title: Randomised clinical trial: a placebo-controlled study of intravenous golimumab induction therapy for ulcerative colitis.
abstract: BACKGROUND
  Tumour necrosis factor alpha (TNFα)-antagonism effectively treats ulcerative colitis (UC). The golimumab clinical programme evaluated subcutaneous (SC) and intravenous (IV) induction, and SC maintenance regimens, in TNFα-antagonist-naïve patients with moderate-to-severe active UC despite conventional treatment.
  
  
  OBJECTIVE
  To evaluate dose-response relationship, select IV golimumab induction doses for continued development, and evaluate the safety and efficacy of selected doses.
  
  
  METHODS
  Adults with Mayo scores of 6-12 and endoscopic subscores ≥2 were enrolled into this multicentre, randomised, double-blind, placebo-controlled, integrated Phase 2/3 dose-finding/dose-confirming study. In Phase 2, 176 patients were randomised (1:1:1:1) to a single IV infusion of placebo, 1-, 2- or 4-mg/kg golimumab. While Phase 2 data were analysed to select doses for continued development, 71 additional patients were randomised. Phase 3 enrolment stopped after 44 additional patients were randomised (1:1:1) to placebo, 2- or 4-mg/kg golimumab. Due to insufficient power for the Phase 3 primary endpoint analysis (clinical response at week 6), efficacy analyses are considered exploratory and include all randomised patients.
  
  
  RESULTS
  No dose-response was observed in Phase 2; however, higher serum golimumab exposure was associated with greater proportions of patients achieving more favourable clinical outcomes, clinical response and greater improvement in Mayo scores compared with placebo-treated patients and those with lower serum concentrations. Among all randomised patients, numerically greater proportions were in clinical response at week 6 in the 2- and 4-mg/kg golimumab groups compared with placebo [44.0% (33/75) and 41.6% (32/77) vs. 30.1% (22/73)].
  
  
  CONCLUSIONS
  Efficacy with single-dose golimumab IV induction was lower than expected and less than observed in the SC induction study. No new safety findings were observed. ClinicalTrials.gov Number, NCT00488774.
authors.affiliation: University Hospital, Gasthuisberg, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, ON, Canada.
authors.forename: B G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Marano
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Padgett
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Strauss
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Johanns
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: O J
authors.initials: OJ
authors.lastname: Adedokun
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Guzzo
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Hôpital Claude Huriez, Lille Cedex, France.|Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J-F
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Universitätsklinik für Innere Medizin IV, Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Alfred Hospital, Melbourne, VIC, Australia.
authors.forename: P R
authors.initials: PR
authors.lastname: Gibson
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab