.46). Apixaban patients averaged 12.2 annual primary care visits, versus 17.1 for warfarin users (p < 0.001). CONCLUSION: Apixaban was associated with reduced rates of discontinuation and primary care visits compared with warfarin.

Development and validation of algorithms to identify newly diagnosed type 1 and type 2 diabetes in pediatric population using electronic medical records and claims data.

PURPOSE: To develop and validate algorithms to classify diabetes type in newly diagnosed pediatric patients with DM. METHOD: Data from the United States Department of Defense health system were used to identify patients aged 10 to 18 years with incident DM. Two independent sets of 200 children were randomly sampled for algorithm development and validation. Algorithms were developed based on clinical insight, published literature, and quantitative approaches. The actual DM type was ascertained via chart review. Finally, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. RESULTS: Among the 400 patients, mean age was 14.2 (±2.5 years), and 50% were female. The best performing algorithms were based on data available in claims. They consisted of several logical expressions based on one predictor or more, which classified patients by use of glucose-lowering drugs or testing, DM ICD-9 diagnosis codes, and comorbidities. The best performing T2DM and T1DM algorithms achieved 90% and 98% sensitivity, 95% and 95% specificity, 87% and 98% PPV, and 96% and 96% NPV, respectively. CONCLUSIONS: Our results suggest that claims algorithms can accurately identify newly diagnosed T1DM and T2DM pediatric patients, which can facilitate large database studies in children with T1DM and T2DM. However, external validation in other data sources is needed.

Real-world utilization of darbepoetin alfa in cancer chemotherapy patients.

OBJECTIVES: To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. STUDY DESIGN: This is a retrospective cohort study using a proprietary outpatient oncology database. METHODS: Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin <10 g/dL during 2011-2015 were identified. The analysis was restricted to the first continuous exposure to chemotherapy agents (maximum allowable gap of 90 days between consecutive exposures) with darbepoetin alfa for each eligible patient. Initial, maintenance, weekly, and cumulative doses of darbepoetin alfa were examined across all darbepoetin alfa users. Subgroup analyses were conducted by chemotherapy type, baseline hemoglobin level, year of chemotherapy, solid tumor type, and initial dosing schedule. Differences in weekly doses across subgroups were evaluated using Wilcoxon rank-sum tests. RESULTS: Among 835 eligible patients, over 90% were 50 years or older. Mean chemotherapy course duration was 248 days, and mean duration of darbepoetin alfa treatment was 106 days. The mean weekly darbepoetin alfa dose was 110 µg. Patients received a mean of 4.3 darbepoetin alfa injections in the first chemotherapy course. There were no statistically significant differences (all P values > .05) in weekly dose by chemotherapy type, baseline hemoglobin level, year of chemotherapy, or solid tumor type. CONCLUSION: The average weekly darbepoetin alfa dose among metastatic cancer patients with chemotherapy-induced anemia from this study was 110 µg, which was lower than the labeled dosage for most adults. This estimate did not differ over time, across chemotherapy regimens, baseline hemoglobin levels, or solid tumor types.