Efficacy and Safety of Tocilizumab in the Treatment of Acute Active Antibody-mediated Rejection in Kidney Transplant Recipients

Abstract

Background. Antibody-mediated rejection (AMR) continues to have a deleterious impact on kidney allograft survival. Recent evidence supports use of tocilizumab for treatment of chronic active AMR, but it has not been assessed for treatment of acute active AMR. Methods. We performed a single-center, observational study of kidney transplant recipients who received at least 1 dose of tocilizumab in addition to conventional therapies for acute active AMR between October 2016 and October 2018 with follow-up through August 2019. Results. Seven patients were included. All 7 patients received tocilizumab 8 mg/kg (max dose, 800 mg) monthly. We noted a 50% or greater reduction in immunodominant donor-specific antibodies in 4 of 6 patients. Renal function improved or stabilized in all patients throughout the duration of therapy. One patient developed cytomegalovirus esophagitis and 1 had a potential hypersensitivity reaction. In the extended follow-up, 1 patient had mixed rejection and 2 patients had T-cell–mediated rejection, which occurred 6 to 24 mo after completion of therapy. Conclusions. Tocilizumab may be considered as an addition to conventional therapies for treatment of acute active AMR. More studies are needed to determine which patients may benefit from therapy and to examine the appropriate duration of treatment.

Chronic Active Antibody-Mediated Rejection Following COVID-19 Infection in a Kidney Transplant Recipient: A Case Report

“…However, the patient did receive tociluzumab as a part of COVID-19 directed therapy, which was followed by an improvement in SCr. Tociluzumab is proposed as a treatment modality for acute ABMR [ 9 ] and for chronic active ABMR [ 10 , 11 ]. When used for rejection, the dose is higher and is given monthly [ 10 ].…”

Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation

“…48,49 Tocilizumab, a humanized monoclonal antibody targeting the IL-6R, has been assessed for the treatment of acute rejection, chronic ABMR, and transplant glomerulopathy following renal transplantation. [50][51][52] Initially, a phase I/II trial was performed in 10 patients prior to kidney transplantation that were unresponsive to desensitization with intravenous Ig and rituximab. 50 Tocilizumab, combined with intravenous Ig, led to a significant reduction in DSA levels and appeared safe.…”

Immunomodulatory Therapies for COVID-19 in Solid Organ Transplant Recipients

“…One patient developed encephalitis of unknown origin 3 months after the initiation of TCZ, with complete recovery following the temporary discontinuation of treatment [ 60 ]. The occurrence of cytomegalovirus esophagitis and hypersensitivity reaction was reported in one case each out of seven KT recipients treated with monthly TCZ for a median of 4 months for acute active AMR [ 61 ]. Of note, all these studies evaluated the safety of TCZ over prolonged courses of therapy, which is in contrast with the one- to three-dose regimen usually administered for COVID-19.…”