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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.

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. 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. 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. 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.

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.

Dionne M Hines,1 Pallavi Rane,2 Jeetvan Patel,2 David J Harrison,2 Rolin L Wade1 1Health Economics and Outcomes Research, IQVIA, Plymouth Meeting, PA, USA; 2Global Health Economics, Amgen Inc., Thousand Oaks, CA, USA 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. Keywords: LDL-C, statin, atherosclerotic cardiovascular disease, ASCVD, heterozygous familial hypercholesterolemia, HeFH, lipid lowering

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.

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. Electronic supplementary material The online version of this article (10.1007/s41669-020-00209-8) contains supplementary material, which is available to authorized users.

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).

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.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.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.This study provides insights into the treatment patterns for metastatic melanoma, including newer agents, in real-world clinical practice.

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.

Chi-Chang Chen,1 Pallavi B Rane,2 Dionne M Hines,1 Jeetvan Patel,2 David J Harrison,2 Rolin L Wade1 1IQVIA, Plymouth Meeting, PA, USA; 2Amgen Inc., Thousand Oaks, CA, USA 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. Keywords: hyperlipidemia, ASCVD, HeFH, LDL-C, statin, lipid-lowering therapy

Introduction Patients with gout have numerous comorbidities. We aimed to estimate the prevalence and incidence rates of renal and cardiovascular morbidities in trial-aligned patients with established gout in Germany (DE), the United Kingdom (UK), the United States (US), and France (FR). Methods This longitudinal cohort study used retrospective data from IMS Disease Analyzer™ (DE, FR), Clinical Practice Research Datalink–Hospital Episode Statistics (UK), and IMS’ PharMetrics Plus database linked with outpatient laboratory results (US). Included patients were ≥18 years at index date (January 1, 2010; all dates +1 year for FR), with continuous enrollment during the pre-index year, had “prevalent established gout” determined by data in the pre-index year, and ≥1 documented visit after index date; additional inclusion/exclusion criteria were aligned with recent gout clinical trials. Look-back for comorbidity prevalence extended to January 1, 2003 (US: January 1, 2009). Follow-up for incidence extended from index date to at most March 26, 2013 (FR: May 31, 2014). Events of interest were identified by diagnostic codes and/or laboratory data. Results The trial-aligned cohorts included 35,118 (DE), 24,607 (UK), 121,591 (US), and 17,338 (FR) patients. Among renal conditions, baseline diagnosis of chronic kidney disease/renal failure was most prevalent in the UK followed by DE; abnormal serum creatinine was most prevalent in the UK. Hypertension was the most prevalent cardiovascular diagnosis in all countries, followed by ischemic heart disease (IHD) and myocardial infarction. Incidence rates (per 100 patient-years) for new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US) and for nephrolithiasis diagnosis from 0.31 (FR) to 3.79 (US). The incidence rates for hypertension diagnosis were highest among cardiovascular-related events, ranging from 3.23 (UK) to 20.27 (US), followed by IHD. Conclusions Patients with established gout such as those included in gout trials have a high burden of established morbidity and new diagnoses of morbid events. Consideration of comorbidities, which greatly exacerbate disease burden, is important in gout management. Funding AstraZeneca. Electronic supplementary material The online version of this article (doi:10.1007/s12325-016-0346-1) contains supplementary material, which is available to authorized users.

e19509 Background: To examine treatment patterns and health care costs of RRAML in the US. Methods: We identified adults with ≥ 2 outpatient or ≥ 1 inpatient claim with a diagnosis of AML from 1/1/2011 to 12/31/2017 (first AML claim = index date) using IQVIA’s fully-adjudicated Health Plan Claims Data. Continuous health plan enrolment for ≥ 12 months prior to the index date and ≥ 1-month post-index, a RRAML diagnosis on or prior to the index date, or with hematopoietic stem cell transplantation (HSCT) or chemotherapy pre-index were required. Patients were grouped by post-index treatment (high- or low-intensity chemotherapy [HIC, LIC] with and with no HSCT, HSCT only, best supportive care [BSC], or no treatment within 90 days of index [NoTx]). Costs were evaluated for 12 months following index. Results: The final sample of patients with RRAML (n = 804) were grouped by age:18-59 (n = 411; 51.2%), 60-74 (n = 318; 39.5%), and ≥75 years (n = 75; 9.3%). Treatment within the three age cohorts was: HIC (13%, 11%, 1%); LIC (27%, 38%, 52%); HIC+HSCT (14%, 7%, 0%); LIC+HSCT (2%, 3%, 0%); HSCT (9%, 9%, 0%); BSC (21%, 21%, 31%); NoTx (13%, 12%, 16%), respectively. Mean monthly costs were lowest for BSC and highest for HSCT or HIC containing treatments, irrespective of age (Table). Inpatient costs were 50 to 100% of total costs. Monthly costs across treatment/age groups were higher earlier in treatment [month 1 range: $28,627 (BSC) to $180,867 (HIC)] and declined over time [month 12 range: $2,853 (BSC) to $53,003 (HIC+HSCT)]. Conclusions: Nearly half of all patients age ≥75 years and 33% of patients < 75 years received BSC or NoTx, which highlights a significant unmet need for new treatment options. Average costs per patient, especially early in treatment are high and driven by hospital service utilization. [Table: see text]

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.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.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.SRE misclassification and residual confounding are possible.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.

Introduction: Carfilzomib (K) was first approved in 2012 for the treatment of relapsed/refractory multiple myeloma (RRMM) at a dose of 27 mg/m2 twice weekly (27 BIW). The K dose has since been optimized; carfilzomib plus dexamethasone (Kd) is approved for patients with RRMM at a recommended K dose of 56 mg/m2 twice weekly (56 BIW) since 2016. Recently, the A.R.R.O.W trial showed that Kd 70mg/m2 once weekly (70 QW) significantly improved progression free survival compared to Kd 27 BIW. Considering the study time-period, however, patients are still treated with 27 BIW in the real-world leaving them possibly under-treated. The Kd 27 BIW, corresponds to a cumulative weekly dose (CWD) of K 120mg. Therefore, in order to understand the relationship between dose and outcomes we examined the impact of K-dosing (CWD >120mg [optimized dose-56 BIW/70 QW] vs. CWD ≤120 mg [27 BIW]) on time to next treatment (TTNT) and overall survival (OS) among patients treated with Kd regimen. Methods: IQVIA's Oncology Electronic Medical Records database was used to identify patients ≥18 years of age, with a diagnosis of MM between 1/1/2010 and 10/31/2017, receiving Kd regimen in any line of therapy, with ≥ 3 doses of K on or after their K-index date (first administration of K in the Kd regimen, between 1/1/2013 and 10/31/2017). Patients were required to have ≥ 3 doses of K in order to establish continuity and for calculating CWD. CWD was calculated as the cumulative sum of weekly dose of K received by the patient divided by the number of weeks with Kd administration. The first two K doses were excluded from the calculation of CWD as these represent the loading dose. OS and TTNT were compared between patients receiving optimized dose-56 BIW/70 QW vs. 27 BIW. OS was evaluated among the subset of patients with a recorded deceased or alive status and measured from the K-index date until death due to any cause or the end of the study period, where they were censored. TTNT was defined as the time from initiation of the Kd regimen until the start of a subsequent regimen that did not contain Kd (treatment progression). Additionally, a landmark analysis at 12 months from initiation of Kd regimen was conducted to measure the proportion of patients alive and the proportion of patients with treatment progression. Kaplan-Meier analysis was used to estimate OS and TTNT and the log-rank test was used to compare the groups. Adjusted hazard ratios for OS and TTNT were evaluated using Cox models. Results : A total of 1,469 eligible MM patients with ≥3 Kd administrations were identified, of which 129 (8.8%; mean age: 63.5, SD: 9.8) received optimized dose-56 BIW/70 QW and 1,340 (91.2%; mean age: 67.0, SD: 10.4) received 27 BIW. The median follow-up time was slightly over a year for patients in both cohorts. The median K dose was 147.0 mg among patients in optimized dose-56 BIW/70 QW group and 88.1 mg among patients in 27 BIW group. Median OS was not estimable (NE), however, OS for the optimized dose-56 BIW/70 QW group (n=78) was significantly longer than that of the 27 BIW group (n=771; p=0.002) (Fig. 1). The proportion of patients in optimized dose-56 BIW/70 QW group alive at 12 months was 90.3% compared to 79.7% for patients in 27 BIW group respectively. Covariate-adjusted cox model showed that patients in optimized dose-56 BIW/70 QW group had a 64% lower risk of death than patients in 27 BIW group (adjusted HR: 0.364; 95% CI: 0.178-0.745; p = 0.0057, Table 1). TTNT was significantly longer for patients in optimized dose-56 BIW/70 QW group compared to patients in 27 BIW group (p=0.023; median TTNT: 17.5 [95% CI: 14.8-NE] and 13.2, [95% CI: 12.4-14.4], respectively) (Fig. 2). Covariate-adjusted cox model showed that patients in optimized dose-56 BIW/70 QW group had a 33% lower risk of treatment progression than patients in 27 BIW group (adjusted HR: 0.669; 95% CI: 0.483-0.927; p=0.0155, Table 1). Conclusion: Among patients treated with Kd regimen, a smaller proportion were prescribed K at optimized dose-56 BIW/70 QW. Patients receiving the optimized dose-56 BIW/70 QW had significantly improved OS and TTNT compared to those receiving 27 BIW. Our findings suggest that these patient-relevant outcomes may be improved in a vast majority of RRMM patients currently under-treated with carfilzomib by optimizing the dose, taking into consideration patients' comorbidities and ability to tolerate therapy. Disclosures Medhekar: Amgen: Employment, Equity Ownership. Hines:Amgen: Consultancy. Panjabi:Amgen: Employment, Equity Ownership. Welliver:Amgen: Employment, Equity Ownership. Wang:Amgen: Consultancy. Wade:Amgen: Consultancy.

Ischemic colitis (IC) incidence rates (IRs) among treated hypertensive patients are poorly understood, and existing literature on the subject is sparse. Antihypertensive drugs may raise the risk of developing IC. Novel antihypertensive agents—such as the direct renin inhibitor aliskiren—have not been assessed for IC risk. The aims of this study were to evaluate (1) the IRs of probable IC (pIC) in treated hypertensive adults, with a focus on aliskiren-treated patients; (2) the antihypertensive therapies used; and (3) the IRs of pIC in non-hypertensive adults. This study selected hypertensive and non-hypertensive patients (N = 2,356,226 each) from a US health plan claims database. pIC was defined as diagnosis of IC within 3 months after colonoscopy, recto-sigmoidoscopy, or colectomy. IRs were calculated per 100,000 person-years (PYs) with 95 % confidence intervals (CIs) and stratified by antihypertensive regimen. IRs of pIC in hypertensive and non-hypertensive subjects were 18.6 (95 % CI 17.6–19.8) and 4.0 (95 % CI 3.4–4.7), respectively. The non-hypertensive cohort consisted of younger patients who may have been less prone to developing IC. The overall (i.e., all antihypertensive regimens combined) monotherapy IR per 100,000 PYs was 17.5 (95 % CI 16.2–18.8), the overall dual-combination regimen IR per 100,000 PYs was 19.5 (95 % CI 17.37–21.83), and the overall triple-plus combination regimen IR per 100,000 PYs was 27.7 (95 % CI 22.72–33.38). Study results indicate that the treated hypertensive patients may have a higher risk of pIC compared with non-hypertensive populations. The quantity of antihypertensive agents prescribed may contribute to IC more than treatment duration.

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with premature atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have shown reductions in LDL-C levels in patients uncontrolled by statin and/or ezetimibe therapy.

Complications associated with diabetes are a major contributor to the burden of the disease. To better inform decision modelling, there is a need for cost estimates of specific diabetes-related complications, stratified by diabetes type and patient age group. To obtain direct medical costs of managing and treating diabetes-related complications over a 2-year period, for adults and children with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), using data from a large commercially insured US subscriber database. We examined records from a large US multi-payer claims database to identify patients with any diabetes-related complications included in nine pre-specified categories, filed between January 2009 and September 2010, and with pre-index evidence of T1DM or T2DM. Patients were required to have continuous health plan enrolment 12 months before and 24 months after each index complication. Patients were classified into cohorts based on their diabetes type and age status at the time of the complication. The direct medical cost associated with each complication was calculated for the 12- and 24-month follow-up periods. Mean paid and allowed total costs were calculated and inflation-adjusted to the year 2011. Of the 119,715 patients who met the inclusion criteria, 211 (0.2 %) were categorized as children with T1DM, 55 (0.05 %) as children with T2DM, 6,227 (5.2 %) as adults with T1DM and 113,222 (94.6 %) as adults with T2DM. The respective mean cohort ages were 13.5, 14.9, 48.5 and 58 years. Proteinuria/albuminuria was the most common complication for T1DM and T2DM child cohorts, with this complication occurring in almost one third of these children. Among the child cohorts, renal disease accounted for the highest mean paid cost for T1DM patients (US$6,053) whereas for T2DM patients, the complication associated with the highest mean paid cost was lactic acidosis (US$25,053). For the adult T1DM cohort, the complications with the highest occurrence and highest mean total paid cost were non-proliferative retinopathy (40.3 %) and renal disease (US$28,076), respectively. Similarly, for the adult T2DM cohort, these complications were neuropathy (26.8 %) and peritoneal dialysis (US$32,826). With the continuing and increasing interest in child and adult T1DM and T2DM, stakeholders will need relevant and timely information to guide treatment decision making. This cost research may directly inform the economic models that are often developed to better identify, understand and manage key economic considerations that drive the costs of this chronic disease.

Background Hyperuricemia and gout are increasingly prevalent, and if not appropriately treated, may cause permanent joint destruction, bone erosion, and kidney damage. Patients typically have worse-than-normal pre-existing health status at diagnosis, and comorbidities such as chronic renal impairment and cardiovascular (CV) diseases are associated with gout. Objectives Estimate prevalence and incidence rates (IRs) of potential treatment- or disease-related renal and CV morbidities (pre-existing and new incident events) in patients with established gout in Germany (DE), the United Kingdom (UK), United States (US), and France (FR). Methods A longitudinal cohort study was conducted using retrospective data from IMS Disease Analyzer™ (DE & FR), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), & IMS9 PharMetrics Plus database linked with outpatient laboratory results (US), from Jan 1, 2009 to Dec 31, 2011. Patients were required to have “prevalent established gout” (treated with urate-lowering treatment [ULT] or eligible for ULT based on ACR guidelines) between Jan 1, 2009 & Dec 31, 2009; age ≥18 yrs on index date (Jan 1, 2010); and ≥1 documented visit both prior to Jan 1, 2009 and after Jan 1, 2010. Variable follow-up extended from index date to Dec 31 2011 (all dates +1 yr for FR). Events of interest were identified based on diagnostic codes/laboratory data. Analyses are presented overall and stratified by type of 1st ULT regimen (allopurinol or febuxostat) after index, with follow-up until treatment discontinued. Results A total of 35,188 (DE), 24,607 (UK), 121,591 (US), and 17,388 (FR) patients were analyzed. Among renal conditions, baseline diagnosis of CKD/renal failure was most prevalent in the UK (10.9%) & DE (6.7%), whereas prevalence of abnormal serum creatinine (sCR) was most prevalent in the UK (30.6%). Hypertension was the most prevalent CV diagnosis in all 4 countries (59.5% [DE], 24.4% [UK], 52.4% [US], 31.2% [FR]), followed by ischemic heart disease and myocardial infarction (Table). IRs (per 100 patient-yrs) of new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US). IRs of nephrolithiasis diagnosis ranged from 0.31 (FR) to 3.79 (US). sCR elevations of 1.5x to Conclusions These findings show that gout patients have comorbid renal and CV disease and are at risk for and develop new renal and events. Comorbid illnesses greatly enhance the overall disease burden in this patient population. Awareness and consideration of these comorbidities are important in the medical management of gout patients. References Zhang W, Doherty M, Bardin T, et al. Ann Rheum Dis. 2011;70:563-570. Kuo CF, Grainge MJ, Mallen C, et al. Ann Rheum Dis. 2014 Nov 14. Grassi D, Ferri L, Desideri G, et al. Curr Pharm Des. 2013;19(13):2432-2438. Acknowledgements Funding for the study was provided by AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. Disclosure of Interest J. Nuevo Employee of: AstraZeneca, F. Nyberg Employee of: AstraZeneca, L. Horne: None declared, R. Morlock Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., C. Storgard Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., L. Aiyer Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., D. Hines Employee of: IMS Health, X. Ansolabehere Employee of: IMS Health, P. Chevalier Employee of: IMS Health

