Safety of Roxadustat Combined with Epoetin Alfa in Hemodialysis Patients with Anemia: A Cohort Study

Abstract Background: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis1, China was the first country in the world to complete phase III clinical trials and was officially approved for marketing in 20182. Recombinant human erythropoietin(rhEPO) is a traditional exogenous supplement of erythropoietin for the treatment of renal anemia.Due to a lack of research on the combination therapy, the FDA(Food and Drug Administration)does not recommend using roxadustat and recombinant human erythropoietin(rhEPO) together3. Methods: This cohort study was carried out at Nanyang Central Hospital in Nanyang, Henan, China, between January 2020 and January 2022.We compared roxadustat combined with epoetin alfa(combination group) with roxadustat and epoetin alfa for post-dialysis systolic pressure, adverse events(AEs) and major adverse cardiovascular events(MACEs) in end-stage renal disease(ESRD) patients with anemia who were undergoing hemodialysis.The primary outcomes were the mean change in the postdialysis systolic pressure from baseline(BL) to 28 weeeks,and the secondary outcomes were MACEs and AEs. Results: A total of 96 participants were included. From baseline to weeks 28,the mean(±SE) change in the postdialysis systolic pressure was -6.6±23.3mmHg in the epoetin alfa group,-5.5±26.9mmHg in the roxadustat group, and 8.8±21.0mmHg in the combination group. During a follow-up of 28 weeks, a worsening hypertension occurred in 3 of 42 patients (7.1%) in the epoetin alfa group, in 1 of 35 patients (2.9%) in the raxadustat group and in 0 of 19 patients(0%) in the combination group. The proportion of patients with MACEs and AEs were similar across the three groups. Conclusions: We found that roxadustat combined with epoetin alfa had greater risk of elevated systolic pressure compared to oral roxadustat or parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis in the 28 weeks, and the proportion of patients experiencing AEs and MACEs was generally similar across the three grouos.At this time, clinical studies with larger sample size and longer follow-up time are needed to confirm.