Combination therapy with macitentan and phosphodiesterase type-5 inhibitor (PDE5i) in pulmonary arterial hypertension (PAH): real-world data from OPUS and OrPHeUS

Abstract Introduction Guidelines for the management of PAH recommend combination therapy for most patients, yet real-world data on treatment patterns in PAH are limited. Purpose To describe the characteristics, safety and clinical outcomes of PAH patients newly treated with double combination therapy with macitentan and PDE5i in the OPsumit® USers (OPUS) Registry and the OPsumit® Historical USers cohort study (OrPHeUS) combined dataset. Methods OPUS is a prospective, US, multicentre, observational drug registry (NCT02126943) ongoing since April 2014. OrPHeUS was a retrospective, US, multicentre chart review (NCT03197688); Oct 2013–Mar 2017. This cohort included patients initiating combination therapy with macitentan and a PDE5i (in any order) ≤60 days apart. Baseline was defined as the start date of the second therapy (i.e., start of combination therapy). Patient characteristics at baseline, changes in 6-minute walk distance (6MWD) and WHO functional class (FC) from baseline to follow-up, safety and outcomes are described. Results Of the 4428 OPUS/OrPHeUS PAH patients initiating macitentan, 2490 received this in combination with a PDE5i; of these patients, 740 (29.7%) initiated macitentan and a PDE5i concurrently (≤60 days apart). Data on disease duration was recorded in 729 patients at baseline; of these, 588 (80.7%) patients were incident (≤6 months since diagnosis) and 141 (19.3%) were prevalent (>6 months since diagnosis); median time from diagnosis to start of combination therapy of was 1.4 (Q1=0.6, Q3=3.6) months. At baseline, median age was 60 (Q1=49, Q3=70) years and 73.6% of patients were female. Mean baseline 6MWD was 264.5 (SD=119.8) m, recorded in 240 (32.4%) patients. WHO FC was recorded at baseline for 347 (46.9%) patients; 263 (75.8%) were in FC III/IV. Median combination therapy exposure was 10.2 (Q1=3.4, Q3=21.8) months, with 58.8% of patients ongoing at data cut. Changes from baseline to follow up in FC and 6MWD are shown in the figure. There was ≥1 adverse event (AE) reported in 455 (61.5%) patients and ≥1 hepatic AE (HAE) in 76 (10.3%) patients. In total, 232 (31.4%) patients discontinued macitentan; 122 (16.5%) due to AEs, 4 (0.5%) due to HAEs, 98 (13.2%) not due to an AE/HAE, and 8 (1.1%) for unknown reasons. Of the 305 patients who discontinued combination therapy, 137 (18.5%) discontinued macitentan only, 73 (9.9%) discontinued PDE5i only, and 95 (12.8%) discontinued both drugs at the same time. Kaplan-Meier estimates (95% CI) showed that 60.7% (56.4, 64.8) of patients were free from hospitalisation and 88.7% (85.7, 91.1) were alive at 12 months. Conclusions In this real-world setting, less than one third of patients treated with macitentan received initial oral combination therapy, despite current expert consensus favouring such therapeutic approaches. Patients initiating macitentan+PDE5i ≤60 days apart had improved 6MWD and WHO FC from baseline to follow-up. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals Ltd

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P4673Macitentan in chronic thromboembolic pulmonary hypertension (CTEPH): combined data from OPUS and OrPHeUS real-world data sets

European Heart Journal ◽

10.1093/eurheartj/ehz745.1055 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R Channick ◽

K Chin ◽

N Kim ◽

J McConnell ◽

D Poch ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Incidence Rate ◽

Real World ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Liver Function Tests ◽

