Objective: We investigated the rheumatoid arthritis (RA) diagnostic performances of anti‐cyclic citrullinated peptide antibody (anti‐CCP) and antifilaggrin antibody (AFA) in comparison with RF and matrix metalloproteinase‐3 (MMP‐3).

Methods: We used a second generation enzyme‐linked immunosorbent assay (ELISA) kit for the detection of anti‐CCP. We constructed recombinant human filaggrin, which was citrullinated in vitro by human peptidylarginine deiminase, and subsequently used it as the coating antigen for AFA‐ELISA. A total of 549 RA patients and 208 other rheumatic disease patients were included in the study.

Results: The specificities of anti‐CCP (88.9%) and AFA (94.7%) were superior to those of RF (81.7%) and MMP‐3 (49.5%). The sensitivity of anti‐CCP (87.6%) was superior to all others. However, the sensitivity of AFA (68.7%) was inferior to those of RF (69.8%) and MMP‐3 (75.7%). Furthermore, receiver operating characteristic curves of anti‐CCP and AFA passed closer to the upper left corner than those of RF and MMP‐3, and the areas under the curves (AUC) of AFA and anti‐CCP were significantly larger. In addition, the AUC of anti‐CCP was significantly larger than that of AFA.

Conclusion: ELISA detection of antibodies to citrullinated antigens, especially a second generation anti‐CCP, showed higher discriminative ability than other assays, including RF, and would be useful to aid the diagnosis of RA in clinical practice.