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Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3-5: An Analysis of a Randomized
Pablo E Pergola1, Michael Davidson2, Camilla Jensen3
1Renal Associates P.A., San Antonio, Texas.
Insights
Ziltivekimab, an anti-inflammatory drug, significantly increased hemoglobin levels and improved iron homeostasis in patients with chronic kidney disease (CKD) and systemic inflammation. This suggests a potential new treatment for anemia in CKD patients.
Area of Science:
- Nephrology
- Immunology
- Hematology
Background:
- Systemic inflammation is a known contributor to anemia in chronic kidney disease (CKD).
- Ziltivekimab, a monoclonal antibody targeting IL-6, reduces inflammation in CKD patients.
- Previous studies showed ziltivekimab increases serum albumin in hemodialysis patients with inflammation.
Purpose of the Study:
- To assess the effect of ziltivekimab on hemoglobin (Hb) and iron homeostasis in CKD patients with systemic inflammation.
- To analyze exploratory endpoints from the RESCUE clinical trial regarding anemia markers.
Main Methods:
- Analysis of data from the RESCUE trial (NCT03926117) involving 264 adults with CKD stage 3-5 and high-sensitivity C-reactive protein ≥2 mg/L.
- Participants received placebo or subcutaneous ziltivekimab (7.5, 15, or 30 mg) every 4 weeks.
- Exploratory endpoints measured changes in Hb and iron homeostasis biomarkers from baseline to week 12.
Main Results:
- Ziltivekimab treatment led to significant increases in Hb levels at week 12 compared to placebo across all doses (P < 0.001).
- Significant improvements were observed in serum iron, total iron-binding capacity, and transferrin saturation (P < 0.05).
- Adverse events like thrombocytopenia and neutropenia were infrequent and similar across treatment groups.
Conclusions:
- Ziltivekimab demonstrated efficacy in improving anemia markers and iron homeostasis in CKD patients with systemic inflammation.
- These findings suggest ziltivekimab may play a role in managing anemia associated with inflammation in CKD.
- Further clinical trials are warranted to confirm these results and explore ziltivekimab's therapeutic potential.
Significance Statement:
Systemic inflammation in CKD can lead to anemia. Ziltivekimab, a fully human monoclonal antibody targeting the IL-6 ligand, has been shown to reduce systemic inflammation in patients with CKD. It has also been shown to increase serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to treatment with erythropoiesis-stimulating agents. This exploratory analysis of the RESCUE clinical trial found that among patients with CKD stage 3-5 and systemic inflammation, ziltivekimab treatment significantly increased hemoglobin (Hb) levels after 12 weeks compared with placebo. Ziltivekimab was also associated with significant increases in serum iron levels, total iron-binding capacity, and transferrin saturation. No major safety concerns were reported. Further clinical trials are warranted to study ziltivekimab's potential for anemia management in patients with CKD.
Background:
In the phase 2 RESCUE clinical trial, ziltivekimab, a fully human monoclonal antibody against the IL-6 ligand, significantly reduced the biomarkers of inflammation compared with placebo, in patients with CKD and systemic inflammation (high-sensitivity C-reactive protein ≥2 mg/L). The aim of this subanalysis of RESCUE trial data was to assess the effect of ziltivekimab on Hb and iron homeostasis in this patient population.
Methods:
This was an analysis of exploratory end points from the RESCUE trial ( NCT03926117 ), which included 264 adults with CKD stage 3-5 and high-sensitivity C-reactive protein ≥2 mg/L. Participants received placebo or subcutaneous ziltivekimab (7.5, 15, or 30 mg) (1:1:1:1) once every 4 weeks, up to 24 weeks. End points for this analysis were changes in Hb and biomarkers of iron homeostasis from baseline to week 12.
Results:
The trial was terminated early due to the coronavirus disease 2019 pandemic, and thus, data up to week 12 are presented. Hb levels significantly increased from baseline to week 12 with ziltivekimab 7.5, 15, and 30 mg (treatment differences versus placebo: +0.57 g/dl [95% confidence interval, 0.27 to 0.86], +1.05 g/dl [0.76 to 1.33], and +0.99 g/dl [0.70 to 1.28], respectively, all P < 0.001). Ziltivekimab was associated with significant increases in serum iron levels, total iron-binding capacity, and transferrin saturation from baseline to week 12 ( P < 0.05 versus placebo for all doses and comparisons). Cases of sustained thrombocytopenia, sustained neutropenia, anemia, and iron deficiency anemia were infrequent and similar across all groups.
Conclusions:
Anti-inflammatory therapy with ziltivekimab improved the markers of anemia and iron homeostasis in people with stage 3-5 CKD and systemic inflammation, suggesting a possible role in anemia management.
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