TRANSITIONING FROM PARENTERAL PROSTACYCLIN THERAPY TO ORAL SELEXIPAG IN PULMONARY ARTERIAL HYPERTENSION

Abstract

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious condition that confers a poor prognosis if not promptly diagnosed and treated. Although parenteral medications targeting the prostacyclin pathway are often prescribed for high-risk patients, the transition to a more convenient and tolerable medication acting on the same pathophysiologic pathway may provide significant benefit in patients with stable disease who are burdened by the multiple complications inherent to parenteral therapy. CASE PRESENTATION: Three patients were successfully transitioned from parenteral prostacyclin therapy to selexipag at a single tertiary-care, expert pulmonary hypertension centre. Prior to transition, two patients were prescribed subcutaneous treprostinil and one intravenous epoprostenol. Reasons for transition included severe site pain with subcutaneous therapy, recurrent line infections, and patient preference. All patients were functional class II at time of transition. Right heart catheterization pre-transition demonstrated pre-capillary pulmonary hypertension in two patients (mPAP of 33mmHg with PVR of 5.2WU in the first, and mPAP of 32mmHg with PVR of 6.3WU in the second), with normal hemodynamics in the third. Transitions were performed in the outpatient setting over the course of 4-8 weeks. All patients achieved maximum daily dosing of selexipag (3200mcg) at the end of transition, with each patient experiencing temporary side effects during transition, e.g. headache, jaw pain, diarrhea, nausea, myalgias, limb pain, and peri-orbital edema. Following transition, there was no incidence of mortality (PAH or otherwise), PAH-related hospitalizations, re-initiation of parenteral therapy, or worsening of functional class or 6-minute walk distance in any of the three patients within 36 months of follow-up (in 6-, 12-, 24-, and 36- months intervals). Echocardiographic and right heart catheterization parameters were stable post-transition. DISCUSSION: All three patients were successfully transitioned from parenteral prostacyclin therapies to selexipag as evidenced by a lack of death, hospitalizations, and/or failure of oral therapy, as well as stability in various functional, echocardiographic, and hemodynamic outcomes with up to 36-months of follow-up. While parental prostacyclin analogues are still required for patients with high-risk or refractory disease, the patients in this study were those who were clinically and hemodynamically stable pre-transition with infusion-related morbidity. This may reflect the phenotype of patient where transition could be considered. CONCLUSIONS: In a carefully selected patient population with PAH on parenteral prostacyclin therapy, transition to selexipag may be a safe and viable option. Further studies are required to better delineate baseline predictors of long-term therapeutic efficacy and safety in a real-world PAH population. REFERENCE #1: Chin KM, McLaughlin V, Kim NH, et al. Clinical Course of Patients Transitioned from Another Prostacyclin Pathway Agent (PPA) to Selexipag in SPHERE. J Hear Lung Transplant. 2019;38(4, Supplement):S486. doi:https://doi.org/10.1016/j.healun.2019.01.1236 REFERENCE #2: Parikh KS, Doerfler S, Shelburne N, et al. Experience in Transitioning From Parenteral Prostacyclins to Selexipag in Pulmonary Arterial Hypertension. J Cardiovasc Pharmacol. 2020;75(4):299-304. doi:10.1097/FJC.0000000000000800 REFERENCE #3: Sargent T, Hansen L, Hohsfield R. Transitions between infused and oral prostacyclin pathway agents in pulmonary arterial hypertension: key considerations. Pulm Circ. 2020;10(3):2045894020931324. doi:10.1177/2045894020931324 DISCLOSURES: No relevant relationships by Brandon Budhram, source=Web Response No relevant relationships by Andrea Gardner, source=Web Response Speaker/Speaker's Bureau relationship with Janssen Please note: 2016-2021 Added 05/01/2021 by Nathan Hambly, source=Web Response, value=Honoraria Advisory Committee Member relationship with Janssen Please note: 2016-2021 Added 05/01/2021 by Nathan Hambly, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Roche Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Honoraria