High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor alpha inhibitors in rheumatoid arthritis.
OBJECTIVE
To investigate whether rheumatoid factor isotypes and anti-cyclic citrullinated peptide (anti-CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor alpha (TNFalpha) inhibitors.


METHODS
The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease-modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow-up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti-CCP antibodies were assessed by ELISA both before anti-TNFalpha treatment and 1 year later.


RESULTS
The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non-responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non-responder group (130.4 U/ml (interquartile range 13.8-276.7) v 24.8 U/ml (10.2-90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti-CCP antibody levels were not significantly affected.


CONCLUSIONS
According to the clinical response, anti-TNFalpha agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFalpha inhibitors.
Bobbio-Pallavicini
Francesca
F
Cattedra di Reumatologia, Policlinico S Matteo, 27100 Pavia, Italy.
Caporali
Roberto
R
Alpini
Claudia
C
Avalle
Stefano
S
Epis
Oscar M
OM
Klersy
Catherine
C
Montecucco
Carlomaurizio
C
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D000068800:Etanercept; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012217:Rheumatoid Factor / Q000097:blood*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept