Ioana R Preston1, Richard N Channick2, Kelly Chin3, Lilla Di Scala4, Harrison W Farber5, Sean Gaine6, Nazzareno Galiè7, Hossein-Ardeschir Ghofrani8, Marius M Hoeper9, Irene M Lang10, Vallerie V McLaughlin11, Ralph Preiss4, Gérald Simonneau12, Olivier Sitbon12, Victor F Tapson13, Lewis J Rubin14. 1. Pulmonary, Critical Care, and Sleep Division, Tufts Medical Center, Boston, Massachusetts. Electronic address: ipreston@tuftsmedicalcenter.org. 2. Pulmonary and Critical Care, Massachusetts General Hospital, Boston, Massachusetts. 3. Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Actelion Pharmaceuticals Ltd, Allschwil, Switzerland. 5. The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts. 6. National Pulmonary Hypertension Unit, Mater Misericordiae Hospital, Dublin, Ireland. 7. Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Bologna, Italy. 8. Department of Internal Medicine, University of Giessen and Marburg Lung Center, Giessen, Germany, member of the German Center of Lung Research, Giessen, Germany; Department of Medicine, Imperial College London, London, United Kingdom. 9. Department of Respiratory Medicine, Hannover Medical School, Hannover, member of the German Center of Lung Research, Giessen, Germany. 10. Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. 11. Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan. 12. Faculté de Médecine, Hôpital Universitaire de Bicêtre, Université Paris-Sud, Le Kremlin Bicêtre, France. 13. Center for Pulmonary Vascular Diseases and Venous Thromboembolism, Cedars-Sinai Medical Center, Los Angeles, California. 14. Department of Medicine, University of California, San Diego Medical School, San Diego, California.
Abstract
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 theProstacyclin (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.
RCT Entities:
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.