title: Higher Adalimumab Levels Are Associated with Histologic and Endoscopic Remission in Patients with Crohn's Disease and Ulcerative Colitis.
abstract: BACKGROUND
  Optimal levels of adalimumab (ADA) have not been defined according to the ultimate goal of inflammatory bowel disease treatment--histologic and/or endoscopic healing. The aim of this study was to assess the relationship between random serum ADA levels and histologic and endoscopic healing in patients with inflammatory bowel disease.
  
  
  METHODS
  This was a cross-sectional study including 66 patients receiving maintenance therapy with ADA for Crohn's disease or ulcerative colitis. ADA levels and anti-adalimumab antibodies (AAA) were measured at the time of colonoscopy. The primary outcome was histologic healing (lack of endoscopic and histologic inflammation) and the secondary outcomes were endoscopic healing and serum levels of C-reactive protein, tumor necrosis factor, ICAM, VCAM, and interleukins 1β, 6, and 8.
  
  
  RESULTS
  Sixty-six patients (59 with Crohn's disease) were included. Mean random ADA levels were significantly lower in patients with histologic and endoscopic inflammation (9.2 [SD: 8.4] versus 14.1 [6.4] μg/mL, P = 0.03 and 8.5 [SD: 7.8] versus 13.3 [SD: 7.7], P = 0.02, respectively). The ADA level that was best associated with histologic healing was 7.8 μg/mL (receiver operating characteristic: 0.76 [P = 0.04]), whereas the ADA level that was best associated with endoscopic healing was 7.5 μg/mL (receiver operating characteristic: 0.73 [P = 0.02]). The presence of AAA was associated with lower random ADA levels (5.7 versus 12.5 μg/mL, P = 0.002) and higher C-reactive protein levels (30.3 versus 12.0, P = 0.01).
  
  
  CONCLUSIONS
  Achievement of histologic and endoscopic healing may require higher levels of ADA than previously described for endoscopic remission. The measurement of random ADA levels and anti-drug antibodies may guide therapy and edify the course of incomplete responses.
authors.affiliation: *Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida; and †Prometheus Laboratories, San Diego, California.
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Yarur
authors.forename: Anjali
authors.initials: A
authors.lastname: Jain
authors.forename: Scott I
authors.initials: SI
authors.lastname: Hauenstein
authors.forename: Maria A
authors.initials: MA
authors.lastname: Quintero
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Barkin
authors.forename: Amar R
authors.initials: AR
authors.lastname: Deshpande
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sussman
authors.forename: Sharat
authors.initials: S
authors.lastname: Singh
authors.forename: Maria T
authors.initials: MT
authors.lastname: Abreu
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D003430:Cross-Sectional Studies; D004724:Endoscopy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D011379:Prognosis; D012074:Remission Induction; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000068879:Adalimumab