Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Abstract

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.