This article has a correction

Please see: Ann Rheum Dis 2011;70:1519

Ann Rheum Dis 68:69-74 doi:10.1136/ard.2007.084715
  • Clinical and epidemiological research

Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis

Open Access
  1. C Potter1,
  2. K L Hyrich1,
  3. A Tracey1,
  4. M Lunt1,
  5. D Plant1,
  6. D P M Symmons1,
  7. W Thomson1,
  8. J Worthington1,
  9. P Emery2,
  10. A W Morgan2,
  11. A G Wilson3,
  12. J Isaacs4,
  13. A Barton1,
  1. 1
    Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK
  2. 2
    Leeds Institute of Molecular Medicine, Section of Musculoskeletal Disease, University of Leeds, Leeds, UK
  3. 3
    Section of Musculoskeletal Sciences, University of Sheffield, Sheffield, UK
  4. 4
    Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
  1. A Barton, ARC-EU, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK; anne.barton{at}
  • Accepted 9 March 2008
  • Published Online First 28 March 2008


Objective: To determine whether rheumatoid factor (RF), anti-cyclic citrullinated peptide (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-tumour necrosis factor (TNF) agents.

Methods: UK-wide multicentre 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. Linear regression analyses were performed to investigate the role of these four factors in predicting response to treatment by 6 months, defined as the absolute change in 28-joint Disease Activity Score (DAS28).

Results: Of the 642 patients analysed, 46% received infliximab, 43% etanercept and 11% adalimumab. In all, 89% and 82% of patients were RF and anti-CCP positive, respectively. Patients that were RF negative had a 0.48 (95% CI 0.08 to 0.87) greater mean improvement in DAS28 compared to patients that were RF positive. A better response was also seen among patients that were anti-CCP negative. 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.