Abstract: Suboptimal adherence to maintenance medication has been associated with poor outcomes in asthma. This study examined single-inhaler inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) adherence and asthma-related outcomes. Methods: This retrospective observational study of patients with asthma initiating ICS/LABA used data from IQVIA PharMetrics Plus (1 January 2014–31 March 2019). Patients included were ⩾18 years old and had ⩾12 months continuous eligibility before, and ⩾180 days follow-up after, the index date. Adherence was measured as proportion of days covered ([PDC] adherent ⩾ 0.8; non-adherent 〈 0.8) each quarter, with outcomes measured each subsequent quarter. Endpoints were asthma-related overall and severe (inpatient/emergency department [ED] visit) exacerbations, rescue medication use, and asthma-related healthcare resource utilization and costs. Regression models evaluated associations between adherence and outcomes, controlling for repeated measures and differences in baseline characteristics. Results: Overall, 50,037 patients were included (mean age 45.3 years; mean follow-up 23.3 months). Adherent patients were less likely to experience asthma-related overall (adjusted odds ratio [aOR] 95% confidence interval [CI] : 0.942 [0.890, 0.998]; p = 0.041), or severe exacerbations (aOR [95% CI] : 0.778 [0.691, 0.877]; p  〈  0.001) per quarter versus non-adherent patients. Adherent patients had lower severe exacerbation rates (adjusted rate ratio [aRR] [95% CI] : 0.792 [0.702, 0.893]; p  〈  0.001) but similar overall exacerbation rates (aRR [95% CI]: 0.993 [0.945, 1.044] ; p = 0.783) versus non-adherent patients. The odds of rescue medication use were lower per 20% PDC increase (aOR [95% CI] short-acting β2 agonist: 0.991 [0.985, 0.996] ; p = 0.001; oral corticosteroid: 0.988 [0.982, 0.995]; p  〈  0.001). Adherent patients were less likely to visit EDs per quarter (aOR [95% CI]: 0.775 [0.680, 0.883] ; p  〈  0.001) and odds of hospitalization were lower per 20% PDC increase (aOR [95% CI]: 0.930 [0.881, 0.982] ; p = 0.009). Across most measures, adherent patients incurred lower costs. Conclusion: This real-world study highlights the short-term clinical and economic benefits of ICS/LABA adherence in asthma, particularly in reducing severe exacerbations.

Abstract: Background: Patients with classical Hodgkin lymphoma (cHL) relapsed or refractory (R/R) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. Recently, the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab were approved by the FDA (May 2016 and March 2017, respectively) as treatment options for R/R cHL patients. In the absence of head-to-head clinical trials, observational data may provide hypothesis-generating insight into the real-world outcomes of patients receiving these PD-1 inhibitors. This study aims to evaluate healthcare resource utilization (HRU) among patients with cHL initiated on pembrolizumab compared to nivolumab in the United States. Methods: A retrospective database analysis was conducted using Symphony Health's Patient Integrated Dataverse® (07/2014-06/2018). The date of the first dispensing or administration of pembrolizumab or nivolumab was assigned as the index date. Patients who received both treatments and who initiated nivolumab prior to pembrolizumab approval, or in the first months after, were classified in the pembrolizumab cohort. Included patients were required to meet the following criteria: ≥12 months of continuous clinical activity prior to the index date, ≥1 inpatient or ≥2 outpatient visits with a cHL diagnosis prior to the index date, no diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma, and ≥18 years of age at the index date. Baseline patient characteristics were assessed in the 12-month baseline prior to the index date. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to adjust for observed differences in baseline covariates between cohorts. Rates per person-year (PPY) of all-cause and cHL-related (i.e., visits with a primary or secondary diagnosis of cHL) HRU were calculated for weighted cohorts during the follow-up period, which spanned from the index date to the end of clinical activity or data availability. Rates of HRU were compared using rate ratios (RRs) from Poisson regression models. Results: A total of 92 patients initiated on pembrolizumab and 218 patients initiated on nivolumab met the selection criteria and were included in the analysis. Of the 92 pembrolizumab patients, 6 patients received nivolumab during the baseline period. After weighting, the mean age was similar at 55 years in both cohorts, while the proportion of female was lower in the pembrolizumab cohort (35.3%) compared to the nivolumab cohort (44.1%; standardized difference [StD]=17.9%). The mean (median) follow-up period was 295 (264) days for pembrolizumab users and 274 (208) days for nivolumab users (StD=9.4%). Mean Quan-Charlson Comorbidity Index score was well balanced after weighting in the pembrolizumab and nivolumab cohorts (4.2 and 4.3, respectively; StD=2.2%); 13.8% and 15.0% had depressive disorders (StD=3.7%), and 8.5% and 10.2% had substance-related and addictive disorders (StD=5.8%), respectively. The mean number of baseline hospitalizations (pembrolizumab=1.6, nivolumab=1.5; StD=3.1%) was also well balanced after weighting. The total person-time of observation was 74.6 and 163.6 years for the weighted pembrolizumab and nivolumab cohorts, respectively. Over this period, patients in the pembrolizumab cohort had significantly lower rates of all-cause hospitalizations (0.46) PPY than those in the nivolumab cohort (1.39; RR [95% confidence interval, CI]=0.33 [0.09-0.80] , P=0.014; Figure). Furthermore, the rate of cHL-related hospitalizations PPY was significantly lower in the pembrolizumab cohort (0.06) compared to the nivolumab cohort (0.42; RR [95% CI]=0.14 [0.02-0.37] , P 〈 0.001; Figure). A similar trend (i.e., ratio below 1) was observed for all-cause and cHL-related outpatient visits, but the difference was not statistically significant (all-cause RR [95% CI]=0.84 [0.56-1.11] , P=0.200; cHL-related RR [95% CI]=0.90 [0.47-1.42] , P=0.647). Conclusion: In this real-world study, adult cHL patients treated with pembrolizumab had significantly lower rates of all-cause and cHL-related hospitalizations than those treated with nivolumab. Fewer all-cause and cHL-related outpatient visits were also observed among pembrolizumab users. Additional research is warranted to further investigate these early trends in real-world HRU observed among patients with cHL receiving anti-PD1 therapies. Disclosures Laliberté: Janssen Scientific Affairs, LLC: Research Funding; Merck & Co., Inc.: Research Funding. Raut:Merck & Co., Inc.: Employment. Yang:Merck & Co.: Employment. Germain:Janssen Scientific Affairs, LLC: Research Funding; Merck & Co., Inc.: Research Funding. Sen:Merck & Co., Inc.: Employment. MacKnight:Merck & Co., Inc.: Research Funding; Janssen Scientific Affairs, LLC: Research Funding. Desai:Merck & Co., Inc.: Employment. Duh:Analysis Group, Inc., a consulting firm that has received research funding from Shire, a Takeda company, to conduct this study: Employment; Shire: Research Funding; Merck: Research Funding.

Abstract: Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations are at risk of further readmissions, increased treatment costs, and excess mortality. This study evaluated inpatient admissions and readmissions in patients receiving initial maintenance therapy with umeclidinium/vilanterol (UMEC/VI) versus tiotropium (TIO). Methods This retrospective, matched cohort study identified patients with COPD who initiated maintenance therapy with UMEC/VI or TIO from Optum’s de-identified Clinformatics Data Mart database between January 1, 2013, and December 31, 2018 (index date defined as earliest dispensing). Eligibility criteria included: ≥ 1 medical claim for COPD pre-index or on the index date; ≥ 12 months of continuous eligibility pre-index; age ≥ 40 years at index; no pre- or post-index asthma diagnosis; and no pre-index claims for medications containing inhaled corticosteroids, long-acting β 2 -agonists, or long-acting muscarinic antagonists. Outcomes included time to first on-treatment COPD-related inpatient admission, rate of on-treatment COPD-related admissions, and rate of all-cause and COPD-related readmissions within 30 and 90 days. Propensity score matching was used to adjust for potential confounders. Results Matched UMEC/VI and TIO cohorts each included 7997 patients and were balanced on baseline characteristics (mean age 70.9 years; female 47.1–47.6%). Over 12 months, patients initiating UMEC/VI had significantly reduced risk (hazard ratio [95% CI]: 0.87 [0.79, 0.96] ; p  = 0.006) and rates (rate ratio [95% CI]: 0.80 [0.72, 0.92] ; p  = 0.008) of COPD-related inpatient admissions compared with TIO. While all-cause readmission rates were similar between treatment cohorts, readmission rates among patients with an initial admission length of stay of 1–3 days were numerically lower for UMEC/VI versus TIO (30-day readmissions: 10.5% vs. 12.4%; 90-day readmissions: 15.5% vs. 19.8%). Similar patterns were observed for COPD-related readmissions. Conclusions These findings highlight the real-world benefits of dual therapy with UMEC/VI versus TIO in reducing inpatient admissions and readmissions in patients with COPD, which may translate to lower healthcare costs.

Abstract: Patients with a severe mental illness such as bipolar I disorder (BP-I) have a higher prevalence of obesity and related metabolic comorbidities than the general population. This study evaluated the impact of cariprazine on weight and blood pressure in patients with BP-I depression using electronic medical records (EMRs) from a nationally representative database. Methods Analyses were based on data from EMRs in the Symphony Health’s Integrated Dataverse ® from March 2015 to October 2018. Patients ≥18 years of age with ≥2 cariprazine fills (first dispensing=index date) and clinical activity for ≥12 months pre-index (baseline) and ≥1 month post-index were included. Patients also had a diagnosis of BP-I depression at their most recent episode prior to cariprazine initiation. The on-treatment period spanned from the index date to the earliest of cariprazine discontinuation, a switch to another atypical or long-acting injectable antipsychotic, end of clinical activity, or end of data. Metabolic outcomes of interest were weight and blood pressure (systolic and diastolic). For each outcome, patients were required to have ≥1 measurement in both the baseline and on-treatment periods. Linear trajectories during those periods were estimated using mixed-effects models; 95% confidence intervals (CIs) were calculated using non-parametric bootstrap procedures. Results In total, 1702 patients who met study eligibility criteria had ≥1 weight measurement recorded in the baseline and on-treatment periods; of these patients, 178 had bipolar I depression as their most recent episode. Patients gained an average of 2.43 kg/year during the baseline period and 0.60 (95% CI: -1.97, 3.70) kg/year during the on-treatment period. Analyses of blood pressure change (n=179) showed that cariprazine had neutral effects over the on-treatment period. Patients’ systolic blood pressure increased at 1.12 mmHg/year during baseline and decreased at -0.63 (95% CI: -3.59, 2.25) mmHg/year during the on-treatment period. For diastolic blood pressure, increases of 0.25 mmHg/year during baseline and 0.44 (95% CI: -1.65, 2.16) mmHg/year during the on-treatment period were observed. Conclusions Although patient weight was increasing prior to cariprazine initiation, a neutral weight trajectory was seen with long-term cariprazine treatment among those with a most recent BP-I depression episode. Cariprazine also had minimal impact on systolic or diastolic blood pressure. Overall, these findings are consistent with prior short- and long-term studies showing that cariprazine has a neutral weight and metabolic profile. Funding AbbVie

