P4673Macitentan in chronic thromboembolic pulmonary hypertension (CTEPH): combined data from OPUS and OrPHeUS real-world data sets

Abstract

Abstract Introduction The OPsumit® USers Registry (OPUS) provides real-world data in patients (pts) with pulmonary hypertension newly started on macitentan. The OPsumit® Historical USers cohort (OrPHeUS) study was conducted to supplement OPUS to fulfil the FDA request to characterise the safety of macitentan in clinical practice. Both studies included pts with CTEPH. Purpose To describe the characteristics and safety outcomes of CTEPH pts newly treated with macitentan. Methods OPUS is a prospective, US, multicentre, long-term, observational drug registry (NCT02126943) ongoing since Apr 2014. OrPHeUS was a retrospective, US, multicentre medical chart review (NCT03197688); data collected Oct 2013-Mar 2017. This subgroup analysis describes CTEPH patient characteristics at macitentan initiation, hospitalisations, survival and liver function tests (LFTs) in the combined OPUS/OrPHeUS data set. LFTs are also provided for the OPUS/OrPHeUS pulmonary arterial hypertension (PAH) population. Results As of Oct 2018, OPUS/OrPHeUS included 144 CTEPH pts with follow-up data. At macitentan initiation, median (Q1, Q3) age was 66 (56, 73) years; of the 53 pts with a WHO functional class (FC) assessment, 35.8%, 49.1% and 15.1% were in FC II, III and IV, respectively. Median (Q1, Q3) time from CTEPH diagnosis was 18.6 (7.4, 56.4) months (n=141). At macitentan initiation, 32.6% of pts had no PAH therapy, 63.9% were receiving one and 3.5% were receiving two PAH therapies. Median (Q1, Q3) exposure to macitentan was 15.9 (4.3, 30.4) months. There were 43 (29.9%) CTEPH pts who discontinued treatment; 23 due to an adverse event (AE), 0 due to a hepatic AE (HAE) and 20 not due to an AE/HAE. There were 58 (40.3%) CTEPH pts who experienced ≥1 hospitalisation and 9 (6.3%) pts died. LFTs are presented in the table. LFTs CTEPH follow-up pts PAH follow-up pts (N=144) (N=4072) ALT or AST ≥3x ULN Pts with ≥1 event, n (%) 1 (0.7) 132 (3.2) Incidence rate per 1 person-year (95% CI) 0.005 (0.001, 0.035) 0.024 (0.020, 0.029) ALT or AST ≥3x ULN and total bilirubin ≥2x ULN Pts with ≥1 event, n (%) 1 (0.7) 27 (0.7) Incidence rate per 1 person-year (95% CI) 0.005 (0.001, 0.035) 0.005 (0.003, 0.007) ALT: alanine aminotransferase; AST: aspartate aminotransferase; CI: confidence interval; ULN: upper limit of normal. Conclusions Analysis of OPUS/OrPHeUS data provides further insight into real-world use of macitentan in CTEPH pts. The observed hepatic safety profile in CTEPH pts is in line with that of PAH pts. Acknowledgement/Funding Actelion Pharmaceuticals Ltd