IL-6 Inhibition with Tocilizumab to Promote Tregs and Control Renal Graft Inflammation: A Prospective Randomized Controlled Trial
UCSF, San Francisco.
Meeting: 2018 American Transplant Congress
Abstract number: 458
Keywords: Inflammation, Kidney transplantation, Rejection, T helper cells
Session Information
Session Name: Concurrent Session: Kidney: Acute Cellular Rejection
Session Type: Concurrent Session
Date: Tuesday, June 5, 2018
Session Time: 2:30pm-4:00pm
Presentation Time: 3:42pm-3:54pm
Location: Room 6A
Background: IL-6, a proinflammatory cytokine & key regulator of Treg/Th17, is strongly associated with renal graft rejection. In theory, IL-6 blockade with tocilizumab (TCZ), a monoclonal antibody to IL-6R, could control graft inflammation.
Methods: Single center randomized controlled clinical trial (2014-) of stable (eGFR>30 ml/min/1.73m2) kidney transplant recipients on tacrolimus+MMF±prednisone with subclinical graft inflammation within year 1. Subjects received TCZ (8 mg/kg IV q4 weeks X6) or no treatment (controls). Kidney biopsies at baseline and 6 months later were analyzed by Banff classification. PBMCs were collected for phenotypic & functional analysis at baseline, 3 & 6 months. T-test was used for statistical comparisons.
Results: 22 of 29 enrolled patients have completed 6 months of follow up.
| Control gp(n=11) | TCZ gp(n=11) | |
| Mean age,yrs(SD) | 53.3(11.1) | 52.1(11.4) |
| Male(%) | 45.4 | 63.6 |
| White(%) | 27.3 | 27.3 |
| cPRA>80%(%) | 27.3 | 36.4 |
| Kidney biopsy Banff ti-score, mean(SD) | ||
| -Baseline | 0.82(0.75) | 0.91(0.7) |
| -6 month | 1.00(0.89) | 0.55(0.69) |
Mean Banff ti-score in both groups was similar at baseline. On follow up, it declined (-39.5%) in the TCZ group & increased (+21.9%) in the control group. More patients in the TCZ group than the control group had a decline in the ti-score (7/11 vs. 2/11, p=0.08). Mean circulating CD4+CD25+FoxP3+ Treg frequency (n=20) was similar at baseline (4.3% vs 5.1%, p=0.58); it increased in the TCZ group (+50%) & declined in the control group (-22.5%) over 6 months (p=0.012). PMA/ionomycin stimulated production of IL-17 by CD4+ T cells decreased in the TCZ group and increased in the control group at 6 months. There were no cases of death or graft loss.
Conclusions: TCZ treatment for 6 months was well tolerated in kidney transplant recipients. It was associated with a significant increase in circulating Tregs, a significant decrease in CD4+ T cell cytokine production & a trend towards decreased graft inflammation. IL-6 blockade is a novel treatment option to modulate the alloimmune response.
CITATION INFORMATION: Chandran S., Leung J., Laszik Z., Tang Q., Hu C., Sarwal M., Vincenti F. IL-6 Inhibition with Tocilizumab to Promote Tregs and Control Renal Graft Inflammation: A Prospective Randomized Controlled Trial Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Chandran S, Leung J, Laszik Z, Tang Q, Hu C, Sarwal M, Vincenti F. IL-6 Inhibition with Tocilizumab to Promote Tregs and Control Renal Graft Inflammation: A Prospective Randomized Controlled Trial [abstract]. https://atcmeetingabstracts.com/abstract/il-6-inhibition-with-tocilizumab-to-promote-tregs-and-control-renal-graft-inflammation-a-prospective-randomized-controlled-trial/. Accessed November 21, 2024.« Back to 2018 American Transplant Congress