Search

Charles D Burger,1 Yuen Tsang,2 Marie Chivers,3 Riya Vijay Vekaria,3 Gurinderpal Doad,2,4 Nikki Atkins,3 Sumeet Panjabi2,4 1Division of Pulmonary Medicine, Mayo Clinic Florida, Jacksonville, FL, USA; 2Janssen Scientific Affiars, Titusville, NJ, USA; 3Avalere Health, Fleet, UK; 4Actelion Pharmaceuticals US, Inc, A Johnson and Johnson Co., Titusville, NJ, USACorrespondence: Marie Chivers, Avalere Health, Fleet, UK, Email MarieChivers@facilipharma.comPurpose: Pulmonary arterial hypertension (PAH) is a rare and progressive pulmonary vascular disease that can result in right heart failure and death. Oral prostacyclins play an important role in the management of intermediate-low risk PAH. This targeted literature review (TLR) aimed to identify and compare evidence supporting use of oral prostacyclin pathway agents (PPAs: selexipag and oral treprostinil) in intermediate-low risk PAH.Methods: A targeted literature review was conducted. Literature databases (MEDLINE, Embase, and Cochrane reviews) were searched for studies describing clinical practice and treatment outcomes for oral treprostinil and selexipag globally, published in English (2012 to 2022). Electronic searches were supplemented by manual-searches of targeted conferences (2020 to 2022), and reference lists of identified publications were reviewed. One reviewer assessed studies for eligibility.Results: In total, 95 publications met inclusion criteria: 47 full-text articles (selexipag n = 22; oral treprostinil n = 16; selexipag and oral treprostinil n = 9) and 48 conference materials. Selexipag and oral treprostinil target the prostacyclin pathway differently; their label-supporting trials had different primary endpoints (disease progression and hospitalization vs exercise capacity and disease progression), differing baseline therapy (0, 1 or 2 vs 0 or 1 baseline treatments), titration duration and dosing (personalized dose capped at 1600 ug twice daily (BID) vs increasing doses over time with no maximum dose), respectively. While both oral PPAs have demonstrated reduced risk of disease progression, only selexipag showed reduction in hospitalization rates. Oral PPAs have been shown to reduce healthcare costs in real-world clinical practice. This difference is reflected in labeled indications.Conclusion: Given differences in trial- and real-world outcomes, number of prior therapies, and dosing, personalizing the choice of oral PPA is critical to maximizing the benefit for individual patients.Plain Language Summary: PAH is a condition that causes heart failure. It is important to take medicines to slow down this process. For people with early disease, there are some medicines that can be taken as a tablet rather than as an injection to slow down disease progression. The differences between two of the tablet options – selexipag and oral treprostinil, are unclear. We reviewed publications describing how, when and why these medicines are used and how well they work, to improve our understanding of the value of these medicines to people with PAH.Keywords: treprostinil, selexipag, pulmonary hypertension, outcomes

Background: Mortality risk assessment informs clinical management of pulmonary arterial hypertension (PAH). The Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 is a simplified risk calculator discriminating 1-year mortality risk., Methods: This post-hoc analysis of the phase 3 GRIPHON study assessed changes in REVEAL Lite 2 risk score with selexipag versus placebo and whether changes were prognostic or predictive of time to first morbidity/mortality (M/M) event., Results: REVEAL Lite 2 risk category discriminated M/M risk (landmark concordance indices: 0.68-0.76, selexipag; 0.65-0.70, placebo). Across baseline risk categories, hazard ratios supported a lower risk of M/M events with selexipag versus placebo: low, 0.573 (95% confidence interval [CI] 0.361-0.908; p = 0.0178); intermediate, 0.423 (95% CI 0.274-0.655; p = 0.0001); and high, 0.711 (9% CI 0.520-0.972; p = 0.0326). Odds ratios for risk improvement were 2.0 (95% CI 1.50-2.65), 1.8 (95% CI 1.38-2.43), and 2.0 (95% CI 1.43-2.72) for selexipag versus placebo at 16, 26, and 52 weeks, respectively (all p < 0.001). REVEAL Lite 2 risk improvement at week 16 explained 19.1% of the treatment effect in all patients and 47.0% in patients with REVEAL Lite 2 baseline risk score of ≥7., Conclusions: REVEAL Lite 2 can monitor PAH M/M risk and facilitate treatment optimization. Baseline REVEAL Lite 2 risk score was prognostic of M/M risk in patients with PAH and mediates treatment effect up to 47% for those at higher risk. Lower M/M risk with selexipag versus placebo occurred irrespective of baseline risk category (ClinicalTrials.gov identifier: NCT01106014)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Information on factors leading to pulmonary arterial hypertension (PAH) treatment discontinuation is limited. This study analyzed 12,902 new PAH medication users to identify predictors of treatment discontinuation. Treatment by accredited pulmonary hypertension centers and combination therapy with PAH agents from different classes were less likely to result in discontinuation., Competing Interests: Hayley D. Germack, Sumeet Panjabi, and Carly Worden were employees of Janssen Scientific Affairs, LLC at the time of this study and Gurinderpal Doad is an employee of Janssen Pharmaceuticals and may own stocks. Nicole Croteau, Jason Simeone, and Fei Tang are employees of Cytel, which has received consultancy fees from Janssen Scientific Affairs, LLC for the conduct of this study. Harrison Farber and Teresa DeMarco provided consulting services to Janssen Scientific Affairs, LLC. Harrison Farber has received speaking honoraria from Bayer and SAB fees from Acceleron (Merck), Actelion (Janssen), Altavant, Aerami, Aerovate, and United Therapeutics. Teresa De Marco is a United Therapeutics advisory board member and has received consulting fees from Aerovate, Actelion/Janssen/Johnson & Johnson, Boston Scientific, Natera, NXT, Pulnovo, Scope‐Bial, and Tectonic., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)