In the present study, we investigated the effects and mechanisms of action of a combined treatment with etanercept, a soluble tumor necrosis factor receptor (p75) Fc fusion protein, and tacrolimus, a calcineurin inhibitor on the progression of arthritis in human tumor necrosis factor-α (TNF-α) transgenic (hTNF-Tg) mice. Here, TNFRSF1B is linked to arthritic joint disease.