Emerging drugs for antibody-mediated rejection after kidney transplantation: a focus on phase II & III trials

Abstract

Introduction: Antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Its therapy continues to be challenge, and no treatment has been approved for the market thus far.

Areas covered: In this article, we discuss the pathophysiology and phenotypic presentation of ABMR, the current level of evidence to support the use of available therapeutic strategies, and the emergence of tailored drugs now being evaluated in systematic clinical trials. We searched PubMed, Clinicaltrials.gov and Citeline's Pharmaprojects for pertinent information on emerging anti-rejection strategies, laying a focus on phase II and III trials.

Expert opinion: Currently, we rely on the use of apheresis for alloantibody depletion and intravenous immunoglobulin (referred to as standard of care), preferentially in early active ABMR. Recent systematic trials have questioned the benefits of using the CD20 antibody rituximab or the proteasome inhibitor bortezomib. However, there are now several promising treatment approaches in the pipeline, which are being trialed in phase II and III studies. These include interleukin-6 antagonism, CD38-targeting antibodies, and selective inhibitors of complement. On the basis of the information that has emerged so far, it seems that innovative treatment strategies for clinical use in ABMR may be available within the next 5-10 years.

Keywords: Antibody-mediated rejection; apheresis; bortezomib; clazakizumab; complement blockade; felzartamab; imlifidase; plasmapheresis; tocilizumab; transplantation.