title: Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.
abstract: OBJECTIVE
  Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -α, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment.
  
  
  METHODS
  We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore ≥ 2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change.
  
  
  RESULTS
  In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0% and 54.9% among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3% among those given placebo (both, P ≤ .0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P ≤ .0014, all comparisons). Rates of serious adverse events were 6.1% and 3.0%, and rates of serious infection were 1.8% and 0.5%, in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess.
  
  
  CONCLUSIONS
  Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo. ClinicalTrials.gov Number: NCT00487539.
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Colleen
authors.initials: C
authors.lastname: Marano
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Richard
authors.initials: R
authors.lastname: Strauss
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Jewel
authors.initials: J
authors.lastname: Johanns
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Omoniyi J
authors.initials: OJ
authors.lastname: Adedokun
authors.affiliation: Janssen Services, LLC, Horsham, Pennsylvania.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Guzzo
authors.affiliation: Department of Hepatogastroenterology and Centre D'Investigation Clinique Chu Lille, Université Lille Nord De France, Lille, France; Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Department of Gastroenterology and Hepatology, Universitätsklinik für Innere Medizin III, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Department of Gastroenterology, Monash University, Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Gibson
authors.affiliation: Division of Gastroenterology, Department of Medicine, Oregon Health Sciences University, Portland, Oregon.
authors.forename: Judith
authors.initials: J
authors.lastname: Collins
authors.affiliation: Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Järnerot
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Minato, Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.affiliation: Department of Gastroenterology, University Hospital, Gasthuisberg, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000636:Aminosalicylic Acids / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000305:Adrenal Cortex Hormones; D000636:Aminosalicylic Acids; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D015122:Mercaptopurine; D001379:Azathioprine; D008727:Methotrexate
keywords: AZA; C-reactive protein; CRP; Dose−Response; Human Monoclonal Antibody; IBDQ; Inflammatory Bowel Disease; Inflammatory Bowel Disease Questionnaire; PK; PURSUIT-SC; Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment−Subcutaneous; SC; TNF; TNF Antagonist; UC; azathioprine; pharmacokinetic; subcutaneous; tumor necrosis factor; ulcerative colitis