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Abstract
Recent progress of genetics has dramatically improved pharmacogenetics for human diseases. Several pharmacogenetic assays such as TPMT/azathioprine and CYP2C9/VKORC1/warfarin have been introduced in clinical practice at the present time. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that leads to irreversible joint damage and disability if it is not adequately treated. Although the introduction of anti-TNF therapy has improved the outcome of therapy in RA, a substantial proportion of patients (approximately 30-40%) fail to respond to the drugs. Recently, pharmacogenetic studies have widely been performed to search for genetic and mRNA expression biomarkers to predict the response of anti-TNF therapy in RA. Other potential serum biomarkers of response have also been explored including cytokines and autoantiboides. None has yet been validated for biomarkers that predict the response of biologic drugs in clinical rheumatology practice. However, future medicine using pharmacogenetic applications in RA might make personalized therapy possible.
Figures and Tables
Fig. 1
Simple x-rays of hands of patients with rheumatoid arthritis shows the ulnar deviation of both hands, joint space narrowing of wrist and metacarpophalangeal joints, and periarticular osteopenia.
Fig. 2
Genetic and environmental factors influence on both stages of rheumatoid arthritis (RA) development, asymptomatic autoantibody positive preclinical RA and clinical RA.
Table 2
Recommended Daily Warfarin doses (mg/day) to Achieve a Therapeutic INR Based on CYP2C9 and VKORC1 Genotype using the Warfarin Product Insert Approved by the United States Food and Drug Administration. Reproduced from Updated Warfarin (Coumadin®) Product label [6]
Ref. 6 with permission from Nature Publishing Group
Table 4
Clinical Markers to Predict the Response of anti-TNF Therapy
DMARD, disease modifying anti-rheumatic drug; DAS28, Disease Activity Score 28; EULAR, The European League Against Rheumatism; ACR, American College of Rheumatology; HAQ, Health assessment questionnaire
Ref. 15 with permission from BMJ Publishing Group
Table 6
Pharmacogenetic study for anti-TNF therapy in rheumatoid arthritis (candidate gene approach) (*E-Etanercept, I-Infliximab, A-Adalimumab) [19]
TNF, Tumor necrosis factor; ACR, American College of Rheumatology; DAS28, Disease Activity Score 28; EULAR, The European League Against Rheumatism
Ref. 19 with permission from Future Medicine
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