MACITENTAN IN PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH CONNECTIVE TISSUE DISEASE: REAL-WORLD EVIDENCE FROM THE COMBINED OPUS/ORPHEUS DATA SETS

SESSION TITLE: Pulmonary Hypertension: Characteristics and Treatment SESSION TYPE: Original Investigations PRESENTED ON: 10/21/2019 1:30 PM - 2:30 PM PURPOSE: Patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) have a poor prognosis compared to other PAH etiologies. OPsumit® USers (OPUS) Registry and OPsumit® Historical USers cohort study (OrPHeUS) provide real-world data in PAH patients newly started on macitentan, including those with PAH-CTD. Here, we evaluate macitentan-treated patients with PAH associated with systemic sclerosis (PAH-SSc). METHODS: OPUS is a prospective, US, multicenter, long-term, observational drug registry (Apr 2014-present; NCT02126943). OrPHeUS was a retrospective, multicenter, US, medical chart review (Oct 2013-Mar 2017; NCT03197688). This subgroup analysis describes PAH-SSc patient characteristics, discontinuations, liver function tests, hospitalizations and survival in the combined OPUS/OrPHeUS data set. For context, data are also provided for idiopathic PAH (IPAH)/heritable PAH (HPAH) patients and descriptively compared to PAH-SSc patients. RESULTS: By Oct 2018, patients with follow-up data in OPUS/OrPHeUS included 1094 with PAH-CTD, the majority of whom had PAH-SSc (n=659), PAH-systemic lupus erythematosus (n=152) or PAH-mixed connective tissue disease (n=108), and 2283 with IPAH/HPAH. For PAH-SSc patients at macitentan initiation, median age (Q1, Q3) was 64 (55, 71) years; of the 282 patients with a WHO functional class (FC) assessment at initiation, 202 (71.6%) were in FC III/IV; and 402 (61.0%) were receiving another PAH therapy. Median (Q1, Q3) macitentan exposure was 14.7 (5.6, 28.0) months in PAH-SSc patients and 13.2 (5.0, 26.5) months in IPAH/HPAH patients. At macitentan initiation, 288 (45%) PAH-SSc patients and 1014 (45.5%) IPAH/HPAH patients had been diagnosed within 6 months. There were 199 (30.2%) PAH-SSc patients and 748 (32.8%) IPAH/HPAH patients who discontinued treatment: 114 (17.3%) and 390 (17.1%) due to an adverse event (AE), 5 (0.8%) and 3 (0.1%) due to a hepatic AE (HAE), 78 (11.8%) and 350 (15.3%) not due to an AE/HAE, and 2 (0.3%) and 5 (0.2%) for unknown reasons. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3x upper limit of normal (ULN) was experienced by 26 (3.9%) PAH-SSc patients and 61 (2.7%) IPAH/HPAH patients. ALT/AST ≥3x ULN and total bilirubin ≥2x ULN was experienced by 3 (0.5%) PAH-SSc patients and 6 (0.3%) IPAH/HPAH patients. There were 265 (40.2%) PAH-SSc and 829 (36.3%) IPAH/HPAH patients who experienced ≥1 hospitalization. The 12-month Kaplan-Meier survival estimate was 92% (95% CI, 89, 94) for PAH-SSc and 93% (95% CI, 91, 94) for IPAH/HPAH patients. CONCLUSIONS: In this real-world data set, the clinical outcomes and safety profile in patients with PAH-SSc are generally consistent with those of IPAH/HPAH patients. CLINICAL IMPLICATIONS: These data add to the body of evidence supporting the use of macitentan for the treatment of PAH-SSc. DISCLOSURES: Employee relationship with Actelion Please note: >$100000 Added 03/13/2019 by Monika Brand, source=Web Response, value=Shares Removed 03/14/2019 by Monika Brand, source=Web Response Employee relationship with Actelion Please note: >$100000 Added 03/14/2019 by Monika Brand, source=Web Response, value=Salary Removed 03/14/2019 by Monika Brand, source=Web Response Employee relationship with Actelion Please note: >$100000 Added 03/14/2019 by Monika Brand, source=Web Response, value=Salary Employee relationship with Actelion Pharmaceuticals Ltd Please note: >$100000 Added 03/21/2019 by Monika Brand, source=Web Response, value=Salary Advisory Committee Member relationship with Actelion Please note: $5001 - $20000 Added 03/12/2019 by Richard Channick, source=Web Response, value=Consulting fee Consultant relationship with Actelion Please note: $5001 - $20000 Added 03/12/2019 by Richard Channick, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Arena Please note: $5001 - 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