Martin-Mola Emilio, Balsa Alejandro, García-Vicuna Rosario, Gómez-Reino Juan, González-Gay Miguel Angel, Sanmartí Raimon, Loza Estíbaliz
Reumatology Department, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research IdiPAZ, Madrid, Spain.
Rheumatology Unit, D-Médical Clinic, Príncipe de Vergara 44, 28001, Madrid, Spain.
Rheumatol Int. 2016 Aug;36(8):1043-63. doi: 10.1007/s00296-016-3506-3. Epub 2016 Jun 6.
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.
抗瓜氨酸化肽抗体（ACPAs）在类风湿关节炎（RA）的发病及病程中均发挥着重要的致病作用。这些抗体在类风湿关节炎临床症状出现之前就已存在，且在临床和放射学方面均与预后较差相关。本研究的目的是对截至2015年9月发表的关于ACPAs作为RA患者生物制剂治疗反应预测指标的研究进行全面综述。该综述还包括ACPAs的生物学特性、检测方法，以及ACPAs与关节疾病和心血管疾病的关系，还有血清转化的可能作用。对研究肿瘤坏死因子（TNF）抑制剂和托珠单抗的文献综述结果为阴性。对于利妥昔单抗，数据表明与抗环瓜氨酸肽抗体阴性（ACPA(-)）患者相比，抗环瓜氨酸肽抗体阳性（ACPA(+)）患者临床获益的可能性更大，类风湿因子也有过类似描述。尽管如此，其效果并不显著且存在异质性。另一种可能对ACPA(+)患者更有效的药物是阿巴西普。一些研究表明，该药物对ACPA(+)患者更有效，且这些患者的药物留存率更高。在AMPLE试验的一项亚分析中，与滴度较低的患者相比，接受阿巴西普治疗的ACPA滴度非常高的患者有统计学意义的反应。总之，现有研究表明，ACPA的存在或高滴度可能预示着对利妥昔单抗和/或阿巴西普有更好的反应。缺乏关于肿瘤坏死因子抑制剂（TNFi）和托珠单抗的证据。然而，缺乏设计合理的研究来证明某些药物对ACPA(+)患者优于其他药物。
