Systemic sclerosis (SSc) was underrepresented (52 patients) in preapproval trials for bosentan in pulmonary artery hypertension (PAH). PURPOSE: Increase the experience of bosentan in PAH secondary to SSc (SSc-PAH) including those with concomitant interstitial lung disease (ILD).
Retrospective review of 48 SSc patients with PAH (> 35 mm Hg pulmonary artery systolic pressure [PASP] by echocardiogram), WHO classes II-IV, and data available for ≥ 9 months. Bosentan dose was 62.5 mg bid 4 wk than 125 mg bid thereafter. Outcomes were WHO class, PASP and PFTs at baseline, 3, 6 and 9 months.
WHO class (± SD): baseline, 3.0 ± 0.6 (n = 41); 3 months 2.3 ± 0.7* (n=37); 6 months 2.3 ± 0.8* (n=37); 9 months 2.1 ± 0.8* (n=32) (* P<0.001 vs. baseline by Mann-Whitney U test), indicating a significant improvement in clinical status at 3 months that was sustained during therapy. Reduction in WHO class ≥ one rank occurred at 3 months in 20/41 (49%), none worsened; at 6 months, 18/37 (49%) improved, 3% worsened; at 9 months, 19/32 (59%) improved, 3% worsened. Mean PSAP at baseline (n=38) was 46 ± 13 mm Hg (± SD), and there was no significant change during therapy. Mean PFTs at baseline (all % predicted ± SD) were TLC 72 ± 16 (n=48), FVC 69 ± 14 (n=43), and DLco 39 ± 13 (n=48), and none changed significantly during therapy. Abnormal transaminases occurred 8 times in 4 patients (10%), necessitating discontinuation of drug in two. No deaths were ascribed to bosentan therapy.CONCLUSIONS: Bosentan is beneficial in SSc-PAH including patients with ILD. Pulmonary hemodynamics (PASP, DLco) remain stable during treatment.
The lack of change in PFTs and PASP does not support an antiproliferative or antifibrotic benefit of endothelin receptor antagonism during 9 months treatment of SSc-PAH.
A. Joglekar, None.