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Objectives To investigate demographic, clinical characteristics, treatment patterns and healthcare resource utilisation (HCRU) among patients with portopulmonary hypertension (PoPH). Design Retrospective analysis of a real-world cross-sectional survey, the pulmonary arterial hypertension (PAH) Disease Specific Programme. Setting Secondary care settings in the USA. Participants Pulmonologists (n=22), cardiologists (n=17) and internists (n=7) who saw ≥2 patients with PAH/month provided data on 90 PoPH patients. Mean age of patients was 56.8 years, 51.1% were male, 76.7% were white/Caucasian. Primary and secondary outcome measures Demographic characteristics, initial presentation/diagnosis, disease trajectory, symptoms, comorbidities, treatment patterns and HCRU. Results The most common diagnostic tests were echocardiogram (62.2%), right heart catheterisation (56.7%) and electrocardiogram (48.9%). Dyspnea on exertion (64.4%), dyspnea following exertion (51.1%) and fatigue (48.9%) were the most common symptoms prior to PAH diagnosis as well as the most bothersome. Overall, 13.3% patients had mild disease before treatment vs 42.2% at time of survey. Most (60.0%) had stable disease (21.1% were improving and 18.8% were deteriorating at the time of the survey). Most common recent symptoms were dyspnea on exertion (51.1%), fatigue (37.8%) and dyspnea following exertion (32.2%). Patients had a mean of 1.8 comorbidities. In total, 80.0% of PoPH patients were receiving PAH-specific treatment; 41.7%, 22.2% and 12.5% received monotherapy, dual therapy and triple therapy, respectively. Patients had seen their physician 4.1 times in the past 12 months (3.5 visits specifically for PAH), while 31.1% had been hospitalised for PAH. Most (70.0%) patients were managed in a multidisciplinary team, and 8.9% of patients relied on a caregiver. Conclusions This study highlights the high symptomatic burden coupled with mostly moderate-to-severe disease status and a high hospitalisation rate despite the majority of PoPH patients being on therapy. Therefore, new treatment options in PoPH are in great need.

ImportanceA subgroup analysis of a randomized clinical trial established the efficacy of selexipag plus background therapy (monotherapy or double oral therapy [DOT]) vs placebo plus background therapy and found that the addition of selexipag within 6 months had an added benefit. However, the timing of selexipag addition to DOT and the incremental benefit in clinical practice is not well studied.ObjectiveTo compare triple oral therapy (TOT) consisting of selexipag, endothelin receptor antagonist (ERA), and phosphodiesterase type 5 inhibitor (PDE5i) vs DOT consisting of ERA and PDE5i.Design, Setting, and ParticipantsThis comparative effectiveness study was conducted using data from the US Komodo claims database to emulate a randomized trial. Patients aged 18 years or older with pulmonary arterial hypertension (PAH) treated with ERA plus PDE5i with records from July 2015 through June 2022 were duplicated to TOT and DOT and artificially censored when observed treatment deviated from assigned treatment. Hypothetical randomization was emulated using inverse probability of treatment weighting, and the study accounted for censoring-induced selection bias using inverse probability of censoring weighting. A pooled logistic model estimated the per-protocol difference between treatment groups. Data were analyzed from November 2022 through July 2023.InterventionsTOT (addition of selexipag within 3, 6, and 12 months of initiating DOT) vs DOT.Main Outcomes and MeasuresAdjusted risk of all-cause hospitalization, PAH-related hospitalization, and PAH-related disease progression over a 2-year follow-up.ResultsA total of 2966 patients with PAH (mean [SD] age, 54.3 [14.0] years; 2125 female [71.6%]) met eligibility criteria. Adding selexipag within 6 months of ongoing DOT was associated with a reduction in risk for all-cause hospitalization (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.72-0.94), PAH-related hospitalization (aHR, 0.81; 95% CI, 0.70-0.95), and PAH-related progression (aHR, 0.82; 95% CI, 0.70-0.95) vs DOT alone. There were no associations if selexipag was initiated within 12 months for all-cause hospitalization, PAH-related hospitalization, or PAH-related disease progression. The association remained with a greater decrease in risk for disease progression vs DOT for selexipag initiation within 3 months (aHR, 0.74; 95% CI, 0.61-0.90).Conclusions and RelevanceThis study found that early selexipag addition to ERA plus PDE5i was associated with a reduction in risk of hospitalization and disease progression. These findings suggest that delays in selexipag initiation likely contribute to suboptimal patient and health system outcomes.

AbstractSelexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real‐world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH‐related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200–400 µg bid), medium (600–1000 µg bid), and high (1200–1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real‐world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed‐claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all‐cause and PAH‐related hospitalization across ID groups. The findings in this diverse, real‐world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit‐risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies.

AbstractPulmonary arterial hypertension (PAH) is a rare, life‐limiting disease. PAH registries provide real‐world data that complement clinical trial data and inform treatment decisions. The TRIO comprehensive, integrated patient data repository (TRIO CIPDR), is an innovative US repository capturing data on contemporary patients diagnosed with pulmonary hypertension and receiving US Food and Drug Administration‐approved PAH therapies. This repository uniquely combines clinical data from electronic medical records with the ability to track drug‐prescription and drug‐dispensing characteristics, and includes 946 adult patients with PAH (data collected January 2019 to December 2020) enrolled from nine representative US specialist tertiary care centers. Potentially eligible patients were identified based on dispensing data from specialty pharmacies. Hemodynamic and clinical data, as well as dispensing information on prescribed PAH medications, were provided by tertiary centers. At enrollment, 75% of patients were female, 67% were White, median age at PAH diagnosis was 53 years (median time from diagnosis to enrollment was 5 years), and 37% were obese. Comorbidity profiles were as expected for a PAH population, although the proportion with atrial fibrillation (34%) was higher than expected. Overall, 38% of patients had idiopathic PAH and 30% had connective tissue disease‐related PAH. Among 917 patients receiving PAH‐specific therapy, 40% were on monotherapy, 43% on dual therapy, and 17% on triple therapy. Longitudinal data from this repository will allow tracking of the PAH treatment journey in relation to clinical characteristics and outcomes.

Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real‐world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare costs in pulmonary arterial hypertension patients treated with endothelin receptor antagonists or phosphodiesterase type‐5 inhibitors. From the IQVIA Adjudicated Health Plan Database, patients with pulmonary arterial hypertension were identified based on diagnostic codes and prescriptions for endothelin receptor antagonists (ambrisentan, bosentan, macitentan) or phosphodiesterase type‐5 inhibitors (sildenafil, tadalafil) approved for pulmonary arterial hypertension. Patients were assigned to the class of their most recently initiated (index) pulmonary arterial hypertension therapy between 1 January 2009 and 30 June 2015. Medication adherence was measured by proportion of days covered; patients with proportion of days covered ≥80% were considered adherent. The proportion of adherent patients was higher for endothelin receptor antagonists (571/755; 75.6%) than for phosphodiesterase type‐5 inhibitors (970/1578; 61.5%; P < 0.0001). In both groups, hospitalizations declined as proportion of days covered increased. Among adherent patients, those on endothelin receptor antagonists had a significantly lower hospitalization rate than those on phosphodiesterase type‐5 inhibitors (23.1% versus 28.5%, P = 0. 0218), fewer hospitalizations (mean (standard deviation) 0.4 (0.8) versus 0.5 (0.9); P = 0.02), and mean hospitalization costs during the six‐month post‐index ($9510 versus $15,726, P = 0.0318). Increasing adherence reduced hospitalization risk more for endothelin receptor antagonists than for phosphodiesterase type‐5 inhibitors (hazard ratio 0.176 versus 0.549, P = 0.001). Rates and numbers of rehospitalizations within 30 days post‐discharge were similar between groups. Mean total costs were higher with endothelin receptor antagonists than phosphodiesterase type‐5 inhibitors in all patients ($91,328 versus $72,401, P = 0.0003) and in adherent patients ($88,867 versus $56,300, P < 0.0001), driven by higher drug costs.