True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin α?. Issue 10 (19th March 2004)

• Record Type: Journal Article
• Authors: Buch, M H; Conaghan, P G; Quinn, M A; Bingham, S J; Veale, D; Emery, P
• Is Part Of: Annals of the rheumatic diseases. Volume 63:Issue 10(2004)
• Page Start: 1344
• Page End: 1346
• Publication Date: 2004-03-19
• Subjects: 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; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2003.014878
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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.