The Impact of Therapy on Anti-Carbamylated Protein Antibody Isotypes and Serostatus in Patients with Early RA Treated with Abatacept and MTX

LA Trouw¹, SE Connolly², A Johnsen², J Ye², MA Maldonado², REM Toes¹ and TWJ Huizinga¹, ¹Leiden University Medical Center, Leiden, Netherlands, ²Bristol-Myers Squibb, Princeton, NJ

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Abatacept and autoantibodies

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Clinical Aspects Poster I: Treatment Patterns and Response

Session Type: ACR Poster Session A

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

Background/Purpose: Maturation of autoantibody responses has been suggested to be a proxy for disease maturation. Autoantibody responses against post-translationally modified antigens are present in autoimmune diseases and antibodies directed against carbamylated proteins (anti-CarP antibodies) are a marker of RA. Anti-CarP antibody analysis in patients (pts) with early RA offers the opportunity to estimate whether specific intervention during such early stages of autoantibody development may have an impact on the maturation of the anti-CarP antibody response. We assessed the relationship between changes in anti-CarP isotypes and rates of seroconversion to negative (–ve) in pts with early RA. Methods: In the AVERT study (NCT01142726), pts with early RA were treated with abatacept (ABA)+MTX, ABA monotherapy or MTX alone.¹ Pts were anti-cyclic citrullinated peptide-2 positive (+ve) at baseline for study entry.¹ In this post hoc analysis, concentrations of anti-CarP isotypes were measured using custom ELISAs. Anti-CarP ELISAs for immunoglobulin (Ig)G, IgM or IgA isotypes were performed in pt serum at baseline, and at Days 85 and 365 on treatment. Baseline levels of each anti-CarP antibody isotype and % seropositivity were comparable across treatment arms. Adjusted mean change from baseline was calculated using a longitudinal repeated measures model. Results: At baseline, 51.3, 42.5 and 29.3% of all pts with serum available in AVERT were +ve for IgG, IgM (indicative of an ongoing immunoresponse) and IgA anti-CarP isotypes, respectively. Overall, ~65% of pts were +ve for ≥1 anti-CarP antibody isotype. Median % change from baseline (25%, 75%) for anti-CarP isotype levels from baseline to Days 85 and 365 are shown (Table). Analyzing pts who were +ve at baseline for each of the isotypes, we observed that 19/48 (40%), 16/43 (37%) and 11/48 (23%) of pts +ve for the IgG isotype became –ve on ABA+MTX, ABA and MTX, respectively, at 1 year. For the IgM isotype, 26/48 (54%), 14/36 (39%) and 15/38 (39%) became –ve on ABA+MTX, ABA and MTX, respectively. For the IgA isotype, 12/26 (46%), 10/23 (43%) and 13/31 (42%) became –ve on ABA+MTX, ABA and MTX, respectively.

Conclusion: Concentrations of all anti-CarP isotypes (IgM, IgA, IgG) were numerically reduced by abatacept+MTX therapy compared with MTX or abatacept alone. Abatacept+MTX trended towards higher rates of seroconversion to –ve for all isotypes over 1 year of treatment. These results indicate that the extent of the anti-CarP antibody response can be modulated by intervention with abatacept on background MTX in anti-citrullinated protein antibody +ve pts with early RA.

1. Emery P, et al. Ann Rheum Dis 2015;74:19–26. Original abstract © EULAR/BMJ. First presented at EULAR 2017 and published in Ann Rheum Dis 2017;76 (Suppl 2):1135. Any reprints, promotional options, education material etc have to be done through the original source (ARD/BMJ).

Table. Median % Change from Baseline (25%, 75%) for Anti-CarP Isotypes
	Day 85			Day 365
	IgG	IgM	IgA	IgG	IgM	IgA
Abatacept	–17.3 (–55.7, 0.0)	–26.3 (–57.9, 0.0)	–6.8 (–35.1, 0.0)	–31.2 (–67.4, 0.0)	26.0 (-81.2, 0.0)	–26.7 (–72.9, 13.0)
MTX	–19.3 (–53.6, 0.0)	–35.7 (–54.4, –6.9)	–27.2 (–42.4, –3.9)	–17.7 (–65.1, 0.0)	–38.3 (–63.7, 0.0)	–21.9 (–50.3, 0.0)
Abatacept+ MTX	–38.8 (–62.3, 0.0)	–44.2 (–59.5, –13.8)	–41.3 (–54.9, –28.3)	–55.7 (–76.7, 0.0)	–45.7 (–72.5, –0.2)	–46.4 (–66.7, 0.0)

CarP=carbamylated proteins; Ig=immunoglobulin

Disclosure: L. Trouw, None; S. Connolly, Bristol-Myers Squibb, 3,Bristol-Myers Squibb, 1; A. Johnsen, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; J. Ye, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; M. Maldonado, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; R. Toes, None; T. Huizinga, Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, 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.

To cite this abstract in AMA style:

Trouw L, Connolly S, Johnsen A, Ye J, Maldonado M, Toes R, Huizinga T. The Impact of Therapy on Anti-Carbamylated Protein Antibody Isotypes and Serostatus in Patients with Early RA Treated with Abatacept and MTX [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-impact-of-therapy-on-anti-carbamylated-protein-antibody-isotypes-and-serostatus-in-patients-with-early-ra-treated-with-abatacept-and-mtx/. Accessed .

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