Macitentan in Pulmonary Hypertension (PH) Due to Chronic Lung Disease: Real-World Evidence from OPUS/OrPHeUS

Purpose PH associated with chronic lung disease (WHO Group 3 PH) has a poor prognosis compared with pulmonary arterial hypertension (PAH [WHO Group 1 PH]). OPUS and OrPHeUS provide real-world data on Group 1 and Group 3 patients initiating macitentan. This analysis aims to describe characteristics and clinical outcomes of macitentan-treated Group 3 patients, including those with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). Methods OPUS was a prospective, US, multicenter, observational drug registry (Apr 2014-Apr 2020; NCT02126943). OrPHeUS was a US multicenter chart review (Oct 2013-Mar 2017; NCT03197688). The data cut-off for these analyses was February 2020. ILD, COPD, and other non ILD/COPD Group 3 patients are descriptively compared with Group 1 idiopathic/heritable PAH (I/HPAH) patients. Results By February 2020, OPUS/OrPHeUS (N = 5549) included 361 Group 3 patients, of whom 143 (40%) had ILD, 119 (33%) had COPD, 99 (27%) had neither ILD nor COPD; and 4540 Group 1 patients, of whom 2462 (54%) had I/HPAH. Characteristics at macitentan initiation and follow up are shown in the table. Kaplan-Meier survival estimates (% [95% CL]) at 12 months were 88 (80, 93) for ILD, 81 (71, 88) for COPD, 90 (81, 95) for non ILD/COPD, and 91 (89, 92) for I/HPAH. In OPUS only, the number of patients who reported ≥1 adverse event was (n/N) 46/59 (78%) for ILD, 33/39 (85%) for COPD, 39/44 (89%) for non ILD/COPD, and 915/1204 (76%) for I/HPAH. Safety profiles were similar between groups. Conclusion In OPUS/OrPHeUS, 6.5% of patients were in Group 3. In general, COPD patients were older, more likely to be male, and a greater proportion were in WHO FC III/IV compared to ILD and I/HPAH patients. Rates of discontinuation due to an AE were higher in ILD and COPD patients than in non ILD/COPD and I/HPAH patients. A higher hospitalization rate and worse survival were observed in COPD patients at 12 months compared to the other subgroups. Safety was consistent with the known profile of macitentan.