Treating anaemia in patients receiving peritoneal dialysis – vadadustat shows potential as oral alternative over intravenous treatments
As the condition progresses, people with advanced chronic kidney disease (CKD) eventually require transplant or dialysis. Traditional treatment of anaemia of kidney disease was with red blood cell transfusions and the administration of intravenous iron. The arrival of erythropoiesis-stimulating agents (ESAs) delivered by subcutaneous injection was a revolution in the management of anaemia of kidney disease. However, for some patients with CKD, including those receiving peritoneal dialysis at home, self-administering ESAs can be challenging.
This post-hoc analysis assesses adults with CKD and anaemia who were receiving peritoneal dialysis at baseline in the phase 3, randomised, non-inferiority INNO2VATE trials. The authors compared the efficacy and safety of oral vadadustat (n=152; varying dosage, maximum 600 mg/day) with the standard of care (SoC) ESA, intravenous darbepoetin alfa (n=157; dosage based on regional guidelines). The primary safety endpoint was the time to first major cardiovascular event (MACE; all-cause mortality or stroke or non-fatal myocardial infarction), and the primary efficacy endpoint was the mean haemoglobin change from baseline to the primary efficacy period of weeks 24–36.
The safety analysis (MACE) showed similar outcomes in patients receiving vadadustat vs darbepoetin alfa (HR, 1.10 [95% CI, 0.62–1.93]), with no new safety signals for vadadustat. In the efficacy assessment, vadadustat showed non-inferiority to SoC at week 52, with baseline haemoglobin increasing from 10.1 g/dL and 10.0 g/dL to 10.6 g/dL and 10.5 g/dL, respectively (mean least squares haemoglobin change between weeks 24–36: 0.47±0.16 g/dL vs 0.57±0.17 g/dL). 88.2% of the patients in the vadadustat group experienced treatment-emergent adverse events (TEAEs) vs 95.5% in the darbepoetin alfa group, with lower serious TEAEs with vadadustat vs darbepoetin alfa (52.6% vs 73.2%). Throughout the 156-week treatment, both groups remained within geography-specific mean haemoglobin ranges.
Although these outcomes are limited by the smaller sample, the self-reporting of TEAEs and the regional differences in haemoglobin targets, the results suggest that vadadustat is non-inferior to intravenous darbepoetin alfa in this population. Additionally, the participants likely reflect real-life populations because the analysis included patients with a broad range for haemoglobin, iron, baseline dialysis modality, and with varying treatment and red blood cell transfusion history.
These outcomes highlight the potential of vadadustat as an alternative oral anaemia treatment for a population already undergoing peritoneal dialysis.
The full article can be read here.
