A vivid cytokines interaction model on psoriasis with the effect of impulse biologic (TNF-α inhibitor) therapy.

ABSTRACT

Psoriasis is a chronic skin condition that produces plaques of condensed, scaling skin due to excessively rapid proliferation of keratinocytes. During the disease progression, keratinocyte proliferation is influenced by many immune cells and cytokines. This article deals with a five dimensional deterministic model, which has been derived using quasi-steady-state approximation for describing the dynamics of psoriasis in various cytokines environment. Equilibrium analysis of the system shows that either the system converges to a stable steady state or exhibits a periodic oscillation depending upon system parameters. Finally, introducing a one dimensional impulsive system, we have determined the perfect dose and perfect dosing interval for biologic (TNF-α inhibitor) therapy to control the hyper-proliferation of keratinocytes. We have studied the effect of TNF-α inhibitor by considering both perfect and imperfect dosing during the inductive phase. The maximum possible number of drug holidays and the minimal number of doses that must subsequently be taken while avoiding drug resistance have been calculated for imperfect dosing. Since, psoriasis is non-curable but treatable disease, so the aim is to investigate the minimum dose with highest efficacy and proper dosing interval of TNF-α inhibitor for a psoriatic patient. Through numerical simulations, we have given a detailed prediction about the maximum drug holidays, tolerable for a patient, without loss of previous drug effects. Our theoretical predictions and numerical outcomes may be useful in guiding the design of future clinical trials.