A randomized controlled pilot trial of anakinra for hemodialysis inflammation.

Laura M Dember, Adriana Hung, Rajnish Mehrotra, Jesse Y Hsu, Dominic S Raj, David M Charytan, Finnian R Mc Causland, Renu Regunathan-Shenk, J Richard Landis, Paul L Kimmel, Alan S Kliger, Jonathan Himmelfarb, T Alp Ikizler

Journal: Kidney international 2022;102(5):1178-1187

PMID: 35863559

Free Full Text on Elsevier Science View on PubMed

Abstract

Chronic inflammation is highly prevalent among patients receiving maintenance hemodialysis and is associated with morbidity and mortality. Inhibiting inflammation with anti-cytokine therapy has been proposed but not well studied in this population. Therefore, we conducted the ACTION trial, a pilot, multicenter, randomized, placebo-controlled trial of an IL-1 receptor antagonist, anakinra, to evaluate safety, tolerability, and feasibility, and explore efficacy. Eighty hemodialysis patients with plasma concentrations of high sensitivity C-reactive protein (hsCRP) 2 mg/L and above were randomized 1:1 to placebo or anakinra 100 mg, three times per week via the hemodialysis circuit for 24 weeks, with an additional 24 weeks of post-treatment safety monitoring. Efficacy outcomes included changes in hsCRP (primary), cytokines, and patient-reported outcomes. Rates of serious adverse events and deaths were similar with anakinra and placebo (serious adverse events: 2.71 vs 2.74 events/patient-year; deaths: 0.12 vs 0.22 events/patient-year). The rate of adverse events of interest (including infections and cytopenias) was significantly lower with anakinra than placebo (0.48 vs 1.40 events/patient-year). Feasibility was demonstrated by attaining the enrollment target, a retention rate of 80%, and administration of 72% of doses. The median decrease in hsCRP from baseline to Week 24 was 41% in the anakinra group and 6% in the placebo group, a between-group difference that was not statistically significant. For IL-6, the median decreases were significant: 25% and 0% in the anakinra and placebo groups, respectively. An effect of anakinra on patient-reported outcomes was not evident. Thus, anakinra was well tolerated and did not increase infections or cytopenias. The promising safety data and potential efficacy on CRP and IL-6 provide support for conducting definitive trials of IL-1 inhibition to improve outcomes in hemodialysis patients.

Published by Elsevier Inc.

Address: Renal, Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt O'Brien Kidney Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.; Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA; Division of Nephrology, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, Washington, USA.; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Division of Renal Diseases and Hypertension, George Washington University School of Medicine, Washington, DC, USA.; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Yale New Haven Health System, New Haven, Connecticut, USA.; Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA. Electronic address: [email protected].; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt O'Brien Kidney Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA. Electronic address: [email protected].

DOI: 10.1016/j.kint.2022.06.022

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/dialysis.html

Miscellaneous:

https://assays.cancer.gov/CPTAC-1478

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-CRP-1

MeSH Terms: Humans, C-Reactive Protein, Double-Blind Method, Inflammation, Interleukin 1 Receptor Antagonist Protein, Interleukin-1, Interleukin-6, Pilot Projects, Receptors, Interleukin-1, Renal Dialysis, Treatment Outcome