TY - JOUR
T1 - Temporary treatment interruptions with oral selexipag in pulmonary arterial hypertension
T2 - Insights from the Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study
AU - Preston, Ioana R.
AU - Channick, Richard N.
AU - Chin, Kelly
AU - Di Scala, Lilla
AU - Farber, Harrison W.
AU - Gaine, Sean
AU - Galiè, Nazzareno
AU - Ghofrani, Hossein Ardeschir
AU - Hoeper, Marius M.
AU - Lang, Irene M.
AU - McLaughlin, Vallerie V.
AU - Preiss, Ralph
AU - Simonneau, Ge´rald
AU - Sitbon, Olivier
AU - Tapson, Victor F.
AU - Rubin, Lewis J.
N1 - Funding Information:
GRIPHON was funded by Actelion Pharmaceuticals Ltd. and participated in the design of the study, data analysis, data interpretation, and preparation of the manuscript. Medical writing support, funded by the sponsor, was provided by Ruth Lloyd of nspm Ltd. (Meggen, Switzerland). All authors reviewed and edited the manuscript, had access to the data, were involved in the decision to submit the manuscript for publication and vouch for the accuracy and completeness of the analyses.
Funding Information:
K.C. has received grants from the National Institutes of Health.
Publisher Copyright:
© 2018
PY - 2018/3
Y1 - 2018/3
N2 - Background: Parenteral prostacyclin analogs that target the prostacyclin pathway have been used to treat pulmonary arterial hypertension (PAH) since the 1990s. Abrupt discontinuation of parenteral prostacyclin analogs can be associated with acute deterioration of PAH. Less is known about temporary interruption of oral therapies that target the prostacyclin pathway, such as selexipag. Methods: We evaluated the frequency, duration, reasons, and consequences of temporary selexipag interruptions among PAH patients enrolled in the Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study. In GRIPHON, patients were randomized to selexipag or placebo and titrated to an individualized highest tolerated dose (200 to 1,600 µg twice daily) over 12 weeks, after which patients entered the maintenance phase. Treatment interruptions were allowed; if the interruption was < 3 days, treatment was restarted at the previous highest tolerated dose; if the interruption was ≥ 3 days, retitration from 200 µg twice daily was required. Descriptive analyses were performed. Results: At least 1 treatment interruption occurred in 111 of 574 patients (19.3%) in the selexipag group and in 58 of 582 (10.0%) in the placebo group. Baseline characteristics were similar between patients with and without an interruption. Of the 111 patients in whom selexipag was temporarily interrupted, 94 (85%) were receiving background PAH therapy. Adverse events were the most common reason for selexipag interruption. Selexipag interruptions and reinstitution of treatment were well tolerated. There were no episodes of acute deterioration during treatment interruption. Conclusions: Based on observations from GRIPHON, selexipag interruptions can be expected in clinical practice. However, temporarily interrupting selexipag was well tolerated and manageable.
AB - Background: Parenteral prostacyclin analogs that target the prostacyclin pathway have been used to treat pulmonary arterial hypertension (PAH) since the 1990s. Abrupt discontinuation of parenteral prostacyclin analogs can be associated with acute deterioration of PAH. Less is known about temporary interruption of oral therapies that target the prostacyclin pathway, such as selexipag. Methods: We evaluated the frequency, duration, reasons, and consequences of temporary selexipag interruptions among PAH patients enrolled in the Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study. In GRIPHON, patients were randomized to selexipag or placebo and titrated to an individualized highest tolerated dose (200 to 1,600 µg twice daily) over 12 weeks, after which patients entered the maintenance phase. Treatment interruptions were allowed; if the interruption was < 3 days, treatment was restarted at the previous highest tolerated dose; if the interruption was ≥ 3 days, retitration from 200 µg twice daily was required. Descriptive analyses were performed. Results: At least 1 treatment interruption occurred in 111 of 574 patients (19.3%) in the selexipag group and in 58 of 582 (10.0%) in the placebo group. Baseline characteristics were similar between patients with and without an interruption. Of the 111 patients in whom selexipag was temporarily interrupted, 94 (85%) were receiving background PAH therapy. Adverse events were the most common reason for selexipag interruption. Selexipag interruptions and reinstitution of treatment were well tolerated. There were no episodes of acute deterioration during treatment interruption. Conclusions: Based on observations from GRIPHON, selexipag interruptions can be expected in clinical practice. However, temporarily interrupting selexipag was well tolerated and manageable.
KW - pharmacotherapy
KW - prostanoid receptor agonist
KW - pulmonary arterial hypertension
KW - selexipag
KW - treatment interruption
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U2 - 10.1016/j.healun.2017.09.024
DO - 10.1016/j.healun.2017.09.024
M3 - Article
C2 - 29096938
AN - SCOPUS:85032829530
VL - 37
SP - 401
EP - 408
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
SN - 1053-2498
IS - 3
ER -