C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept

Arthritis Rheum. 2005 Jan;52(1):42-8. doi: 10.1002/art.20711.


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%.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • C-Reactive Protein / metabolism*
  • Cohort Studies
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Infliximab
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use
  • Retreatment
  • Severity of Illness Index
  • Time Factors
  • Treatment Failure


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • C-Reactive Protein
  • Infliximab
  • Etanercept