title: C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept.
abstract: OBJECTIVE
  Nonresponse to anti-tumor necrosis factor alpha in patients with rheumatoid arthritis (RA) is poorly understood. The aims of this study were to define nonresponse patterns using infliximab and C-reactive protein (CRP) profiles, to assess the predictive power of a CRP response for outcome, and to correlate these findings with subsequent response to etanercept.
  
  
  METHODS
  We studied 207 patients with resistant RA who were started on treatment with infliximab. After 12 weeks, the American College of Rheumatology 20% improvement criteria (ACR20) were used to classify patients as responders (ACR20 response or greater) or nonresponders (NRs). The NRs were further subdivided into 3 groups according to the CRP response at weeks 2, 6, and 12. Within the NR group, those with a suppressed CRP at week 12 continued taking infliximab for a further 12 weeks; those without a CRP response were switched to etanercept, and the ACR response at 12 weeks was calculated.
  
  
  RESULTS
  At week 12, 54% of patients achieved an ACR20 response, and 46% failed to achieve a response. Of the NRs, 63% demonstrated a significant reduction in the CRP level at week 12, 59% of whom achieved an ACR20 response at week 24 on continuation of infliximab. Of the patients who did not demonstrate a significant reduction in the CRP level after the first infusion, 86% failed to show a biochemical or ACR20 response by week 12. Twenty-four percent of the NRs had a temporary reduction in the CRP level, and 13% of the NRs showed no CRP reduction. Seventy-five percent of these NRs switched to etanercept, and 68% of this group achieved an ACR20 response at week 12 (51% achieved an ACR50 response), with a CRP response in 63%.
  
  
  CONCLUSIONS
  Infliximab NRs comprise subtypes with distinct CRP patterns. Failure to suppress the CRP at week 2 identified the majority of patients who were NRs at week 12. CRP suppression at week 12 in the NRs was associated with a late clinical improvement with infliximab treatment (24 weeks), whereas failure to suppress the CRP at week 12 was associated with a good response on switching to etanercept.
authors.affiliation: University of Leeds, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
authors.forename: Maya H
authors.initials: MH
authors.lastname: Buch
authors.forename: Yohei
authors.initials: Y
authors.lastname: Seto
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Bingham
authors.forename: Victoria
authors.initials: V
authors.lastname: Bejarano
authors.forename: Domini
authors.initials: D
authors.lastname: Bryer
authors.forename: Jo
authors.initials: J
authors.lastname: White
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D019233:Retreatment; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D002097:C-Reactive Protein; D000069285:Infliximab; D000068800:Etanercept