RT Journal Article
SR Electronic
T1 Early selexipag initiation and long-term outcomes: Insights from RCTs in PAH
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00456-2022
DO 10.1183/23120541.00456-2022
A1 J Gerry Coghlan
A1 Sean Gaine
A1 Richard Channick
A1 Kelly M Chin
A1 Camille du Roure
A1 J Simon R Gibbs
A1 Marius M Hoeper
A1 Irene M Lang
A1 Stephen C Mathai
A1 Vallerie V McLaughlin
A1 Lada Mitchell
A1 Gérald Simonneau
A1 Olivier Sitbon
A1 Victor F Tapson
A1 Nazzareno Galiè
YR 2022
UL http://openres.ersjournals.com/content/early/2022/10/06/23120541.00456-2022.abstract
AB Further understanding of when to initiate therapies in pulmonary arterial hypertension (PAH) is important to improve long-term outcomes. Post-hoc analyses of GRIPHON (NCT01106014) and exploratory analyses of TRITON (NCT02558231) suggested benefit of early selexipag initiation on long-term outcomes, despite no additional benefit versus initial double combination on haemodynamic and functional parameters in TRITON. Post-hoc analyses investigated the effect of early selexipag initiation on disease progression and survival in a large, pooled PAH cohort. Data from newly diagnosed (≤6 months) PAH patients from GRIPHON and TRITON were pooled. Patients on active therapy with selexipag (pooled selexipag group) were compared with those on control therapy with placebo (pooled control group). Disease progression endpoints were defined as per the individual studies. Hazard ratios (HR) and 95%CI for time to first disease progression event up to end of double-blind treatment (selexipag/placebo)+7 days and time to all-cause death up to end of study were estimated using Cox regression models. The pooled dataset comprised 649 patients, with 44% on double background therapy. Selexipag reduced the risk of disease progression by 52% versus control (HR: 0.48; 95% CI: 0.35, 0.66). HR for risk of all-cause death was 0.70 (95% CI: 0.46, 1.10) for the pooled selexipag versus control group. Sensitivity analyses accounting for the impact of PAH background therapy showed consistent results, confirming the appropriateness of data pooling. These post-hoc, pooled analyses build on previous insights, further supporting selexipag use within 6 months of diagnosis, including as part of triple therapy, to delay disease progression.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflicts of interest: J.G.C. has received grants, speaker fees and support for attending meetings from Janssen Pharmaceutical Companies of Johnson & Johnson; has received consulting fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Acceleron, Bayer, and Vicore.Conflicts of interest: S.G. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer and AOP; has served on advisory boards / data safety monitoring boards for Janssen Pharmaceutical Companies of Johnson & Johnson, United Therapeutics, Gossamer Bio and Altavant.Conflicts of interest: R.C. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has served on an advisory board for Janssen Pharmaceutical Companies of Johnson & Johnson and Bayer; has received consultancy fees from Bayer, Gossamer, Third Pole, Acceleron, Arena Pharmaceuticals and Janssen Pharmaceutical Companies of Johnson & Johnson; has received speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson and Bayer.Conflicts of interest: K.M.C. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson, Altavant, Acceleron, United Therapeutics, Pfizer, Merck, Gossamer Bio; has received support for travel to meetings from Janssen Pharmaceutical Companies of Johnson & Johnson; has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Altavant, Acceleron, United Therapeutics and Gossamer Bio.Conflicts of interest: C.D.R. is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson.Conflicts of interest: J.S.R.G. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson, Complexa and Acceleron/Merck; has received consultancy fees from Acceleron/Merck; has served as a clinical endpoints committee member for Pfizer, Aerovate, Janssen Pharmaceutical Companies of Johnson & Johnson, and United Therapeutics; has served as a data and safety monitoring board member for Janssen Pharmaceutical Companies of Johnson, Merck Sharp & Dohme, Gossamer Bio and Bial.Conflicts of interest: M.M.H. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received speaker and consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, GlaxoSmithKline, Merck Sharp & Dohme, and Pfizer; has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson.Conflicts of interest: I.M.L. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson and AOP Orphan Pharmaceuticals; has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, AOP Health, Bayer, Ferrer and United Therapeutics; has received speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson, AOP Health and Bayer; has received support for attending meetings from Janssen Pharmaceutical Companies of Johnson & Johnson, AOP Health, Bayer, Ferrer and Medtronic.Conflicts of interest: S.C.M. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received consultancy fees from Acceleron, Bayer, United Therapeutics and Janssen Pharmaceutical Companies of Johnson & Johnson; has received speaker fees from Practice Point CME; has participated on an advisory board for United Therapeutics; has had a leadership role on the PCORI, Rare Disease Advisory Panel and served as ACCP PVD Network Chair.Conflicts of interest: V.V.M. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; reports grant support from Aerovate, Altavant, Gossamer-Bio, Janssen Pharmaceutical Companies of Johnson & Johnson, Merck and Sonovie; has received consultancy fees from Aerami, Aerovate, Altavant, Bayer, Caremark, L.L.C., Corvista, Gossamer Bio, Janssen Pharmaceutical Companies of Johnson & Johnson, Merck and United Therapeutics.Conflicts of interest: L.M. is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson.Conflicts of interest: G.S. has served as a steering committee member for and received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson; and has received speaker and consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, GlaxoSmithKline, Merck Sharp & Dohme and Pfizer.Conflicts of interest: O.S. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson and Gossamer Bio; has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson, Acceleron Pharmaceuticals, GlaxoSmithKline, and Merck Sharp & Dohme; has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, AOP Orphan, Ferrer Gossamer Bio and Merck Sharp & Dohme and United Therapeutics; has received speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson, AOP Orphan, Ferrer and Merck Sharp & Dohme; has served on an advisory board for Acceleron Pharmaceuticals, Altavant Pharmaceuticals, Gossamer Bio, Janssen Pharmaceutical Companies of Johnson & Johnson and Merck Sharp & Dohme.Conflicts of interest: V.T. has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, and United Therapeutics; has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Arena Pharmaceuticals, Bayer, Daiichi-Sankyo, EKOS/BTG, and United Therapeutics; has received research grants from Arena Pharmaceuticals, Arena, and Bayer has received speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson; serves as VP of Medical Affairs at Inari Medical.Conflicts of interest: N.G. is a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received grant support from Janssen Pharmaceutical Companies of Johnson & Johnson; has received consulting fees and speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Ferrer and Pfizer.