Bosentan is an experimental antifibrotic agent and approved for the management of PAH. Patients with ILD often manifest PAH as pulmonary fibrosis (PF) advances to endstage. To determine the safety, tolerance and clinical status of consecutive patients who were dyspneic with exertion and received bosentan (>3 months) for PAH secondary to advanced PF, available clinical data was retrospectively analyzed.
Echocardiogram confirmed the presence of PAH in all patients. Diagnosis of ILD and underlying specific diagnosis was in accordance with accepted clinical criteria. Exclusions: coexisting COPD (FEV1/FVC <0.7 and RV >120%), concurrent treatment indicated for PAH, other than bosentan, and LVEF<35%. Pulmonary function tests (PFTs) and 6MWT were obtained at baseline and at 3-6-month intervals.
During 1/2000-3/2005, 50 adult, consecutive endstage ILD patients (25 IPF, 12 PF associated with collagen vascular disease, 4 idiopathic nonspecific interstitial pneumonia, 5 sarcoid, 4 other ILD) received bosentan. Mean treatment duration and follow up was 11.1±8.0, range 3-30 months. Concomitant medications included prednisone in 45, azathioprine in 18, N-acetylcysteine in 31, interferon-gamma in 3 and 24h O2 therapy in 39 patients. Compared to pretreatment values, hemodynamics and PFTs did not deteriorate during bosentan treatment (baseline→ 6 mo →12 mo): estimated mean PA systolic pressure±SEM: 54±2.7 → 56 ±2.9→ 53± 6.4 mmHg; FVC predicted: 55.0 ±2.6 →56.5 ±2.8 → 58.5 ±4.1%; DLCO predicted: 33.0 ±1.6→ 35.1 ±2.1 →36.1 ±3.0 %; 6MWT (n=25): Δ resting and lowest SpO2: 8.5 ±0.8→ 9.7 ± 1.5→ 7.0 ± 1.0; 6MWT distance: 670± 79→ 828±105→ 525±249 feet. At last follow-up, 38 patients are alive and stable and 2 lost to follow-up. Abnormal liver function tests > 3x ULN occurred in 1, mild anemia in 4, and leg edema in 8 patients.
Bosentan was well tolerated in patients with advanced PF in endstage ILD. During the study period, the vast majority of patients stabilized in PFTs and SpO2 during 6MWT.
Bosentan may have a useful clinical role in advanced stages of PF associated with ILD.
Ganesh Raghu, Grant monies (from industry related sources) GR is a consultant and advisor for research studies for IPF and scleroderma lung for Actelion,and has received research grants from Actelion. The study was sponsored by Actelion Pharmaceuticals, Allschwil, Switzerland.