Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Anti-citrullinated protein antibodies (ACPA) are a marker of RA and may contribute to disease progression.1,2 ACPA analysis in patients offers the opportunity to estimate whether specific intervention during early disease may have an impact on the maturation of the ACPA response and a subsequent altering effect on the course of the disease process. Here we assessed the impact on ACPA isotypes and the number of specific epitopes recognized in patients with early RA from the AVERT study who were treated with abatacept (ABA) + methotrexate (MTX), ABA monotherapy or MTX alone.
Methods: Patients enrolled in AVERT had symptomatic synovitis in ≥2 joints for ≥8 weeks with an onset of symptoms ≤2 years, were anti-cyclic citrullinated peptide 2 positive and naïve to both MTX and biologic treatment.3 ACPA isotype and the epitope analysis of 6 specificities were performed using custom ELISA assays and were measured in patient serum at baseline, and at Days 85 and 365.1,2 Adjusted mean change from baseline was calculated using a longitudinal repeated measures model.
Results: Baseline means for the IgG isotype were 585.0 (ABA + MTX), 515.2 (ABA) and 575.5 (MTX) U/mL. IgM baseline means were 23,613 (ABA + MTX), 24,221 (ABA) and 28,377 (MTX) U/mL. Baseline means for the IgA isotype were 10,127 (ABA + MTX), 11,098 (ABA) and 12,335 (MTX) U/mL. Adjusted mean (+95% CI) unit changes in ACPA isotype from baseline to Days 85 and 365 are shown (Table). Of the 6 epitopes tested, the average baseline net numbers recognized were 2.6 (ABA + MTX), 2.69 (ABA) and 2.88 (MTX). Consistent with reductions in the ACPA isotypes, from baseline to Day 365, treatment with ABA + MTX reduced the average (+95% CI) net number of epitopes recognized by -0.82 (-1.03, -0.61) compared with -0.32 (-0.54, -0.10) for ABA alone or -0.42 (-0.64, -0.20) for MTX alone.
Table: Adjusted mean change from baseline (+95% CI) for ACPA isotypes (U/mL)
|
Day 85 |
Day 365 |
||||||
|
IgG |
IgM |
IgA |
IgG |
IgM |
IgA |
||
|
ABA |
-47.26 (-88.85, -5.66) |
-3270 (-4898, -1642) |
636.1 (-930.4, 2202) |
-13.81 (-67.79, 40.17) |
-356 (-3096, 2382) |
3186 (843.2, 5529) |
|
|
MTX |
-22.94 (-63.66, 17.78) |
-4604 (-6204, -3004) |
-1794 (-3331, -256.6) |
-30.07 (-84.51, 24.38) |
-4591 (-7345, -1838) |
-1914 (-4269, 440.1) |
|
|
ABA + MTX |
-70.58 (-110.9, -30.27) |
-6392 (-7975, -4809) |
-2434 (-3957, -910.8) |
-135.6 (-178.4, -83.82) |
-6363 (-8991, -3735) |
-2230 (-4479, 19.30) |
|
Conclusion: Baseline levels of each ACPA isotype and net number of epitopes recognized were comparable across the 3 treatment arms. Concentrations of all ACPA isotypes (IgM, IgA, IgG) were substantially reduced by abatacept + MTX therapy to a greater extent than by either MTX or abatacept alone. Abatacept + MTX also reduced the average number of epitopes recognized over 1 year of treatment more than either monotherapy arms. These results indicate that abatacept impacts the maturation of the ACPA response in patients with early RA, suggesting an alteration in the course of the autoimmune disease process.
1. Verpoort KN, et al. Arthritis Rheum 2006;54:3799-808.
2. van der Woude D, et al. Ann Rheum Dis 2010;69:1554-61.
3. Emery P, et al. Ann Rheum Dis 2014:73(Suppl 2):69.
Disclosure:
T. W. J. Huizinga,
Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly,
5,
Meteor Board,
6,
EU & Dutch Arthritis Foundation,
2,
Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough,
8,
Abbott Laboratories, Roche,
9;
S. E. Connolly,
Bristol-Myers Squibb,
3,
Bristol-Myers Squibb,
1;
D. E. Furst,
AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
2,
AbbVie, Actelion, Amgen, BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
5,
AbbVie, Actelion, UCB,
8;
V. P. Bykerk,
Amgen, Pfizer, BMS, Janssen, UCB, Roche/Genentech,
2;
G. Burmester,
AbbVie, Pfizer, Roche, UCB,
2,
AbbVie, BMS, MSD, Medimmune, Novartis, Pfizer, Roche, Sandoz, UCB,
5,
AbbVie, BMS, MSD, Pfizer, Roche, Sandoz, UCB,
8;
B. G. Combe,
Pfizer, Roche-Chugai,
2,
BMS, Merck, Pfizer, Roche-Chugai, UCB,
8;
C. S. Karyekar,
Bristol-Myers Squibb,
3;
D. Wong,
Bristol-Myers Squibb,
1,
Bristol-Myers Squibb,
3;
L. Trouw,
None;
R. E. M. Toes,
None;
P. Emery,
AbbVie, BMS, Merck, Pfizer, Roche, Takeda,
5,
AbbVie, BMS, Merck, Pfizer, Roche,
2.
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