Actelion (United States)

Rationale: Management of PAH in the US is decentralized, with potential healthcare differences across regions.We used real-world data from OPUS/OrPHeUS to describe PAH patient characteristics and treatment patterns across four US regions.Methods: OPUS (NCT02126943) was a prospective, multicenter, long-term, US observational drug registry, (April 2014-April 2020).OrPHeUS (NCT03197688) was a retrospective, multicenter, US medical chart review (October 2013-March 2017); data cut-off was February 2020.This analysis describes baseline characteristics and treatment patterns in PAH patients newly initiated on macitentan in the combined OPUS/OrPHeUS dataset in four US regions: West, Midwest, Northeast and South.Results: By February 2020, 4540 PAH patients had follow-up data in the combined dataset.Of these, 4456 patients were from one of four US regions: West (N=928), Midwest (N=980), Northeast (N=690), and South (N=1858).Patient characteristics at macitentan initiation are shown in the table.Median age ranged from 57 years in West to 63 years in South.Compared to other regions, the proportion of patients with idiopathic PAH was higher in South; the proportion of PAH associated with connective tissue disease was higher in Midwest and Northeast; while the proportions of drug and toxininduced PAH and PAH associated with congenital heart diseases were higher in West.The majority of patients in all regions had prevalent disease and were in World Health Organization functional class (WHO FC) III/IV.Median 6-minute walk distance was lowest in Northeast and highest in West.Median (Q1, Q3) macitentan exposure in months was 14.6 (5.6, 28.6) in West, 15.3 (4.8, 30.5) in Midwest, 15.2 (5.4,30.7) in Northeast and 13.4 (5.1, 27.4) in South.Percentages of patients receiving mono/double/triple therapy at macitentan initiation, respectively, were: 36%/48%/15% in West; 31%/51%/18% in Midwest; 44%/45%/11% in Northeast; 43%/45%/12% in South.At 2 years, across regions, 52-60% of patients who had initiated on monotherapy were still receiving monotherapy.Conclusions: Baseline characteristics and treatment patterns in PAH patients initiating macitentan were comparable across the four US regions.The majority of patients had prevalent disease, were in WHO FC III/IV and initiated macitentan as part of a combination therapy regimen, with a slightly higher proportion of patients receiving combination therapy at macitentan initiation in West and Midwest.Despite recommendations for use of combination therapy, across all regions a considerable proportion of patients were initiated and maintained on monotherapy, and the proportion of patients receiving triple therapy was low.

BackgroundAccurate and regular risk assessment is important for evaluation and treatment of pulmonary arterial hypertension (PAH) patients, including those with functional class (FC) II symptoms, a population considered at low risk for disease progression. Risk assessment methods include subjective and objective evaluations. Multiparametric assessments include tools based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines (COMPERA and FPHR methods, respectively) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL; REVEAL 2.0 tool). To better understand risk status determination in FC II patients, we compared physician-reported risk assessments with objective multiparameter assessment tools.MethodsThis retrospective chart analysis included PAH patients with FC II symptoms receiving monotherapy or dual therapy. Physicians were surveyed (via telephone) to obtain an assessment of patient risk using their typical methodology, which might have been informed by objective risk assessment. Patient risk was then calculated independently using COMPERA, FPHR and REVEAL 2.0 tools. Factors associated with incongruent risk assessment were identified.ResultsOf the 153 patients, 41%, 46%, and 13% were classified as low, intermediate, and high risk, respectively, by physicians. Concordance between physician gestalt and objective methods ranged from 43%–54%. Among patients considered as low risk by physician gestalt, 4%–28% were categorized as high risk using objective methods. The most common physician factor associated with incongruent risk assessment was less frequent echocardiography during follow-up (every 7–12 months vs. every 3 months; p = 0.01).ConclusionsMore than half of FC II PAH patients were classified as intermediate/high risk using objective multiparameter assessments. Incorporating objective risk-assessment algorithms into clinical practice may better inform risk assessment and treatment strategies.

Abstract Background CTD-PAH has historically represented a PAH subtype with poor prognosis. New therapies, as well as combination therapy approaches targeting multiple pathways have been approved for PAH based on RCTs. CTD-PAH patients comprise a subgroup of the RCT populations and efficacy analyses are based on subgroup analyses which can be less reliable than the overall analysis. We conducted a meta-analysis of RCTs of approved PAH therapies to evaluate outcomes of patients with CTD-PAH. Purpose To use meta-analysis to determine response to treatment in patients with CTD-PAH. Methods The PubMed and EMBASE databases were searched for English-only articles published between January 1, 2000 and November 25, 2019. Inclusion criteria were multicenter RCTs that enrolled adults with WHO group 1 pulmonary hypertension (PAH); enrollment in 2000 or later; long-term clinical morbidity and/or mortality event or 6-minute walk distance (6MWD) as an efficacy endpoint reported for ≥30 patients with CTD-PAH; and evaluation of a US Food and Drug Administration-approved PAH therapy. The primary outcomes were treatment effect as measured by the study time to first morbidity or morality event and change in 6MWD from baseline to between 3–6 months, per the data provided in each article. Results from individual studies were combined using a random-effects model for overall study population (PAH patients) and the subgroup of CTD-PAH patients. Results Ten RCTs (N=4329 PAH patients; n=1263 (29%) with CTD-PAH) met inclusion criteria and were included in the meta-analysis. At baseline, PAH patients had a mean age of 50 years, approximately 78% were female, and approximately 58% had functional class III or IV disease. These characteristics were balanced between treatment and control groups. Baseline 6MWD was 356 m for the overall population and 337 m for patients with CTD-PAH. Five RCTs (N=3172; n=941 with CTD-PAH [30%]) reported hazard ratios (HRs) for time to a morbidity or mortality event by drug treatment and PAH etiology: overall population HR=0.63 (95% confidence interval [CI], 0.56–0.72; P<0.001); CTD-PAH population HR=0.64 (95% CI, 0.51–0.80; P<0.001) (Figure). Nine RCTs reported mean change with drug treatment from baseline to 3 to 6 months in 6MWD for PAH and CTD patients: 33.9 m (95% CI, 21.9–45.9; P<0.001) in the overall population; 20.2 m (95% CI, 10.8–29.7; P<0.001) in CTD-PAH patients. Conclusions The improvement in 6MWD in patients with CTD-PAH is smaller than in those with other types of PAH, perhaps reflecting comorbidities and CTD-induced mobility constraints, independent of their cardiopulmonary capacity. Data from long term clinical morbidity/mortality endpoint studies in this large group of patients with CTD-PAH demonstrate that these patients derive significant benefit from currently available PAH therapies which, in many patients, comprised the addition of a drug targeting a second or third pathway involved in the pathophysiology of PAH. Treatment effect on morbidity/mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Actelion Pharmaceuticals US, Inc.

Quantitative metrics are used to develop profiles of health care institutions, including hospitals, nursing homes, and dialysis clinics. These profiles serve as measures of quality of care, which are used to compare institutions and determine reimbursement, as a part of a national effort led by the Center for Medicare and Medicaid Services in the United States. However, there is some concern about how misclassification in case-mix factors, which are typically accounted for in profiling, impacts results. We evaluated the potential effect of misclassification on profiling results, using 20 744 patients from 2740 dialysis facilities in the US Renal Data System. In this case study, we compared 30-day readmission as the profiling outcome measure, using comorbidity data from either the Center for Medicare and Medicaid Services Medical Evidence Report (error-prone) or Medicare claims (more accurate). Although the regression coefficient of the error-prone covariate demonstrated notable bias in simulation, the outcome measure—standardized readmission ratio—and profiling results were quite robust; for example, correlation coefficient of 0.99 in standardized readmission ratio estimates. Thus, we conclude that misclassification on case-mix did not meaningfully impact overall profiling results. We also identified both extreme degree of case-mix factor misclassification and magnitude of between-provider variability as 2 factors that can potentially exert enough influence on profile status to move a clinic from one performance category to another (eg, normal to worse performer).

<b>Background:</b> Portopulmonary hypertension (POPH) is defined as the development of pulmonary arterial hypertension (PAH) in the setting of portal hyperension. To date, there is paucity of studies that examine the economic implications of this disease. <b>Objective:</b> To compare healthcare resource utilization and costs between patients with POPH and a matched cohort of portal hypertension patients without PH (control). <b>Methods:</b> In this retrospective cohort analysis, POPH and control patients were identified using the Optum database betweeen July 2014 and June 2018. POPH patients were required to have &gt; 2 diagnostic claims for both portal hypetension and PH. POPH patients with liver transplant were excluded. The date of the first PH claim was defined as the index date. Control patients were assigned a random index date. All patients were required to have continuous enrollment for &gt; 12 months before and after index and age &gt; 18 years. Annual healthcare costs and utilization measures of these patients were examined. <b>Results:</b> Each of the cohort had 146 patients. During the 1-year follow-up, the POPH patients were more likely to experience a hospitalization (36% vs. 32%, p = 0.001) and emergency room visits (55% vs. 41%, p = 0.03) than their matched controls. The average annual total cost was higher in POPH patients than for matched controls ($119,912 vs. $81,839, p &lt; 0.0001). The majority of POPH patients (86%) were not prescribed a PAH approved medication during the 1-year follow-up. <b>Conclusions:</b> These findings suggest that POPH patients are at a greater risk for hospitalization and incurred higher mean annual total costs than portal hypertension patients without PH.

Introduction:Since its introduction to the market in 2016, selexipag has been an alternative oral therapy among both treatment-naïve patients and those with mono or dual therapy failure; however, limited information is available regarding the presentation and management of patients with pulmonary arterial hypertension (PAH) prior to selexipag initiation. This study examined treatment patterns, healthcare utilization, and costs in the 12 months prior to and the 6 months following selexipag initiation.Methods:This was a retrospective study of adult commercial and Medicare Advantage with Part D (MAPD) health plan members with a medical or pharmacy claim for selexipag from 1 January 2016 through 31 May 2017, a diagnosis of pulmonary hypertension, and continuous health plan enrollment for 12 months prior to selexipag initiation (baseline period). Treatment patterns, healthcare utilization, and costs were measured over the baseline period and the 6 months following selexipag initiation (among patients with ⩾6 months of follow up).Results:After inclusion and exclusion criteria were applied, 95 patients were included in the analysis. At study start, 57.9% of patients were prescribed combination therapy, increasing to 69.5% immediately prior to selexipag initiation. Approximately 60% of patients had one baseline regimen. Emergency visits and inpatient admissions during the baseline period occurred in 63.2% and 48.4% of patients, respectively. Baseline medical costs rose steadily, increasing 266.8% in commercial and 26.7% in MAPD enrollees from the beginning to the end of the 12-month baseline period. PAH-related healthcare costs accounted for more than 80% of total costs. Mean medical costs in the 6 months following selexipag initiation were US$17,215 in commercial and US$23,976 in MAPD enrollees.Conclusions:The majority of patients with PAH remained on the same therapy in the 12 months prior to selexipag initiation despite high rates of healthcare utilization and increasing costs. Mean medical costs appeared to decrease after adding or switching to selexipag.

Several new medications for pulmonary arterial hypertension (PAH) have recently been introduced; however, current real-world data regarding US patients with PAH are limited. We conducted a retrospective administrative claims study to examine PAH treatment patterns and summarize healthcare utilization and costs among patients with newly diagnosed PAH treated in US clinical practice. Patients newly treated for PAH from 1 January 2010 to 31 March 2015 were followed for ≥12 months. Patient characteristics, treatment patterns, healthcare resource utilization, and costs were described. Adherence (proportion of days covered), persistence (months until therapy discontinuation/modification), and the probability of continuing the index regimen were analyzed by index regimen cohort (monotherapy versus combination therapy). Of 1637 eligible patients, 93.8% initiated treatment with monotherapy and 6.2% with combination therapy. The most common index regimen was phosphodiesterase type 5 inhibitor (PDE-5I) monotherapy (70.0% of patients). A total of 581 patients (35.5%) modified their index regimen during the study. Most patients (55.4%) who began combination therapy did so on or within six months of the index date. Endothelin receptor agonists (ERAs) and combination therapies were associated with higher adherence than PDE-5Is and monotherapies, respectively. Healthcare utilization was substantial across the study population, with costs in the combination therapy cohort more than doubling from baseline to follow-up. The majority of patients were treated with monotherapies (most often, PDE-5Is), despite combination therapies and ERAs being associated with higher medication adherence. Index regimen adjustments occurred early and in a substantial proportion of patients, suggesting that inadequate clinical response to monotherapies may not be uncommon.

<b>Introduction:</b> The OPsumit® USers Registry (OPUS; NCT02126943) provides real-world experience with macitentan in patients with pulmonary hypertension, including CTEPH. <b>Aims and objectives:</b> To describe characteristics and safety in CTEPH patients enrolled in OPUS. <b>Methods:</b> OPUS is an ongoing, long-term, prospective, US, multicentre, observational drug registry of patients newly treated with macitentan. This subgroup analysis describes CTEPH patients in OPUS. Adverse events (AEs) are descriptively compared with the overall PAH follow-up set. <b>Results:</b> As of October 2017, OPUS included 40 CTEPH patients with follow-up data. At macitentan initiation, median age (range) was 66.5 (18–87) years; 67.5% were female. Median time (Q1, Q3) from CTEPH diagnosis was 15.1 (7.1, 42.8) months (n=36); 27 (68%) were receiving combination therapy. Median (Q1, Q3) exposure to macitentan was 5.6 (3.3, 18.0) months. AEs that occurred in &gt;5% of patients are shown in the table. One patient died. <b>Conclusions:</b> OPUS provides insight into real-world use of macitentan for CTEPH. There were no unexpected safety findings in these patients.