By integrating IL-6-mediated suppression of hepatic enzyme expression into a mechanistic PBPK framework, the authors successfully predicted the altered pharmacokinetics of several CYP substrates (including caffeine, S-warfarin, omeprazole, dextromethorphan, midazolam, and simvastatin) in the RA population. This evidence concerns the gene IL6 and rheumatoid arthritis.