Efficacy of anti-TNF biologic agent, infliximab, for RA patients using transcriptome analysis of white blood cells

Introduction of biologics, such as infliximab, to the therapy of rheumatoid arthritis (RA) patients has revolutionized the treatment of this disease. However, biomarkers for predicting the efficacy of the drug at an early phase of treatment for selecting real responders have not been found. We here present predictive markers based on a thorough transcriptome analysis of white blood cells from RA patients. RNA from whole blood cells of consecutive 42 patients before the first infusion was analyzed with microarrays for training studies. Samples from the subsequent 26 consecutive patients were used for a prospective study. We categorized the results into no inflammation and residual inflammation groups using the serum C-reactive protein (CRP) level at 14 weeks after the first infusion. The accuracy of prediction in our study was 65.4%. Forty-two and 26 consecutive RA patients followed at Saitama Medical Center, for retrospective and verification studies, respectively, who were resistant to standard MTX treatment, were enrolled. The serum CRP level was used for the definition of the level of inflammation of each patient, 0.3 mg/dl or less as “no inflammation” (NI), and more than 0.3 mg/dl as “residual inflammation” (RI) at 14 weeks after the first treatment with infliximab infusion. Differentially expressed genes between the NI and RI patients in the retrospective/training set were extracted, and these genes were verified using the verification set.