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True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin α?


Background: The combination of methotrexate and the anti-tumour necrosis factor α (TNFα) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNFα independent disease or insufficient drug at the site of action.

Case report: A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNFα staining but also confirmed the presence of lymphotoxin α (LTα or TNFβ) on immunohistochemistry. Subsequent treatment with etanercept (which blocks LTα as well as TNFα) resulted in clinical remission of disease.

Conclusion: This case suggests that resistance to TNF blockade may occur when TNFα is not the dominant inflammatory cytokine and suggests that LTα may have a pathogenic role in RA.

  • CRP, C reactive protein
  • EMS, early morning stiffness
  • HACAs, human anti-chimeric antibodies
  • IA, intra-articular
  • LTα, lymphotoxin α
  • RA, rheumatoid arthritis
  • SJC, swollen joint count
  • TJC, tender joint count
  • TNFα, tumour necrosis factor α
  • rheumatoid arthritis
  • anti-tumour necrosis factor
  • infliximab
  • lymphotoxin α

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