TNF-α level affects etanercept clearance: TNF-α concentration as a new correction factor of allometric scaling to predict individual etanercept clearances in patients with ankylosing spondylitis.

Etanercept (ETN) is a widely used anti-tumour necrosis factor-alpha (TNF-alpha) agent, which relieves the symptoms of ankylosing spondylitis (AS) by binding to TNF-alpha to inhibit its inflammation effects. In this study, the effect of TNF-alpha level on ETN clearance (CL) was investigated, and the TNF-alpha concentration was initially set as a correction factor for allometric scaling to improve the predictions of individual ETN CLs. Individual ETN CLs and TNF-alpha concentrations in healthy volunteers and patients with AS were determined by performing ETN pharmacokinetic studies in the two cohorts. Accordingly, individual ETN CLs in both healthy volunteers and patients with AS were predicted from data of two animal species using different methods, including simple allometric scaling, scaling with a correction factor of maximum life span potential or brain weight, and scaling with a correction factor of the TNF-alpha concentration. The accuracies of such predictions were evaluated by the percentage errors. Consequently, increased TNF-alpha concentration was shown to improve ETN CL, by comparing both ETN CLs and TNF-alpha concentrations between healthy volunteers and patients with AS. More importantly, better predictions of individual ETN CLs were achieved in patients with AS using allometric scaling with TNF-alpha concentration as the correction factor. In conclusion, in vivo levels of TNF-alpha can affect ETN CL, and allometric scaling corrected with the TNF-alpha concentration can be used to estimate the individual CLs of anti-TNF-alpha monoclonal antibodies based on preclinical data.