Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Gene Polymorphisms of Signal Transducers and Activator of Transcription 4 and Tumor Necrosis Factor Receptor-Associated Factor 1 Predict Clinical Response to Disease-Modifying Anti-Rheumatic Drugs in Japanese Patients with Rheumatoid Arthritis.

Nishimoto,  Tetsuya, Seta,  Noriyuki, Anan,  Ryusuke, Yamamoto,  Tatsuya, Kaneko,  Yuko, Kuwana,  Masataka, Takeuchi,  Tsutomu

Background/Purpose:

Several single nucleotide polymorphisms (SNPs) associated with pathophysiology of rheumatoid arthritis (RA) have been identified in recent genome-wide association studies. Although disease-modifying anti-rheumatic drugs (DMARDs) including biologic agents, such as anti-tumor necrosis factor (TNF) drugs, have excellent efficacy against RA, a substantial number of patients still show inadequate responses. The aim of this study is to identify genetic predictors of response to non-biologic DMARDs, especially methotrexate (MTX), and anti-TNF drugs in RA patients using database of a single-centre prospective cohort study of Japanese patients with newly diagnosed and DMARDs-naïve RA (SAKURA study).

Methods:

Fc receptor-like protein 3 (FCRL3) (-169A/G), signal transducers and activator of transcription 4 (STAT4) (+56293G/T), cytotoxic T lymphocyte antigen 4 (CTLA4) (+49G/A), peptidyl arginine deminase type IV (PADI4) (+163A/G), interferon regulatory factor 5 (IRF5) (+198G/T), and TNF receptor-associated factor 1 (TRAF1) (+16860A/G) were genotyped using TaqMan® SNP genotyping assay. We enrolled 114 untreated newly diagnosed Japanese RA patients, and prospectively analyzed the association between the SNPs and clinical response to treatment with DMARDs including biologics or MTX monotherapy as a first line treatment using the 28-joint Disease Activity Score (DAS28) at 24 weeks after registration. Moreover, in 28 RA patients treated with anti-TNF drugs in combination with MTX as a first biologic agent, such as infliximab, etanercept and adalimumab, we prospectively analyzed the association between SNPs and the clinical response using DAS28 and Simplified Disease Activity Index (SDAI) at 24 weeks of treatment.

Results:

There was no association between each SNP and disease activity at baseline. Of 114 RA patients enrolled, 69 (60.5%) were treated with MTX, 41 (36.0%) with other non-biologic DMARDs, and 19 (16.7%) with biologic agents at 24 weeks after registration, although 34 (29.8%) patients were treated with more than one agent. Among them, 51 (44.7%) achieved a good response based on the DAS28 response criteria. FCRL3 (-169A/G) G allele (47.2% versus 30.8%, P=0.011, OR 2.01, 95%CI 1.17–3.45) and STAT4 (+56293G/T) G allele (76.9% versus 58.3%, P=0.003, OR 2.37, 95%CI 1.33–4.21) were increased in patients with a good response, compared with those with a moderate or no response. In 46 RA patients received MTX monotherapy for 24 weeks from diagnosis, 24 (52.2%) achieved a good response, and STAT4 (+56293G/T) G allele (75.0% versus 45.5%, P=0.003, OR 3.60, 95%CI 1.49–8.70) was also increased in patients with a good response. Interestingly, in 28 RA patients treated with anti-TNF drugs in combination with MTX as a first biologic agent, TRAF1 (+16860A/G) A allele was increased in patients with a good response based on DAS28 (88.9% versus 60.0%, P=0.012, OR 5.33, 95%CI 1.35–21.02), and a remission based on SDAI (92.3% versus 66.7%, P=0.020, OR 6.00, 95%CI 1.18–30.62).

Conclusion:

STAT4 (+56293G/T) and TRAF1 (+16860A/G) are possibly useful in predicting the clinical response to MTX monotherapy as a first DMARD and anti-TNF drugs as a first biologic agent respectively.

To cite this abstract, please use the following information:
Nishimoto, Tetsuya, Seta, Noriyuki, Anan, Ryusuke, Yamamoto, Tatsuya, Kaneko, Yuko, Kuwana, Masataka, et al; Gene Polymorphisms of Signal Transducers and Activator of Transcription 4 and Tumor Necrosis Factor Receptor-Associated Factor 1 Predict Clinical Response to Disease-Modifying Anti-Rheumatic Drugs in Japanese Patients with Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2165
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