CYP3A4 and rheumatoid arthritis: Clinical guidelines recommend an initial cyclosporine dose of 1.25 mg/kg BID in RA patients, and our simulations indicated that this dose generally achieved therapeutic trough concentrations prior to tocilizumab initiation; however, a subset of patients exhibited trough levels above the toxic threshold, likely reflecting baseline variability in IL-6-mediated CYP3A4 suppression (Figure 6).