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

Charles D Burger,1 Mohamedanwar Ghandour,1 Divya Padmanabhan Menon,2 Haytham Helmi,3 Raymond L Benza4 1Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, 2Department of Internal Medicine, Mayo Clinic, 3Division of Transplant Medicine and Research Administration, Mayo Clinic, Jacksonville, FL, USA; 4Advanced Heart Failure, Transplant, Mechanical Circulatory Support and Pulmonary Hypertension, Allegheny Health Network, Pittsburg, PA, USA Abstract: Pulmonary arterial hypertension (PAH) has a high morbidity rate and is fatal if left untreated. Increasing evidence supports early intervention, possibly with initial combination therapy. PAH-specific pharmaceuticals, however, are expensive and may have serious adverse effects, particularly when used in combination. The currently dynamic health care economy reinforces the need for a review of early intervention from both outcomes and economic perspectives. We aimed to review the clinical and economic impact of PAH therapy, particularly examining drug cost, hospitalization burden, and health care economics impact, and the effect of early intervention on clinical outcomes. We searched PubMed, Scopus, Ovid, and MEDLINE databases from 2005 to 2017 for studies comparing drug cost, clinical outcomes, and hospitalization burden associated with therapy for PAH. Emerging data indicate that early therapy is effective, but drug therapy is expensive, particularly with combination therapy. Efficacy studies also generally show benefit of combination therapy for patients in World Health Organization functional class II, with a consistent decrease in hospitalization. Pharmacoeconomic studies are limited but indicate that increased pharmacy costs are at least partially offset by decreased health care utilization, particularly inpatient care. Modeling also shows a cost benefit with combination therapy at 2 years. Nonetheless, more rigorously collected health care economic data should be incorporated into future drug efficacy trials to provide a clearer understanding of the impact and the associated cost benefit of early PAH therapy. Increasing evidence in support of early intervention and combination therapy for PAH is associated with rising medication costs that are largely offset by reduced hospitalization, on the basis of the currently available literature. Nonetheless, the studies performed to date have methodologic limitations that highlight the need for prospective studies using more robust economic modeling. Keywords: combination therapy, health care costs, hospitalization, pulmonary arterial hypertension