Anti‑citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review

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Rheumatol Int DOI 10.1007/s00296-016-3506-3

Emilio Martin‑Mola1,7 · Alejandro Balsa1 · Rosario García‑Vicuna2 · Juan Gómez‑Reino3 · Miguel Angel González‑Gay4 · Raimon Sanmartí5 · Estíbaliz Loza

Abstract Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs’ role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA+ patients versus ACPA− patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA+ patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA+ patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA+ patients.

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