title: Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease.
abstract: BACKGROUND
  Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure.
  
  
  OBJECTIVE
  To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP).
  
  
  METHODS
  We performed a cross-sectional study using trough sera from adalimumab-treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling.
  
  
  RESULTS
  One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut-off drug level of 5.85 μg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = -0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model.
  
  
  CONCLUSIONS
  Adalimumab drug levels were inversely related to disease activity. High levels of anti-adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.
authors.affiliation: Gastroenterology Department, Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Mazor
authors.forename: R
authors.initials: R
authors.lastname: Almog
authors.forename: U
authors.initials: U
authors.lastname: Kopylov
authors.forename: D
authors.initials: D
authors.lastname: Ben Hur
authors.forename: A
authors.initials: A
authors.lastname: Blatt
authors.forename: A
authors.initials: A
authors.lastname: Dahan
authors.forename: M
authors.initials: M
authors.lastname: Waterman
authors.forename: S
authors.initials: S
authors.lastname: Ben-Horin
authors.forename: Y
authors.initials: Y
authors.lastname: Chowers
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood*; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein; D000068879:Adalimumab