To test the hypothesis that etanercept with concomitant tacrolimus is one of the preferable treatment options to control disease activities for patients with RA, we verified the antirheumatic effects and modes of action of etanercept with concomitant tacrolimus using the hTNF-Tg mouse model, which reflects characteristic features of patients with inadequate responses to anti-TNF-α biologics [11]. The gene discussed is TNF; the disease is rheumatoid arthritis.