TY - JOUR
T1 - Long-Term Survival, Safety and Tolerability with Selexipag in Patients with Pulmonary Arterial Hypertension
T2 - Results from GRIPHON and its Open-Label Extension
AU - Galiè, Nazzareno
AU - Gaine, Sean
AU - Channick, Richard
AU - Coghlan, J. Gerry
AU - Hoeper, Marius M.
AU - Lang, Irene M.
AU - McLaughlin, Vallerie V.
AU - Lassen, Cheryl
AU - Rubin, Lewis J.
AU - Hsu Schmitz, Shu Fang
AU - Sitbon, Olivier
AU - Tapson, Victor F.
AU - Chin, Kelly M.
N1 - Funding Information:
Funding for the study and for the journal’s rapid service and open access fees was provided by Actelion Pharmaceuticals, Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson.
Funding Information:
Medical writing support was provided by Jatta Huotari and Laura Corbett of eluSCIdate ltd (Meggen, Switzerland) and was funded by Actelion Pharmaceuticals, Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson.
Funding Information:
Nazzareno Galiè is a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received grant support, personal fees and non-financial support from Janssen Pharmaceutical Companies of Johnson & Johnson; and has received grant support and personal fees from Bayer Healthcare, Pfizer and GlaxoSmithKline. Sean Gaine 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; has received advisory board fees from Janssen Pharmaceutical Companies of Johnson & Johnson, and Daiichi-Sankyo; and has served on a data and safety monitoring board for United Therapeutics. Richard Channick 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 and Arena Pharmaceuticals; and has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson and United Therapeutics. J. Gerry Coghlan has received grant support, speakers’ fees and travel support from Janssen Pharmaceutical Companies of Johnson & Johnson and has served as a member of working groups for Janssen Pharmaceutical Companies of Johnson & Johnson, Acceleron and Bayer. Marius M. Hoeper 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; and has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson. Irene M. Lang 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, Merck Sharp & Dohme, and AOP Orphan Pharmaceuticals; and has received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson and AOP Orphan Pharmaceuticals. Vallerie V. McLaughlin has served as a as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson. She receives consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Acceleron, Bayer, Caremark LLC, CiVi Biopharma, United Therapeutics, Altavant, Gossamer Bio, and Liquidia and research/grant support from Janssen Pharmaceutical Companies of Johnson & Johnson, Acceleron, United Therapeutics, Reata Pharmaceuticals, SoniVie and NIH. Cheryl Lassen is an employee of Actelion Pharmaceuticals Ltd. Lewis J. Rubin has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; and has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Arena Pharmaceuticals, GENO Pharmaceuticals, Gilead, Karos Pharmaceuticals, Pfizer, and SoniVie Ltd. Shu-Fang Hsu Schmitz is an employee of Actelion Pharmaceuticals Ltd. Olivier Sitbon has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has served as an advisory board member for and received research grants from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, GlaxoSmithKline, and Merck Sharp & Dohme; has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Arena, Bayer, GlaxoSmithKline and Merck Sharp & Dohme; has received speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, GlaxoSmithKline, and Merck Sharp & Dohme; has served on a scientific advisory board for Arena Pharmaceuticals and Gossamer Bio; and has received writing assistance from Janssen Pharmaceutical Companies of Johnson & Johnson and GlaxoSmithKline. Victor F. Tapson 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, Gilead Sciences, Janssen, Reata, and United Therapeutics; has received research grants from Arena Pharmaceuticals, Arena, Bayer, EKOS/BTG, and Riata; has received speaker fees from Bayer, Gilead Sciences, and Janssen. Kelly M. Chin 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, NIH, Ironwood Pharmaceuticals, National Institutes of Health and SoniVie Ltd; has served on an advisory board for Bayer Healthcare (through UCSD) and Flowonix; has served as an adjudication committee member for Arena Pharmaceuticals; is Circulation Associate Editor for the American Heart Association; and has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson.
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/1
Y1 - 2022/1
N2 - Introduction: In the event-driven GRIPHON randomised-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag. Methods: Patients randomised to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3 days and 30 days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019. Results: Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7 months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomised to selexipag in GRIPHON. Kaplan–Meier survival estimates (95%CI) at 1, 3, 5 and 7 years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively. Conclusions: These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen. Trial Registration: ClinicalTrials.gov Identifiers: NCT01106014 and NCT01112306.
AB - Introduction: In the event-driven GRIPHON randomised-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag. Methods: Patients randomised to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3 days and 30 days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019. Results: Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7 months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomised to selexipag in GRIPHON. Kaplan–Meier survival estimates (95%CI) at 1, 3, 5 and 7 years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively. Conclusions: These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen. Trial Registration: ClinicalTrials.gov Identifiers: NCT01106014 and NCT01112306.
KW - Combination therapy
KW - GRIPHON
KW - Long-term outcomes
KW - Open-label extension
KW - PAH
KW - Pulmonary arterial hypertension
KW - Safety
KW - Selexipag
KW - Survival
KW - Tolerability
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UR - http://www.scopus.com/inward/citedby.url?scp=85118424924&partnerID=8YFLogxK
U2 - 10.1007/s12325-021-01898-1
DO - 10.1007/s12325-021-01898-1
M3 - Article
C2 - 34727317
AN - SCOPUS:85118424924
SN - 0741-238X
VL - 39
SP - 796
EP - 810
JO - Advances in Therapy
JF - Advances in Therapy
IS - 1
ER -