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

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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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Funding

We received an unrestricted grant from BMS to perform this review. They did not intervene in the discussions or in the elaboration of the manuscript. BMS only support us updating references when required.

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Authors and Affiliations

  1. Reumatology Department, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research IdiPAZ, Madrid, Spain

    Emilio Martin-Mola & Alejandro Balsa

  2. Reumatology Department, Hospital Universitario la Princesa, IIS-IP, Madrid, Spain

    Rosario García-Vicuna

  3. Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

    Juan Gómez-Reino

  4. Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Department, IDIVAL, Universidad de Cantabria, Santander, Spain

    Miguel Angel González-Gay

  5. Arthritis Unit, Rheumatology Service, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain

    Raimon Sanmartí

  6. Instituto de Salud Musculoesquelética, Madrid, Spain

    Estíbaliz Loza

  7. Rheumatology Unit, D-Médical Clinic, Príncipe de Vergara 44, 28001, Madrid, Spain

    Emilio Martin-Mola

Authors
  1. Emilio Martin-Mola
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  2. Alejandro Balsa
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  3. Rosario García-Vicuna
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  4. Juan Gómez-Reino
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  5. Miguel Angel González-Gay
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  6. Raimon Sanmartí
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  7. Estíbaliz Loza
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Corresponding author

Correspondence to Emilio Martin-Mola.

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Conflict of interest

E.M.M. received grants as advisor and honorarium as speaker bureau from: MSD, Roche, BMS, Hospira; Kern Pharma, Biogen, and Janssen. A.B. received funding for research from Roche, Abbvie, Pfizer, and UCB, has participated on advisory boards for BMS, UCB, Pfizer, and Roche, and has participated as speakers for Roche, BMS, MSD, Pfizer, UCB, and Abbvie. R.G.V. received funding for research or teaching from MSD, Roche, BMS, Abbvie, and UCB, has participated on advisory boards for Actelion, BMS, UCB, Pfizer, Roche, Hospira, Janssen, and Sandoz, and has delivered presentations sponsored by Roche, BMS, Pfizer, UCB, and Sandoz. J.G.R. is on the advisory boards of AbbVie, BMS, Hospira, Jansen, MSD, Pfizer, Roche, and UCB, has received lecture fees from BMS, Roche, MSD, and Pfizer, and has received research grants from Pfizer and Roche. M.A.G.-G. received grants/research support from Abbott, MSD, and Roche and consultation/ participation fees in company-sponsored speaker’s bureaus from Abbott, Pfizer, Roche, and MSD. R.S. is member of the Advisory Board of the la MHDA Evaluation Committee, Cat-Salut, Generalitat de Catalunya; conferences/advisory boards sponsored by Abbott/Abbvie, BMS, MSD, Roche, UCB, Pfizer, funding for research projects from BMS, MSD, Roche, UCB, Pfizer, FER, and SCR, and funding for training projects from MSD, BMS, and Abbvie. E.L. received funding for research projects from BMS, Abbvie, Roche, MSD, Pfizer, UCB, Gebro, and Novartis.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Martin-Mola, E., Balsa, A., García-Vicuna, R. et al. Anti-citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review. Rheumatol Int 36, 1043–1063 (2016). https://doi.org/10.1007/s00296-016-3506-3

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  • DOI: https://doi.org/10.1007/s00296-016-3506-3

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