Physicians' Academy for Cardiovascular Education

IL-6 inhibition reduces neutrophil-lymphocyte ratio in patients with CKD and elevated hsCRP

Association of Interleukin 6 Inhibition With Ziltivekimab and the Neutrophil-Lymphocyte Ratio: A Secondary Analysis of the RESCUE Clinical Trial

Literature - Adamstein NH, Cornel JH, Davidson M, et al. - JAMA Cardiol. 2023 Feb 1;8(2):177-181. doi: 10.1001/jamacardio.2022.4277.

Introduction and methods


The neutrophil-lymphocyte ratio (NLR) is a biomarker for innate and adaptive immunity [1]. NLR, which can be determined from routine blood cell counts, may be relevant for monitoring anti-inflammatory therapies. A recent analysis of 5 contemporary clinical trials that included data from over 60,000 patients demonstrated that NLR predicts CV events and that IL-1β inhibition reduced NLR [2]. The RESCUE (Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition) trial previously demonstrated that IL-6 inhibition with the monoclonal antibody ziltivekimab reduced several inflammatory and coagulation markers relevant to atherosclerosis (including hsCRP) in patients with CKD and elevated hsCRP [3].

Aim of the study

In this secondary analysis of the RESCUE trial, the authors evaluated whether ziltivekimab has an effect on 3 cell-based inflammatory biomarkers - NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC).


The RESCUE trial was a double-blind, randomized, placebo-controlled, multicenter, phase 2 trial conducted in the US. 264 adults with CKD (stage 3 to 5) and elevated hsCRP (≥ 2 mg/L) were randomized to subcutaneous administration of ziltivekimab (7.5 mg, 15 mg, or 30 mg) or placebo every 4 weeks up to 24 weeks. Patients with an ANC of less than 2.0x10⁹/L were excluded. In this analysis, a total of 215 patients were included, of whom 187 patients (71%) had diabetes and 126 patients (48%) had known atherosclerosis.


The primary outcome was the change in NLR at 12 weeks after starting treatment. Secondary outcomes were changes in the ANC and ALC at 12 weeks.

Main results


This secondary analysis of the RESCUE trial demonstrated that targeted inhibition of IL-6 with the monoclonal antibody ziltivekimab was associated with a dose-dependent reduction in NLR by lowering ANC. These results have potential clinical significance as there is an association of NLR with atherosclerotic risk. The authors are currently conducting a phase 3 trial with 6000 patients with atherosclerosis, CKD, and elevated hsCRP to determine whether the effects of ziltivekimab on inflammation correspond to beneficial outcomes on CV events and kidney function [4].


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Find this article online at JAMA Cardiol.

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