title: Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease.
abstract: OBJECTIVE
  To investigate if the combined assessment of anti-infliximab antibodies (Ab) and the degree of TNF-alpha binding capacity (TNF-alpha-BC) afforded by infliximab may predict the response to infliximab treatment in patients with Crohn's disease (CD).
  
  
  METHODS
  Three groups of CD patients, in total 33 patients, treated with infliximab were retrospectively selected: (a) patients with a maintained response throughout treatment; (b) patients with good initial response, but subsequent loss of response; and (c) patients with inadequate response to the first two or three doses. Blood samples were analyzed for TNF-alpha-BC and Ab using fluid-phase radioimmunoassay (RIA).
  
  
  RESULTS
  At 8 wk after last infliximab infusion, TNF-alpha-BC was significantly higher (P = 0.002) in patients maintaining response (median [interquartile range] 2.9 [0.9-4.3] microg/mL), as compared to patients losing response (0.0 [0-0.1] microg/mL). Conversely, Ab levels were significantly lower (P < 0.0001) in patients maintaining response (1.3 [0-6]% bound tracer/total tracer), as compared to patients losing response (19 [14-27]%). Ab were not present and TNF-alpha-BC was high (30 [20-32]) in patients with no primary response.
  
  
  CONCLUSIONS
  While secondary loss of response to infliximab is associated with high levels of Ab and low levels of TNF-alpha-BC, primary response failure may be seen in the presence of high effective levels of TNF-alpha-BC afforded by infliximab. The results suggest that combined assessment of anti-infliximab Ab and serum TNF-alpha-BC may pave the way for a more rational use of infliximab in patients with CD.
authors.affiliation: Department of Medical Gastroenterology, Copenhagen University Hospital, Herlev, Herlev, Denmark.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ainsworth
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011863:Radioimmunoassay / Q000379:methods; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab