Benefit of early treatment in inflammatory polyarthritis patients with anti–cyclic citrullinated peptide antibodies versus those without antibodies

OBJECTIVE To compare the clinical utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) testing in predicting both functional outcome and response to treatment in early inflammatory polyarthritis (IP) patients. METHODS A total of 916 IP subjects from a primary care incidence registry (1990-1994) had anti-CCP antibody and RF status determined at baseline. Mean change in Health Assessment Questionnaire (HAQ) score between baseline and 5 years was compared by antibody status. The effect of treatment with disease-modifying antirheumatic drugs and/or steroids over 5 years, early (<6 months of symptom onset) versus late initiation, and duration of treatment were also compared by anti-CCP antibody status. The analysis was adjusted for treatment decisions and censoring over the followup, using marginal structural models. RESULTS Anti-CCP antibody-positive patients (n = 268) had more severe disease both at presentation and 5 years of followup, and this was independent of RF. On adjustment, anti-CCP antibody-negative patients treated early experienced a significant improvement in functional disability compared with anti-CCP antibody-negative patients who were never treated (-0.31; 95% confidence interval [95% CI] -0.53, -0.08), and experienced additional benefit for each additional month of early treatment. Anti-CCP antibody-positive patients treated early did not have a significant improvement in HAQ score compared with those not treated (-0.14; 95% CI -0.52, 0.24). CONCLUSION In this first observational study to examine the influence of anti-CCP antibody status on treatment response, anti-CCP antibody-positive IP patients showed less benefit from treatment, particularly early treatment, than anti-CCP antibody-negative patients. This provides support for the inclusion of anti-CCP antibodies as well as RF in the classification criteria for rheumatoid arthritis and for stratification by anti-CCP antibody status in clinical trials.