Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization

The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies. Sensitized kidney-transplant candidates treated monthly with TCZ (8 mg/kg) for desensitization were retrospectively included. TCZ concentrations were determined by liquid chromatography-tandem mass spectrometry. Seventy-four TCZ concentrations from 10 patients were analyzed. The TCZ trough concentration ranged from <1.0 to 52.5 mg center dot L-1, with a median of 25.6 mg center dot L-1 [25th-75th percentiles: 13.2-35.3 mg center dot L-1). The inter- and intra-individual coefficients of variation were 55.0% and 33.0%, respectively. The TCZ trough concentration was not related to IL-6 (rho = -0.46, p = 0.792), soluble IL-6R (rho = -0.81, p = 0.65) concentrations or reduction of anti-HLA antibodies (mixed-effects model adjusting, effect of TCZ trough concentration: rho = -0.004, p = 0.26). The individual median TCZ concentration tended to be associated with the number of antibodies, with an initial MFI > 3000 that dropped to <3000 after TCZ treatment (rho = 0.397, p = 0.083). TCZ trough concentrations in kidney-transplant candidates treated for desensitization were highly variable. Further studies on larger cohorts are needed to study the possible link between TCZ concentrations and the reduction of anti-HLA antibodies.

Automated summary

The presence of anti-HLA antibodies is a growing challenge in kidney transplantation. Tocilizumab, a potential supplement to conventional desensitization therapy, was studied for its plasma trough concentrations and the relationship with the evolution of anti-HLA antibodies.