Soluble Interleukin-2 Receptor Levels and The CD4/CD8 Ratio As Predictors Of The Efficacy Of Abatacept In Biologics-naïve Rheumatoid Arthritis Patients

Hajime Sano¹, Masahiro Sekiguchi¹, Masayasu Kitano¹, Naoto Azuma¹, Shinichiro Tsunoda¹, Kiyoshi Matsui¹ and Tsuyoshi Iwasaki², ¹Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya-city, Japan, ²Department of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: abatacept and remission, CD T cells, Disease Activity

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy III

Session Type: Abstract Submissions (ACR)

Background/Purpose: Abatacept (ABT) is a recombinant fusion protein consisting of the extracellular domain of human CTLA-4, binding to CD80/86 on antigen presenting cells and thereby inhibits the interaction between these molecules and CD28 on T cells. ABT suppresses T cell activation and has been reported to have the therapeutic benefit for patients with rheumatoid arthritis (RA). However, there are limited data to compare the efficacy of ABT and biomarkers of T cell activation. Soluble IL-2 receptor (sIL-2R) is a marker of T-cell activation in diseases including RA and various cancers. The aim of this study was to investigate the relationship between the efficacy of ABT and biomarkers of T cell activation such as sIL-2R and CD4/CD8 ratio in biologics-naïve RA patients.

Methods: We analyzed 24 biologic-naïve RA patients treated with ABT from January 2010 to May 2012. (Patients received 10 mg/kg abatacept plus MTX during 24 weeks). To evaluate the efficacy of the treatment, we measured DAS28-CRP (DAS), CRP and MMP-3 levels at week 0, 4, 12 and 24 after treatment. We also examined serum levels of sIL-2R and peripheral blood CD4/CD8 ratio before and after treatment with ABT. sIL-2R and peripheral blood CD4+/CD8+ lymphocytes were analyzed using ELISA and flow cytometry.

Results: At week 0, 4 and 24 after ABT treatment, the mean DAS score and serum CRP/ MMP-3/sIL-2R levels were DAS (4.5→3.5→2.8), CRP (2.1→1.1→0.8 mg/dl), MMP-3 (219.1→169.7→114.1 ng/dl), and sIL-2R (441→259→232 U/ml), respectively. We observed statistically significant reduction of DAS scores and serum CRP/MMP-3/sIL-2R levels at week 4 after ABT treatment. The reduction of DAS scores was higher in patients who reduced more than 50% of sIL-2R than in patients who reduced less than 50% at week 4 after treatment (1.18 vs 0.61, p=0.023). At week 0 and 4 after ABT treatment, the mean CD4/CD8 ratio was not statistically different (2.00 vs 2.05). However, the reduction of DAS scores was higher in patients who reduced CD4/CD8 ratio after treatment than in patients who increased CD4/CD8 ratio (1.09 vs 0.60, p=0.014).

Conclusion: We observed the efficacy of ABT at week 4 after treatment of biologic-naïve RA patients. We also observed that the reduction of sIL-2R and CD4/CD8 ratio after treatment correlated with improvement of DAS scores. These results indicate that the decreased serum sIL-2R levels and peripheral blood lymphocyte CD4/CD8 ratio after treatment is a predictor of the efficacy of ABT in biologics-naïve RA patients.

Disclosure:

H. Sano,
None;

M. Sekiguchi,
None;

M. Kitano,
None;

N. Azuma,
None;

S. Tsunoda,
None;

K. Matsui,
None;

T. Iwasaki,
None.

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