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

C P Denton¹, J E Pope², H-H Peter³, A Gabrielli⁴, A Boonstra⁵, F H J van den Hoogen⁶, G Riemekasten⁷, S De Vita⁸, A Morganti⁹, M Dölberg⁹, O Berkani⁹, L Guillevin¹⁰, (on behalf of the TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators)

¹ Royal Free Hospital, London, UK
² St Joseph’s Healthcare, London, Ontario, Canada
³ Med. Universitätsklinik Freiburg, Freiburg, Germany
⁴ Azienda Ospedaliera Umberto I, Ancona, Italy
⁵ Vrije Universteit Medisch Centrum, Amsterdam, The Netherlands
⁶ Universitair Medisch Centrum St. Radboud, Nijmegen, The Netherlands
⁷ Charité Universitätsmedizin, Berlin, Germany
⁸ Rheumatology Clinic, DPMSC, Azienda Ospedaliero Universitaria, Udine, Italy
⁹ Actelion Pharmaceuticals Ltd., Allschwil, Switzerland
¹⁰ Hopital Cochin, Paris, France

C Denton, Center for Rheumatology, Royal Free Hospital, Pond Street, Rheumatology Unit, Lower Ground Floor, London NW3 2QG, UK; c.denton{at}medsch.ucl.ac.uk

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

Methods: A total of 53 patients with PAH related to connective tissue diseases (PAH–CTD) in World Health Organization (WHO) functional class III received bosentan 62.5 mg twice a day for 4 weeks and then 125 mg twice a day 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.

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