Theory-based analysis of the anti-inflammatory effect of TNF inhibitors on rheumatoid arthritis.

TNF inhibitors are used as therapeutic agents for rheumatoid arthritis (RA). Each has a different dosage regimen and it is thought that the differences among them have implications on efficacy. However, those differences have not been analyzed in a theoretical manner. In the present study, we tried to explain theoretically the differences. We theoretically analyzed the anti-inflammatory effect of infliximab (IFX), etanercept (ETN), and adalimumab (ADA) for RA by using a pharmacokinetic and pharmacodynamic model. Then, we simulated values for sequential changes of tender joint count (TJC) after repeated administrations of TNF inhibitors by using the model. The sequential changes of TJC obtained with our model were in good agreement with observed TJC ratio data, which was considered to show the validity of our analytical method. The following results were obtained: the onset of clinical response was fastest with IFX, the fluctuation of IFX was greater than that of the others, and the clinical response with ADA was as stable as that with ETN. The present model was useful to analyze theoretically the anti-rheumatic effect of TNF inhibitors. Our results showed that different dosage regimens have implications on the onset and fluctuation of clinical response.