title: Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement.
abstract: BACKGROUND
  Evidence suggests that tumor necrosis factor (TNF)-alpha plays an important role in the pathophysiology of sarcoidosis.
  
  
  OBJECTIVE
  To assess the efficacy of infliximab in sarcoidosis.
  
  
  METHODS
  A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52.
  
  
  RESULTS
  The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment.
  
  
  CONCLUSIONS
  Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.
authors.affiliation: University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. bob.baughman@uc.edu
authors.forename: Robert P
authors.initials: RP
authors.lastname: Baughman
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
authors.forename: Mani
authors.initials: M
authors.lastname: Kavuru
authors.forename: Marc A
authors.initials: MA
authors.lastname: Judson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.forename: Roland
authors.initials: R
authors.lastname: du Bois
authors.forename: Carlo
authors.initials: C
authors.lastname: Albera
authors.forename: Martin
authors.initials: M
authors.lastname: Brutsche
authors.forename: Gerald
authors.initials: G
authors.lastname: Davis
authors.forename: James F
authors.initials: JF
authors.lastname: Donohue
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.forename: Rozsa
authors.initials: R
authors.lastname: Schlenker-Herceg
authors.forename: Susan
authors.initials: S
authors.lastname: Flavin
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lo
authors.forename: Barry
authors.initials: B
authors.lastname: Oemar
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D007703:Peptidyl-Dipeptidase A