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Abstract Number: 2869

Significant Decrease of T-Cells but Not Macrophages in the Synovium of Patients with Active Rheumatoid Arthritis after Treatment with Tocilizumab

Katerina Chatzidionysiou1, Marianne Engström1, Erik af Klint1, Aase Hensvold1 and Anca I Catrina2, 1Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 2Department of Medicine, Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: rheumatoid arthritis, synovium and tocilizumab, T cells

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Session Information

Date: Tuesday, November 7, 2017

Session Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy IV: Pharmacodynamic Markers and Therapeutic Intervention

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Tocilizumab (TCZ) is an anti-IL6R monoclonal antibody approved for the treatment of Rheumatoid Arthritis (RA). There is limited data on synovial tissue histology changes. The aim of this study was to characterize the synovial tissue histological changes after treatment with TCZ and to investigate the effect of treatment on citrullination.

Methods: 15 patients with definite RA, according to ACR 1987 criteria, independent of disease duration, who failed treatment with at least one conventional synthetic or biologic disease modifying anti-rheumatic drug (DMARD) were included. Synovial biopsies were obtained before and after 8 weeks of treatmentwith TCZ from all patients. Clinical evaluation was performed at baseline and at the time of the second synovial biopsy. We evaluated by immunohistochemistry (IHC) expression of citrullinated proteins (CP) and protein arginine deiminase (PAD) enzymes in synovial tissue before and after treatment with TCZ (C03, B09, BVCA1, PAD2, PAD4). Negative controls were used for each antibody. Expression of CD68, CD3 and CD55 was also evaluated. Evaluation of all IHC variables was performed by two blinded independent observers using a semiquantitative score on a 0–3 scale (0, no staining; 1, low amounts of staining; 2, moderate amounts of staining; 3, high amounts of staining). Paired-wised Wilcoxon Signed Ranks Test was used to compare the median value before and after treatment.

Results:

The median (IQR) age, disease duration, N. prior biologic DMARDs and DAS28 at baseline was 66 (58-79), 4 (1-13), 1 (0-2), 6 (5-7), respectively. 93% were female, 53% were RF + and 60% ACPA+, 53% had concomitant glucocorticoids and only 27% had concomitant conventional synthetic DMARDs. Significant reductions in DAS28, swollen and tender joint count (SJC and TJC, respectively), and acute phase reactants (ESR and CRP) were observed between baseline and 8 weeks (table 1). By IHC, TCZ induced significant decrease in the number of CD3, C03 and CD55, but not in the number of the other CP, PAD2, PAD4 and CD68 (table 1). No significant correlations between reduction in disease activity (by ΔDAS28, ΔSJC, ΔTJC, ΔESR, ΔCRP) and reduction in CP, CD68 or CD3 were found.

Conclusion: IL6R blockade leads to significant decrease in synovial T-cell count. No clear impact on citrullination was observed. Interestingly, no effect on the number of macrophages was found.

Basline

12 weeks

Wilcoxon Signed Ranks Test

DAS28 BL

5.9 (4.7-6.8)

2.98 (2.0-3.8)

0.028

SJC BL

9 (3-14)

1 (0-4.25)

0.009

TJC BL

10 (4-15)

1 (0-2.25)

0.017

ESR BL

34 (15-69)

6 (5-16)

0.001

CRP BL

11 (5-27)

1 (1-2)

0.005

CD68

2 (1-3)

2 (0.75-3)

0.41

CD3

2 (1-3)

1 (0-2)

0.046

G09 (cit)

0 (0-2)

0 (0-2)

0.862

C03 (cit)

1 (0-1)

0 (0-1)

0.025

BVCA1 (cit vim)

1 (0-1)

0 (0-1)

0.18

B09 (cit)

2 (1-2)

2 (1-2)

0.20

PAD2

3 (2-3)

2 (1.5-3)

0.16

PAD4

2 (2-3)

2 (2-3)

0.37

CD55

2 (2-3)

1.5 (1-2)

0.05

Table 1. Clinical and IHC changes between 0 and 8 weeks after treatment with TCZ.

Disclosure: K. Chatzidionysiou, Lilly, AbbVie, Roche, Pfizer, 5; M. Engström, None; E. af Klint, None; A. Hensvold, None; A. I. Catrina, None.

To cite this abstract in AMA style:

Chatzidionysiou K, Engström M, af Klint E, Hensvold A, Catrina AI. Significant Decrease of T-Cells but Not Macrophages in the Synovium of Patients with Active Rheumatoid Arthritis after Treatment with Tocilizumab [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/significant-decrease-of-t-cells-but-not-macrophages-in-the-synovium-of-patients-with-active-rheumatoid-arthritis-after-treatment-with-tocilizumab/. Accessed August 12, 2022.
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