Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases.
OBJECTIVE
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.
Denton
C P
CP
Center for Rheumatology, Royal Free Hospital, Pond Street, Rheumatology Unit, Lower Ground Floor, London NW3 2QG, UK. c.denton@medsch.ucl.ac.uk
Pope
J E
JE
Peter
H-H
HH
Gabrielli
A
A
Boonstra
A
A
van den Hoogen
F H J
FH
Riemekasten
G
G
De Vita
S
S
Morganti
A
A
Dölberg
M
M
Berkani
O
O
Guillevin
L
L
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D003240:Connective Tissue Diseases / Q000150:complications*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D005938:Glucocorticoids; D013449:Sulfonamides; D000077300:Bosentan