#3105 Tocilizumab for treatment of antibody mediated rejection in kidney transplant patients Free

Chronic active antibody-mediated rejection (caABMR) causes 40% of long-term graft failure after kidney transplantation (KT). Early treatment is of great importance, however, hard clinical evidence is still lacking. Currently the combination of plasmapheresis (PF), rituximab and intravenous immunoglobulin is used as standard treatment. Tocilizumab (TCZ) is a monoclonal antibody, IL-6 receptor antagonist, and it inhibits the production of donor-specific antibodies (DSA). We hypothesized that tocilizumab administration has an additional effect on graft survival and non-inferior to standard therapy in KT patients with ABMR.

Retrospective single-center noninferiority case-control study was performed by involving 73 KT patients (43.5 ± 14.3 years, females 31, eGFR 19.5 ± 13.4) with biopsy proven ABMR diagnosed between June 2017 and May 2022. 19 patients received 8 mg/kg intravenous TCZ therapy for 6 months (12 aABMR, 7 caABMR, 38.6 ± 12.8 years, females 6). In the control group (C, n=54, 10 aABMR, 44 caABMR, 45.2 ± 14.5 years, females 25), 20 patients received plasmapheresis treatment, the rest stayed on optimized maintenance therapy (tacrolimus, mycophenolic acid, prednisolone). Baseline demographic data, standard laboratory data, proteinuria and DSA level were also monitored and analyzed.

Graft loss occurred in 13 cases (6 aABMR, 7 caABMR) in KT on TCZ therapy and 43 (6 aABMR, 37 caABMR) in C group, meaning significantly lower risk of graft loss in the TCZ group (RR 0.69, p=0.036) during the median follow-up of 11.3 (IQR 2.5-23.1) months. In TCZ group, all caABMR patients lost their graft during the observation. In TCZ group, 1 year after the TCZ treatment, DSA (pooled) was lower (7028 (575-17782) versus 1605 (551-16903), p<0.05).

Early administration of TCZ seems to be noninferior to standard therapy and effective to prevent early graft loss as part of standard therapy in aABMR. Further clinical studies are needed to clarify clinical indications of TCZ and its long-term effects on the course of chronic active ABMR.