Early Impact of Interleukin-6 Blockade on the Distribution of Peripheral Blood Immune Cell Subpopulations – 3-Month Results of a Phase 2 Trial Evaluating Clazakizumab in Late Antibody-Mediated Rejection
1Department of Medicine III, Medical University of Vienna, Vienna, Austria, 2Charité Universitätsmedizin Berlin, Institute of Medical Immunology, Berlin, Germany, 3Center of Translational Research, Medical University of Vienna, Vienna, Austria, 4Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria, 5Vitaeris Inc., Vancouver, BC, Canada, 6Division of Nephrology and Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
Meeting: 2020 American Transplant Congress
Abstract number: B-075
Keywords: Kidney transplantation, Leukocytes, Monoclonal antibodies, Rejection
Session Information
Session Name: Poster Session B: Kidney Chronic Antibody Mediated Rejection
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Interleukin-6 (IL-6) is considered to play a critical role within the multifacted pathophysiological process of antibody-mediated rejection (ABMR), including modulation of regulatory T cells (Treg), B cell activation/differentiation and plasma cell function. In this secondary endpoint analysis of a bi-center phase 2 pilot trial evaluating IL-6 antibody clazakizumab in late ABMR, we studied the early impact of IL-6 blockade on absolute frequencies of immune cell subsets in peripheral blood, including Tregs, naïve and memory B cells and plasma cells.
*Methods: The study included 20 renal allograft recipients diagnosed with late ABMR after a median of 10.6 years post-transplantation. For the first 12 weeks patients were randomized to receive clazakizumab (25 mg in 4-weekly intervals; n=10) or placebo (n=10), followed by an open-label study with all subjects receiving clazakizumab for another 40 weeks (3 patients still active). For serial flow cytometric immune cell phenotyping standardized pre-formulated dry antibody panels (whole blood DuraClone system) were used. The present analysis included phenotyping results obtained at baseline and after 12 weeks.
*Results: Unsupervised cluster analysis precluded relevant inter-center and inter-group variability in immune phenotyping results. After 3 months, there were no significant differences in counts of Tregs [clazakizumab vs. placebo: 8.5×106 cells/L (interquartile range: 3.2-19.4) vs. 12.4×106 cells/L (6.6-20.2), p=0.68], naïve B cells [38.5×106 cells/L (12.9-67.1) vs. 33.3×106 cells/L (13.5-55.5), p=0.92], memory B cells [12×106 cells/L (3.3-21.9) vs. 10.10×106 cells/L (5.6-24.8), p=0.97] and plasma cells [1.5×106 cells/L (0.5-2.5) vs. 1.2×106cells/L (0.9-2.3), p=0.68]. Non-parametric rank-based ANOVA-type statistic did not reveal significant differential changes over time between treatment and control groups.
*Conclusions: These initial results suggest that a three month course of anti-IL-6 antibody treatment does not cause substantial shifts in frequencies of studied cell subsets. The second part of our trial will clarify whether prolonged clazakizumab treatment leads to significant changes in peripheral blood immune cell patterns.
To cite this abstract in AMA style:
Doberer KA, Boehmig GA, Streitz M, Schlickeiser S, Bauernfeind F, Spittler A, Jilma B, Eskandary F, Chong E, Schranz S, Budde K, Dürr M. Early Impact of Interleukin-6 Blockade on the Distribution of Peripheral Blood Immune Cell Subpopulations – 3-Month Results of a Phase 2 Trial Evaluating Clazakizumab in Late Antibody-Mediated Rejection [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/early-impact-of-interleukin-6-blockade-on-the-distribution-of-peripheral-blood-immune-cell-subpopulations-3-month-results-of-a-phase-2-trial-evaluating-clazakizumab-in-late-antibody-mediated-rejecti/. Accessed November 24, 2024.« Back to 2020 American Transplant Congress