Primary lack of response and secondary loss of response (LOR) are major obstacles to the use of anti–tumor necrosis factor (TNF)-based therapies in patients with rheumatoid arthritis or inflammatory bowel disease. Here, we review the mechanisms and methods for predicting LOR and the currently used methods for overcoming the ineffectiveness of anti-TNFs. The complex functions of TNF and anti-TNF antibodies, which can promote both pro- or anti-inflammatory actions, and the factors that affect the induction of immune tolerance to their effects are presented. The lack of rules and the continuous dynamics of the immune processes partly underlie the unpredictability of the response to anti-TNFs. Variability is inherent to biological systems, including immune processes, and intra/inter-patient variability has been described in the response to drugs. This variability is viewed as a compensatory adaptation mechanism of the immune system in response to drugs and may contribute to treatment LOR. Dose reductions and drug holidays have been tested in patients treated with anti-TNFs. Regular dose-based regimens may be incompatible with physiological variability, further contributing to treatment inefficacy. We present the concept of overcoming immune system adaptation to anti-TNFs by introducing patient-tailored patterns of variability to treatment regimens.
|Journal||Frontiers in Immunology|
|State||Published - 20 Nov 2019|
Bibliographical noteFunding Information:
This work was supported in part by a grant from The Roman-Epstein Research Foundation (to YI).
© Copyright © 2019 Khoury and Ilan.
- inflammatory bowel disease
- loss of response
- rheumatoid arthritis