High Treprostinil Doses Delay PAH-Related and All-Cause Hospitalizations

This article is part of Pulmonology Advisor‘s coverage of the CHEST 2018 meeting, taking place in San Antonio, Texas. Our staff will report on medical research related to COPD, critical care medicine, and more conducted by experts in the field. Check back regularly for more news from CHEST 2018.

SAN ANTONIO — Patients given higher doses of oral and subcutaneous treprostinil experience a significantly longer time before their first pulmonary arterial hypertension (PAH)-related and all-cause hospitalization than those receiving lower dosages, according to research presented at the CHEST Annual Meeting, held October 6-10, 2018, in San Antonio, Texas.

Researchers retrospectively analyzed the drug manufacturer’s global safety database for any hospitalizations occurring after the initiation of subcutaneous or oral treprostinil treatment. They then evaluated the effect of treprostinil dosage to first PAH-related and all-cause hospitalizations for participants in pivotal, randomized, or open-label extension studies.

Pharmacovigilance physicians, who were employed by the manufacturer, adjudicated hospitalizations for relatedness to PAH and hospitalizations were considered unrelated if the patient experienced a decompensation as a result of an acute medical problem or was being treated for a separate underlying etiology. Eligible patients (n=759 oral treprostinil; n=860 subcutaneous treprostinil) were grouped into tertiles based on treprostinil dosages, with oral doses being converted into ng/kg/min equivalents: group 1: <15.7, group 2: 15.7-37.4, and group 3: >37.4 ng/kg/min. Subcutaneous treprostinil patients were also separated into 3 ng/kg/min tertiles: group 1: <8.3, group 2: 8.3-30.0, and group 3: >30.0 ng/kg/min. To evaluate differences in time to first PAH-related and all-cause hospitalizations, the researchers made pairwise comparisons between tertiles.

Of the 759 patients who received oral treprostinil included in the long-term analysis, 50.2% (n=381) were hospitalized, 31.1% (n=236) of these due to PAH. Median time to PAH-related hospitalization was 339, 412, and 658 days for groups 1, 2, and 3, respectively. Median time to all-cause hospitalization was 293, 400, and 552 days for groups 1, 2, and 3, respectively, with a significant difference between groups 1 and 2 for all-cause hospitalizations (P =.003), and between groups 1 and 3 for both PAH-related and all-cause hospitalizations (both P <.001).

Of the 860 patients who received subcutaneous treprostinil, 40.6% (n=349) were hospitalized, 18.6% (n=160) of these due to PAH. Median time to PAH-related hospitalization was 83, 318, and 428 days for groups 1, 2, and 3, respectively. Median time to all-cause hospitalization was 95, 266, and 310 days for groups 1, 2, and 3, respectively, with significant differences between groups 1 and 3 and groups 1 and 2 for all types of hospitalizations (P <.001 for all).

The  investigators concluded that higher doses of treprostinil significantly delayed time to first hospitalization for patients with PAH, adding that the “results suggest the importance of aggressive oral and [subcutaneous treprostinil] dose up titration in patients with PAH.”

Disclosures: Four of the study investigators report being employed by United Therapeutics.

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Reference

Broderick M, Ramani G, Borg E, Saunders A, Nelsen A. The effect of treprostinil dose on time to all cause and pulmonary arterial hypertension-related hospitalizations. Presented at: CHEST Annual Meeting 2018; October 6-10, 2018; San Antonio, TX.