Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases

Christopher P Denton ^1*, Janet E Pope ², Hans-Hartmut Peter ³, Armando Gabrielli ⁴, Anco Boonstra ⁵, Frank H. J. van den Hoogen ⁶, Gabriela Riemekasten ⁷, Salvatore De Vita ⁸, Adele Morganti ⁹, Ouali Berkani ⁹ and Loic Guillevin ¹⁰

¹ Royal Free Hospital, United Kingdom
² St. Joseph’s Healthcare, Canada
³ Med. Universitätsklinik Freiburg, Germany
⁴ Azienda Ospedaliera Umberto I, Italy
⁵ Vrije Universteit Medisch Centrum, Netherlands
⁶ Universitair Medisch Centrum St. Radboud, Netherlands
⁷ Charité Universitätsmedizin, Germany
⁸ Azienda Ospedaliero Universitaria, Italy
⁹ Actelion Pharmaceuticals Ltd., Switzerland
¹⁰ Hopital Cochin, France

^* To whom correspondence should be addressed. E-mail: c.denton{at}medsch.ucl.ac.uk.

Accepted 25 November 2007

Abstract

Objectives: This study investigated the long-term effects of bosentan, an oral endothelin ETA/ETB receptor antagonist, in patients with pulmonary arterial hypertension (PAH) exclusively related to connective tissue diseases (CTD).

Methods: Fifty-three patients with PAH related to connective tissue diseases (PAH-CTD) in WHO functional class III received bosentan 62.5 mg b.i.d. for 4 weeks and then 125 mg b.i.d. for 44 weeks in this open non-comparative study. Assessments at Weeks 16 and 48 included WHO class, clinical worsening, quality of life (Short-Form Health Survey (SF-36) and health assessment questionnaire (HAQ) modified for scleroderma), and survival (Week 48 only). Safety and tolerability were monitored throughout the study.

Results: At Week 48, WHO class improved in 27% of patients (95% CI: [16%:42%]) and worsened in 16% (95% CI: [7%:29%]). Kaplan-Meier estimates were 68% (95% CI: [55%:82%]) for absence of clinical worsening and 92% (95% CI: [85%:100%]) for survival. Overall changes in quality of life were minimal. There were no unexpected side effects observed during the study.

Conclusions: In most patients, bosentan was associated with improvement or stability of clinical status. The 92% estimate for survival at 48 weeks is a significant achievement in this patient population.

Keywords: Bosentan, connective tissue diseases, endothelin, endothelin receptors, pulmonary arterial hypertension

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