For a better understanding of Tregalizumab's dose–response effects in patients, a pharmacokinetic–pharmacodynamic model was developed using the downmodulation of the CD4 molecule on the T-cell surface as pharmacodynamic marker (Rharbaoui et al., manuscript in preparation).32 The pharmacokinetic–pharmacodynamic model based on clinical data from RA and healthy volunteer trials surprisingly showed higher CD4 downmodulation in healthy subjects compared with RA patients (Figure 1b). The gene discussed is CD4; the disease is rheumatoid arthritis.