PRO2 MEDICAL THERAPY FOR CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION: AN INDIRECT TREATMENT COMPARISON OF MACITENTAN AND RIOCIGUAT

Abstract

Based on CHEST-1, riociguat was the first medical therapy approved for inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH)1. In MERIT-1, macitentan improved 6-minute walk distance (6MWD) and reduced pulmonary vascular resistance (PVR) in inoperable CTEPH patients, including patients receiving phosphodiesterase type-5 inhibitors2. This analysis compares the efficacy and safety of macitentan vs riociguat in CTEPH patients. An intention-to-treat analysis was performed using matching-adjusted indirect comparison (MAIC)3. MERIT-1 individual patient data (IPD) were re-weighted to match published baseline characteristics (sex, WHO Functional Class, age, BMI, 6MWD, and PVR) of inoperable CHEST-1 patients. Least-squares mean difference and 95% confidence intervals (CI) were calculated to compare the treatment effects of macitentan vs placebo on 6MWD and PVR (recalculated using re-weighted MERIT-1 IPD) with the treatment effects of riociguat vs placebo published for the inoperable patient population of CHEST-1. Safety analysis matched the MERIT-1 population to the overall CHEST-1 population. After matching the MERIT-1 population to the inoperable CHEST-1 population, the difference in treatment effect for macitentan vs riociguat was -13.7m (95% CI -58.2, 30.8) for change in 6MWD and 114.9 dyn.s/cm5 (95% CI -25.4, 255.2) for change in PVR. Analyses on MERIT-1 patients without background therapy resulted in differences of -0.1m (95% CI -82.5, 82.3) and 120.3 dyn.s/cm5 (95% CI -82.7, 323.3) for change in 6MWD and PVR, respectively. Estimated odds ratios for macitentan vs riociguat were 0.78 (95% CI 0.19, 3.16) for the risk of any adverse event (AE), 0.53 (95% CI 0.10, 2.90) for serious AEs, and 0.68 (95% CI 0.40, 1.16) for exposure-adjusted AEs. MAIC of MERIT-1 and CHEST-1 showed comparable efficacy and safety for macitentan and riociguat in inoperable CTEPH.