title: Serum adalimumab concentration and clinical remission in patients with Crohn's disease.
abstract: BACKGROUND
  Drug concentration monitoring may be useful to guide therapeutic adjustments for anti-tumor necrosis factor agents in Crohn's disease. The relationship between serum adalimumab concentrations and clinical outcomes was assessed using data from CLinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease (CLASSIC) I/II.
  
  
  METHODS
  Serum adalimumab concentrations at week 4 of CLASSIC I and weeks 4, 24, and 56 of CLASSIC II were compared by clinical remission status (yes/no). Logistic regression and Classification and Regression Tree analyses explored factors associated with remission at weeks 4, 24, and 56. Threshold analyses and receiver operating characteristic curves evaluated the relationship between serum concentrations and clinical remission/response.
  
  
  RESULTS
  Serum adalimumab concentrations for 275 patients were available. Median adalimumab concentrations were significantly higher in patients who achieved clinical remission than those who did not at week 4 of CLASSIC I (8.10 versus 5.05 µg/mL, P < 0.05). At all time points, adalimumab concentrations demonstrated considerable variability and overlap between patients with and without remission. With Classification and Regression Tree analyses, baseline Crohn's Disease Activity Index, baseline C-reactive protein, and adalimumab concentrations were associated with early remission at week 4 of CLASSIC I and week 4 of CLASSIC II, but not at weeks 24 and 56. Receiver operating characteristic curves demonstrated low utility of cutoff thresholds to discriminate by clinical response/remission status.
  
  
  CONCLUSIONS
  A positive association between serum adalimumab concentration and remission was identified at several time points. A threshold concentration reliably associated with remission was not identified. Further prospective evaluations are needed before recommendations for adalimumab concentration monitoring can be made.
authors.affiliation: Biometrics Clinical Pharmacology and Pharmacometrics, AbbVie, AbbVie Inc., North Chicago, Illinois 60064, USA. yi-lin.chiu@abbvie.com
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: David T
authors.initials: DT
authors.lastname: Rubin
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Anne M
authors.initials: AM
authors.lastname: Robinson
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Lomax
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pollack
authors.forename: Susan K
authors.initials: SK
authors.lastname: Paulson
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab