The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population.
OBJECTIVE
To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha).


METHODS
In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR).


RESULTS
A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab.


CONCLUSIONS
This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.
Marotte
H
H
Clinical Immunology Unit, Departments of Immunology and Rheumatology, Hôpital Edouard Hérriot, 69437 Lyon Cedex 03, France.
Pallot-Prades
B
B
Grange
L
L
Tebib
J
J
Gaudin
P
P
Alexandre
C
C
Blond
J L
JL
Cazalis
M A
MA
Mougin
B
B
Miossec
P
P
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D000939:Epitopes / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011110:Polymorphism, Genetic; D011358:Product Surveillance, Postmarketing; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016207:Cytokines; D000939:Epitopes; D005819:Genetic Markers; D000069285:Infliximab