Association of RF and anti-CCP positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-TNF response in RA.

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Abstract

OBJECTIVE: To determine whether rheumatoid factor (RF), anti-CCP antibodies, or carriage of shared epitope (SE) and PTPN22 genetic susceptibility variants predict response to therapy in patients with rheumatoid arthritis (RA) treated with anti-TNF agents. METHODS: UK-wide multi-centre collaborations were established to recruit a large cohort of patients treated with anti-TNF drugs for RA. Serum RF, anti-CCP antibody and SE status were determined using commercially available kits. PTPN22 R620W genotyping was performed by Sequenom MassArray(R). Linear regression analyses were performed to investigate the role of these 4 factors in predicting response to treatment by 6 months, defined as the absolute change in DAS28. RESULTS: Of the 642 patients analysed, 46% received infliximab, 43% etanercept and 11% adalimumab. 89% and 82% of patients were RF and anti-CCP positive, respectively. RF negative patients had a 0.48 (95% CI: 0.08, 0.87) greater mean improvement in DAS28 compared to RF positive patients. A better response was also seen among anti-CCP negative patients. No association was demonstrated between drug response and SE or PTPN22 620W carriage. CONCLUSION: The presence of RF or anti-CCP antibodies was associated with a reduced response to anti-TNF drugs. However, these antibodies only account for a small proportion of the variance in treatment response. It is likely that genetic factors will contribute to treatment response, but these do not include the well-established RA susceptibility loci, SE and PTPN22.

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