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43. Kongress der Deutschen Gesellschaft für Rheumatologie, 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 25. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

02.-05. September 2015, Bremen

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Effect of Anti-Cyclic Citrullinated Peptide 2 Immunoglobulin M Serostatus on Efficacy Outcomes Following Treatment with Abatacept Plus Methotrexate in the AVERT Trial

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  • Tom Huizinga - Leiden University Medical Center, Department of Rheumatology, Leiden, The Netherlands
  • S.E. Connolly - Bristol-Myers Squibb, Princeton, United States of America
  • A. Johnsen - Bristol-Myers Squibb, Princeton, United States
  • J. Zhu - Bristol-Myers Squibb, Princeton, United States of America
  • D. Furst - University of California at Los Angeles, Los Angeles, United States of America
  • Vivian Bykerk - Weill Cornell Medical College, New York, United States of America
  • Gerd-Rüdiger Burmester - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Bernard Combe - Montpellier University, Montpellier, France
  • D. Wong - Bristol-Myers Squibb, Princeton, United States of America
  • Leendert Trouw - Leiden University Medical Center, Department of Rheumatology, Leiden, The Netherlands
  • René Toes - Leiden University Medical Center, Department of Rheumatology, Leiden, The Netherlands
  • Paul Emery - Johns Hopkins University, Baltimore, United States

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Bremen, 02.-05.09.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocRA.18

doi: 10.3205/15dgrh185, urn:nbn:de:0183-15dgrh1852

Published: September 1, 2015

© 2015 Huizinga et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Introduction: Anti-citrullinated protein antibodies (ACPA) are a marker of RA, and the presence of the immunoglobulin M (IgM) isotype indicates an ongoing immune response involving the recruitment of naïve B cells [1]. Abatacept (ABA) modulates T-cell co-stimulation and has been shown to impact ACPA maturation, including seroconversion of IgM, in the AVERT (Assessing Very Early Rheumatoid arthritis Treatment) trial [2]. Here, we assessed the efficacy of treatment with ABA+MTX, ABA monotherapy or MTX alone in patients from AVERT based on their anti-cyclic citrullinated peptide 2 (CCP2; a surrogate for ACPA) IgM serostatus at baseline, and seroconversion (anti-CCP2 IgM positive to negative) through 1 year.

Methods: The AVERT trial has been described previously [3]. In this post hoc analysis, patient samples were analysed using ELISA to determine anti-CCP2 IgM serostatus. Efficacy outcomes analysed by baseline anti-CCP2 IgM serostatus included remission rate at 12 months (CDAI, SDAI, Boolean and DAS28 [CRP] <2.6-defined remission), and adjusted mean change in DAS28 (CRP) and HAQ-DI over time (samples taken every 28 days up to Month 12 and analysed with a longitudinal repeated-measures model). Boolean remission was analysed in patients who seroconverted.

Results: In the ABA+MTX arm, a higher proportion of patients who were anti-CCP2 IgM positive at baseline achieved remission by all indices compared with patients who were baseline IgM negative (Figure 1 [Fig. 1]). This trend was most clearly observed in the stringent indices of CDAI, SDAI and Boolean remission, compared with DAS28 (CRP)-defined remission. This trend was not observed in the ABA monotherapy and MTX alone arms. Mean improvement in DAS28 (CRP) and HAQ-DI over time was also greatest in baseline anti-CCP2 IgM-positive patients treated with ABA+MTX. A numerically higher proportion of patients who seroconverted from anti-CCP2 IgM positive at baseline to negative at Month 12 achieved Boolean remission versus patients who remained seropositive in the ABA+MTX and ABA monotherapy arms (Table 1 [Tab. 1]).

Conclusion: Abatacept in combination with MTX had greater clinical efficacy in patients who were anti-CCP2 IgM positive at baseline than in those who were negative at baseline, and in those who seroconverted over time than those who did not, suggesting that the impact on ACPA is associated with clinical benefit.

Note: This abstract was first presented at the EULAR Congress, 10–13 June 2015, Rome, Italy (THU0114) and published in the corresponding supplement of Ann Rheum Dis.

Outline

References

1.
Verpoort KN, Jol-van der Zijde CM, Papendrecht-van der Voort EA, Ioan-Facsinay A, Drijfhout JW, van Tol MJ, Breedveld FC, Huizinga TW, Toes RE. Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response. Arthritis Rheum. 2006 Dec;54(12):3799-808.
2.
Huizinga TWJ, et al. Arthritis Rheum. 2014;66:S666. Poster 1515.
3.
Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barré E, Karyekar CS, Wong DA, Huizinga TW. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015 Jan;74(1):19-26. DOI: 10.1136/annrheumdis-2014-206106 External link