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 — In patients with portopulmonary hypertension (PoPH), pulmonary arterial hypertension (PAH) associated with portal hypertension, data from the OPsumit Users (OPUS) Registry (ClinicalTrials.gov Identifier: NCT02126943) suggest that the endothelin receptor antagonist macitentan can be used to target the endothelin pathway. Research was presented at the 2018 CHEST Annual Meeting, held October 6 through October 10 in San Antonio, Texas.

Approximately 5% to 10% of patients with PAH also have PoPH. There is a relative dearth of data available on the use of PAH-specific treatments in the PoPH population. The OPUS Registry enrolls patients with PAH newly treated with macitentan, including those with PoPH. The current subgroup analysis includes patients with PoPH who were treated in the OPUS Registry.

As of October 2017, the OPUS Registry has included a total of 45 patients with PoPH who have follow-up data available (which translates to 3.5% of the overall enrolled population of patients with PAH and available follow-up data). At the initiation of macitentan therapy, the median participant age was 59.0 years (range, 37-73 years); 44.4% of the patients were women. Median time from PoPH diagnosis was 6.4 months.

World Health Organization functional class was evaluated in 36 of the patients, with 5.6% in functional class 1, 41.7% in functional class 2, and 52.8% in functional class III. The median 6-minute walking distance, which was evaluated in 29 patients, was 360 meters. At study enrollment, 5.9% (2 of 34) of patients had alanine aminotransferase/aspartate aminotransferase elevations ≥3 times the upper limit of normal (ULN), and 37.5% (12 of 32) of patients had total bilirubin levels ≥2 times the ULN.

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Macitentan was used as monotherapy in 15 patients, as part of double combination therapy in 25 patients, and as part of triple combination therapy in 5 patients. At the last patient follow-up, the median exposure to macitentan was 11.8 months, and 16 patients had discontinued macitentan: 4 because of an adverse event, 1 because of a hepatic adverse event, 6 not because of an adverse event or a hepatic adverse event, and 5 with no reason for their discontinuation reported.

During exposure to macitentan, 80.0% of patients experienced ≥1 adverse event, with the most commonly reported events including dyspnea (22.2%), increased total bilirubin levels (17.8%), dizziness (13.3%), and fall (13.3%). At the last follow-up, none of the patients experienced ALT/AST elevations ≥3 times the ULN, and 37.9% experienced total bilirubin levels ≥2 times the ULN. Moreover, 35.6% of patients experienced ≥1 hospitalization, 13.3% of participants experienced ≥1 PAH-associated hospitalization, and 13.3% of patients died.

The investigators concluded that the macitentan can be tolerated in a population of patients with PoPH, with the most frequently reported adverse events reflective of the PoPH disease process and its complications.

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Reference

Chin K, Kim N, McLaughlin V, et al. Macitentan in portopulmonary hypertension: real-world evidence from the OPsumit Users Registry. Presented at: CHEST Annual Meeting 2018; October 6-10, 2018; San Antonio, TX.