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

Background: The combination of methotrexate and the antitumour necrosis factor alpha (TNFalpha) 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 TNFalpha 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 TNFalpha staining but also confirmed the presence of lymphotoxin alpha (LTalpha or TNFbeta) on immunohistochemistry. Subsequent treatment with etanercept ( which blocks LTalpha as well as TNFalpha) resulted in clinical remission of disease. Conclusion: This case suggests that resistance to TNF blockade may occur when TNFalpha is not the dominant inflammatory cytokine and suggests that LTalpha may have a pathogenic role in RA.