True Remicade resistance in RA; a role for lymphotoxin-alpha?

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Ann Rheum Dis. 2004 Mar 19 [Epub ahead of print]

True infliximab resistance in rheumatoid arthritis; a role for

lymphotoxin-alpha?

Buch MH, Conaghan PG, Quinn MA, Bingham SJ, Veale D, Emery P.

Academic Unit of Musculoskeletal Disease, University of Leeds, UK.

Introduction: The combination of methotrexate and the anti-tumour

necrosis factor alpha (TNF-alpha) antibody infliximab is a very

effective treatment of rheumatoid arthritis (RA). However a proportion

of patients are not responsive to this therapy. Inefficacy may represent

a TNF-alpha independent disease or insufficient drug at the site of

action. Case Report: This case report describes a patient with RA

resistant to repeated high-dose infliximab infusions and intra-articular

infliximab into an inflamed knee. No beneficial clinical effect was

observed. Pre-injection arthroscopic biopsy of the study knee

demonstrated TNF-alpha staining but also confirmed presence of

lymphotoxin-alpha (LT-alpha or TNF-beta) on immunohistochemistry.

Subsequent treatment with etanercept (which blocks LT-alpha as well as

TNF-alpha) resulted in clinical remission of disease.

CONCLUSION: This case suggests that resistance to TNF blockade may occur

when TNF-alpha is not the dominant inflammatory cytokine and implicates

LT-alpha as possessing a pathogenic role in RA.

PMID: 15033655

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