Comparative Treatment Persistence and Adherence to Endothelin Receptor Antagonists Among Patients with Pulmonary Arterial Hypertension in Japan: A Real-World Administrative Claims Database Study

Abstract

Introduction: Real-world data on the comparative effectiveness of endothelin receptor antagonists (ERAs; macitentan, bosentan, ambrisentan) for pulmonary arterial hypertension (PAH), particularly in Asian countries, are scarce. We evaluated the persistence of these ERAs before and after macitentan approval in Japan (2015).

Methods: We used real-world data from the Japanese Medical Data Vision administrative claims database between April 2008 and November 2020. Patients with PAH were identified from the dataset. Persistence to ERA treatment before and after approval of macitentan in Japan was defined as the time between start of the index ERA and treatment discontinuation or death. Propensity score adjustment was applied to minimize confounding effects among treatment groups.

Results: In the pre-macitentan approval cohort, 153 and 51 patients received bosentan and ambrisentan, respectively. In the post-macitentan approval cohort, 331, 284, and 91 patients received macitentan, bosentan, and ambrisentan, respectively. Unadjusted median persistence for ambrisentan- and bosentan-treated patients was 19 and 10 months, respectively (adjusted HR 0.87 [95% CI 0.61-1.24]; P = 0.434 [bosentan as reference]). In the post-macitentan approval cohort, unadjusted median persistence was 18 months for macitentan-treated patients versus 6 and 8 months for ambrisentan- and bosentan-treated patients, respectively. Adjusted HRs for ambrisentan and bosentan were 1.48 (95% CI 1.12-1.95; P = 0.006) and 1.63 (95% CI 1.30-2.04; P < 0.001 [macitentan as reference]), respectively.

Conclusions: Real-world data for Japanese patients with PAH showed that persistence was significantly higher for macitentan, versus ambrisentan and bosentan, since its approval.

Keywords: Endothelin receptor antagonists; Japanese patients; Pulmonary arterial hypertension; Real-world data; Treatment persistence.

Fig. 1

Patient disposition. ECHO indicates echocardiography, ERA endothelin receptor antagonist, MDV Medical Data Vision database, PAH pulmonary arterial hypertension, RHC right heart catheterization. ^aBoth RHC and ECHO were considered in the diagnostic algorithm for PAH based on preliminary analysis in MDV with stricter diagnostic criteria for PAH, which demonstrated that with RHC alone, initial treatment for PAH was predominantly monotherapy, with combination therapy not being observed to increase during treatment. In addition, ECHO is widely used in the real-world setting for the diagnosis of PAH in daily practice. ^bApproval date for macitentan in Japan was June 9, 2015. ERA index date before June 9 was considered as pre-approval use. ^cApproval date for macitentan in Japan was June 9, 2015. ERA index date after June 9 was considered as post-approval use

Fig. 2

Adherence rates (60%, 70%, and 80%) among patients by treatment group and time before or after approval of macitentan in Japan. ^aOverall, 20% of patient data were missing. ^bOverall, 17% of patient data were missing

Fig. 3

Pre-approval of macitentan: persistence to treatment. ERA endothelin receptor antagonist

Fig. 4

Post-approval of macitentan: persistence to treatment. ERA endothelin receptor antagonist