title: Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial.
abstract: OBJECTIVE
  The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor α (TNF), for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis.
  
  
  METHODS
  This 8-week, multicentre, randomised, double-blind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of ≥ 6 points and endoscopic subscore of ≥ 2 points despite treatment with corticosteroids and/or immunosuppressants. Under the original study protocol, 186 patients were randomised (1:1) to subcutaneous treatment with ADA160/80 (160 mg at week 0, 80 mg at week 2, 40 mg at weeks 4 and 6) or placebo. Subsequently, at the request of European regulatory authorities, the protocol was amended to include a second induction group (ADA80/40: 80 mg at week 0, 40 mg at weeks 2, 4 and 6). The primary efficacy endpoint was clinical remission (Mayo score ≤ 2 with no individual subscore >1) at week 8, assessed in 390 patients randomised (1:1:1) to ADA160/80, ADA80/40, or placebo. Safety was assessed in all enrolled patients. Patients, study site personnel, investigators, and the sponsor were blinded to treatment assignment.
  
  
  RESULTS
  At week 8, 18.5% of patients in the ADA160/80 group (p = 0.031 vs placebo) and 10.0% in the ADA80/40 group (p = 0.833 vs placebo) were in remission, compared with 9.2% in the placebo group. Serious adverse events occurred in 7.6%, 3.8% and 4.0% of patients in the placebo, ADA80/40, and ADA160/80 groups, respectively. There were two malignancies in the placebo group, none in the ADA groups. There were no cases of tuberculosis and no deaths.
  
  
  CONCLUSIONS
  ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and/or immunosuppressants. Clinical trial NCT00385736.
authors.affiliation: Medical University Vienna, Vienna, Austria. walter.reinisch@meduniwien.ac.at
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Tighe
authors.forename: Bidan
authors.initials: B
authors.lastname: Huang
authors.forename: Wendy
authors.initials: W
authors.lastname: Kampman
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazar
authors.forename: Roopal
authors.initials: R
authors.lastname: Thakkar
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab