title: Clinical utility of newly developed immunoassays for serum concentrations of adalimumab and anti-adalimumab antibodies in patients with Crohn's disease.
abstract: OBJECTIVE
  The appearance of anti-adalimumab antibodies (AAAs) is associated with low serum adalimumab (ADA) trough levels and a decrease of clinical response. The goal of this study was to assess the accuracy and clinical utility of new immunoassays for serum ADA and AAA levels.
  
  
  METHODS
  Serum ADA trough levels and AAA levels were measured using new immunoassays in 40 patients with Crohn's disease (CD) receiving ADA maintenance therapy.
  
  
  RESULTS
  Serum ADA trough levels were 12.3 ± 9.6 μg/ml (n = 40) in CD patients, and 14 of 40 patients (35 %) were positive for AAAs. A negative correlation was observed between serum AAA levels and ADA trough levels (y = -6.02x + 18.7, r = -0.54, P < 0.001, n = 40). The ROC (receiver-operator curve) analyses indicated that an ADA trough of 5.9 μg/ml was optimal to maintain negative CRP (C-reactive protein) levels (≤0.3 mg/dl). The ADA trough levels were significantly lower in patients positive for AAAs (5.5 ± 5.4 μg/ml, n = 14) than in patients negative for AAAs (16.0 ± 9.5 μg/ml, n = 26). The CRP and ESR levels were significantly higher in AAA-positive patients than in AAA-negative patients. Serum albumin levels were significantly lower in AAA-positive patients. The positive rate for AAAs in patients who lost a response to infliximab (50 %) was significantly higher than that of anti-TNF-α drug naïve patients (12.5 %).
  
  
  CONCLUSIONS
  These new assays for serum AAA trough and AAA levels are useful for routine clinical use and may help guide selection of optimal management strategies for IBD patients with a loss of response to ADA.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, 520-2192, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takehide
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Bamba
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007118:Immunoassay / Q000379:methods; D000069285:Infliximab; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab; D000068879:Adalimumab