Effectiveness and safety of anticoagulants among patients with venous thromboembolism and active cancer who also had prior bleed or prior renal disease.

OBJECTIVE: Patients with active cancer and venous thromboembolism (VTE) have elevated risk of recurrent VTE (rVTE) and major bleeding (MB). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of rVTE and MB of commonly used anticoagulants among these high-risk patients. METHODS: VTE patients with active cancer and treated with apixaban, warfarin, or low molecular weight heparin (LMWH) within 30 days of VTE were identified from five claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. The post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions between treatment and prior bleed or renal disease on risk of rVTE and MB, with p value <.1 considered significant. RESULTS: Study criteria were met by 30,586 VTE cancer patients: 35.0% had prior bleed and 29.0% had renal disease. For apixaban, LMWH, and warfarin cohorts, the incidence (events per 100 person-years) of MB was higher in patients with prior bleed (17.48 vs 7.58, 25.61 vs 13.11, and 20.38 vs 8.97) or renal disease (15.79 vs 8.71, 22.11 vs 15.90, and 18.49 vs 10.39) vs those without the conditions. Generally, there were no significant interactions between anticoagulant use and prior bleed or renal disease on rVTE and MB (p for interaction >.1). CONCLUSION: The incidence of MB was higher among those with prior bleed or renal disease. Effects of apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and common cancers or cancers with high venous thromboembolism risk.

Aim: Treatment effects among anticoagulant-treated patients with venous thromboembolism (VTE) and cancer across tumor types were evaluated. Methods: Patients initiating an anticoagulant within 30 days after VTE were identified. After inverse probability treatment weighting, patients were stratified by tumor type. Interactions between treatment and tumor type on recurrent VTE, major bleeding and clinically relevant non-major bleeding were assessed using Cox proportional hazard models. Results: Treatment effects were generally not significantly different among patients with or without the following cancer types: prostate, breast, lung, pancreatic or multiple myeloma. Few significant interactions were observed for lung and pancreatic cancer. Conclusion: Anticoagulant treatment effects were generally consistent across tumor types. The significant interactions may indicate tumor-specific effects of anticoagulants, but further research is needed.

Payer approval and rejection of oral anticoagulant prescriptions and prescription abandonment patterns among patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a major public health condition that renders patients at risk of recurrent events, which significantly increases their morbidity, mortality, and health care costs. Apart from warfarin, direct oral anticoagulants, such as apixaban, dabigatran, or rivaroxaban, are approved for VTE treatment. Cardiovascular drugs are largely impacted by formulary restrictions; however, the impact on oral anticoagulants (including warfarin and direct oral anticoagulants) in VTE has not been well studied. OBJECTIVE: To describe the extent of payer-rejected claims for oral anticoagulants for VTE and the factors associated with rejected claims. Prescription abandonment of oral anticoagulants and the time to an eventual fill for oral anticoagulant after rejection or abandonment were also evaluated. METHODS: A retrospective cohort study was conducted among patients with VTE newly prescribed an oral anticoagulant (first claim was the index) between October 2016 and October 2021. Descriptive statistics were used to describe the proportion of patients with paid (ie, filled), rejected, or abandoned index oral anticoagulant prescription and journey to paid prescription among those with initial rejection. Multivariable logistic regression was used to identify factors associated with initial rejection. RESULTS: Among the overall sample (N = 297,312), 74.3% had initial oral anticoagulant prescriptions approved, 9.1% had them rejected, and 16.7% abandoned them. Of the patients with initial rejection, 82.1% eventually filled their oral anticoagulant prescriptions; however, for 14.2% of these patients, the first fill was for an oral anticoagulant other than that initially prescribed. The mean time to a first fill for an oral anticoagulant after an initial rejection was 18.3 days. More than half of the patients with an initial rejected oral anticoagulant claim had at least 1 additional rejection during the follow-up period. Of the patients who abandoned their initial oral anticoagulant prescription, 83.9% filled an oral anticoagulant prescription during follow-up; the mean time to fill for the index oral anticoagulant was 15.6 days. Oral anticoagulant type, Medicare payer coverage, prescribing physician specialty, and VTE diagnosis setting of care were significantly associated with index oral anticoagulant claim rejection (P < 0.05). CONCLUSIONS: Rejection and abandonment may delay access to oral anticoagulant treatment. Factors contributing to these scenarios should be understood and addressed for proper VTE management.

Journey to anticoagulant access following payer rejection of apixaban.

OBJECTIVES: To investigate the journey to oral anticoagulant (OAC) access following formulary-related rejection of apixaban (Eliquis) and evaluate characteristics associated with failure to achieve OAC access among patients with atrial fibrillation (AF). STUDY DESIGN: Retrospective study using the Optum Market Clarity Data from January 2016 through February 2020. METHODS: Patients had at least 1 claim rejection for apixaban due to prior authorization (PA), formulary exclusion (FE), or quantity limit (QL) and at least 1 AF diagnosis on or before the rejected claim. Descriptive statistics summarized transaction journeys by type of formulary restriction. Multivariable regression assessed patient characteristics associated with not receiving an OAC within 60 days after initial rejection. RESULTS: Among 18,434 patients in the analytic sample, QL was the most common reason for rejection (68.7%), followed by PA (21.2%) and FE (10.2%). Most patients received a paid OAC claim within 60 days after rejection (82.2%-85.5% across restriction types). Mean time from rejection to paid claim ranged from 5.2 to 10.7 days among patients with a paid OAC claim and 12.4 to 17.6 days among those with multiple attempts before OAC receipt. Characteristics associated with higher odds of not receiving OAC treatment included being male, beingAfrican American, having Medicaid coverage, possessing a high stroke risk score, exhibiting no evidence of prior apixaban treatment, and being prescribed a low dose of apixaban on the initial rejected claim. CONCLUSIONS: Most patients with a claim rejection for apixaban received approval for apixaban within 60 days, suggesting that initial rejection merely created a delay in treatment. Vulnerable populations were at greater risk of not receiving a paid OAC claim.

The Association between Direct Oral Anticoagulants Prescribing Behavior and Non-Valvular Atrial Fibrillation Outcomes: An Instrumental Variable Analysis of Real-World Data.

Several observational studies have compared apixaban with rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), but these analyses may be confounded by unmeasured characteristics. This study used provider prescribing preference (PPP) as an instrumental variable (IV) to assess the association between prescriber choice of rivaroxaban vs. apixaban and the study outcomes of stroke/systemic embolism (SE), major bleeding, and death in a retrospective cohort of NVAF patients in the US. Initiators of either medication were linked to their prescribers and followed until the first of the study outcome, the end of rivaroxaban/apixaban use, or 365 days after initiation. PPP for each patient was the percent of rivaroxaban initiations issued by the provider for the prior 10 NVAF patients. Cox regression models tested associations between quintiles of PPP and each outcome. A total of 61,155 patients and 1726 providers were included. The IV was a strong predictor of rivaroxaban prescription (OR = 17.9; 95% CI: 16.6, 19.3). There were statistically significant associations between increasing preference for rivaroxaban and rates of major bleeding (ptrend = 0.041) and death (ptrend = 0.031), but not stroke/SE (ptrend = 0.398). This analysis provides evidence of the relative safety of apixaban over rivaroxaban for the risk of major bleeding and death.

Payer formulary tier increases of apixaban: how patients respond and potential implications.

OBJECTIVE: To assess potential impacts of formulary tier increases of apixaban-an efficacious oral anticoagulant (OAC) for preventing stroke in patients with atrial fibrillation (AF)-on patients' prescription drug plan (PDP) switching and OAC treatment patterns. METHODS: Nationwide claims data for Medicare beneficiaries with Parts A, B, and D (100% sample) were used to assess apixaban-treated AF patients who faced a formulary tier increase for apixaban in 2017 by their Part D PDP. Patients' out-of-pocket (OOP) costs for apixaban were described, along with PDP switching and OAC treatment patterns. RESULTS: Among 1845 included patients, 97.7% had apixaban on tier 3 of their plan's formulary in 2016 and faced its increase to tier 4 for 2017. Approximately 4% (N = 81) of patients pre-emptively switched to a different PDP for 2017 with almost all switching to plans with apixaban on a lower formulary tier and 85.2% continuing apixaban treatment. Among the 96% (N = 1764) of patients who remained on the same PDP for 2017, over half (57.5%) continued apixaban treatment, despite increased OOP costs ($54 vs. $135 for a 30-day supply in 2016 vs. 2017). Only 12.4% of those who remained on the same plan for 2017 switched to another OAC, while as much as 30.1% discontinued OACs. These discontinuers exhibited higher comorbidity burdens than patients continuing on any OAC. CONCLUSION: The majority of patients continued on apixaban despite higher OOP cost, suggesting patients' reluctance to change treatment for non-medical reasons; however, 30% of patients discontinued OAC treatment after higher apixaban tier placement.

A Real-World Evaluation of Primary Medication Nonadherence in Patients with Nonvalvular Atrial Fibrillation Prescribed Oral Anticoagulants in the United States.

BACKGROUND: Nonadherence to oral anticoagulants (OACs) is a challenge to stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data on primary medication nonadherence (PMN) in NVAF are lacking. OBJECTIVES: Our aim was to assess the rates and predictors of PMN among NVAF patients who were newly prescribed an OAC. METHODS: This was a retrospective database analysis of linked healthcare claims and electronic health record data. Adult NVAF patients with a prescription order for an OAC (apixaban, rivaroxaban, dabigatran, or warfarin) between January 2016 and June 2019 were identified (date of first prescription order = index date). Patients had a 1-year baseline and a 6-month post-index period to assess the rates of PMN, defined as having a prescription order but no paid claim for any OAC on or within 30 days after the index date. Sensitivity analyses explored 60-, 90- and 180-day PMN thresholds. Logistic regression models were used to examine the predictors of PMN. RESULTS: Among 20,393 patients, the overall 30-day PMN rate was 28.4%; PMN rates decreased to 17% with a 180-day threshold. PMN was numerically lowest for warfarin among OACs and numerically lowest for apixaban among direct OACs. A CHA2DS2-VASc score of ≥ 3, commercial insurance, and African American race were associated with higher odds of PMN. CONCLUSIONS: More than one-quarter of patients experienced PMN within 30 days of their initial prescription order. This rate decreased over a longer period, suggesting a delay in fills. Understanding the factors associated with PMN is warranted to develop effective interventions for improving OAC treatment rates in NVAF.

Effectiveness and safety of anticoagulants among venous thromboembolism cancer patients with and without brain cancer.

INTRODUCTION: Patients with brain cancer are at a high risk of developing venous thromboembolism (VTE) and are underrepresented in clinical trials. This study compared the risk of recurrent VTE (rVTE), major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among VTE cancer patients initiating apixaban, low molecular weight heparin (LMWH), or warfarin stratified by patients with brain vs other cancer types. MATERIALS AND METHODS: Active cancer patients initiating apixaban, LMWH, or warfarin within 30 days after VTE diagnosis were identified from 4 US commercial and the Medicare databases. Inverse probability of treatment weights (IPTW) was used to balance patient characteristics. Cox proportional hazards models were used to evaluate the interaction between brain cancer status and treatment on outcomes (rVTE, MB, and CRNMB), with a p-value <0.1 indicating a significant interaction. RESULTS: Of 30,586 patients with active cancer (5 % had brain cancer), apixaban (vs. LMWH and warfarin) was associated with lower risk of rVTE, MB, and CRNMB. Generally, no significant interactions (P > 0.1) were found between brain cancer status and anticoagulant treatment across outcomes. The exception was MB for apixaban [vs LMWH (p-value for interaction = 0.091)] with a higher reduction among those with brain cancer (HR = 0.32) than those with (HR = 0.72) other cancer. CONCLUSIONS: Among VTE patients with all types of cancer, apixaban (vs LMWH and warfarin) was associated with a lower risk of rVTE, MB, and CRNMB. In general, anticoagulant treatment effects were not significantly different between VTE patients with brain cancer and those with other cancer.

Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences.

INTRODUCTION: Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. METHODS: Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). RESULTS: A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67-0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64-0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80-0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding. CONCLUSION: Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.

Payer formulary exclusions of apixaban: how patients respond and potential implications.

