title: Effect of Bosentan on systemic sclerosis-associated interstitial lung disease ineligible for cyclophosphamide therapy: a prospective open-label study.
abstract: OBJECTIVE
  To evaluate the clinical benefits of the endothelin receptor antagonist bosentan on interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) who are ineligible for cyclophosphamide (CYC) therapy.
  
  
  METHODS
  In this prospective open-label study, 9 patients with SSc and ILD received bosentan for 24 months. The main reasons for avoiding CYC included severely impaired lung function, long disease duration, and relapse after CYC treatment. Pulmonary function tests and Doppler echocardiograms were evaluated every 6 months, and high-resolution computed tomography (HRCT) was performed every 12 months. For an extended survival analysis, 17 historical controls who met the inclusion criteria at referral and had not used any immunosuppressive or antifibrotic agents thereafter were selected from the SSc database.
  
  
  RESULTS
  Two patients did not finish the study; one developed vasculitis requiring high-dose corticosteroids and another died of bacterial pneumonia. The remaining 7 patients tolerated bosentan and completed the study period. There were trends toward mildly reduced forced vital capacity, total lung capacity, and diffusing capacity for carbon monoxide over time. Two patients developed pulmonary hypertension during the 24-month period. HRCT scores for ground-glass opacity, pulmonary fibrosis, and honeycomb cysts gradually increased. In the extended study, there was no difference in cumulative survival rate between the bosentan-treated and historical control groups.
  
  
  CONCLUSIONS
  The gradual worsening of pulmonary function and HRCT findings in patients treated with bosentan was consistent with the natural course of SSc-associated ILD. This study does not support the use of bosentan for SSc-associated ILD even when CYC treatment is inadvisable.
authors: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. kuwanam@z5.keio.jp
authors: Yoshiaki
authors: Y
authors: Furuya
authors: Masataka
authors: M
authors: Kuwana
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications* / Q000503:physiopathology; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D003520:Cyclophosphamide; D000077300:Bosentan