EXTENDED REPORT

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

Francesca Bobbio-Pallavicini¹, Roberto Caporali¹, Claudia Alpini², Stefano Avalle², Oscar M Epis¹, Catherine Klersy³, Carlomaurizio Montecucco⁴

¹ Cattedra di Reumatologia, IRCCS Policlinico S Matteo, Pavia, Italy
² Laboratori Analisi Chimico-Cliniche, IRCCS Policlinico S.Matteo, Pavia, Italy
³ Servizio di Biometria ed Epidemiologia Clinica, IRCCS Policlinico S Matteo, Pavia, Italy
⁴ Cattedra di Reumatologia, Policlinico S Matteo, Pavia, Italy

Correspondence to:
Prof C Montecucco
Cattedra di Reumatologia, Policlinico S Matteo, 27100 Pavia, Italy; montecucco{at}smatteo.pv.it

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 (TNF) 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-TNF 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-TNF 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 TNF inhibitors.

Abbreviations: CCP, cyclic citrullinated peptide; CRP, C reactive protein; DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; HAQ, Health Assessment Questionnaire; TNF, tumour necrosis factor

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