RESEARCH - The SE is a marker of severity associated with selection for Remicade in a large RA population

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Ann Rheum Dis. 2005 Aug 11; [Epub ahead of print]

The Shared Epitope is a marker of severity associated with selection for,

but not with response to infliximab in a large rheumatoid arthritis

population.

Marotte H, Pallot-Prades B, Grange L, Tebib J, Gaudin P, andre C, Blond

J, Cazalis M, Mougin B, Miossec P.

Hospices Civils de Lyon-bioMerieux Research Unit on Rheumatoid Arthritis,

69437 Lyon Cedex 03, France.

OBJECTIVE: To determine if joint destruction, indication and response to

infliximab in rheumatoid arthritis (RA) are associated with the shared

epitope (SE) or selected cytokine gene polymorphisms (IL-1B, IL1- RN and

TNFA). METHODS: /B> In a large RA population of 930 patients from the same

area (Rhone-Alpes, France), patients with (n=198) or without infliximab

therapy were compared according to their genetic status. Clinical,

biological and radiological data were collected. Typing for the SE status

and cytokine polymorphisms was performed by ELOSA. Chi-squared statistical

analysis and odds ratios (OR) were performed. RESULTS: A dose relationship

was observed between the number of SE copies and joint damage in the whole

RA population (OR 1 vs. 0 SE copy = 2.38; 95% C.I. 1.77, 3.19, p<0.001; OR 2

vs. 0 SE copy = 3.92; 95% C.I. 2.65, 5.80, p<0.001). The SE effect increased

with disease duration but was not significant before two years. Selection

for infliximab therapy (n=198) was associated with increased disease

activity, joint damage and the presence of the SE with a dose effect. 66.2%

patients achieved an ACR20 improvement. No clinical or genetic factors could

predict the clinical response to infliximab.

CONCLUSION: This post marketing study in a large cohort of RA patients

indicates a linkage between RA severity, selection for treatment with

infliximab and the presence and dose of the SE.

PMID: 16096333

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6096333 & dopt=Abstract

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