title: Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis.
abstract: OBJECTIVE
  We analyzed data collected during the Active Ulcerative Colitis Trials (ACT-1 and ACT-2) to assess relationships between serum concentrations of infliximab and outcomes of adults with moderate-to-severe ulcerative colitis.
  
  
  METHODS
  We compared serum concentrations of infliximab with outcomes of 728 patients with moderately-to-severely active ulcerative colitis who participated in ACT-1 or ACT-2; efficacy data were collected at weeks 8, 30, and 54 (for ACT-1 only). Relationships between serum concentration of infliximab and efficacy outcomes were assessed using trend, logistic regression, and receiver operating characteristic curve analyses. We also evaluated factors that affected the relationship between exposure and response.
  
  
  RESULTS
  Median serum concentrations of infliximab at weeks 8, 30, and/or 54 were significantly higher in patients with clinical response, mucosal healing, and/or clinical remission than in patients who did not meet these response criteria. There were statistically significant relationships between quartile of infliximab serum concentration and efficacy at these time points (P < .01). Infliximab therapy was effective for a smaller proportion of patients in the lowest quartile, and these patients had lower serum levels of albumin and a higher incidence of antibodies to infliximab than patients in other quartiles. Although the relationship between exposure to infliximab and response varied among patients, approximate serum concentrations of 41 μg/mL infliximab at week 8 of induction therapy and 3.7 μg/mL at steady-state during maintenance therapy produced optimal outcomes in patients.
  
  
  CONCLUSIONS
  Serum concentrations of infliximab are associated with efficacy in patients with moderate-to-severe ulcerative colitis; however, complex factors determine the relationship between exposure to this drug and response. A prospective evaluation of the value of measuring serum concentrations of infliximab should be performed before these data can be included in patient management strategies. Clinicaltrials.gov numbers: NCT00036439 and NCT00096655.
authors.affiliation: Biologics Clinical Pharmacology, Biostatistics, Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania. Electronic address: OAdedoku@its.jnj.com.
authors.forename: Omoniyi J
authors.initials: OJ
authors.lastname: Adedokun
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Immunology, Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Department of Gastroenterology, University Hospital Leuven, Herestraat, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Biologics Clinical Pharmacology, Biostatistics, Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Biologics Clinical Pharmacology, Biostatistics, Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Colleen W
authors.initials: CW
authors.lastname: Marano
authors.affiliation: Biologics Clinical Pharmacology, Biostatistics, Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Jewel
authors.initials: J
authors.lastname: Johanns
authors.affiliation: Biologics Clinical Pharmacology, Biostatistics, Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Biologics Clinical Pharmacology, Biostatistics, Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.affiliation: Department of Medicine, Janssen Biologics BV, Leiden, The Netherlands.
authors.forename: Freddy
authors.initials: F
authors.lastname: Cornillie
authors.affiliation: Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; McMaster University, Hamilton, Ontario, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000493:pharmacokinetics; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005765:Gastrointestinal Agents / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000069285:Infliximab
keywords: Anti–Tumor Necrosis Factor; Inflammatory Bowel Disease; Monoclonal Antibody; Pharmacokinetics