WASHINGTON—Inhibition of the proinflammatory cytokine interleukin-6 (IL-6) with the  monoclonal antibody ziltivekimab significantly improved markers of malnutrition-inflammation, increased hemoglobin, and reduced erythropoiesis stimulating agent (ESA) requirements in hyporesponsive patients on hemodialysis with inflammation, investigators reported at the American Society of Nephrology’s Kidney Week 2019 meeting.

Patients with chronic kidney disease on hemodialysis (HD) and hyporesponsiveness to ESA treatment exhibit functional blockade in iron release from body stores because of inflammation-induced expression of hepcidin, Pablo E. Pergola, MD, of Renal Associates in San Antonio, Texas, and colleagues explained.

Dr Pergola’s team compared ziltivekimab with placebo in a randomized trial that included 61 HD patients with high IL-6 (4 pg/mL or higher) and a genotypic variation in the TMPRSS6 gene, which is hypothesized to increase susceptibility of hepcidin to IL-6-induced inflammation. Ziltivekimab-treated patients received 2, 6, or 20 mg IV of the drug every 2 weeks during HD for 12 weeks.

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Ziltivekimab-treated patients experienced significant declines in levels of high sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation. Median levels of hsCRP decreased by 0.2 mg/L among placebo recipients compared with significant decreases of 3.5, 12.1, and 13.0 mg/L in recipients of the 2, 6, and 20 mg doses of ziltivekimab, respectively, Dr Pergola and his colleagues reported.

Hemoglobin levels did not increase in the placebo group, but increased by a significant 0.76 g/dL in the 20 mg ziltivekimab recipients. The median ESA dose did not change in the placebo arm and was decreased by a significant 15000 U in the 2 and 6 mg and by 33000 U in the 20 mg ziltivekimab groups, respectively.

Placebo recipients experienced no increase in serum albumin, whereas median levels of serum albumin rose by a significant 0.34 g/dL in 20 mg ziltivekimab patients.

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Pergola PE, Kakkar R, Chonchol M, et al. Effects of ziltivekimab, an antibody to IL-6, on inflammation, nutritional markers, and anemia in hemodialysis patients: A randomized, double-blind, placebo-controlled trial. Presented at the American Society of Nephrology’s Kidney Week 2019 meeting held November 5 to 10 in Washington, DC. Abstract TH-OR025.