In recent years, US payers have increased usage of formulary exclusions as a means to help manage costs. Earlier this year, one of the largest pharmacy benefit managers in the country added Eliquis (apixaban), the most widely used anticoagulant, to its list of excluded medicines from its formulary, raising concerns by physicians and patients. In this commentary, we examine the potential impacts of formulary exclusion of a drug like apixaban-a treatment for patients with atrial fibrillation and venous thromboembolism to help prevent stroke and clotting events and which has been demonstrated to have a strong efficacy and safety profile. We discuss the effect of formulary exclusions on patients' ability to access the most clinically appropriate treatment for their health needs, along with possible effects on their health and well-being. We also report descriptive results on apixaban-treated patients with traditional Medicare coverage who faced a formulary exclusion of apixaban in 2017, and these patients' observed behaviors. We found that the majority of these patients remained on apixaban either through pre-emptively switching to a different Part D drug plan with apixaban coverage or applying for formulary exception. Our findings suggest that formulary exclusion did not help to achieve the goal of switching patients to less costly medications but created additional hurdles for patients to access their preferred treatment and increased patient burden. Alternative ways to manage payer costs may be needed to help avoid poor outcomes and reduce the burden placed on patients in their efforts to access life-saving medications.

Risk of stroke/systemic embolism, major bleeding, and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran, or rivaroxaban compared with warfarin in the United States medicare population: updated analysis.

OBJECTIVE: To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Adults (≥65 years) initiating warfarin or DOACs between 1 January 2013 and 31 December 2014 were selected from the Medicare database and propensity scores matched 1:1 to balance baseline characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major bleeding-related medical costs in each matched cohort. RESULTS: Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38-0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63-0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51-0.63) and dabigatran (HR = 0.80; 95% CI 0.70-0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07-1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs. CONCLUSIONS: This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

Real-World Effectiveness of Dupilumab in Atopic Dermatitis Patients: Analysis of an Electronic Medical Records Dataset.

INTRODUCTION: While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch. METHODS: From Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy). RESULTS: More than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p < 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p < 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p < 0.0001 compared with pre-index). CONCLUSIONS: Consistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point.

Real-world evidence for carfilzomib dosing intensity on overall survival and treatment progression in multiple myeloma patients.

INTRODUCTION: Carfilzomib dosing as a single agent or in combination with dexamethasone (Kd) has evolved from the initial 27 mg/m2 twice-weekly (legacy dose), to more recently approved doses of 56 mg/m2 twice-weekly and 70 mg/m2 once-weekly (optimized doses). The objective of this study was to evaluate the overall survival (OS), and time to next treatment (TTNT) among multiple myeloma patients treated with Kd optimized vs legacy doses. METHODS: A retrospective analysis of patients receiving Kd between 01/01/2013-07/31/2017 was conducted using IQVIA's oncology electronic medical records database. Kd dose was estimated based on body surface area. OS was measured from the Kd-initiation date until death. TTNT was defined as the time from Kd-initiation until the start of subsequent treatment. Kaplan-Meier analysis and Cox models were used to evaluate OS and TTNT. RESULTS: Of the 1,469 patients evaluated, 129 (8.8%) received optimized dose and 1,340 (91.2%) received legacy dose. Risk of mortality was 64% lower for patients receiving the optimized doses (HR: 0.36, 95% CI: 0.178-0.745). Patients receiving the optimized doses had significantly longer TTNT compared to patients receiving the legacy dose (median TTNT: 17.5 months [95% CI: 14.8-NE] and 13.2 months, [95% CI: 12.4-14.4], respectively; p = 0.023), and 33% lower risk of progressing to the subsequent treatment (HR: 0.67, 95% CI: 0.48-0.93). CONCLUSIONS: Patient outcomes could be improved if eligible MM patients are treated with the optimized, recently approved Kd doses (56 mg/m2 twice-weekly and 70 mg/m2 once-weekly).

Erenumab patient characteristics, medication adherence, and treatment patterns in the United States.

