Background/Purpose:  Systemic sclerosis (SSc) is a systemic autoimmune disease in which the damage of microcirculation is critical to develop the disease. In SSc, vascular complications have very similar pathogenic findings, which are relevant in the disease. For example, digital ulcers (DU) are a frequent complication in SSc patients and pulmonary arterial hypertension (PAH) is one of the leading causes of death. The use of endothelin receptor antagonists (ERAs) has been shown to be useful for the treatment of PAH related to SSc, and to prevent new episodes of DU in patients with the disease. However, it is not known if ERAs are useful for the prevention of PAH.The aim of our study is to determine if ERAs are useful to prevent PAH in SSc patients. Furthermore, we aim to determine if there are any differences in echocardiographic or pulmonary function tests for patients treated with or without ERAs.

Methods:  This was a retrospective, multicentre case-control study with 237 SSc patients with DU. Data were analysed during follow-up for patients treated or not treated with Bosentan (BOS) to prevent DU. The occurrence of pulmonary hypertension (PH) was defined by an echocardiogram (ECO) exhibiting systolic pulmonary arterial pressure (sPAP) > 40 mmHg at any stage of the follow up. For all patients, demographic variables, gender, SSc subtype, clinical involvement, autoimmunity data, capillaroscopy findings and different echocardiographic and pulmonary function test data, performed from baseline to follow-up were collected. Statistical significance was denoted by p values less than 0.05

Results:  Fifteen patients had ECO values of sPAP> 40mmHg and were excluded from the analyses. Of the remaining 222 patients the majority were women (91%) with a mean age (±SD) of 63.9 (±19.6) years. The first manifestation of the disease occurred at 40.7 (±17.9) years, while Raynaud’s phenomenon was the most frequent initial finding (85.6%). Fifty-nine patients (26.6%) were treated with BOS. The most common dose was 250mg daily (60%) and BOS was taken for a median of 34 months. In 21% of patients, PH was suspected due to ECO findings. During the follow up 13.8% of patients treated with BOS presented with PH, in comparison to 23.7% of untreated patients (OR 0.52, 95% CI: 0.22-1.19; p = 0.13). Adjusted regression analyses showed patients not treated with BOS were 3.9 times more likely to develop PH during follow-up (OR 3.913, CI95%:1.32-11.58; p < 0.02). Analysis of the tools of patient evaluation showed that the percentage of diffusing capacity for carbon monoxide (DLCO) in BOS-treated patients did not significantly decrease from baseline to the end of follow-up (61.8±14% vs 57±20.1%, p=0.89). This was statistically significant (p < 0.04) when compared to BOS-untreated patients who showed a significant decrease in the percentage of DLCO at the end of follow-up (65.5±20.2% vs 60.5±19.9%; p < 0.01).

Conclusion:  Our retrospective study shows that those patients treated with BOS to prevent UD have a lower risk to develop PH during the disease as well as stabilization of DLCO percentages. Our results support the need for a prospective, randomized, clinical trial to study the effect of ERA in prevention of PAH in SSc patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/usefulness-of-bosentan-in-the-prevention-of-pulmonary-hypertension-in-patients-with-systemic-sclerosis/