Abstract: Introduction: Venous thromboembolism (VTE) is directly and indirectly associated with mortality in cancer patients. Cancer patients who experience VTE are known to be at higher risk for mortality than cancer patients without VTE, yet information regarding mortality based on differences in VTE risk level is limited in real-world data. The purpose of this study was to evaluate and compare mortality among patients with recently diagnosed cancer with and without VTE stratified by Khorana score (KS). Methods: The Optum® ClinformaticsTM Data Mart database (January 1, 2012 - September 30, 2017) was used to identify patients aged ≥18 years with ≥1 hospitalization or ≥2 outpatient medical claims for cancer (index date) who were initiated on treatment for their cancer (antineoplastics and adjunctive therapies or radiation therapy) within 45 days from the index date. Additionally, patients were selected if they met all of the following criteria: a) continuous eligibility for ≥6 months prior to their first diagnosis of cancer (baseline period), b) no evidence of a VTE before the index date, c) no anticoagulant treatment used prior to the index date or up until a VTE event during the observation period, and d) no evidence of a surgery during a hospitalization (e.g., major surgery, abdominopelvic surgery, and neurosurgery or orthopedic surgery) following the index date. Patients were also required to have ≥1 test result for hemoglobin, leukocyte, and platelet count within 28 days before their cancer therapy initiation. The KS was calculated using the index cancer site, body mass index, and laboratory test results prior to treatment initiation (i.e., hemoglobin, leukocyte, and platelet counts). Based on the risk score, patients were classified into cohorts of 0, 1, or ≥2 KS. Patients in each cohort were further stratified into two distinct groups: patients experiencing VTE during the observation period vs. patients who did not experience a VTE. Patients were observed from the index date up until the earliest date between end of data availability, death, end of insurance coverage, or 12 months post-index. All-cause mortality was assessed and survival rates were reported for all patients with vs. without a VTE event and further stratified by cohorts based on VTE risk levels using Kaplan-Meier (KM) analysis. KM survival rates at 12 months were reported and compared between patients with vs. without VTE using Cox proportional hazards models controlling for baseline characteristics (including: age, sex, insurance type, year of index date, Charlson comorbidity index [CCI] score, Elixhauser comorbidities, index cancer type, and healthcare resource utilization and costs). Incidence rates and rate ratios of mortality were also calculated using a Poisson regression model controlling for the same baseline characteristics. Results: In this study, 7,475 patients (KS=0: 3,192; KS=1: 2,463; KS≥2: 1,820) were identified. Approximately half of the patients were female (49%-52%) with a mean age of 68 years. The mean CCI was 1.2 (range, 1.0 - 1.4). For the full study population, the KM survival rate at 12 months was significantly lower at 71.0% for patients with a VTE event compared to 90.5% for patients without a VTE event (adjusted hazard ratio [HR]: 3.4; p-value 〈 0.001). In cohorts stratified by KS, patients without a VTE event in the KS=0 and KS=1 cohorts had higher survival rates than those in the KS≥2 cohort (Figure 1). For patients with VTE, survival rates were similar between KS=0 and KS=1 cohorts but lower for patients in KS≥2 cohort. Corresponding incidence rates and rate ratios of mortality are presented in Table 1. Conclusions: In this large real-world retrospective study of newly diagnosed cancer patients, VTE events were associated with lower survival rates across all KS cohorts. We independently confirm prior findings that the Khorana score is prognostic beyond VTE itself. Disclosures Khorana: Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. McCrae:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Other: Travel, Accommodations, Expenses; Myriad Genetics: Consultancy; Pfizer: Consultancy; Celldex: Consultancy; Coherus Biosciences: Consultancy, Other: Travel, Accommodations, Expenses; Halozyme: Consultancy; Mylan: Consultancy, Other: Travel, Accommodations, Expenses. Milentijevic:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Laliberté:Merck & Co., Inc.: Research Funding; Janssen Scientific Affairs, LLC: Research Funding. Germain:Janssen Scientific Affairs, LLC: Research Funding; Merck & Co., Inc.: Research Funding. MacKnight:Janssen Scientific Affairs, LLC: Research Funding; Merck & Co., Inc.: Research Funding. Lefebvre:Janssen Scientific Affairs, LLC: Research Funding. Lyman:G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy; Amgen Inc.: Other: Research support, Research Funding; Janssen Scientific Affairs, LLC: Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees. Streiff:Daiichi-Sankyo: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria; Portola: Consultancy, Honoraria; Roche: Research Funding; Bayer: Consultancy, Honoraria.

Abstract: To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values. Methods This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment. Results Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values. Conclusions In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation.