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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
  1. C P Denton1,
  2. J E Pope2,
  3. H-H Peter3,
  4. A Gabrielli4,
  5. A Boonstra5,
  6. F H J van den Hoogen6,
  7. G Riemekasten7,
  8. S De Vita8,
  9. A Morganti9,
  10. M Dölberg9,
  11. O Berkani9,
  12. L Guillevin10,
  13. (on behalf of the TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators)
  1. 1
    Royal Free Hospital, London, UK
  2. 2
    St Joseph’s Healthcare, London, Ontario, Canada
  3. 3
    Med. Universitätsklinik Freiburg, Freiburg, Germany
  4. 4
    Azienda Ospedaliera Umberto I, Ancona, Italy
  5. 5
    Vrije Universteit Medisch Centrum, Amsterdam, The Netherlands
  6. 6
    Universitair Medisch Centrum St. Radboud, Nijmegen, The Netherlands
  7. 7
    Charité Universitätsmedizin, Berlin, Germany
  8. 8
    Rheumatology Clinic, DPMSC, Azienda Ospedaliero Universitaria, Udine, Italy
  9. 9
    Actelion Pharmaceuticals Ltd., Allschwil, Switzerland
  10. 10
    Hopital Cochin, Paris, France
  1. C Denton, Center for Rheumatology, Royal Free Hospital, Pond Street, Rheumatology Unit, Lower Ground Floor, London NW3 2QG, UK; c.denton{at}


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: 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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  • Funding: The study was supported by an investigational grant from Actelion Pharmaceuticals Ltd. The database was retained by the sponsor, but the investigators had access to the complete database. The statistical analysis was performed by a statistician who is an employee of the sponsoring company and is listed among the authors (AM); the manuscript was reviewed and approved by the academic authors. The academic authors assume full responsibility for the completeness and accuracy of the content of the manuscript. Grant support: This research was supported by Actelion Pharmaceuticals Ltd.

  • Competing interests: CPD has been a consultant to, or received research grants from the following companies: Genzyme Corporation, Actelion Pharmaceuticals, Aspreva Pharmaceuticals, Encysive Corporation, DigNa Pharmaceuticals. JJEP, H-HP, AG, GR, SDeV have no significant industry affiliation (all under 10 000 USD). AB has received speaking fees or consultancy fees from GSK, Actelion Pharmaceuticals and Pfizer less than 2K US$. AB’s employing Institution is involved in contract research for GSK, Actelion Pharmaceuticals, Pfizer, United Therapeutics, Encysive, Myogen, Merck. AB’s employing Institution’s research foundation has received unrestricted educational grants from GSK and Actelion Pharmaceuticals. FHJvdH is a consultant for Bristol Myers Squibb (BMS) and Abbott. LG is a consultant for Actelion Pharmaceuticals (advisory boards) and a member of the scientific council of Actelion France. AM, MD and OB are employees of Actelion Pharmaceuticals.