title: Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist.
abstract: OBJECTIVE
  Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis (SSc; scleroderma) and lead to pain, impaired function, and tissue loss. We investigated whether treatment with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcers in patients with SSc.
  
  
  METHODS
  This was a randomized, prospective, placebo-controlled, double-blind study of 122 patients at 17 centers in Europe and North America, evaluating the effect of treatment on prevention of digital ulcers. The primary outcome variable was the number of new digital ulcers developing during the 16-week study period. Secondary assessments included healing of existing digital ulcers and evaluation of hand function using the Scleroderma Health Assessment Questionnaire.
  
  
  RESULTS
  Patients receiving bosentan had a 48% reduction in the mean number of new ulcers during the treatment period (1.4 versus 2.7 new ulcers; P = 0.0083). Patients who had digital ulcers at the time of entry in the study were at higher risk for the development of new ulcers; in this subgroup the mean number of new ulcers was reduced from 3.6 to 1.8 (P = 0.0075). In patients receiving bosentan, a statistically significant improvement in hand function was observed. There was no difference between treatment groups in the healing of existing ulcers. Serum transaminase levels were elevated to >3-fold the upper limit of normal in bosentan-treated patients; this elevation is comparable with that observed in previous studies of this agent. Other side effects were similar in the 2 treatment groups.
  
  
  CONCLUSIONS
  Endothelins may play an important role in the pathogenesis of vascular disease in patients with SSc. Treatment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulcers and improving hand function in patients with SSc.
authors.affiliation: Boston University School of Medicine, Boston, MA 02118, USA. jkorn@bu.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Korn
authors.forename: M
authors.initials: M
authors.lastname: Mayes
authors.forename: M
authors.initials: M
authors.lastname: Matucci Cerinic
authors.forename: M
authors.initials: M
authors.lastname: Rainisio
authors.forename: J
authors.initials: J
authors.lastname: Pope
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: E
authors.initials: E
authors.lastname: Rich
authors.forename: P
authors.initials: P
authors.lastname: Carpentier
authors.forename: J
authors.initials: J
authors.lastname: Molitor
authors.forename: J R
authors.initials: JR
authors.lastname: Seibold
authors.forename: V
authors.initials: V
authors.lastname: Hsu
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
authors.forename: H H
authors.initials: HH
authors.lastname: Peter
authors.forename: J
authors.initials: J
authors.lastname: Coppock
authors.forename: A
authors.initials: A
authors.lastname: Herrick
authors.forename: P A
authors.initials: PA
authors.lastname: Merkel
authors.forename: R
authors.initials: R
authors.lastname: Simms
authors.forename: C P
authors.initials: CP
authors.lastname: Denton
authors.forename: D
authors.initials: D
authors.lastname: Furst
authors.forename: N
authors.initials: N
authors.lastname: Nguyen
authors.forename: M
authors.initials: M
authors.lastname: Gaitonde
authors.forename: Carol
authors.initials: C
authors.lastname: Black
mesh_terms: D000203:Activities of Daily Living; D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077300:Bosentan; D004185:Disability Evaluation; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D005260:Female; D005385:Fingers / Q000098:blood supply; D006304:Health Status; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D012883:Skin Ulcer / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan