High IgA Rheumatoid factor levels are associated with poor clinical response to TNF- inhibitors in rheumatoid arthritis

Francesca Bobbio-Pallavicini ¹, Roberto Caporali ¹, Claudia Alpini ², Stefano Avalle ², Oscar Epis ¹, Catherine Klersy ³ and Carlomaurizio Montecucco ^1*

¹ Chair and Division of Rheumatolology, University of pavia, IRCCS Policlinico San Matteo, Pavia, Italy
² Clinical Chemistry Laboratories, Univeristy of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy
³ Service of Biometry and Clinical Epidemiology, IRCCS Policlinico San Matteo, Pavia, Italy

^* To whom correspondence should be addressed. E-mail: montecucco{at}smatteo.pv.it.

Accepted 22 October 2006

Abstract

Objective: The aim of the present observational longitudinal study was to investigate whether Rheumatoid Factor (RF) isotypes and anti-cyclic citrullinated peptide antibodies (anti-CCP) are related to clinical response in rheumatoid arthritis (RA) treated with tumour necrosis factor- (TNF-) inhibitors.

Methods: The study was carried out on 132 patients with advanced RA refractory to DMARDS. Patients were treated with either Infliximab (63 patients), Etanercept (35) or Adalimumab (34). All patients completed one year of follow up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM-, IgA- and IgG-RFs and anti- CCP antibodies were assessed by enzyme linked immunosorbent assay both before anti-TNF- therapy and one year later.

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

Conclusions: According to clinical response, anti- TNF- agents appear to reduce IgM-, IgG-, and IgA- RF levels. More interestingly, high pre-treatment levels of IgA-RF are associated with a poor clinical response to TNF- inhibitors.

Keywords: IgA rheumatoid factor, adalimumab, anti-cyclic citrullinated peptide antibodies, etanercept, infliximab

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