INITIAL TREATMENT COMBINATION WITH MACITENTAN AND TADALAFIL IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION: RESULTS FROM THE OPTIMA STUDY

SESSION TITLE: Pulmonary Hypertension: Characteristics and Treatment SESSION TYPE: Original Investigations PRESENTED ON: 10/21/2019 1:30 PM - 2:30 PM PURPOSE: OPTIMA (NCT02968901) was a prospective, multicenter, single-arm, open-label, Phase IV trial evaluating the efficacy, safety and tolerability of initial oral combination therapy with macitentan and tadalafil in patients with newly diagnosed pulmonary arterial hypertension (PAH). METHODS: Newly diagnosed, treatment-naive adult PAH patients in WHO functional class (WHO FC) II-III were enrolled. Treatment with macitentan 10 mg once daily (o.d.) and tadalafil 20 mg o.d. was initiated on the same day; after 8±3 days, tadalafil dose was increased to 40 mg o.d. Efficacy was assessed at Week 16 and, thereafter, patients continued to be monitored for safety until study closure by the sponsor. Patients with missing data at Week 16 were imputed with baseline values. RESULTS: 46 patients were enrolled and treated (all 46 are included in the efficacy and safety analyses). At Week 16, mean pulmonary vascular resistance (primary endpoint) was reduced by 47% compared with baseline (geometric mean ratio 0.53; 95% CI 0.47, 0.59; p2.5 L/min/m2, mean right atrial pressure 440 m, NT-proBNP 65%. The number of patients meeting at least 3 low-risk criteria increased from 11/46 (23.9%) patients at baseline to 30/44 (68.2%) at Week 16. Median (Q1, Q3) duration of exposure to macitentan and tadalafil was 605.5 days (371.0, 806.0). At least one adverse event (AE) was reported in 43 patients (93.5%), 13 patients (28.3%) reported serious AEs, 3 patients (6.5%) discontinued treatment due to AEs, and 3 patients died. Causes of death were cardiac arrest, heart failure, and multiorgan failure with sepsis. The most frequent AEs were peripheral edema (13 patients), headache (11 patients), diarrhea (9 patients), dyspnea (7 patients), anemia (6 patients) and asthenia (6 patients). Four patients had a decrease in hemoglobin below 10 g/dL and one patient had aminotransferases ≥3 times the upper limit of normal. CONCLUSIONS: In OPTIMA, initial macitentan and tadalafil combination therapy was well tolerated in patients with PAH, and led to hemodynamic improvement, as well as improvements in functional parameters and risk profile. CLINICAL IMPLICATIONS: Initial combination therapy with macitentan and tadalafil offers hemodynamic and functional benefits for patients with PAH. DISCLOSURES: No relevant relationships by Fabrice BAUER, source=Web Response Board Member relationship with Actelion Please note: $1001 - $5000 Added 03/27/2019 by Emmanuel Bergot, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Boeringer Ingelheim Please note: $1001 - $5000 Added 03/27/2019 by Emmanuel Bergot, source=Admin input, value=Honoraria Board Member relationship with Roche Please note: $1001 - $5000 Added 03/27/2019 by Emmanuel Bergot, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Novartis Please note: $1001 - $5000 Added 03/27/2019 by Emmanuel Bergot, source=Admin input, value=Honoraria Board Member relationship with Chiesr Please note: $1001 - $5000 Added 03/27/2019 by Emmanuel Bergot, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Astra Zeneca Please note: $1001 - $5000 Added 03/27/2019 by Emmanuel Bergot, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Actelion Please note: $1-$1000 Added 03/15/2019 by Matthieu Canuet, source=Admin input, value=Honoraria No relevant relationships by Pierre Clerson, source=Web Response Consultant relationship with Actelion Please note: $1001 - $5000 Added 03/17/2019 by Vincent Cottin, source=Web Response, value=Honoraria No relevant relationships by Bruno Degano, source=Web Response No relevant relationships by prevot gregoire, source=Admin input Employee relationship with Actelion Pharmaceuticals Ltd Please note: >$100000 Added 03/14/2019 by Virginie Gressin, source=Web Response, value=Salary Shareholder relationship with Idorsia Pharmaceuticals Ltd Please note: >$100000 Added 03/20/2019 by Virginie Gressin, source=Web Response, value=Shares Employee relationship with Actelion Pharmaceuticals Ltd Please note: >$100000 Added 03/12/2019 by Loic Perchenet, source=Web Response, value=Salary No relevant relationships by Francois Picard, source=Web Response Consultant relationship with Actelion, Please note: $1001 - $5000 Added 03/13/2019 by Gerald Simonneau, source=Web Response, value=Honoraria Consultant relationship with Bayer Please note: $1001 - $5000 Added 03/13/2019 by Gerald Simonneau, source=Web Response, value=Consulting fee Consultant relationship with MSD Please note: $1001 - $5000 Added 03/13/2019 by Gerald Simonneau, source=Web Response, value=Consulting fee Advisory Committee Member relationship with ARENA Please note: $1001 - $5000 Added 03/13/2019 by Gerald Simonneau, source=Web Response, value=Honoraria Consultant relationship with Actelion Please note: $5001 - $20000 Added 03/12/2019 by Olivier Sitbon, source=Web Response, value=Honoraria Consultant