Background Anti-citrullinated protein antibodies (ACPA) aggravate inflammation, activate osteoclasts, and accelerate bone resorption in RA patients.1 We previously reported that a decrease in ACPA was observed during 52 weeks of TCZ therapy, and that there was a possibility of rapid radiographic progression being predicted from ACPA levels.2 However, the predictability of long-term progression of articular destruction in terms of changes in ACPA in patients on TCZ, the only IL-6 inhibitor currently available, remains unclear.
Objectives This study aimed to examine whether changes in ACPA during 104 weeks of TCZ therapy can serve as a predictive factor for long-term progression of articular destruction in RA patients not adequately responding to existing treatment.
Methods This was a long-term administration study carried out in succession to the Actor Study that began in 2008. The observation period in this study was 104 weeks. TCZ at a dose of 8 mg/kg was given every 4 weeks. Anti-CCP antibodies were measured by enzyme-linked immunosorbent assay (ELISA) at each TCZ administration. Changes in ACPA and progression of articular destruction were evaluated over 104 weeks. The relationships between ACPA changes at 4, 12, and 24 weeks of TCZ therapy and the modified total sharp score (mTSS) at 2 years were evaluated.
Results Of 58 patients who enrolled in the Actor Study, 22 in whom the study parameters were measurable over 104 weeks were evaluated in this study. The median ACPA level [interquartile range] decreased from 154 [52-545] before therapy to 70 [19-319] after 104 weeks of therapy (P=0.05). There was no correlation between changes in ACPA and changes in DAS28 or CDAI after 104 weeks of therapy. Progression of articular destruction was found in 4 patients. When patients who showed progression of articular destruction were compared with those without such progression (defined as ΔmTSS<0.5 per year), the ACPA level tended to be higher in the former at 24 weeks (P=0.05).
Conclusions The results confirmed ACPA to also be decreased by TCZ therapy lasting as long as 104 weeks. This study, together with the previous report of the Actor Study, has provided the first evidence of ACPA being decreased by an IL-6 inhibitor. In addition, the fact that the ACPA level was high until 24 weeks in patients with progression of articular destruction raises the possibility that articular destruction over a long period can be predicted by ACPA.
J Clin Invest. 2012;122(5):1791-802.
Sagawa A. Ann Rheum Dis 2013;72(Suppl3):445
Disclosure of Interest None declared
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