OBJECTIVE: To describe patient characteristics, adherence, and treatment patterns, among adult migraine patients in the United States prescribed erenumab. BACKGROUND: Migraine is a highly prevalent and debilitating disease characterized by recurrent attacks of moderate to severe headache accompanied by non-headache symptoms. Erenumab is a first-in-class calcitonin gene-related peptide receptor (CGRP-R) antagonist indicated for migraine prophylaxis in adults. METHODS: This retrospective longitudinal cohort study used IQVIA's open-source longitudinal pharmacy (LRx) and medical (Dx) claims databases to identify adult migraine patients with an initial claim (index date) for erenumab between May 1, 2018 and April 30, 2019. Patients were required to have ≥180 days of follow-up. Erenumab dosing patterns, persistence, and adherence (using medication possession ratio [MPR] and proportion of days covered [PDC]), and discontinuation of other commonly prescribed acute and prophylactic anti-migraine therapies were assessed. Dose changes in acute therapies after initiation of erenumab were assessed in a subset of patients with an adequate trial of erenumab (≥2 additional erenumab claims within the 80 days following the index claim). RESULTS: A total of 64,174 patients met the study criteria. Mean (SD) age was 48 (13) years and 85.2% (n = 54,656) were female. The initial erenumab dose was 70 mg for the majority of patients (65.1%; n = 41,790); most (81.4%; n = 34,019) maintained their index dose during follow-up. Overall, 30.8% (n = 19,797) of patients had a PDC ≥ 0.80 and 41.7% (n = 26,769) had a MPR ≥ 0.80. Discontinuation rates of acute and other prophylactic migraine therapies after initiation of erenumab (among users of the respective therapies) were 48.7% (22,965/47,190) and 36.1% (16,602/46,006), respectively. Dose decreases among triptan, ergot compound, opioid, and barbiturate users were observed after initiation of erenumab. CONCLUSIONS: Almost all patients had prior use of acute or preventive therapy. Adherence to erenumab was higher than traditional oral prophylactic migraine therapies; however, overall adherence was still suboptimal. The decrease in use of acute and preventive prescription medications following initiation of erenumab suggests effectiveness in the real-world setting.

Estimation of the Incremental Cumulative Cost of HIV Compared with a Non-HIV Population.

OBJECTIVE: There are limited real-world data comparing cumulative incremental healthcare costs in people living with HIV (PLWH) and those without HIV. This study evaluated all-cause cumulative and incremental costs in PLWH in the US using a matched-cohort design. MATERIALS AND METHODS: This retrospective, multi-year, cross-sectional analysis evaluated annual costs from 2013 to 2017, and projected cumulative costs of HIV from age 25 to 69 years. IQVIA's commercial adjudicated claims database was used to identify patients with HIV and match them with patients without HIV (controls). Cumulative all-cause costs were derived from the health plan-allowed costs incurred from ages 25-69 years. Undiscounted, discounted, and incremental costs between PLWH and non-HIV populations were reported in 2017 US dollars (US$), and annual all-cause costs were estimated for each year by 10-year age bands. RESULTS: A total of 25,261, 24,134, 31,654, 35,374, and 29,039 PLWH and 75,783, 72,402, 94,962, 106,122, and 87,117 matched controls were identified in the years 2013 through 2017, respectively. The mean undiscounted cumulative costs were $1,840,554 for PLWH and $285,065 for controls, an incremental cost difference of $1,555,489, while the mean discounted cumulative cost for PLWH was $983,897 compared with $133,340 for controls, an incremental cost difference of $850,557. Mean all-cause annual and cumulative costs were up to seven times higher for PLWH compared with controls. There was a trend for costs to increase each year with increasing age. LIMITATIONS AND CONCLUSIONS: While cumulative all-cause cost estimates only approximate total cost burden for any given patient, and the results of this study may not be generalizable to all population subgroups, this is one of the first US studies to examine annual and cumulative costs in a real-world cohort of commercially insured PLWH compared with a population without HIV. In this large, representative sample of commercially insured US adults with HIV, PLWH had substantially higher all-cause cumulative costs than individuals without HIV.

Treatment Adherence And Persistence Among HIV-1 Patients Newly Starting Treatment.

OBJECTIVE: To assess adherence and persistence with first-line single-tablet regimen (STR) and multi-tablet regimen (MTR) antiretroviral therapy (ART) in newly treated HIV-1 patients. METHODS: Retrospective analysis of longitudinal pharmacy claims among US patients initiating ART between 1/1/2016 and 5/31/2016 (index date was defined by first ART claim for STRs, and fill date for the last therapy in the regimen for MTRs). Adherence was assessed over a 12-month period and reported as the proportion of adherent or non-adherent (defined as ≤5-day and > a 5-day gap between successive fills, respectively) patients. Sensitivity analysis using ≤7-day and ≤14-day gap thresholds to define adherence was performed. Persistence was assessed as the number of days on therapy from index until treatment discontinuation (>90 day gap in therapy). Kaplan-Meier curves and Cox Proportional Hazard models were generated to evaluate discontinuation rates. Assessments were performed on STRs vs MTRs overall and by regimen. RESULTS: Patients initiating ART (STR: n=10,623; MTR: n=2504) had a mean age of 42.8 years; 76.0% were male. STR patients were >2 times more likely to be adherent over 12 months than MTR patients (24.9% vs 11.7%, respectively). Patients using EVG/COBI/FTC/TAF had greater adherence than those using other STRs. Among MTRs, patients were more adherent with FTC/TDF+DTG (15.1%) than other MTRs. Persistence was also greater with STRs, with MTR patients being 61% more likely to discontinue therapy. Persistence was best for FTC/TAF-based regimens. Predictors of treatment discontinuation included younger age, female gender, and Medicare or Medicaid insurance type. CONCLUSION: Patients receiving STRs were significantly less likely to discontinue therapy and were more adherent with their regimens, providing further evidence of greater adherence and persistence with STRs versus MTRs. However, there was a large proportion of patients who interrupted or discontinued treatment. Further research examining treatment patterns beyond first line is warranted.

Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors.

PURPOSE: To describe patient characteristics and treatment patterns among early initiators of proprotein convertase subtilisin/kexin type nine inhibitors (PCSK9is) who initiated treatment within the first 6 months of market availability. PATIENTS AND METHODS: This retrospective cohort study used IQVIA's longitudinal open-source point-of-sale pharmacy claims database (LRx) and PharMetrics Plus (P+) health plan claims database to identify patients initiating a PCSK9i between January 1, 2016 and June 30, 2016. The index date was defined as the date of the first PCSK9i prescription (index claim) during the enrollment window; patients were followed for ≥6 months postindex. Patient characteristics including use of baseline lipid-lowering therapy (LLT) and measures such as persistence and adherence to PCSK9i therapy were evaluated with respect to health plan type (commercial vs Medicare). RESULTS: Overall, patients initiating PCSK9i (n=13,151) had a mean age of 66 years, and 51% were male. Approximately 67.4% of patients used some form of LLT (statin and/or ezetimibe) in the 24 months prior to initiating PCSK9i therapy. The proportion of patients covered by a commercial health plan (51.2%) was similar to that covered by Medicare (48.8%). Persistence on PCSK9i was marginally longer for patients with commercial insurance than Medicare (mean days on therapy 202.2 vs 198.5). Overall, 42.6% of patients discontinued their PCSK9i during the 180 days of follow-up. CONCLUSION: This study demonstrates that a large proportion of patients discontinue PCSK9i therapy at 30 and 90 days, which are the time frames for which many health plans require recertification to continue access to PCSK9i. Future studies looking at treatment patterns among patients who initiate PCSK9i therapy after the first 180 days once health plan formularies and utilization management criteria were finalized are needed to understand more comprehensively real-world PCSK9i usage patterns.

Low-density lipoprotein cholesterol outcomes post-non-PCSK9i lipid-lowering therapies in atherosclerotic cardiovascular disease and probable heterozygous familial hypercholesterolemia patients.

BACKGROUND: This study evaluated the proportion of patients with atherosclerotic cardiovascular disease (ASCVD) and probable heterozygous familial hypercholesterolemia (HeFH) achieving ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) or reaching the LDL-C ≤70 mg/dL threshold, after initiating or modifying statin, and/or ezetimibe therapy. MATERIALS AND METHODS: Adult ASCVD patients with baseline LDL-C >70 mg/dL (index) and a subset of patients with probable HeFH (proxied by LDL-C ≥190 mg/dL) were identified between January 1, 2012, and August 31, 2014, from the IQVIA electronic medical record database. Patients were followed for 12 months pre-index to examine baseline lipid-lowering therapy (LLT) use, and 12 months post index to evaluate treatment modifications and post-treatment LDL-C levels, stratified by type of treatment received and LDL-C levels at baseline. RESULTS: Of the sample of ASCVD patients who initiated treatment post-index (n=111,147), only 7.6% patients achieved a ≥50% reduction from baseline LDL-C and 19.1% of patients reached the LDL-C ≤70 mg/dL threshold. Among treated ASCVD patients who modified therapy post-index (n=75,523), 5.6% achieved a ≥50% reduction in LDL-C, and proportion of patients achieving LDL-C ≤70 mg/dL ranged from 6.9% to 26.7%, depending on the baseline LDL-C levels. Approximately 50% of the untreated probable HeFH patients (n=3,064) initiated LLT; however, the mean (SD) post-treatment LDL-C remained high (136.2 [47.8] mg/dL), with only 4.4% reaching LDL-C ≤70 mg/dL. Of the treated probable HeFH patients (n=1,073), 41.5% modified treatment; 22.1% achieved a ≥50% reduction in LDL-C and 1.1% reached LDL-C ≤70 mg/dL. CONCLUSION: This study found that most patients had suboptimal LDL-C responses after initiating or modifying standard LLT (statin and/or ezetimibe). More frequent and aggressive lipid management, including increasing statin intensity and alternative therapies, may be needed in patients with ASCVD and probable HeFH to reduce their cardiovascular risk.

Economic burden of skeletal-related events in patients with multiple myeloma: analysis of US commercial claims database.

AIMS: To estimate incremental healthcare resource utilization (HRU) and costs associated with skeletal-related events (SREs) secondary to multiple myeloma (MM), and HRU and cost differences in patients with one vs multiple SREs. METHODS: Adults with MM diagnosis between January 1, 2010-December 31, 2014, with benefits coverage ≥12 months pre- and ≥6 months post-diagnosis were followed to last coverage date or December 31, 2015, excluding patients with prior anti-myeloma treatment or cancers. SREs were identified by diagnosis or procedure codes (pathological fracture, spinal cord compression, radiation, or surgery to the bone). SRE patients (index = first post-diagnosis SRE) were propensity score matched 1:1 to patients without SRE (assigned pseudo-index) using baseline characteristics, and ≥1 month of continuous enrollment after index/pseudo-index date was required. Per-patient-per year (PPPY) HRU and costs (2016 US$) were determined for inpatient, outpatient, emergency department (ED), and outpatient pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar's tests for proportions were used to assess differences. Negative binomial regression and generalized linear regression analyses estimated differences in HRU and costs, respectively, for the comparison of single vs multiple SREs. RESULTS: Each cohort included 848 patients (mean age = 61 - 62 years, 57% male) with no significant differences in pre-index demographic or clinical characteristics between matched cohorts. Versus non-SRE patients, SRE patients had significantly higher PPPY use (p < .0001) of inpatient hospitalizations, ED visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs $108,160, p < .0001). Adjusted PPPY total costs were $209,820 in patients with multiple SREs; $159,797 in patients with one SRE. LIMITATIONS: SRE misclassification and residual confounding are possible. CONCLUSIONS: Among patients with MM, average annual costs were substantially higher in patients with SRE compared with matched non-SRE patients. The economic burden of SRE increased further with multiple events.

Patterns of use of systemic therapies among patients with metastatic melanoma: a retrospective claims database analysis in the United States.

OBJECTIVES: This retrospective analysis of the IMS PharMetrics Plus claims database aimed to describe the current real-world treatment patterns for metastatic melanoma in the USA. METHODS: Included patients (aged ≥18 years) had ≥1 prescription for ipilimumab, vemurafenib, temozolomide or dacarbazine between 1 January 2011 and 31 August 2013; diagnosis of melanoma and metastasis before first use (index date); no index drug use prior to the index date; continuous health plan enrollment for ≥6 months before and ≥3 months after index date. Proportion of days covered (PDC) was defined as days exposed to index therapy divided by continuously enrolled days between index date and last prescription date. RESULTS: Overall, 1043 patients were included (median age 57 years, 63% male), of whom 39% received the index drug ipilimumab, 35% vemurafenib, 19% temozolomide and 7% dacarbazine. Mean treatment duration (days) was 174 (vemurafenib), 100 (temozolomide) and 64 (dacarbazine). Mean PDC was 81% (vemurafenib), 67% (temozolomide) and 51% (dacarbazine). For patients receiving ipilimumab, 58% had the full 4 doses, 20% 3 doses, 14% 2 doses and 9% 1 dose only for the first induction course; 4% received re-induction, and none had a second re-induction. CONCLUSIONS: This study provides insights into the treatment patterns for metastatic melanoma, including newer agents, in real-world clinical practice.