title: Comparative analysis of the influence of clinical factors including BMI on adalimumab and infliximab trough levels.
abstract: BACKGROUND
  Optimal trough levels of the anti-tumour necrosis factor agents, infliximab and adalimumab, are correlated with clinical remission. Obesity adversely affects response to infliximab and adalimumab, but the influence of BMI on trough levels has not been adequately investigated. We investigated the relationship between clinical variables, including BMI, and trough levels of infliximab and adalimumab.
  
  
  METHODS
  This prospective cross-sectional study included patients treated with infliximab and adalimumab on maintenance therapy, with concurrent measurements of trough levels and BMI. The associations between categorical trough levels and clinical variables, including BMI, were estimated.
  
  
  RESULTS
  Of the 122 patients included in the study, 80 (66%) were on infliximab and 42 (34%) were on adalimumab. Eighty-three per cent had Crohn's disease and the remainder had ulcerative colitis. None of the clinical variables, including smoking, BMI, concurrent immunosuppression, duration of disease and treatment, were associated with categorical trough levels of infliximab or adalimumab. The effect of BMI did not differ between the two anti-tumour necrosis factor agents, although there was a trend towards a lower trough level in adalimumab-treated patients with a BMI greater than 30 (P=0.09). In infliximab-treated patients, antibodies to infliximab (P<0.001) and a C-reactive protein level of at least 5 mg/dl were associated with trough levels less than 3 µg/ml (P=0.008).
  
  
  CONCLUSIONS
  BMI does not differentially influence trough levels of adalimumab and infliximab, although a trend towards a lower trough level was observed in adalimumab-treated patients with a BMI greater than 30. Raised C-reactive protein levels and antibodies to infliximab were associated with subtherapeutic levels of infliximab.
authors.affiliation: aDepartment of Gastroenterology bLiverpool Clinical Laboratories, Royal Liverpool University Hospital cDepartment of Gastroenterology, University Hospital Aintree dCancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Bond
authors.forename: Rebecca
authors.initials: R
authors.lastname: Asher
authors.forename: Richard
authors.initials: R
authors.lastname: Jackson
authors.forename: Khalid
authors.initials: K
authors.lastname: Sager
authors.forename: Kate
authors.initials: K
authors.lastname: Martin
authors.forename: Andrew
authors.initials: A
authors.lastname: Kneebone
authors.forename: Suzannah
authors.initials: S
authors.lastname: Philips
authors.forename: William
authors.initials: W
authors.lastname: Taylor
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Subramanian
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000097:blood*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology / Q000493:pharmacokinetics; D000906:Antibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003430:Cross-Sectional Studies; D016903:Drug Monitoring; D004739:England; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D000069285:Infliximab / Q000032:analysis / Q000097:blood* / Q000276:immunology / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D015415:Biomarkers; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab; D000068879:Adalimumab