NEWS

Our researchers published a paper on efficacies of 3 Arthritis biologic agents: infliximab, tocilizumab, and abatacept.

Journal:

Arthritis Research & Therapy

Title:

Identification of baseline gene expression signatures predicting therapeutic responses to three biologic agents in rheumatoid arthritis: a retrospective observational study.

Authors:

Seiji Nakamura, Katsuya Suzuki, Hiroshi Iijima, Yuko Hata, Chun Ren Lim, Yohei Ishizawa, Hideto Kameda, Koichi Amano, Kenichi Matsubara, Ryo Matoba, Tsutomu Takeuchi.

Abstract:

Background
According to recommendations by EULAR, prescription of biological DMARDs (bDMARDs) such as tumor necrosis factor inhibitor (TNFi), tocilizumab (TCZ), and abatacept (ABT) to rheumatoid arthritis (RA) patients who have shown insufficient response to conventional synthetic DMARDs, are in parallel. For the past decade, although there have been prediction studies of therapeutic response of bDMARDs using gene expression profiles, most focused on only single bDMARD, and implications of the predictive signature from the perspective of RA pathophysiology were not clear. The aim of this study was to identify specific molecular biological features predicting the therapeutic outcomes for multiple bDMARDs, i.e. IFX, TCZ, and ABT, in patients prior to biologic treatment in a unified blood gene expression test platform.

Methods
RA patients who responded inadequately to methotrexate and were later commenced with either IFX (n=140), TCZ (n=38), or ABT (n=31) as their first biologic, were enrolled. Whole blood gene expression data were obtained prior to administration of biologic. The outcomes of the therapy were defined as remission; “REM” and non-remission; “NON-REM”, according to CDAI score at 6 months of biologic therapy. We employed Gene Set Enrichment Analysis (GSEA) to identify functional gene sets differentially expressed between the “REM” and the “NON-REM” groups for each biologic. Then, we compiled “signature scores” for these gene sets and assessed the prediction performances.

Results
GSEA analyses showed that inflammasome genes were significantly upregulated in IFX’s NON-REM compared with its REM. In TCZ’s REM, B cell-specifically expressed genes were upregulated. RNA elongation, apoptosis-related, and NK cell-specifically expressed genes were upregulated in ABT’s NON-REM. Logistic regression analyses showed “signature scores” of inflammasomes, B cell-specifically expressed, and NK cell-specifically expressed genes were significant independent predictive factors for treatment outcome with IFX, TCZ, and ABT, respectively. The AUCs of ROC curves of these signature scores were 0.637, 0.796, and 0.768 for IFX, TCZ, and ABT, respectively.

Conclusions
We have identified original gene expression predictive signatures uniquely underlying the therapeutic effects of IFX, TCZ and ABT. This is, known by far an uprecedented attempt to concomitantly predict therapeutic effects of three drugs using a unified blood gene expression test platform.

RheumaCheck3 (Japanese site)
http://www.dna-chip.co.jp/diagnostic/rheumacheck/index.html

RheumaCheck3 (English site)
http://www.dna-chip.co.jp/en/diagnostic/rheumacheck/index.html