We read with interest the recent reports^1–,³ focusing on the changes of rheumatoid factor and anti-citrullinated peptide antibodies (anti-CCP) during infliximab treatment in refractory rheumatoid arthritis (RA), unresponsive to conventional disease modifying antirheumatic drugs.

Alessandri et al³ reported that 24 weeks’ infliximab treatment reduced anti-CCP levels according to the study of Bobbio-Pallavicini et al.² These results are in contrast with the findings of De Rycke et al, which showed no change of this autoantibody serum level after 30 weeks’ infliximab treatment.¹ However, the levels of anti-CCP returned to baseline values after a long term observation (78 weeks).² In these studies infliximab was frequently associated with methotrexate (MTX), and selection criteria included patients previously treated with MTX. The sole MTX effect on anti-CCP levels cannot be assessed from these reports. For this reason we studied MTX effect on anti-CCP in patients with RA not previously treated with this drug. We determined anti-CCP antibodies (Axis Shields, Dundee, UK) and IgM rheumatoid factor (RF)⁴ by enzyme linked immunosorbent assay (ELISA) at baseline and after 6 months of MTX treatment (dose range 7.5–15 mg/weekly) in 20 patients with RA (mean age 56.6 years (range 39–68); mean disease duration 7.6 years (range 1–21)). Anti-CCP and RF positive samples were respectively defined as ⩾20 units and as binding index (BI) >1. A comparison of these autoantibody levels (median (25th–75th centile)) at baseline and after 6 months of MTX treatment showed that anti-CCP antibody levels were not modified (49.5 (15–77) v 59.5 (5–74) U; NS), whereas IgM RF levels were significantly reduced (4.1 (1.4–5.9) v 2.4 (0.4–4.1) BI; p<0.0001).

At baseline, the presence of anti-CCP antibodies does not seem to be a predictive factor of clinical and laboratory response, evaluated by American College of Rheumatology (ACR) response rate, erythrocyte sedimentation rate, C reactive protein, and IgM RF reduction after 6 months’ MTX treatment (table 1⇓). We observed that only C reactive protein reduction seemed to be more evident, although not significant, in patients without anti-CCP antibodies at baseline.

Our observations showed the lack of MTX effect on anti-CCP production, suggesting that the discrepant results on restricted subsets of patients with RA treated with a tumour necrosis factor blocking agent^1–,³ could not be due to previous or concomitant treatment with MTX. Additionally, our results confirm that anti-CCP antibodies and RF are two independent autoantibody systems.