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

T. W. J. Huizinga¹, SE Connolly², A Johnsen², J Zhu², Daniel E. Furst³, VP Bykerk⁴, Gerd Burmester⁵, BG Combe⁶, DA Wong², LA Trouw¹, René E. M. Toes¹ and Paul Emery⁷, ¹Leiden University Medical Center, Leiden, Netherlands, ²Bristol-Myers Squibb, Princeton, NJ, ³Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, ⁴Weill Cornell Medical College, New York, NY, ⁵Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, ⁶Montpellier University, Montpellier, France, ⁷University of Leeds, Leeds, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Abatacept, anti-CCP antibodies and anti-citrullinated protein/peptide antibodies (ACPA)

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:
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.²The objective of this analysis was to assess the efficacy of treatment
with ABA+MTX, ABA monotherapy or MTX alone in patients
(pts) from the AVERT trial based on their anti-cyclic
citrullinated peptide 2 (CCP2; a surrogate for ACPA) IgM serostatus at baseline (BL), 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, pt samples were analysed by ELISA to
determine anti-CCP2 IgM serostatus. Efficacy outcomes analyzed by BL anti-CCP2
IgM serostatus included remission rate at 12 mths (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 Mth 12 and analyzed
with a longitudinal repeated-measures model). Boolean
remission was analyzed in pts who seroconverted. Results: In the ABA+MTX treatment arm, a higher proportion of pts who were
anti-CCP2 IgM positive at BL achieved remission by all indices compared with
pts who were BL IgM negative (Figure). 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 either the ABA
monotherapy or MTX alone arms. Mean improvement in DAS28 (CRP) and HAQ-DI
over time was also greatest in BL anti-CCP2 IgM-positive pts treated with
ABA+MTX. A numerically higher proportion of pts who
seroconverted from anti-CCP2 IgM positive at BL to negative at Mth 12 achieved
Boolean remission versus pts who remained seropositive in the ABA+MTX and ABA
monotherapy arms (Table).

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

1.
Verpoort
KN, et al. Arthritis Rheum 2006;54:3799–808.

2.
Huizinga
TWJ, et al. Arthritis Rheum 2014;66:S666. Poster 1515.

3.
Emery
P, et al. Ann Rheum Dis 2015:74:19–26.

4.
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.

Disclosure: T. W. J. Huizinga, Merck, UCB, BMS, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer, Takea, Zydus, and Eli Lilly., 5,Roche & Abbott, 9; S. Connolly, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; A. Johnsen, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; J. Zhu, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; D. E. Furst, Gilead, 2,GlaxoSmithKline, 2,NIH, 2,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,Genentech and Biogen IDEC Inc., 2,UCB, 2,Abbvie, 5,Actelion Pharmaceuticals US, 5,Amgen, 5,Bristol-Myers Squibb, 5,Cytori, 5,Janssen Pharmaceutica Product, L.P., 5,Gilead, 5,GlaxoSmithKline, 5,NIH, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,Genentech and Biogen IDEC Inc., 5,UCB, 5,Abbvie, 8,Actelion Pharmaceuticals US, 8,Bristol-Myers Squibb, 2,Amgen, 2,Actelion Pharmaceuticals US, 2,Abbvie, 2,UCB, 8; V. Bykerk, Genentech, BMS, UCB, BIPI, 2,Amgen, Abbvie, BMS, UCB, Antares, Regeneron, Genentech, 5,Novartis and Biogen, 3; G. Burmester, Abbvie, Pfizer, UCB, Roche, 2,Abbvie, BMS, Pfizer, Merck, MedImmune, UCB, Roche, 5,Abbvie, BMS, Pfizer, Merck, UCB, Roche, 8; B. Combe, Pfizer, Roche-Chugai, 2,BMS, Merck, Pfizer, Roche-Chugai, UCB, 8; D. Wong, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; L. Trouw, None; R. E. M. Toes, None; P. Emery, Abbott/Abbvie, Bristol-Myers Squibb, Pfizer, UCB, MSD, Roche, Novartis, Samsung, Takeda, Lilly, 5.

To cite this abstract in AMA style:

Huizinga TWJ, Connolly S, Johnsen A, Zhu J, Furst DE, Bykerk V, Burmester G, Combe B, Wong D, Trouw L, Toes REM, Emery P. Effect of Anti-Cyclic Citrullinated Peptide 2 Immunoglobulin M Serostatus on Efficacy Outcomes Following Treatment with Abatacept Plus Methotrexate [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/effect-of-anti-cyclic-citrullinated-peptide-2-immunoglobulin-m-serostatus-on-efficacy-outcomes-following-treatment-with-abatacept-plus-methotrexate/. Accessed .

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