The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant

Abstract

Background: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antigens (HLAs) on the graft, which results in chronic inflammation and leads to graft dysfunction. One of the recent promising methods of cAMR treatment is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody referred to as Tocilizumab (TCZ). The aim of the presented systematic review is to explore the existing knowledge regarding the effect of tocilizumab treatment on cAMR and to perform a meta-analysis of the available data. Methods: A systematic review was performed using the PRISMA 2020 Checklist and Flow diagram. A systematic review protocol was registered in PROSPERO: CRD42024510996. The bias assessment was obtained with Methodical Index for Non-Randomized Studies (MINORS), whereas meta-analysis was performed using MedCalc. Results: Five clinical trials with a total number of 105 patients were included in our review. The mean loss of eGFR in time was −0.141 mL/min/1.73 m2 (95% CI: −0.409 to 0.126; p = 0.298) and was found to be statistically insignificant. The heterogeneity was low and was equal to I2 = 0.00%. The authors demonstrated a reduction in DSA titer by TCZ (−0.266 MFI (95% CI: −0.861 to 0.329; p = 0.377)). In the majority of studies, eGFR stabilization was associated with a reduction in DSAs. Conclusions: TCZ pharmacotherapy insignificantly reduced DSA titer and eGFR. Despite promising outcomes of potential eGFR stabilization, there is a need for large randomized controlled trials comparing standard management of cAMR and tocilizumab treatment.

Keywords

• cAMR
• DSA
• eGFR
• kidney rejection
• tocilizumab