Investigational drugs for the treatment of kidney transplant rejection

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.This review covers novel and investigational drugs for the pharmacological treatment of kidney transplant rejection. Potential therapeutic strategies and future directions are discussed.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.