The effect of ziltivekimab on hemoglobin levels in individuals with CKD stage 3-5

A recent study has shown that the use of ziltivekimab as an anti-inflammatory treatment led to improvements in anemia markers and iron regulation in individuals with stage 3-5 chronic kidney disease (CKD) and systemic inflammation, indicating a potential role in managing anemia. The Journal of the American Society of Nephrology published the study's findings.

This study analyzed exploratory end points from the RESCUE trial, involving 264 adults with CKD stage 3-5 and high-sensitivity C-reactive protein ≥2 mg/L. The subjects were administered with either a placebo or subcutaneous ziltivekimab (7.5 mg, 15 mg, or 30 mg) in a 1:1:1:1 ratio at four-week intervals for a duration of up to twenty-four weeks. The end points included the biomarkers of iron homeostasis and changes in hemoglobin (Hb) from baseline to twelfth week.

The levels of hemoglobin significantly increased from the starting point to week 12 when administered with ziltivekimab at 7.5 mg, 15 mg, and 30 mg doses. The differences in treatment compared to the placebo were +0.57 g/dl [95% CI, 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 with a P value < 0.001. Ziltivekimab also resulted in significant elevations in total iron-binding capacity, serum iron levels, and transferrin saturation from the baseline to week 12 (P value < 0.05 vs. placebo for all doses and comparisons). Instances of sustained neutropenia, sustained thrombocytopenia, anemia, and iron deficiency anemia were uncommon and similar across all cohorts.

The above study showed that treatment with ziltivekimab, an anti-inflammatory therapy, led to improvements in anemia markers and iron homeostasis in patients with stage 3-5 CKD and systemic inflammation. This indicates a possible role in the treatment of anemia.

The impact of C-reactive protein on the efficacy of roxadustat in managing anemia in chronic kidney disease

A recent study demonstrated that roxadustat displays similar efficacy across different blood C-reactive protein (CRP) levels. Additionally, in the CRP ≥ upper limit of normal (ULN) group, roxadustat can uphold efficacy comparable to erythropoiesis-stimulating agents (ESA) without the need for dose escalation. The study's results were recorded in the publication BMC Nephrology. 
A comprehensive search was conducted across electronic databases, including Web of Science, Pubmed, Embase, Cochrane Library, Wanfang, International Clinical Trials Registry Platform (ICTRP), and CNKI from their inception until 19thMay, 2022. A systematic review was performed on evidence from randomized controlled trials that used hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for treating renal anemia. The meta-analysis findings were derived from the mean difference (MD) in changes in hemoglobin concentration (∆Hb) pre- and post-treatment, utilizing a random-effects model. Groups with CRP levels at or above the upper limit of normal (ULN) were compared with those below the ULN. Further analysis was conducted within the CRP ≥ ULN group, comparing erythropoiesis-stimulating agents (ESA) and HIF-PHIs.
This analysis included a total of seven studies from six publications. When comparing the CRP ≥ ULN group with the CRP < ULN group, 524 patients from four studies were analyzed. All patients were administered roxadustat as the primary intervention. The pooled results showed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (MD: 0.00, 95% CI: -0.32 to 0.33, P value= 0.99). The effectiveness of roxadustat and erythropoiesis-stimulating agents was compared in three studies involving 1399 patients within the CRP ≥ ULN group. The findings revealed no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (MD: 0.24, 95% CI: -0.08 to 0.56, P value = 0.14). Regarding medication dosage, an increase in ESA dose over time was observed in various studies, particularly noticeable in the CRP ≥ ULN group, while the roxadustat dose remained constant over time and was not affected by the baseline CRP levels.
Therefore, roxadustat exhibited similar efficacy regardless of the CRP levels. Additionally, in the CRP ≥ ULN group, roxadustat can sustain effectiveness comparable to erythropoiesis-stimulating agents without the necessity for dose escalation.
 

Superiority of darbepoetin alfa over erythropoietin alpha in the management of chronic kidney disease associated anemia

A recent review article highlighted the numerous advantages of darbepoetin alfa (DPO) compared to conventional recombinant human erythropoietin alpha (EPO) in the treatment of anemia among chronic kidney disease (CKD) patients. These advantages extend to both predialysis and dialysis-dependent (DD) CKD patients. DPO's pharmacokinetic superiority, patient-centered benefits, enhanced compliance, and cost-effectiveness collectively position it as a transformative therapeutic option. This review article was published in the journal, Cureus.

This study provides a comparative analysis of the benefits of DPO over EPO in effectively managing anemia in both predialysis and DD CKD patients. The unique pharmacokinetic advantages of DPO significantly contribute to its effectiveness and safety. DPO's notably longer half-life and substantially higher biological activity, when compared to EPO, allow for extended dosing intervals. In-depth analysis of various clinical trials revealed that DPO consistently exhibits impressive efficacy and safety in enhancing and sustaining hemoglobin (Hb) levels. Additionally, its simplified dosing schedule, along with the convenience of less frequent administration, not only improves patient compliance but also results in reduced healthcare expenses and utilization of resources.

The above review article demonstrated that DPO can be effectively used to manage anemia in patients with both predialysis and DD CKD compared to EPO. The pharmacokinetic advantages of DPO, along with its patient-centered approach, improved compliance, and cost-effectiveness, position DPO as a truly transformative therapeutic option.

The efficacy of daprodustat in treating anemia in dialysis patients

Recent research indicates that dialysis-dependent patients with anemia exhibited a substantial increase in serum hemoglobin and total iron binding capacity (TIBC), along with a decrease in serum ferritin, following the administration of daprodustat, in a manner that depended on the dosage. This study’s findings were published in The Pan African Medical Journal.

A systemic search of the databases PubMed, Scopus, Web of Science, and Cochrane was conducted. Seven distinct trials were ultimately selected for systematic review, with six of them involving a total of 759 patients included in the network meta-analysis (NMA).

The administration of daprodustat 25-30 mg resulted in the largest change in serum hemoglobin (MD=1.86, 95% confidence interval = [1.20; 2.52]), ferritin (MD= -180.84, 95% confidence interval = [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95% confidence interval = [3.15; 18.92]) from initial values.

It can be concluded that the administration of daprodustat resulted in a marked elevation in serum hemoglobin and total iron binding capacity (TIBC), and a reduction in serum ferritin among dialysis-dependent individuals with anemia, in a manner that depended on the dosage.