The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population

• Published in: Annals of the rheumatic diseases Vol. 65; no. 3; pp. 342 - 347
• Main Authors: Marotte, H, Pallot-Prades, B, Grange, L, Tebib, J, Gaudin, P, Alexandre, C, Blond, J L, Cazalis, M A, Mougin, B, Miossec, P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.03.2006; BMJ; BMJ Publishing Group LTD; BMJ Publishing Group; BMJ Group
• Subjects: Adult; Age of Onset; Aged; ANA; anti-TNF; anti-TNF trial in rheumatoid arthritis with concomitant therapy; Antibodies, Monoclonal; Antibodies, Monoclonal - therapeutic use; antinuclear antibodies; Antirheumatic Agents; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; ATTRACT; Biological and medical sciences; Biomedical research; Cytokines; Cytokines - genetics; DAS; Deoxyribonucleic acid; disease activity score; disease modifying antirheumatic drug; Diseases of the osteoarticular system; DMARD; DNA; Epitopes; Epitopes - genetics; EULAR; European League Against Rheumatism; Extended Report; Female; Genes; Genetic Markers; Genetic Predisposition to Disease; HLA; Human health and pathology; human leucocyte antigen; Humans; Immunomodulators; Inflammatory joint diseases; Infliximab; Life Sciences; Male; Medical sciences; Middle Aged; Patient Selection; Pharmacology. Drug treatments; Polymorphism, Genetic; Population; Product Surveillance, Postmarketing; Prognosis; Rheumatism; Rheumatoid arthritis; Rhumatology and musculoskeletal system; Severity of Illness Index; shared epitope; single nucleotide polymorphism; SNP; Studies; TNFα; Treatment Outcome; Tumor necrosis factor-TNF; tumour necrosis factor α; Antigenic determinant; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Monoclonal antibody; Immunomodulator; Chronic; Infliximab; Rheumatoid arthritis; Anticytokine; Immunosuppressive agent; Tumor necrosis factor α
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2005.037150

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 α). 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 χ2 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.