Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis

Mengtao Li, Zhi-Cheng Jing, Yang Li, Yong Huo, Zaixin Yu, Gangcheng Zhang, Ping Zhu, Jinming Liu, Qiushang Ji, Bingxiang Wu, Jinhua Zhong, Pingping Wang, Wenjing Zhu, Xiaofeng Zeng, Mengtao Li, Zhi-Cheng Jing, Yang Li, Yong Huo, Zaixin Yu, Gangcheng Zhang, Ping Zhu, Jinming Liu, Qiushang Ji, Bingxiang Wu, Jinhua Zhong, Pingping Wang, Wenjing Zhu, Xiaofeng Zeng

Abstract

Background: The efficacy and safety of ambrisentan has been previously evaluated in Chinese patients with pulmonary arterial hypertension (PAH). This post-hoc analysis assessed the efficacy and safety of ambrisentan in a subgroup of connective tissue disease (CTD) patients with PAH.

Methods: In this open-label, single-arm study, patients received ambrisentan 5 mg once daily for 12 weeks, followed by 12-week dose titration period (dose up to 10 mg). Efficacy endpoints included change from baseline in exercise capacity (measured by 6-min walk test [6MWT]), N-terminal pro B type natriuretic peptide (NT-proBNP) plasma levels, WHO Functional Class (FC) and Borg Dyspnoea Index (BDI) scores from baseline to weeks 12 and 24. Safety endpoints included time to clinical worsening and incidence of adverse events (AEs).

Results: In total, 71 Chinese patients with CTD-PAH were included in this analysis. Ambrisentan treatment significantly improved exercise capacity (6MWT) from baseline (mean: 366.4 m) to week 12 (63.8 m, p < 0.001) and week 24 (73.2 m, p < 0.001). A significant reduction in NT-proBNP levels was observed from baseline (mean: 1837.5 ng/L) to week 12 (- 1156.8 ng/L, p < 0.001) and week 24 (- 1095.5 ng/L, p < 0.001). BDI scores decreased significantly at week 12 (- 0.6, p < 0.001) and week 24 (- 0.4, p = 0.002) from baseline (mean: 2.7). The WHO FC improved in 29 (40.8%) and 34 (47.9%) patients at weeks 12 and 24, respectively. Adverse events were reported in 52 (73.2%) patients. One patient (1.4%) experienced clinical worsening at week 24.

Conclusion: Ambrisentan showed significant improvement in exercise capacity and no clinical worsening in the majority of Chinese patients with CTD-PAH in the 24-week treatment period. The AEs observed in the CTD-PAH subgroup were consistent with the known safety profile of ambrisentan in the overall Chinese PAH population.

Trial registration: ClinicalTrial.gov Identifier, https://ichgcp.net/clinical-trials-registry/NCT01808313" title="See in ClinicalTrials.gov">NCT01808313 Registration date (first time): February 28, 2013.

Keywords: Ambrisentan; Chinese; Exercise capacity.

Conflict of interest statement

Jinhua Zhong, Wenjing Zhu and Pingping Wang were employees of GSK during the conduct of this study and manuscript development. All other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Improvement in 6MWT over 24 weeks following ambrisentan treatment (patients with connective tissue disease) (ITT population-LOCF): post-hoc analysis. 6MWT, 6-min walk test; ITT, intent-to-treat; LOCF, last observation carried forward
Fig. 2
Fig. 2
Patients categorized under WHO functional classification after treatment with ambrisentan (ITT population-LOCF): post-hoc analysis of CTD-PAH and IPAH/HPAH sub-groups. CTD, connective tissue disease; HPAH, Heritable PAH; IPAH, Idiopathic PAH; ITT, intent-to-treat; LOCF, last observation carried forward; PAH, pulmonary arterial hypertension; WHO, World Health Organisation

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