Functional Class ◽

Real World Data ◽

Data Set ◽

World Data

Abstract Introduction The OPsumit® USers Registry (OPUS) provides real-world data in patients (pts) with pulmonary hypertension newly started on macitentan. The OPsumit® Historical USers cohort (OrPHeUS) study was conducted to supplement OPUS to fulfil the FDA request to characterise the safety of macitentan in clinical practice. Both studies included pts with CTEPH. Purpose To describe the characteristics and safety outcomes of CTEPH pts newly treated with macitentan. Methods OPUS is a prospective, US, multicentre, long-term, observational drug registry (NCT02126943) ongoing since Apr 2014. OrPHeUS was a retrospective, US, multicentre medical chart review (NCT03197688); data collected Oct 2013-Mar 2017. This subgroup analysis describes CTEPH patient characteristics at macitentan initiation, hospitalisations, survival and liver function tests (LFTs) in the combined OPUS/OrPHeUS data set. LFTs are also provided for the OPUS/OrPHeUS pulmonary arterial hypertension (PAH) population. Results As of Oct 2018, OPUS/OrPHeUS included 144 CTEPH pts with follow-up data. At macitentan initiation, median (Q1, Q3) age was 66 (56, 73) years; of the 53 pts with a WHO functional class (FC) assessment, 35.8%, 49.1% and 15.1% were in FC II, III and IV, respectively. Median (Q1, Q3) time from CTEPH diagnosis was 18.6 (7.4, 56.4) months (n=141). At macitentan initiation, 32.6% of pts had no PAH therapy, 63.9% were receiving one and 3.5% were receiving two PAH therapies. Median (Q1, Q3) exposure to macitentan was 15.9 (4.3, 30.4) months. There were 43 (29.9%) CTEPH pts who discontinued treatment; 23 due to an adverse event (AE), 0 due to a hepatic AE (HAE) and 20 not due to an AE/HAE. There were 58 (40.3%) CTEPH pts who experienced ≥1 hospitalisation and 9 (6.3%) pts died. LFTs are presented in the table. LFTs CTEPH follow-up pts PAH follow-up pts (N=144) (N=4072) ALT or AST ≥3x ULN Pts with ≥1 event, n (%) 1 (0.7) 132 (3.2) Incidence rate per 1 person-year (95% CI) 0.005 (0.001, 0.035) 0.024 (0.020, 0.029) ALT or AST ≥3x ULN and total bilirubin ≥2x ULN Pts with ≥1 event, n (%) 1 (0.7) 27 (0.7) Incidence rate per 1 person-year (95% CI) 0.005 (0.001, 0.035) 0.005 (0.003, 0.007) ALT: alanine aminotransferase; AST: aspartate aminotransferase; CI: confidence interval; ULN: upper limit of normal. Conclusions Analysis of OPUS/OrPHeUS data provides further insight into real-world use of macitentan in CTEPH pts. The observed hepatic safety profile in CTEPH pts is in line with that of PAH pts. Acknowledgement/Funding Actelion Pharmaceuticals Ltd

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928-P: Dulaglutide Has Higher Adherence and Persistence than Semaglutide and Exenatide QW: 6-Month Follow-Up from U.S. Real-World Data

Diabetes ◽

10.2337/db20-928-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 928-P

Author(s):

REEMA MODY ◽

MARIA YU ◽

BAL K. NEPAL ◽

MANIGE KONIG ◽

MICHAEL GRABNER

Keyword(s):

Real World ◽

Real World Data ◽

World Data ◽

Exenatide Qw

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P0816CLINICAL CHARACTERISTICS AND EGFR AND UACR DISTRIBUTION ACCORDING TO THE 2012 KDIGO CKD CLASSIFICATION: A REPORT FROM THE US DISCOVER CKD COHORT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0816 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Juan Jose Garcia Sanchez ◽

Juan Jesus Carrero ◽

Supriya Kumar ◽

Roberto Pecoits-Filho ◽

Glen James ◽

...

Keyword(s):

Kidney Disease ◽

Real World ◽

Patient Characteristics ◽

Study Cohort ◽

Diagnostic Code ◽

Inclusion Criteria ◽

Real World Data ◽

Electronic Health Record Data ◽

World Data ◽

Co Morbidity

Abstract Background and Aims In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended categorising and prognosticating chronic kidney disease (CKD) based on estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Contemporary studies describing the prevalence and characteristics of patients with CKD categorised according KDIGO 2012 and how studies of new pharmacotherapies relate to these categories are scarce. One such new therapy class of key interest are the sodium glucose co-transporter 2 inhibitors (SGLT-2i), shown to delay the progression to renal failure and prevent cardiovascular/renal death in patients with CKD. We aimed to describe patient characteristics and the prevalence of CKD according to the 2012 KDIGO categories in a large real-world US cohort of patients with CKD (part A). We also describe a subset of the population according to the DAPA-CKD trial inclusion criteria (eGFR [25-75ml/min/1.73m2] and UACR [200-5000mg/g]) (part B). Method DISCOVER-CKD is an international observational study in patients with CKD. The DISCOVER-CKD retrospective US cohort of patients was extracted using real-world data from the integrated Limited Claims and Electronic Health Record data (IBM Health, Armonk, NY) and HealthVerity. Patients were aged ≥18 years, with ≥1 UACR measure. For part A, required first diagnostic code of CKD (Stages 3A, 3B, 4, 5, or ESRD) or two eGFR of <75 mL/min/1.73 m2 recorded at least 90 days apart and for part B, two measures of eGFR 25-75 mL/min/1.73 m2 recorded at least 90 days apart between 1st January 2008 and September 2018. Index date was diagnostic code or 2nd eGFR. The first UACR, recorded +/-12 months of index, was used to categorise patients. Descriptive analyses were used to summarise prevalence and patient characteristics. Results Of the overall study cohort (N=4330, 49.1% women, mean age 65.3±10.64 years), by KDIGO categories (part A): 85.7% (n=3601) had normal to mildly increased albuminuria, 11.0% (n=463) had moderately increased albuminuria and 3.3% (n=137) had severely increased albuminuria (Figure 1). 4.6% (n=193) fulfilled DAPA-CKD trial inclusion criteria (part B). In both populations, the most common comorbidities were hypertension (HTN, 73.0% for both) and type 2 diabetes (T2D, 57.6% and 56.2%, respectively). Anti-hypertensive drugs were frequently used (76.4% and 76.9%, respectively). Conclusion This study, utilising real-world data, adds to the scarcity of knowledge reporting the characteristics of patients with CKD in different eGFR and UACR strata according to the KDIGO 2012 definitions. We observed a trend in higher UACR in the group of patients with lower eGFR and report a high prevalence of T2D and HTN in the study population, demonstrating the high co-morbidity burden in patients, for whom new therapies may be beneficial.

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550 Real World Treatment Trends for Patients TBSA ≤ 20%: Evaluating Important Shifts in Care and Budget Impact of ASCS Adoption

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa024.178 ◽

2020 ◽

Vol 41 (Supplement_1) ◽

pp. S115-S115

Author(s):

James H Holmes ◽

Stacey Kowal ◽

Cheryl P Ferrufino

Keyword(s):

Survey Data ◽

Resource Use ◽

Real World ◽

Budget Impact ◽

Patient Characteristics ◽

Real World Data ◽

Treatment Pathways ◽

World Data ◽

Burn Care ◽

The Impact

Abstract Introduction Treatment pathways in burn care are typically determined based on burn center (BC) and patient characteristics, although decisions may be influenced by anecdotal experience, personal preference, and hospital policies/purchasing decisions. Health economic (HE) evaluations can support improved decision-making, identifying the most cost-effective interventions for tailored care. A novel burn care model (BEACON) was developed with burn surgeons over several years and validated through numerous publications, including an assessment of the HE impacts of autologous skin cell suspension (ASCS) use for definitive burn closure. To ensure that BEACON accurately represents the current state of care, it is vital to update data that underpins model projections. This study collected real world data on practice patterns and patient outcomes for the most commonly seen burns (TBSA ≤ 20%) to update the current understanding of standard of care (SOC) costs and outcomes and to refine estimates on the impact of ASCS use in TBSA ≤ 20% patients. Methods Data was collected from a 10% sample of BCs, including: BC and patient characteristics, resource use, inpatient costs, and length of stay (LOS). NBR based inputs in BEACON were updated to reflect survey data for patients with TBSA ≤ 20%, with the ability to view data as a national aggregate sample and across BC characteristics. BEACON estimates patient and BC costs and outcomes across a spectrum of patient profiles (age, gender, inhalation injury, comorbidity status, burn depth, TBSA) and combines information on each patient profile to understand annual budget impact. Key outcomes were compared across the survey sample and published NBR trends. Using the updated BEACON, the BC budget impact of ASCS in burns TBSA ≤ 20% was assessed. Results The survey was collected from 16+ BCs, focusing on inpatient encounters in 2018. LOS was lower than NBR estimates, with some centers reporting LOS per %TBSA far below 1 d/%TBSA. Using the detailed bottom-up estimation of cost from BEACON with survey data, trends suggest total hospital costs for SOC are lower than published NBR charges given shorter LOS and updated cost and resource use assumption. Conclusions Compared to NBR 8.0, contemporary data suggests that fewer small TBSA burns are being treated in the inpatient setting; those treated have a LOS below NBR estimates. When using real world data, the impact of ASCS use in burns TBSA ≤ 20% was still calculated to be cost saving to a BC overall, given reductions in LOS and number of definitive closure procedures. Incorporating ASCS into appropriate TBSA ≤ 20% procedures can still result in a positive financial impact for BCs. Applicability of Research to Practice

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Application of Health Technology Assessment (HTA) to Evaluate New Laboratory Tests in a Health System: A Case Study of Bladder Cancer Testing

Academic Pathology ◽

10.1177/2374289520968225 ◽

2020 ◽

Vol 7 ◽

pp. 237428952096822

Author(s):

Erik J. Landaas ◽

Ashley M. Eckel ◽

Jonathan L. Wright ◽

Geoffrey S. Baird ◽

Ryan N. Hansen ◽

...

Keyword(s):

Bladder Cancer ◽

Pilot Study ◽

Health Technology Assessment ◽

Technology Assessment ◽

Real World ◽

Health Technology ◽

Test System ◽

Real World Data ◽

World Data

We describe the methods and decision from a health technology assessment of a new molecular test for bladder cancer (Cxbladder), which was proposed for adoption to our send-out test menu by urology providers. The Cxbladder health technology assessment report contained mixed evidence; predominant concerns were related to the test’s low specificity and high cost. The low specificity indicated a high false-positive rate, which our laboratory formulary committee concluded would result in unnecessary confirmatory testing and follow-up. Our committee voted unanimously to not adopt the test system-wide for use for the initial diagnosis of bladder cancer but supported a pilot study for bladder cancer recurrence surveillance. The pilot study used real-world data from patient management in the scenario in which a patient is evaluated for possible recurrent bladder cancer after a finding of atypical cytopathology in the urine. We evaluated the type and number of follow-up tests conducted including urine cytopathology, imaging studies, repeat cystoscopy evaluation, biopsy, and repeat Cxbladder and their test results. The pilot identified ordering challenges and suggested potential use cases in which the results of Cxbladder affected a change in management. Our health technology assessment provided an objective process to efficiently review test performance and guide new test adoption. Based on our pilot, there were real-world data indicating improved clinician decision-making among select patients who underwent Cxbladder testing.

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