SUMMARY

• Clinical research studies designed to investigate a methodology for transitioning from iloprost to oral UPTRAVI in the treatment of pulmonary arterial hypertension (PAH) have not been performed.
• A search of the published literature identified 2 case reports^1,2 and a conference abstract³ outlining the transition from inhaled iloprost to oral UPTRAVI.

CLINICAL DATA

Bhura et al (2019)¹ reported the case of a 52-year-old female patient with systemic lupus erythematosus associated with systemic sclerosis, Raynaud’s Phenomenon, PAH associated with connective tissue disease (stable at World Health Organization [WHO] Functional Class II) who had been on bosentan 125 mg twice daily (BID) and iloprost 5 mcg 6 inhalations a day for many years and requested to be switched to UPTRAVI.

Parallel up titration of UPTRAVI with down titration of iloprost was performed, while the patient continued to take bosentan. For the first week, UPTRAVI was started at 200 mcg BID in addition to the usual 6 inhalations daily of iloprost. UPTRAVI was increased by 200 mcg BID weekly, while iloprost was decreased by 3 inhalations weekly. By the third week, the patient was receiving 600 mcg BID of UPTRAVI, the highest tolerated dose. Throughout the transition, the patient was in regular communication with the provider and a visiting specialty pharmacy nurse.

The patient maintained WHO Functional Class II and stopped iloprost by the second week, while continuing the up titration of UPTRAVI to tolerance. Nausea and episodic vomiting were reported, which were resolved with supportive care. No clinical signs of right heart failure were reported.

Verlinden et al (2020)² reported the case of a 57-year-old female patient with heritable PAH. The patient had been diagnosed with PAH 15 years earlier, and, at the time of transition, her PAH medication regimen consisted of inhaled iloprost 5 mcg 6 times daily, ambrisentan 10 mg daily, and riociguat 2.5 mg 3 times daily (TID). The decision to transition the patient from inhaled iloprost to oral UPTRAVI was considered upon the patient’s request for an oral alternative with less frequent administration. The patient was deemed clinically stable prior to transition with stable WHO FC I symptoms and 6-minute walk distance (6MWD) in the previous 6 months.

The patient was instructed to continue her current dosing of inhaled iloprost at 5 mcg 6 times daily while starting UPTRAVI at a dose of 200 mcg BID. Her UPTRAVI was increased by 200 mcg BID every week as tolerated to a goal dose of 1600 mcg BID. The patient was monitored with 3 times weekly phone calls from her nurse coordinator throughout the transition.

The patient tolerated the transition but reported mild headaches upon starting UPTRAVI and mildly increased lower extremity musculoskeletal pain once she reached an UPTRAVI dose of 600 mcg BID. She maintained her planned weekly UPTRAVI titration, and, after reaching a dosage of 1000 mcg BID, she discontinued the inhaled iloprost. No symptoms related to PAH worsening or further side effects were reported with UPTRAVI, and the patient reached an UPTRAVI dose of 1600 mcg BID after 8 weeks. Four months after completing the transition, the patient described stable WHO FC I symptoms, and mild improvements were observed in 6MWD, level of N-terminal pro-B-type natriuretic peptide, and pulmonary hemodynamics from right heart catheterization. Authors report that 2 years after completing the transition from inhaled iloprost to UPTRAVI, the patient was deemed clinically stable on a regimen of ambrisentan 10 mg daily, riociguat 2.5 mg TID, and UPTRAVI 1600 mcg BID.

Cullivan et al (2021)³ described the initiation of UPTRAVI in 25 patients with PAH. Of them, 2 patients (9%) were receiving triple combination therapy including inhaled iloprost. No further specific details on the transition protocol or the efficacy and/or safety outcomes in these 2 patients are reported. UPTRAVI was started at 200 mcg BID in all cases, following the protocol used in the GRIPHON⁴ study. In general, maintenance doses were achieved at an average time of 65 days (±26) and the mean total daily maintenance dose was 1800 mcg (±500). All patients reported side effects during UPTRAVI titration with gastrointestinal side effects being the most common.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 22 July 2024.