Investigational drugs for the treatment of kidney transplant rejection

Lukas K. van Vugt*, Maaike R. Schagen, Annelies de Weerd, Marlies E.J. Reinders, Brenda C.M. de Winter, Dennis A. Hesselink

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

9 Citations (Scopus)
209 Downloads (Pure)

Abstract

Introduction: Kidney transplant rejection remains an important clinical problem despite the development of effective immunosuppressive therapy. Two major types of rejection are recognized, T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), which have a different pathophysiology and are treated differently. Unfortunately, long-term outcomes of both TCMR and ABMR remain unsatisfactory despite current therapy. Hence, alternative therapeutic drugs are urgently needed. Areas covered: This review covers novel and investigational drugs for the pharmacological treatment of kidney transplant rejection. Potential therapeutic strategies and future directions are discussed. Expert opinion: The development of alternative pharmacologic treatment of rejection has focused mostly on ABMR, since this is the leading cause of kidney allograft loss and currently lacks an effective, evidence-based therapy. At present, there is insufficient high-quality evidence for any of the covered investigational drugs to support their use in ABMR. However, with the emergence of targeted therapies, the potential arises for individualized treatment strategies. In order to generate more high-quality evidence for such strategies and overcome the obstacles of classic randomized controlled trials, we advocate the implementation of adaptive trial designs and surrogate clinical endpoints. We believe such adaptive trial designs could help to understand the risks and benefits of promising drugs such as tocilizumab, clazakizumab, belimumab, and imlifidase.

Original languageEnglish
Pages (from-to)1087-1100
Number of pages14
JournalExpert Opinion on Investigational Drugs
Volume31
Issue number10
Early online date7 Oct 2022
DOIs
Publication statusPublished - 2022

Bibliographical note

Funding Information:
D.A. Hesselink has received lecture fees and consulting fees from Astellas Pharma, Chiesi Pharma, Medincell, Novartis Pharma, Sangamo Therapeutics, and Vifor Pharma. He has received grant support from Astellas Pharma, Bristol-Myers Squibb, and Chiesi Pharma.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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