title: Higher Adalimumab Drug Levels are Associated with Mucosal Healing in Patients with Crohn's Disease.
abstract: OBJECTIVE
  The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 µg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn's disease (CD).
  
  
  METHODS
  A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey-Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay.
  
  
  RESULTS
  Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl (p = 6.93×10(-6)). Higher adalimumab trough level was significantly associated with MH (median 14.7 µg/mL in those with MH vs 3.4 µg/mL in those without, p = 6.25×10(-5)). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 µg/mL, p = 5.36×10(-3)). A cut-off of 8.14 µg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively).
  
  
  CONCLUSIONS
  Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 μg/mL.
authors.affiliation: Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada Institute of Gastroenterology and Liver Diseases, Emek Medical Center, Afula, Israel eranzittan@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Zittan
authors.affiliation: Mount Sinai Hospital, Zane Cohen Center, Toronto, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Kabakchiev
authors.affiliation: Mount Sinai Hospital, Zane Cohen Center, Toronto, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Milgrom
authors.affiliation: Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: G C
authors.initials: GC
authors.lastname: Nguyen
authors.affiliation: Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Croitoru
authors.affiliation: Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: A H
authors.initials: AH
authors.lastname: Steinhart
authors.affiliation: Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Silverberg
mesh_terms: D000068879:Adalimumab / Q000097:blood* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003106:Colon / Q000000981:diagnostic imaging / Q000473:pathology; D003113:Colonoscopy; D003424:Crohn Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003430:Cross-Sectional Studies; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007082:Ileum / Q000000981:diagnostic imaging / Q000473:pathology; D060828:Induction Chemotherapy; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000068879:Adalimumab
keywords: Adalimumab; Crohn’s disease; endoscopic remission