TY - JOUR
T1 - Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension
T2 - Results from the TRANSIT-1 study
AU - Frost, Adaani
AU - Janmohamed, Munir
AU - Fritz, Jason S.
AU - McConnell, John W.
AU - Poch, David
AU - Fortin, Terry Ann
AU - Miller, Chad E.
AU - Chin, Kelly M
AU - Fisher, Micah
AU - Eggert, Michael
AU - McEvoy, Colleen
AU - Benza, Raymond L.
AU - Farber, Harrison W.
AU - Kim, Nick H.
AU - Pfister, Thomas
AU - Shiraga, Yoko
AU - McLaughlin, Vallerie
N1 - Funding Information:
A.F. reports grants, personal fees, and non-financial support from Actelion Pharmaceuticals Ltd., grants and personal fees from Gilead Sciences Inc. and United Therapeutics; and grants from Bayer Healthcare, Intermune, GSK, Reata Pharmaceuticals, GeNO, and Novartis. M.J. received financial support from Actelion Pharmaceuticals Ltd. J.S.F. received financial support and personal fees from Actelion Pharmaceuticals Ltd. J.W.M. received financial support, research grants, and personal fees from Actelion Pharmaceuticals Ltd; personal fees and financial support from Bayer Pharmaceuticals, United Therapeutics, and Reata Pharmaceuticals; and financial support from Eiger Pharmaceuticals and Bellerophon. D.P. reports grants from Actelion Pharmaceuticals Ltd. and personal fees from Bayer Healthcare. T.A.F reports grants from Actelion Pharmaceuticals Ltd. and Bayer and grants and personal fees from United Therapeutics and Gilead. C.E. M. reports personal fees from Actelion Pharmaceuticals Ltd., United Therapeutics, Gilead, and Bayer. K.M.C. has served as a steering committee member for Actelion Pharmaceuticals Ltd.; has received research grants from Actelion Pharmaceuticals Ltd., Bayer Healthcare, United Therapeutics, and SoniVie; and has received consultancy fees from Actelion Pharmaceuticals Ltd. and United Therapeutics. M.F. reports grants from United Therapeutics. M.E. reports grants and personal fees from Actelion Pharmaceuticals Ltd., United Therapeutics; personal fees from Bayer Healthcare; grants from Lung LLC; and financial support from Reata Pharmaceuticals. C.E. reports personal fees from Gilead and Actelion Pharmaceuticals Ltd. R.B. reports grants from Actelion Pharmaceuticals Ltd. and United Therapeutics. H.F. reports non-financial support, grants, and personal fees from Actelion Pharmaceuticals Ltd.; grants and personal fees from Gilead and United Therapeutics; and personal fees from Bayer, Bellerophon, and Arena. N.K. reports grants from Bellerophon, Eiger, and Lung Biotechnology and personal fees from Bayer, Arena, Merck, and Actelion Pharmaceuticals Ltd. V.M, reports grants, personal fees, and non-financial support from Actelion Pharmaceuticals Ltd., Bayer, Gilead, Ikaria, and Arena; grants from Novartis, Eiger, and SoniVie; personal fees from SteadyMed Therapeutics and St. Jude Medical; and personal fees and non-financial support from United Therapeutics. T.P. and Y.S. are employees of Actelion Pharmaceuticals Ltd. and in the past held stock/stock options for Actelion Pharmaceuticals Ltd. and currently hold stock/stock options in the parent company Johnson & Johnson.
Funding Information:
K.M.C. has received research grants from the National Institutes of Health (1K23HL105784-01A1).
Funding Information:
Actelion Pharmaceuticals Ltd. funded the study and participated in the design of the study, data analysis, interpretation, and preparation of the manuscript. Medical writing support was provided by Mariana Thomson of nspm Ltd. (Meggen, Switzerland), funded by Actelion Pharmaceuticals Ltd.
PY - 2019/1
Y1 - 2019/1
N2 - BACKGROUND: A long-term trial showed that the oral prostacyclin (PGl2) receptor (IP) agonist, selexipag, delayed disease progression in patients with pulmonary arterial hypertension (PAH). Transition to selexipag in patients treated with more burdensome inhaled therapies that target the prostacyclin pathway may be considered by patients and physicians. The Phase 3b, prospective, open-label TRANSIT-1 (Tolerability and Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension) study evaluated the safety and tolerability of transition from inhaled treprostinil to oral selexipag. METHODS: Patients receiving non-prostanoid oral PAH therapy and inhaled treprostinil at stable doses, in World Health Organization Functional Class II/III, with 6-minute walk distance ≥ 300 meters were enrolled. The 16-week main treatment period included downtitration of inhaled treprostinil over 8 weeks and parallel uptitration of selexipag over 12 weeks. Sustained treatment transition at Week 16 was defined as (1) receiving selexipag at Week 16; (2) no selexipag interruption(s) totaling ≥ 8 days; and (3) no inhaled treprostinil or other prostanoids after Week 8. Clinical parameters and patient-reported treatment satisfaction outcomes were assessed at Week 16. RESULTS: All 34 enrolled patients completed the study. At Week 16, 32 patients (94.1%) had stopped inhaled treprostinil and were receiving selexipag. Twenty-eight patients (82.4%) met all criteria for sustained treatment transition. During the study, 3 patients discontinued selexipag due to adverse events. Overall, most adverse events were typical of prostanoid therapies and started during the uptitration phase. In general, patients remained clinically stable throughout treatment and reported improved convenience. CONCLUSIONS: Transition to oral selexipag from inhaled treprostinil in PAH patients was successful and well tolerated in most patients, and associated with greater convenience. CLINICAL TRIAL NUMBER: NCT02471183
AB - BACKGROUND: A long-term trial showed that the oral prostacyclin (PGl2) receptor (IP) agonist, selexipag, delayed disease progression in patients with pulmonary arterial hypertension (PAH). Transition to selexipag in patients treated with more burdensome inhaled therapies that target the prostacyclin pathway may be considered by patients and physicians. The Phase 3b, prospective, open-label TRANSIT-1 (Tolerability and Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension) study evaluated the safety and tolerability of transition from inhaled treprostinil to oral selexipag. METHODS: Patients receiving non-prostanoid oral PAH therapy and inhaled treprostinil at stable doses, in World Health Organization Functional Class II/III, with 6-minute walk distance ≥ 300 meters were enrolled. The 16-week main treatment period included downtitration of inhaled treprostinil over 8 weeks and parallel uptitration of selexipag over 12 weeks. Sustained treatment transition at Week 16 was defined as (1) receiving selexipag at Week 16; (2) no selexipag interruption(s) totaling ≥ 8 days; and (3) no inhaled treprostinil or other prostanoids after Week 8. Clinical parameters and patient-reported treatment satisfaction outcomes were assessed at Week 16. RESULTS: All 34 enrolled patients completed the study. At Week 16, 32 patients (94.1%) had stopped inhaled treprostinil and were receiving selexipag. Twenty-eight patients (82.4%) met all criteria for sustained treatment transition. During the study, 3 patients discontinued selexipag due to adverse events. Overall, most adverse events were typical of prostanoid therapies and started during the uptitration phase. In general, patients remained clinically stable throughout treatment and reported improved convenience. CONCLUSIONS: Transition to oral selexipag from inhaled treprostinil in PAH patients was successful and well tolerated in most patients, and associated with greater convenience. CLINICAL TRIAL NUMBER: NCT02471183
KW - inhaled treprostinil
KW - prostacyclin-pathway targeting therapy
KW - pulmonary arterial hypertension
KW - selexipag
KW - treatment transition
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U2 - 10.1016/j.healun.2018.09.003
DO - 10.1016/j.healun.2018.09.003
M3 - Article
C2 - 30391194
AN - SCOPUS:85055734826
VL - 38
SP - 43
EP - 50
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
SN - 1053-2498
IS - 1
ER -