Background ACPA has been reported to exacerbate inflammation, activate osteoclasts, and stimulate bone resorption1). At least thus far ACPA has been no more than a diagnostic marker, and its potential for use in treatment monitoring has not been considered. There has also been almost no research on this point with TCZ, a unique drug which inhibits IL-6.
Objectives Changes in ACPA during TCZ treatment and whether those changes can predict RRP were examined prospectively in RA patients with inadequate response to existing treatment.
Methods The subjects were patients diagnosed with RA by the 1987 classification criteria of the American College of Rheumatology (ACR). The enrollment period was for 2 years from May 2008, and the observation period was 52 weeks. TCZ 8 mg/kg was administered at 4-week intervals. Anti-CCP antibody was measured using enzyme-linked immunosorbent assay (ELISA) at each TCZ administration. Disease activity was assessed using DAS28-ESR and CDAI. The inhibitory effect on joint destruction was assessed by the correlation of the rate of change in ACPA after 4 weeks and 12 weeks of TCZ administration and RRP [Δmodified Total Sharp Score(mTSS) >3] after 1 year. The chi-squared test and the Wilcoxon test were used for the statistical analysis.
Results Fifty-eight patients were enrolled. The subjects of analysis who could be evaluated before and after administration were 44 patients for ACPA measurement and 39 patients for inhibitory effect on joint destruction. Median [IQR] ACPA levels after 1 year decreased from 91 [26-373] to 50 [12-194] (P<0.05, Fig 1). No correlation of ACPA changes with changes DAS28-ESR or CDAI was observed. After 1 year, ΔmTSS/y improved from 12.3 to -0.1. RRP was observed in 4 patients. When the RRP group and non-RRP group were compared, the mean change in ACPA after 4 weeks was a 2% decrease in the RRP group, but it was a 16% decrease in non-RRP group (P=0.09, Fig2).
Conclusions It was confirmed that ACPA significantly decreased after 52 weeks due to TCZ treatment. This was the first time that such a decrease was reported from treatment for the inhibition of IL-6. Since the rate of change in ACPA after 4 weeks tended to be low in the RRP group, it is possible that RRP after 52 weeks can be predicted.
J Clin Invest. 2012; 122(5):1791-802.
Disclosure of Interest: None Declared