title: Factors associated with short- and long-term outcomes of therapy for Crohn's disease.
abstract: OBJECTIVE
  Our post hoc analysis assessed the association of early (at weeks 26-30) clinical, endoscopic, biologic, and pharmacokinetic outcomes with corticosteroid-free remission at week 50 (CSFR50); CSFR50 was observed in 55.2% and 65.4% of patients treated with infliximab, alone or in combination with azathioprine, respectively.
  
  
  METHODS
  We analyzed data from 203 patients: 96 received infliximab monotherapy and 107 received combination therapy. Receiver operating characteristic analysis was used to set cut-off points for the week 30 trough serum infliximab concentration (SIC30) and percentage change, from baseline, in the C-reactive protein (CRP) level at week 26, to predict CSFR50. Univariate and multivariate procedures analyzed predictive parameters of CSFR50 (odds ratio [OR] and 95% confidence interval [CI]). Mucosal healing (MH, zero ulcers) and CRP normalization (<8.0 mg/L) also were assessed.
  
  
  RESULTS
  Trough SIC30 was higher in patients with than without CSFR50. Patients given combination therapy had higher trough SIC30s than those given monotherapy. Median trough SIC30 was significantly higher in patients with than without CSFR50 among those on infliximab monotherapy (2.14 vs 0.80 μg/mL; P = .006), but not for those on combination therapy (3.56 vs 3.54 μg/mL; P=.31). In patients with increased baseline levels of CRP (n = 120), corticosteroid-free remission at week 26 (CSFR26) (OR, 4.09; 95% CI, 1.65-10.11), and trough SIC30s of 3.0 μg/mL or greater (OR, 3.20; 95% CI, 1.38-7.42) were associated significantly with CSFR50. In patients evaluable for MH (n = 123), trough SIC30s of 3.0 μg/mL or greater (OR, 3.34; 95% CI, 1.53-7.28) and CRP normalization (OR, 2.69; 95% CI, 1.10-6.54) were associated significantly with MH at week 26 (MH26). Furthermore, CSFR26 (OR, 4.43; 95% CI, 1.81-10.82) and MH26 (OR, 3.01; 95% CI, 1.33-6.81) were associated significantly with CSFR50.
  
  
  CONCLUSIONS
  Trough SIC30 is associated positively with MH26; CSFR26 and MH26 are independent predictors of CSFR50. Trough SIC30 of 3.0 μg/mL or greater early during maintenance treatment is an important determinant of clinical and endoscopic Crohn's disease outcomes. ClinicalTrials.gov number, NCT00094458.
authors.affiliation: Department Internal Medicine III, Medical University of Vienna, Vienna, Austria; Department Internal Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: reinisw@univmail.cis.mcmaster.ca.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Department of Hepatogastroenterology, Centre Hospitalier Universitaire de Lille, Lille, France; Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
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: Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
authors.forename: Gerassimos J
authors.initials: GJ
authors.lastname: Mantzaris
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Asher
authors.initials: A
authors.lastname: Kornbluth
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Omoniyi J
authors.initials: OJ
authors.lastname: Adedokun
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Kezhen L
authors.initials: KL
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Janssen Biologics BV, Leiden, The Netherlands.
authors.forename: Freddy
authors.initials: F
authors.lastname: Cornillie
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D002097:C-Reactive Protein; D000069285:Infliximab; D001379:Azathioprine
keywords: Anti-TNF Agent; Drug; SONIC; Tumor Necrosis Factor