Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor alpha blockade

Maya H Buch, Sarah J Bingham, Yohei Seto, Dennis McGonagle, Victoria Bejarano, Jo White, Paul Emery

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: In patients with rheumatoid arthritis (RA) treated with tumor necrosis factor alpha (TNF alpha)- blocking therapy, there is heterogeneity of response. This raises the possibility that in certain circumstances, cytokines such as interleukin-1 (IL-1) may dominate the drive toward joint inflammation. This study was undertaken to investigate whether blocking the action of IL-1 with an IL-1 receptor antagonist (IL-1Ra) is efficacious in patients with disease that did not respond to TNF alpha blockade.

METHODS: We identified 26 RA patients whose disease had failed to respond to TNF alpha-blocking therapy, defined as failure to achieve or sustain a 20% improvement in disease activity according to the criteria of the American College of Rheumatology (ACR20 response). These patients were then treated with anakinra (100 mg/day subcutaneously) for 12 weeks, and their levels of response were assessed.

RESULTS: After 3 months of anakinra therapy, only 2 of 26 patients (8%) achieved an ACR20 response; none achieved an ACR50 or ACR70 response. A rise in the mean C-reactive protein level and an increase in the mean swollen joint count were noted during the study period.

CONCLUSION: This study demonstrates that patients with disease that fails to respond to TNF alpha blockade also do not respond to IL-1Ra. These data do not provide evidence of a dominant role for IL-1 in patients who do not respond to TNF alpha blockade, but they do not exclude a role for other proinflammatory mediators.

Original languageEnglish
Pages (from-to)725-8
Number of pages4
JournalArthritis and Rheumatism
Issue number3
Publication statusPublished - Mar 2004


  • Adult
  • Aged
  • Antirheumatic Agents/therapeutic use
  • Arthritis, Rheumatoid/drug therapy
  • C-Reactive Protein/metabolism
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Joints/pathology
  • Male
  • Middle Aged
  • Retreatment
  • Sialoglycoproteins/therapeutic use
  • Treatment Failure
  • Tumor Necrosis Factor-alpha/antagonists & inhibitors


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