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Clinical Trial
. 2008 Sep;67(9):1222-8.
doi: 10.1136/ard.2007.079921. Epub 2007 Nov 30.

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

C P Denton  1 , J E Pope, H-H Peter, A Gabrielli, A Boonstra, F H J van den Hoogen, G Riemekasten, S De Vita, A Morganti, M Dölberg, O Berkani, L Guillevin; TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators
Affiliations
Clinical Trial

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

C P Denton et al. Ann Rheum Dis. 2008 Sep.

Abstract

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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Conflict of interest statement

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.

Figures

Figure 1
Figure 1. Improvement/worsening in World Health Organization (WHO) functional class at week 16 and week 48. Two patients at week 16 and three at week 48 were discontinued because of pulmonary arterial hypertension (PAH) worsening/death and were assigned WHO functional class IV at week 16 and week 48, respectively, as per protocol. (n = 51). Confidence intervals (95%) are indicated in brackets.
Figure 2
Figure 2. Kaplan–Meier estimates for time to clinical worsening, defined as the combined endpoint of death, hospitalisation due to pulmonary arterial hypertension (PAH) complications, use of epoprostenol or prostacyclin analogues for worsening of PAH, lung transplantation, or discontinuation due to worsening of PAH. The Kaplan–Meier estimate was 88% (95% CI 79–97%) at week 16, and 68% (95% CI 55–82%) at week 48.
Figure 3
Figure 3. Kaplan–Meier estimates of survival (deaths occurring after treatment discontinuation for an adverse event were counted as an event). The Kaplan–Meier estimate was 92% (95% CI 85–100%) at week 48.
See this image and copyright information in PMC

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