Time to Next Treatment, Health Care Resource Utilization, and Costs Associated with Ibrutinib Use Among U.S. Veterans with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Real-World Retrospective Analysis.

BACKGROUND: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia, accounting for ≈ 37% of all leukemias in the United States. Limited real-word evidence is available on the outcomes of ibrutinib use among previously untreated patients in the U.S. Veterans Health Administration (VHA) population diagnosed with CLL/SLL. OBJECTIVES: To (a) evaluate time to next treatment (TTNT) among U.S. veterans with CLL/SLL who initiated ibrutinib versus chemoimmunotherapy (CIT) in first line (1L) and 1L ibrutinib versus ibrutinib in later lines (2L+) and (b) compare health care resource utilization (HRU) and costs between the 1L ibrutinib and CIT cohorts. METHODS: Adults with CLL/SLL and claims for 1L single-agent ibrutinib or CIT (index date = first prescription claim date) were included from Veterans Health Administration Data (April 1, 2013-March 31, 2018). A subset of the CIT 1L cohort with evidence of ibrutinib in 2L/3L was defined as the ibrutinib 2L+ cohort. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate TTNT, and generalized linear models were used to determine all-cause per patient per month (PPPM) HRU and costs during 1L among propensity score-matched (PSM) cohorts. RESULTS: After PSM, 614 patients were included in each of the 1L ibrutinib and 1L CIT cohorts, and 149 were included in each of the 1L ibrutinib and 2L+ ibrutinib cohorts. The 1L ibrutinib cohort had significantly longer TTNT compared with each of the 1L CIT and 2L+ ibrutinib cohorts (P <0.0001 and P =0.0001, respectively) and was less likely to have a next line of treatment than the CIT 1L cohort (HR = 0.52; 95% CI = 0.42-0.65; P < 0.0001) and the 2L+ ibrutinib cohort (HR = 0.39; 95% CI = 0.22-0.69; P = 0.0012). The 1L ibrutinib cohort had significantly fewer inpatient visits (rate ratio [RR] = 0.38; 95% CI = 0.28-0.52; P ≤ 0.05) and outpatient visits PPPM (RR =0.72; 95% CI = 0.68-0.77; P ≤ 0.5) compared with the CIT 1L cohort. Additionally, the 1L ibrutinib cohort had $7,308 significantly lower monthly medical costs (95% CI = -$9,892 to -$4,895; P ≤ 0.05) versus the 1L CIT cohort, resulting in comparable monthly total health care cost (medical and pharmacy) between real-world 1L patients treated by ibrutinib and CIT (-$2,160; 95% CI = -$4,840-$347; P > 0.05). CONCLUSIONS: These findings demonstrate that among U.S. veterans with CLL/SLL, 1L ibrutinib use was associated with significantly longer TTNT versus that of 1L CIT. Similarly, early treatment with ibrutinib was associated with longer TTNT as compared to ibrutinib use in later lines of therapy. Moreover, 1L ibrutinib was associated with lower HRU and medical costs compared with 1L CIT, completely offsetting the higher pharmacy costs related to 1L ibrutinib treatment. DISCLOSURES: This research was sponsored by Janssen Scientific Affairs. The analyses were performed by STATinMED Research. Huang is an employee of Janssen Scientific Affairs and may own company stock. Sundaram was an employee of Janssen Scientific Affairs at the time this study was conducted. Borra and Janjan are employees of STATinMED Research, a paid consultant to the study sponsor. Wang, Li, and Shrestha were employees of STATinMED Research at the time this study was conducted.

Healthcare resource utilization and costs associated with patients prescribed afatinib or erlotinib as first-line therapy for EGFR mutation-positive NSCLC in the United States.

Aims: To assess healthcare resource utilization (HCRU) and costs in patients with non-small cell lung cancer treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors afatinib or erlotinib as first-line treatment.Materials and methods: This retrospective analysis used data from three large administrative claims databases in the US: Truven MarketScan, IMS PharMetrics Plus, and Optum Clinformatics Data Mart. Patients with diagnosis codes of lung cancer treated with afatinib or erlotinib were included in the sample. Treatment cohorts were matched on baseline characteristics using propensity scores to account for potential selection bias. HCRU and healthcare costs were compared between the matched afatinib and erlotinib cohorts.Results: In total, 3,152 patients met the study inclusion criteria; propensity score matching of the afatinib and erlotinib patients yielded 525 matched pairs with well-balanced baseline characteristics. The afatinib cohort had significantly fewer patients with ≥1 inpatient visits (40.4% vs 52.2%, p = 0.0001) and outpatient emergency room (ER) visits (45.7% vs 54.1%, p = 0.0066). Per patient per month (PPPM) visits were significantly different between afatinib compared to erlotinib for inpatient visits (0.1 vs 0.2, p = 0.0152), other outpatient visits PPPM (2.6 vs 3.0, p = 0.022) and outpatient office visits (2.0 vs 1.7, p = 0.0059). Although costs of outpatient office ($1,624 vs $1,070; p = 0.0086) and pharmacy ($6,709 vs $5,932; p < 0.0001) visits were higher for afatinib vs erlotinib, total costs did not differ significantly between cohorts ($14,972 vs $14,412; p = 0.4415).Limitations: Retrospective claims data can be subject to coding errors or data omissions; patients were required to have continuous health plan enrolment; EGFR mutation status was not confirmed.Conclusions: Patients treated with afatinib as first-line monotherapy experienced fewer inpatient stays and ER visits compared with erlotinib. Total costs were not significantly different between the two treatment cohorts.

Elevated White Blood Cell Levels and Thrombotic Events in Patients With Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data.

BACKGROUND: Patients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). The objective of the present analysis was to describe the association between white blood cell (WBC) levels and occurrence of TEs among patients with PV from a large real-world population. PATIENTS AND METHODS: The present retrospective analysis using Veterans Health Administration claims data (October 1, 2005, to September 30, 2012) evaluated adult patients assigned to 4 WBC count categories (WBC count < 7.0, 7.0-8.4, 8.5 to < 11.0, and ≥ 11.0 × 109/L) to compare the risk of TEs (reference, WBC count, < 7.0 × 109/L group). Analysis was performed using a Cox proportional hazards model, considering WBC status as a time-dependent covariate. RESULTS: Of the 1565 patients with PV included in the present analysis, the WBC count was < 7.0 × 109/L for 428 (27.3%), 7.0 to 8.4 × 109/L for 375 (24.0%), 8.5 to < 11.0 × 109/L for 284 (18.1%), and ≥ 11.0 × 109/L for 478 (30.5%). Of the 1565 patients, 390 (24.9%) had experienced a TE during the study period. The mean follow-up ranged from 3.6 to 4.5 years. Compared with the reference group (WBC count < 7.0 ×109/L), the hazard ratio for TEs was 1.10 (95% confidence interval [CI], 0.82-1.48; P = .5395), 1.47 (95% CI, 1.10-1.96; P = .0097), and 1.87 (95% CI, 1.44-2.43; P < .0001) for patients with a WBC count of 7.0 to 8.4, 8.5 to < 11.0, and ≥ 11.0 ×109/L, respectively. CONCLUSION: A positive, significant association between an increased WBC count of ≥ 8.5 ×109/L and the occurrence of TEs was observed in patients with PV. The potential thrombogenic role of WBCs in patients with PV supports the continued inclusion of WBC count control in disease management and evaluation of the response to therapy.

Risk of Venous Thromboembolism after New Onset Heart Failure.

New-onset heart failure (HF) is associated with cardiovascular morbidity and mortality. It is uncertain to what extent HF confers an increased risk of venous thromboembolism (VTE). Adults ≥65 years old hospitalized with a new diagnosis of HF were identified from Medicare claims from 2007-2013. We identified the incidence, predictors and outcomes of VTE in HF. We compared VTE incidence during follow-up after HF hospitalization with a corresponding period 1-year prior to the HF diagnosis. Among 207,535 patients with a new HF diagnosis, the cumulative incidence of VTE was 1.4%, 2.5%, and 10.5% at 30 days, 1 year, and 5 years, respectively. The odds of VTE were greatest immediately after new-onset HF and steadily declined over time (OR 2.2 [95% CI 2.0-2.3], OR 1.5 [1.4-1.7], and OR 1.2 [1.2-1.3] at 0-30 days, 4-6 months, and 7-9 months, respectively). Over 26-month follow-up, patients with HF were at two-fold higher risk of VTE than patients without HF (adjusted HR 2.31 [2.18-2.45]). VTE during follow-up was associated with long-term mortality (adjusted HR 1.60, 95% CI 1.56-1.64). In conclusion, patients with HF are at increased risk of VTE early after a new HF diagnosis. VTE in patients with HF is associated with long-term mortality.

Hematocrit levels and thrombotic events in patients with polycythemia vera: an analysis of Veterans Health Administration data.

Patients with polycythemia vera (PV) have a high incidence of thrombotic events (TEs), contributing to a greater mortality risk than the general population. The relationship between hematocrit (HCT) levels and TE occurrence among patients with PV from the Veterans Health Administration (VHA) was evaluated to replicate findings of the CYTO-PV trial with a real-world patient population. This retrospective study used VHA medical record and claims data from the first claim with a PV diagnosis (index) until death, disenrollment, or end of study, collected between October 1, 2005, and September 30, 2012. Patients were aged ≥ 18 years at index, had ≥ 2 claims for PV (ICD-9-CM code, 238.4) ≥ 30 days apart during the identification period, continuous health plan enrollment from 12 months pre-index until end of study, and ≥ 3 HCT measurements per year during follow-up. This analysis focused on patients with no pre-index TE, and with all HCT values either < 45% or ≥ 45% during the follow-up period. The difference in TE risk between HCT groups was assessed using unadjusted Cox regression models based on time to first TE. Patients (N = 213) were mean (SD) age 68.9 (11.5) years, 98.6% male, and 61.5% white. TE rates for patients with HCT values < 45% versus ≥ 45% were 40.3% and 54.2%, respectively. Among patients with ≥ 1 HCT before TE, TE risk hazard ratio was 1.61 (95% CI, 1.03-2.51; P = 0.036). This analysis of the VHA population further supports effective monitoring and control of HCT levels < 45% to reduce TE risk in patients with PV.

Duration of treatment among patients prescribed afatinib or erlotinib as first-line therapy for EGFR mutation-positive non-small-cell lung cancer in the USA.

Aim: Evaluate duration of therapy among patients treated with afatinib or erlotinib as first-line therapy for non-small-cell lung cancer (NSCLC). Materials & methods: NSCLC patients initiating afatinib or erlotinib between 2014 and 2017 were identified in three large claims databases in the USA. Propensity score matching was conducted to compare the duration of treatment between patients by treatment. Results: Patients prescribed afatinib had a significantly longer median duration of treatment compared with those prescribed erlotinib (12.1 vs 9.9 months; p = 0.035) and experienced a 14% reduction in risk of discontinuing therapy (adjusted hazard ratio: 0.86; CI: 0.75-0.99). Conclusion: First-line treatment duration in a real-world setting was significantly longer for patients prescribed afatinib compared with erlotinib.

Cytoreductive treatment patterns among US veterans with polycythemia vera.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited. METHODS: This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics. RESULTS: The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years. CONCLUSION: The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA.

Effect of Renal Function on Dosing of Non-Vitamin K Antagonist Direct Oral Anticoagulants Among Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Non-vitamin K antagonist direct oral anticoagulants (DOACs) are fixed-dose regimens indicated for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary among patients with renal insufficiency to optimize efficacy and safety. OBJECTIVE: To assess DOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients. METHODS: Adult NVAF patients with ≥1 DOAC pharmacy claim (January 1, 2013, to December 31, 2014), continuous enrollment for ≥12 months post-index DOAC claim, and documented creatinine clearance within 3 months preindex date in the Optum/Humedica SmartFile database were eligible. DOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per US prescription information. Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate DOAC dosage. RESULTS: Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed, and rivaroxaban had the highest inappropriate dosing rate. Most inappropriately dosed patients were underdosed. Inappropriately dosed patients were more likely to be older, female, and have a body weight of ≤60 kg; they also had higher mean CHA2DS2-VASc and Charlson comorbidity index scores (all P < 0.05). Overtreated patients had a higher risk of bleeding (hazard ratio [HR] = 5.4; P = 0.006) than undertreated patients (HR = 3.1; P = 0.025) relative to appropriately dosed patients. However, no significant difference in stroke risk was observed, most likely because very few stroke events were observed in the study. CONCLUSIONS: Inappropriate dosing occurred among patients with normal and insufficient renal function. The consideration of clinical factors beyond renal function is necessary to reduce bleeding risk associated with DOAC therapy.

Burden of Atopic Dermatitis in the United States: Analysis of Healthcare Claims Data in the Commercial, Medicare, and Medi-Cal Databases.

INTRODUCTION: Comparative data on the burden of atopic dermatitis (AD) in adults relative to the general population are limited. We performed a large-scale evaluation of the burden of disease among US adults with AD relative to matched non-AD controls, encompassing comorbidities, healthcare resource utilization (HCRU), and costs, using healthcare claims data. The impact of AD disease severity on these outcomes was also evaluated. METHODS: Adult AD patients in the Commercial (n = 83,106), Medicare (n = 31,060), and Medi-Cal (n = 5550) databases were matched (1:1) to non-AD controls by demographic characteristics. AD patients were stratified by disease severity (higher, lower) using treatment as a surrogate measure of severity. The comorbidity burden, HCRU, and costs were evaluated during a 12-month follow-up period. RESULTS: In the Commercial, Medicare, and Medi-Cal populations, patients with AD had a significantly higher overall comorbidity burden (P < 0.0001), an increased risk of asthma and allergic rhinitis (both P < 0.0001), higher HCRU (P < 0.05), and higher mean total per patient costs (Commercial: US$10,461 versus US$7187; Medicare: US$16,914 versus US$13,714; Medi-Cal; US$19,462 versus US$10,408; all P < 0.0001), compared with matched non-AD controls. Higher disease severity was associated with an increased comorbidity burden (P < 0.0001), HCRU (P < 0.05), and total costs (Commercial: US$14,580 versus US$7192; Medicare: US$21,779 versus US$12,490; Medi-Cal; US$22,123 versus US$16,639; all P < 0.0001) relative to lower severity disease. CONCLUSION: In this large-scale, healthcare claims database analysis, AD patients had a significantly higher comorbidity burden, HCRU, and costs compared with matched non-AD controls. Higher disease severity was associated with an even greater comorbidity and economic burden. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.