Background Gout affects 1–4% of the population in developed Western countries. The goal of gout treatment is lowering serum uric acid (sUA) levels to treat and prevent urate crystal deposition, thereby improving signs and symptoms of gout, e.g., acute flares and tophus formation. Objectives Describe impact of current urate-lowering treatment (ULT) on sUA, gout flares and tophi in patients with established gout in France (Fr), Germany (DE), the United Kingdom (UK) and the United States (US). Methods A retrospective database analysis was conducted using Disease Analyzer database (Fr, DE), IMS9 PharMetrics Plus™ database linked with outpatient laboratory results (US), and Clinical Practice Research Datalink-Hospital Episode Statistics (UK) from Jan 1, 2009 to Dec 31, 2011. Patients were required to have evidence of “prevalent established gout” (ie, treated with or eligible for ULT based on ACR guidelines) between Jan 1, 2009 and Dec 31, 2009; be age ≥18 on index date (Jan 1, 2010); and have ≥1 documented visit prior to Jan 1, 2009 and ≥1 documented visit for gout after Jan 1, 2010. Follow-up extended from Jan 1, 2010 to Dec 31, 2011 (all dates +1 yr for France). Univariate descriptive statistics were conducted to describe elevated sUA occurrence (≥6 mg/dL), gout flares, and tophi by ULT (allopurinol [ALLO] and febuxostat [FBX]). Results A total of 22126 (Fr), 58672 (DE), 36188 (UK) and 169085 (US) patients met selection criteria. ALLO:FBX populations were 13995:1,785 (Fr), 36251:429 (DE), 21409:101 (UK), and 82415:3610 (US). Mean (SD) age 68.0 (12.3), 69.2 (11.0), 64.6 (12.3) and 54.5 (9.6) years, respectively. Most patients were male (Fr: 74.9%; DE: 70.3%; UK: 85.6%; US: 89.2%). Availability of sUA results varied by country, but was low, ranging from 2.4% (US) to 41.0% (DE). For sUA, study population included only patients with ≥1 sUA measure. Observed incidence rates of elevated sUA episodes (8 to 58 per 100 patient yrs), 1st gout flare during follow-up (1.1 to 60 per 100 patient yrs), and percentage of patients with reported tophus (up to 2.3%), by country and stratified by ULT, are provided (Figure). Conclusions Current ULT (eg, ALLO, FBX) often do not achieve recommended sUA goals and gout-related outcomes, with many patients experiencing elevated sUA levels. In this multinational database analysis of ULT-treated patients, high number of elevated sUA episodes, evidence of continued flares, and percentage of patients with reported tophus over the observation period present continued need for improvement in gout treatment. Notably, sUA testing rates were low ( References Soriano LC, Rothenbacher D, Choi HK, Rodriguez LAG. Arthritis Res Ther. 2011;13:R39-47. Zhang W, Doherty M, Pascual E et al. Ann Rheum Dis 2006;654:1301-1311. Roddy E, Doherty M. Arthritis Res Ther. 2010;12:223-233. Acknowledgements This study was funded by AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. Disclosure of Interest J. Nuevo Employee of: AstraZeneca, F. Nyberg Employee of: AstraZeneca, L. Horne: None declared, R. Morlock Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group, C. Storgard Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group, L. Aiyer Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group, D. Hines Employee of: IMS Health, X. Ansolabehere Employee of: IMS Health, P. Chevalier Employee of: IMS Health

e20086 Background: Real-world evidence on the use of melanoma therapy is limited. This study was to describe the real-world treatment patterns of current melanoma therapies among patients with meta...

