Long-term outcome of bosentan treatment in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with the scleroderma spectrum of diseases.
BACKGROUND
Bosentan improves clinical outcomes in pulmonary arterial hypertension (PAH), particularly in the idiopathic (IPAH) subset. Scant data are available regarding PAH associated with the scleroderma spectrum of diseases (APAH-SSD). Here we review our experience with bosentan in these 2 groups.


METHODS
Included were all patients at our center with either IPAH or APAH-SSD in whom bosentan was the first-line, single-agent therapy with at least 6 months of follow-up. Changes in the World Health Organization (WHO) functional class from baseline to the most recent follow-up on monotherapy were compared between the 2 groups, as well as overall survival and time to a composite end point of hepatotoxicity requiring discontinuation, use of additional therapy, or death.


RESULTS
Nineteen IPAH and 17 APAH-SSD subjects with similar baseline clinical characteristics and a median follow-up 9 months (range, 6-44) were analyzed. In IPAH subjects, WHO class improved from 3.1 +/- 0.5 at baseline to 2.4 +/- 0.8 (p = 0.005). No change occurred in the APAH-SSD group: 2.9 +/- 0.3 vs. 2.8 +/- 0.8; p = 0.5. Hepatotoxicity requiring discontinuation developed in 6 patients (17%). Seven (37%) IPAH and 8 SSD patients (47%) reached the composite end point (p = NS). Overall survival at 1 and 2 years was 100% and 100% vs 87% and 79% for IPAH and APAH-SSD patients, respectively (p = 0.075).


CONCLUSIONS
First-line bosentan monotherapy is associated with long-term improvement in functional class and good overall survival in patients with WHO class III IPAH. Most APAH-SSD patients experienced stability or decline in functional class and tended to have a higher mortality.
Girgis
Reda E
RE
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA. rgirgis@jhmi.edu
Mathai
Stephen C
SC
Krishnan
Jerry A
JA
Wigley
Fredrick M
FM
Hassoun
Paul M
PM
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012595:Scleroderma, Systemic / Q000150:complications*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan