title: Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease.
abstract: BACKGROUND
  In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD).
  
  
  OBJECTIVE
  In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy.
  
  
  METHODS
  Patients with steroid-dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C-reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored.
  
  
  RESULTS
  Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated.
  
  
  CONCLUSIONS
  Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C-reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011-002640-27.).
authors.affiliation: Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Monteleone
authors.affiliation: First Department of Internal Medicine, St. Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Sabatino
authors.affiliation: Department of Surgery, "L. Sacco" University Hospital, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ardizzone
authors.affiliation: Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pallone
authors.affiliation: Celgene Corporation, Warren, NJ, USA.
authors.forename: K
authors.initials: K
authors.lastname: Usiskin
authors.affiliation: Celgene Corporation, Warren, NJ, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Celgene Corporation, Warren, NJ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Rossiter
authors.affiliation: Department of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: M F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000494:pharmacology* / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D051906:Smad7 Protein / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D051906:Smad7 Protein; D002097:C-Reactive Protein; C000588548:GED0301