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.
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.


CONCLUSIONS
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.
Potter
C
C
Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK.
Hyrich
K L
KL
Tracey
A
A
Lunt
M
M
Plant
D
D
Symmons
D P M
DP
Thomson
W
W
Worthington
J
J
Emery
P
P
Morgan
A W
AW
Wilson
A G
AG
Isaacs
J
J
Barton
A
A
D000368:Aged; D000483:Alleles; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood*; D000939:Epitopes; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000032:analysis; D059811:HLA-DRB1 Chains; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012217:Rheumatoid Factor / Q000097:blood*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D006113:United Kingdom
D018501:Antirheumatic Agents; D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D000068800:Etanercept