Background Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation that eventually results in joint destruction and functional damages. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) are useful diagnostic tools for subclinical and early RA. RF titers decrease with successful drug therapy. Some reports have shown that tumor necrosis factor (TNF)-alpha blockers reduce anti-CCP.

Objectives To analyze the effect of tocilizumab (TCZ) therapy on anti-CCP and IgM RF in patients with RA.

Methods Forty-six patients (38 women and 8 men; mean age 58.3 years, range 25 – 76 years) treated with TCZ were enrolled. All patients met the American College of Rheumatology classification criteria for RA. Patients received 8 mg/kg TCZ intravenously every 4 weeks. Serum samples were collected at baseline, 12 weeks, and 52 weeks. Sera were stored at -80 degree until they were assayed. Anti-CCP was measured by enzyme-linked immunosorbent assay (ELISA), and RF was detected by immune nephelometry. Anti-CCP was considered positive when the titer was greater than 5 U/mL. RF was considered positive when the titer was greater than 15 IU/mL.

Results At baseline, 37 patients were positive for anti-CCP (80%) and 35 were positive for RF (76%). Thirty-two patients (70%) were positive for both anti-CCP and RF. There was a weak correlation between anti-CCP and RF at baseline (r =0.186). No differences were noted in disease activity relative to the patient’s anti-CCP and RF positivity. Three patients who were positive for anti-CCP at baseline became anti-CCP negative after TCZ therapy, with titers below 10 U/mL. RF titers in 8 patients changed from positive to negative during the course of treatment. These RF titers ranged from 22 to 102 IU/mL. Anti-CCP levels decreased at 12 weeks (p=0.06), and then increased at 52 weeks (p<0.005). The concentrations of anti-CCP at baseline, 12 weeks, and 52 weeks were 201±40, 188±39, and 248±52 U/mL, respectively. These changes in anti-CCP levels were greater than in biologics- naïve patient group. RF titers decreased in association with the improvement in RA disease activity (p<0.0001). RF titers at baseline, 12 weeks, and 52 weeks were 157±37, 107±26, and 98±26 IU/mL, respectively.

Conclusions RF titers may be useful for RA treatment not only as a diagnostic tool but also for monitoring the efficacy of TCZ therapy. However, although TCZ treatment directly influenced anti-CCP titers, these changes were not associated with clinical response to TCZ therapy. These results suggested that TCZ treatment had different effects on anti-CCP and RF production in RA patient sera. We conclude that anti-CCP and RF might be independent antibodies in the immune network of RA.

Disclosure of Interest None Declared