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Front. Immunol. | doi: 10.3389/fimmu.2019.02726

Introducing patterns of variability for overcoming compensatory adaptation of the immune system to immunomodulatory agents: A novel method for improving clinical response to anti-TNF therapies

Tawfik Khoury1 and  Yaron Ilan2*
  • 1Institute of Gastroenterology, Galilee Medical Center, Israel
  • 2Hebrew University of Jerusalem, Israel

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.

Keywords: Anti-TNF, Rheumatoid arthritis;, inflammatory bowel disease, Loss of response, variability

Received: 12 Jun 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Khoury and Ilan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Yaron Ilan, Hebrew University of Jerusalem, Jerusalem, Israel,