title: Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases.
abstract: OBJECTIVE
  Little is known about the association between pharmacokinetic features of adalimumab and mucosal healing in patients with inflammatory bowel disease (IBD).
  
  
  METHODS
  We conducted a cross-sectional study of 40 patients with Crohn's disease (CD) or ulcerative colitis (UC) who received adalimumab maintenance therapy and underwent endoscopic evaluation of disease activity and pharmacokinetic analysis (measurements of trough levels and antibodies against adalimumab). Patients in clinical remission were identified based on CD activity index scores less than 150 or Mayo scores less than 3 (for those with UC). Patients with mucosal healing were identified based on Mayo endoscopic scores less than 2 (for UC) or the disappearance of all ulcerations (for CD).
  
  
  RESULTS
  The median trough level of adalimumab was higher in patients in clinical remission (6.02 μg/mL) than in patients with active disease (3.2 μg/mL; P = .012). Trough levels of adalimumab were also higher in patients with mucosal healing (6.5 μg/mL) than in patients without (4.2 μg/mL;  P  <  .005). These results did not vary with type of IBD. On multivariate analysis, trough levels of adalimumab (relative risk, 0.62; 95% confidence interval, 0.40-0.94; P = .026) and duration of adalimumab treatment (relative risk, 0.82; 95% confidence interval, 0.68-0.97; P = .026) were associated independently with healing mucosa. An absence of mucosal healing was associated with trough levels of adalimumab less than 4.9 μg/mL (likelihood ratio, 4.3; sensitivity, 66%; specificity, 85%).
  
  
  CONCLUSIONS
  Trough levels of adalimumab are significantly higher in IBD patients who are in clinical remission and in those with mucosal healing. Detection of antibodies against adalimumab predicts a lack of mucosal healing.
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, University Hospital de Saint-Etienne, France. Electronic address: xavier.roblin@chu-st-etienne.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
authors.affiliation: Service de Rhumatologie, University Hospital de Saint-Etienne, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Marotte
authors.affiliation: Laboratoire d'Immunologie et d'Immunomonitoring, University Hospital de Saint-Etienne, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Rinaudo
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, University Hospital de Saint-Etienne, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Del Tedesco
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, University Hospital de Saint-Etienne, France.
authors.forename: Amelie
authors.initials: A
authors.lastname: Moreau
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, University Hospital de Saint-Etienne, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Phelip
authors.affiliation: Laboratoire d'Immunologie et d'Immunomonitoring, University Hospital de Saint-Etienne, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
authors.affiliation: Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Henri Poincaré University, Nancy 1, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Service de Gastrologie-Entérologie-Hépatologie, University Hospital de Saint-Etienne, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
mesh_terms: D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003430:Cross-Sectional Studies; D004724:Endoscopy; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000068879:Adalimumab
keywords: AAA; ADA; AUROC; Anti-Adalimumab; C-reactive protein; CD; CDAI; CRP; Crohn's Disease Activity Index; Crohn’s disease; IBD; LHR; MH; Outcome; Prognostic Factor; ROC; Response to Therapy; TNF; UC; adalimumab; antibodies against adalimumab; area under the receiver-operating characteristic curve; inflammatory bowel disease; likelihood ratio; mucosal healing; receiver-operating characteristic; tumor necrosis factor; ulcerative colitis