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Methotrexate effect on anti-cyclic citrullinated peptide antibody levels in rheumatoid arthritis
  1. A Spadaro,
  2. V Riccieri
  1. Dip. Clinica e Terapia Medica Applicata-Div, Reumatologia—Università “La Sapienza” Rome, Italy
  1. Correspondence to:
    Professor A Spadaro

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We read with interest the recent reports1–3 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.

Table 1

 Clinical and laboratory changes from baseline in patients with or without anti-CCP antibodies after 6 months’ MTX treatment

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 agent1–3 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.


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