Interleukin 6 (IL-6) has been identified as a canonical cytokine responsible for inflammation and pathological immune responses critical to mediation of allograft rejection. Data confirming these observations comes from animal studies and clinical observations in human transplant rejection. These observations have led to important studies using monoclonal antibodies directed at IL-6 which have shown great promise in treating this important and, as yet, untreatable condition. Here, the IMAGINE trial is a placebo-controlled, randomized trial of the anti-IL-6 monoclonal antibody, clazakizumab, aimed at improving clinical outcomes in patients with chronic active antibody-mediated rejection.

For a long time, transplant providers have had no effective, approved treatment option for chronic active ABMR, a major cause of late allograft dysfunction and failure in kidney transplant recipients. In recent years, our increased understanding of the underlying pathophysiology of ABMR has paved the way for clinical evaluation of new potential therapeutic options. One such therapy is clazakizumab, a promising anti-IL-6 monoclonal antibody, that has the potential to bring hope to kidney transplant recipients with chronic active ABMR through the IMAGINE clinical trial.

Chronic active ABMR is an important cause of late allograft failure after kidney transplantation. There are currently no FDA‑approved therapies to treat this process of rejection. It is the responsibility of the transplant community to generate evidence‑based medicine to make an impact on the lives of our patients and prolong the function of the transplanted graft. The IMAGINE trial provides that opportunity, and uses change in eGFR as a surrogate endpoint for long‑term allograft outcomes.