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

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.

• Authors: C P Denton, 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
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 67 Issue 9 Pg. 1222-8 (Sep 2008) ISSN: 1468-2060 [Electronic] England
• PMID: 18055477 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Glucocorticoids
• Sulfonamides
• Bosentan

Topics

• Adult
• Aged
• Antihypertensive Agents (adverse effects, therapeutic use)
• Bosentan
• Connective Tissue Diseases (complications)
• Drug Administration Schedule
• Drug Therapy, Combination
• Epidemiologic Methods
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Hypertension, Pulmonary (drug therapy, etiology)
• Male
• Middle Aged
• Quality of Life
• Severity of Illness Index
• Sulfonamides (adverse effects, therapeutic use)
• Treatment Outcome