The combination of methotrexate and the anti-tumour 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.
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.
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.