Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series.

Abstract

Background:

Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR.

Methods:

Ten adult recipients of KTs with biopsy-proven caAbMR were treated with TCZ at 8 mg/kg per month. Patients were monitored for adverse events, and therapy was interrupted in the setting of serious infections. Six patients (60%) underwent post-treatment biopsies.

Results:

Patients (mean age of 43 years) were initiated on TCZ at a median of 36 months post-KT. A majority of patients were black (70%), underwent regrafts (40%), and were sensitized (mean cPRA=41%). Patients received a median of six doses of TCZ (range=3-10). At a median follow-up of 12 months (range=8-24 months), renal function did not show improvement (mean eGFR, 42±18 ml/min per 1.73 m2 to 37±24 ml/min per 1.73 m2; P=0.27). The slope of decline in eGFR remained unchanged (-0.14±0.9 to -0.33±1.1; P=0.25). There was no improvement in mean MVI (g+ptc) (4.8±1.4 to 4.2±2.0; P=0.39) scores or Molecular Microscope Diagnostic System (MMDx) AbMR scores (0.79±0.17 to 0.78±0.26; P=0.86). There was a numeric worsening of chronicity (ci+ct) scores (2.5±0.8 to 3.3±1.7; P=0.38) and MMDx atrophy fibrosis scores (0.36±0.24 to 0.58±0.15; P=0.21). Patient survival was 90%, with one patient death due to complications from a hip infection. Overall death-censored graft survival was 80%, with two graft losses in patients who had recurrent infections requiring hospitalization.

Conclusions:

In this early experience, we report a lack of efficacy and toxicity with the use of TCZ for caAbMR. Prospective clinical trials are needed to clarify the role of IL-6 blockade and the possibility of increased incidence of infections in patients with caAbMR who are treated with TCZ.

• Authors: Dhiren Kumar, Idris Yakubu, Frough Safavi, Marlon Levy, Irfan Moinuddin, Pamela Kimball, Layla Kamal, Anne King, Davis Massey, Philip Halloran, Gaurav Gupta
• Journal: Kidney360 (Kidney360) Vol. 1 Issue 7 Pg. 663-670 (07 30 2020) ISSN: 2641-7650 [Electronic] United States
• PMID: 35372943 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 by the American Society of Nephrology.

Chemical References

• Antibodies, Monoclonal, Humanized
• tocilizumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (adverse effects)
• Graft Rejection (etiology)
• Humans
• Kidney Transplantation (adverse effects)
• Prospective Studies