Tocilizumab for treatment of chronic active antibody‐mediated rejection in kidney transplant recipients

Abstract

AbstractBackgroundThe optimal treatment for chronic active antibody‐mediated rejection (ca‐AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL‐6, has been proposed as a therapeutic option. We reported our experience treating ca‐AMR with TCZ either as the first line option or as a rescue therapy.MethodsWe studied 11 adult kidney transplant recipients with biopsy‐proven ca‐AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd‐cfDNA. Clinical monitoring included dd‐cfDNA and DSA testing every 3 months during the treatment with TCZ.ResultsIn this cohort, ca‐AMR was diagnosed at a median of 90 months (range 14–224) post‐transplant, and 4 of 11 patients had DSA negative ca‐AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd‐cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd‐ cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd‐cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections.ConclusionsIn our early short‐term experience, TCZ appears to reduce graft injury as measured by dd‐cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.