title: Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab.
abstract: OBJECTIVE
  Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission in which the drug is titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab.
  
  
  METHODS
  We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn's disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery.
  
  
  RESULTS
  Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09-0.27; P < .001), IBD-related surgery (HR, 0.30; 95% CI, 0.11-0.80; P = .017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07-0.33; P < .001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07-0.84; P = .025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04-0.78; P = .023).
  
  
  CONCLUSIONS
  In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papamichael
authors.affiliation: Department of Medicine, Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Chachu
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ravy K
authors.initials: RK
authors.lastname: Vajravelu
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Byron P
authors.initials: BP
authors.lastname: Vaughn
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Josephine
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Osterman
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: acheifet@bidmc.harvard.edu.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Cheifetz
mesh_terms: D000293:Adolescent; D000328:Adult; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab / Q000008:administration & dosage* / Q000097:blood*; D008297:Male; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D000069285:Infliximab
keywords: CD; Immunogenicity; Monitoring Therapy; Ulcerative Colitis