Ann Rheum Dis 66:302-307 doi:10.1136/ard.2006.060608
  • Extended report

High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor α inhibitors in rheumatoid arthritis

  1. Francesca Bobbio-Pallavicini1,
  2. Roberto Caporali1,
  3. Claudia Alpini2,
  4. Stefano Avalle2,
  5. Oscar M Epis1,
  6. Catherine Klersy3,
  7. Carlomaurizio Montecucco4
  1. 1Cattedra di Reumatologia, IRCCS Policlinico S Matteo, Pavia, Italy
  2. 2Laboratori Analisi Chimico-Cliniche, IRCCS Policlinico S.Matteo, Pavia, Italy
  3. 3Servizio di Biometria ed Epidemiologia Clinica, IRCCS Policlinico S Matteo, Pavia, Italy
  4. 4Cattedra di Reumatologia, Policlinico S Matteo, Pavia, Italy
  1. Correspondence to:
    Prof C Montecucco
    Cattedra di Reumatologia, Policlinico S Matteo, 27100 Pavia, Italy; montecucco{at}
  • Accepted 22 October 2006
  • Published Online First 1 November 2006


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 α (TNFα) 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-TNFα 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-TNFα 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 TNFα inhibitors.


  • Published Online First 1 November 2006

  • Funding: This work was supported by a grant of IRCCS Policlinico S Matteo Foundation of Pavia, Italy.

  • Competing interests: None declared.