6582 Background: Prior real-world (RW) studies of advanced non-small cell lung cancer (adv NSCLC) have described overall survival (OS) from diagnosis (Dx) for all patients (pts) as well as separate...

Nitric oxide (NO) is a vasodilator that also possesses lipogenic properties. In rats, lipid accumulation and lipogenic enzymes are induced by NO and insulin-stimulated glucose uptake is dependent on intact NO synthesis in white adipose tissue. Mice in which the gene encoding inducible NO synthase was disrupted are protected from high-fat induced insulin resistance and NO inhibition in rodents on a high fat diet reduces hepatic lipid accumulation. These biological actions of NO are mediated by soluble guanylate cyclase (sGC) and importantly human adipocytes express the genes GUCY1A2, GUCY1A3, GUCY1B3 encoding for the alpha and beta subunits of sGC. The single nucleotide polymorphism rs13139571 is located within an intron of GUCY1A3 and its minor allele is associated with higher blood pressure and odds of hypertension in a recent genome wide association study. For the first time, we investigated the metabolic phenotype associated with rs13139571 in a random sample (n1⁄4 2007) of the general population from Olmsted County, MN. Frequencies of rs13139571 genotypes were CC: 59%, AC: 36%, AA: 5%. In age and gender adjusted analysis, carriers of the A minor allele had significantly higher plasma values of total cholesterol (CC: 202 36, AC: 204 36, AA: 208 34 mg/dl, p value1⁄4 0.04) and triglycerides (CC: 145 85, AC: 150 86, CC: 169 101 mg/dl, p value1⁄4 0.01). Metabolic syndrome trended toward increased prevalence in carriers of the minor allele (CC: 21%, AC: 23%, AA: 28%, p value1⁄4 0.06). Genotypes did not differ in terms of systolic blood pressure (CC: 132 22, AC: 134 21, CC: 132 21 mmHg, p value1⁄4 0.45), diastolic blood pressure (CC: 74 10, AC: 74 10, CC: 73 12 mmHg, p value1⁄4 0.77), BMI (CC: 28 5, 29 5, 28 5 Kg/m, p value1⁄4 0.43) and percentage of subjects on antilipemic therapy (CC: 17%, AC: 19%, AA: 18%, p value1⁄4 0.56). These studies suggest that the minor allele of rs13139571 may be associated with increased NO activity and influence lipid metabolism by favoring lipid accumulation and insulin resistance. Alternatively, rs13139571 may be in linkage disequilibrium with another genetic locus that affects cardiometabolic phenotype. Additional studies are warranted to confirm our findings and further investigate the metabolic phenotype associated with this genetic variant.

The present study aimed to assess disease control, health resource utilization (HRU), and healthcare costs, and their predictors in gout patients across the USA, UK, Germany, and France.Data were extracted from the PharMetrics Plus (USA), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), and Disease Analyzer databases (Germany and France) for adult gout patients over a 3-year period: 2009-2011 (all dates +1 year for France). Patients had "prevalent established gout" (i.e., were treated with urate-lowering therapy [ULT] or eligible for ULT based on American College of Rheumatology guidelines) in the preindex panel-year, with January 1 of the second study year as the study index date. Assessments of disease control (uncontrolled gout definition: ≥1 serum urate (sUA) elevation or ≥2 flares; analysis limited to the subpopulation with sUA) data, HRU, and costs were in the second post-index panel-year, while potential predictors (demographics and gout treatment characteristics) were identified in the first post-index panel-year.Treatment rates were high (70% with chronic urate-lowering treatment in all countries but France), while between 31.3% (France) and 62.9% (USA) of patients remained uncontrolled. Predictors of control included female gender and high adherence. In Germany, the UK, and France, lack of disease control predicted increased gout-attributed costs and increased HRU, both gout-attributed (also in the USA) and non-gout-attributed.Gout management remains suboptimal, as many patients remain uncontrolled despite using urate-lowering treatment. Effective and convenient treatment options are needed to improve disease control and minimize additional HRU and costs.AstraZeneca.