Safety Profile of Roxadustat in Anemic Patients - A Meta-Analysis of 21 RCTs

Sep 28, 2026

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Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with chronic kidney disease. A meta-analysis of randomized controlled trials evaluated safety and tolerability versus placebo and versus erythropoiesis-stimulating agents (ESA). Twenty-one RCTs including 11,686 patients were pooled using inverse-variance-weighted random-effects models. Serious TEAEs and cardiac SAEs were generally comparable across comparators, while hyperkalemia was higher versus placebo and withdrawals due to adverse events were higher versus ESA.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

Objective

Methods

Results

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DOI: 10.4274/MMJ.galenos.2025.44045 Medeni Med J 2025;40:250-261 Original Article Safety Profile of Roxadustat in Anemic Patients: A MetaAnalysis of 21 RCTs Anemili Hastalarda Roksadustat’ın Güvenlilik Profili: 21 RCT’nin Meta-Analizi Lokman Hekim TANRIVERDI1, Ahmet SARICI2, Mehmet Ali ERKURT2, Hacı Bayram BERKTAS3 1Inonu University Faculty of Medicine, Department of Medical Pharmacology, Malatya, Türkiye 2Inonu University Faculty of Medicine, Department of Hematology, Malatya, Türkiye 3Inonu University Faculty of Medicine, Department of Nephrology, Malatya, Türkiye ABSTRACT Objective: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with chronic kidney disease. We aimed to assess its safety and tolerability profile through a meta-analysis of randomized controlled trials (RCTs) . Methods: A systematic search of the Cochrane CENTRAL, Ovid Medline R, PubMed, and Web of Science databases was conducted up to January 1, 2025 was conducted. RCTs comparing roxadustat with control groups were included. Inverse-variance-weighted random-effects models were used. The primary outcome was the risk of any serious treatment-emergent adverse event (TEAE) . Subgroup analyses were based on etiology, comparator, and prior erythropoiesis-stimulating agent (ESA) use. Results: Twenty-one RCTs involving 11.686 patients were included. Roxadustat was not associated with a higher risk of any serious TEAE compared with placebo [risk ratio (RR) =1 . 37, 95% confidence interval (CI): 0.79-2. 37] or with ESA (RR=1 . 05, 95% CI: 0.99-1. 10) . Similarly, cardiac serious adverse events (SAEs) did not differ significantly when compared with ESA (RR=1 . 11, 95% CI: 0 .75-1. 12) or placebo (RR=1 . 11, 95% CI: 0 .92-1. 35) . Hyperkalemia incidence was significantly higher compared with placebo (RR=1 .25, 95% CI: 1.02-1. 53) but not compared with ESA (RR=1 . 03, 95% CI: 0.77-1. 36) . There were also no significant differences in the incidence of serious infections (RR=0 .74, 95% CI: 0.21-2. 59), azotemia (RR=0 . 96, 95% CI: 0.46-2. 00), hypertension (RR=1 . 06, 95% CI: 0.93-1.21), or pneumonia (RR=0 . 96, 95% CI: 0.81-1. 14) compared with ESA. Notably, withdrawal due to adverse events (RR=2 . 11, 95% CI: 1.59-2.79) was significantly higher compared with ESA. TEAEs leading to death were similar compared with ESA (RR=0 . 98, 95% CI: 0.85-1. 13) but were increased compared with placebo (RR=1 .21, 95% CI: 1.04-1. 42) . All-cause mortality was significantly lower than with placebo (RR=0 . 40, 95% CI: 0.28-0. 57) but was similar to ESA (RR=0 . 89, 95% CI: 0.57-1. 37) . Subgroup analyses for the primary outcome by etiology and prior ESA use were not consistent with the main findings. Conclusions: Roxadustat demonstrated a SAE profile generally comparable to that of ESA, with no significant differences in cardiac SAEs, serious infections, azotemia, hypertension, or pneumonia. Hyperkalemia was more frequent compared with placebo, and withdrawals due to adverse events were more frequent compared with ESA. TEAEs leading ÖZ Amaç: Roxadustat, kronik böbrek hastalığına bağlı aneminin tedavisinde kullanılan oral bir hipoksi ile indüklenebilir faktörprolil hidroksilaz inhibitörüdür. Bu çalışmada, randomize kontrollüçalışmaların (RKÇ) meta-analizi ile roksadustatın güvenlilik ve tolereedilebilirlik profilini değerlendirmeyi amaçladık. Yöntemler: Cochrane CENTRAL, Ovid Medline R, PubMed ve Web of Science veritabanlarında 1 Ocak 2025 tarihine kadar sistematik literatürtaraması yapıldı. Roksadustat ile kontrol gruplarını karşılaştıran RKÇ’ler dahil edildi. Ters varyans ağırlıklı rastgele etki modeli kullanıldı. Birincil sonlanım noktası, herhangi bir ciddi tedaviyle ilişkili advers olay (TEAE) riskiydi. Alt grup analizleri etiyoloji, kontrol grubu ve geçmişteeritropoez uyarıcı ajan (ESA) kullanımı temelli yapıldı. Bulgular: Toplam 11,686 hastayı içeren 21 RKÇ dahil edildi. Roksadustat, pla

FAQs

What is the primary safety outcome in the meta-analysis of roxadustat?

The primary outcome is the risk of any serious treatment-emergent adverse event (TEAE).

How did roxadustat safety compare with placebo for serious TEAEs?

Roxadustat was not associated with a higher risk of serious TEAEs versus placebo (RR=1.37, 95% CI: 0.79–2.37).

Which adverse event and tolerability measure differed most by comparator?

Hyperkalemia incidence was significantly higher versus placebo, and withdrawal due to adverse events was significantly higher versus ESA.

Sep 28, 2026

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