title: Meta-analysis using individual patient data: efficacy and durability of topical alicaforsen for the treatment of active ulcerative colitis.
abstract: BACKGROUND
  The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry.
  
  
  OBJECTIVE
  To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features.
  
  
  METHODS
  Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests.
  
  
  RESULTS
  Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious.
  
  
  CONCLUSIONS
  This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC.
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Vegter Health Economic Research, Groningen, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Vegter
authors.forename: K
authors.initials: K
authors.lastname: Tolley
authors.forename: T
authors.initials: T
authors.lastname: Wilson Waterworth
authors.forename: H
authors.initials: H
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: D
authors.initials: D
authors.lastname: Jewell
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004733:Enema; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D054735:Phosphorothioate Oligonucleotides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D054735:Phosphorothioate Oligonucleotides; D018799:Intercellular Adhesion Molecule-1; D019804:Mesalamine; C089753:alicaforsen