Advanced lung disease—medical aspect
Long-Term Outcome of Bosentan Treatment in Idiopathic Pulmonary Arterial Hypertension and Pulmonary Arterial Hypertension Associated with the Scleroderma Spectrum of Diseases

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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.

Section snippets

Methods

This project was reviewed by the Johns Hopkins University institutional review board and determined to meet criteria for exempt research. We reviewed our pulmonary hypertension clinical database to identify all patients with the following:

  • 1

    a diagnosis of either idiopathic PAH (IPAH), formerly known as primary pulmonary hypertension,6 or APAH-SSD;

  • 2

    the absence in patients with APAH-SSD of significant interstitial lung disease defined as a total lung capacity of 70% or more of predicted, or between

Subjects

We identified 19 IPAH and 17 APAH-SSD consecutive subjects who met the study inclusion criteria. Table 1 summarizes their demographic and baseline clinical characteristics. All variables were similar between the 2 groups with the exception of a trend for a lower diffusion capacity of the lung for carbon monoxide in the APAH-SSD group (p = 0.08). One patient, originally thought to have IPAH and treated with bosentan as initial therapy, was later shown to have had pulmonary veno-occlusive disease

Discussion

We believe this study is the first report comparing the long-term outcomes of bosentan treatment in patients with IPAH and APAH-SSD. Although a large proportion in both groups (37% and 47%, respectively) failed bosentan as single-agent therapy during the mean follow-up period of 20 months owing to a lack of clinical efficacy or hepatotoxicity, functional class improved in 58% of IPAH patients compared with only 25% of APAH-SSD patients. WHO class was significantly decreased in the IPAH group,

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