Dialysis-dependent patients treated with roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), have no higher risk for ophthalmic abnormalities over 24 weeks than those treated with darbepoetin alfa, according to results from a new study presented at the European Renal Association-European Dialysis and Transplant Association 2020 virtual congress.
Nonclinical data had suggested that stimulation of hypoxia-inducible factor might promote angiogenesis and thereby increase the risk of retinal pathologies. In the Japanese phase 3, randomized double-blind, study (CL-0307), previous or concurrent retinal vascular disorders were present at baseline in 41.3% (62/150) and 37.5% (57/152) of patients treated with roxadustat and darbepoetin alfa, respectively. Nearly a third of patients in each group also had a history of both diabetes mellitus and retinal vascular disorders.
Over 24 weeks, new or worsening retinal hemorrhages occurred in 32.4% vs 36.6% of the overall roxadustat and darbepoetin alfa groups, respectively, Tadao Akizawa, MD, PhD, of Showa University School of Medicine in Tokyo, and colleagues reported in Nephrology Dialysis Transplantation and during the conference. Among the subset of patients free of retinal hemorrhage at baseline, new retinal hemorrhages occurred in 19.1% vs 25.0%, respectively. Among patients with history of 1 or more retinal hemorrhages, new or worsening retinal hemorrhages occurred in 58.3% vs 59.2%, respectively. The investigators found no clinically meaningful changes in visual acuity, retinal thickness, intra-/sub-retinal fluid, hard exudates, or cotton wool spots in either group.
Despite concerns, roxadustat did not appear to increase the risk of ophthalmic abnormalities, including retinal hemorrhages and retinal thickness, over 24 weeks, Dr Akizawa’s team concluded.
Disclosure: This clinical trial was supported by Astellas Pharma. Please see the original reference for a full list of authors’ disclosures.
Sepah Y, Nguyen QD, Yamaguchi Y, Majikawa Y, Reusch M, Akizawa T. Ophthalmological effects of roxadustat in the treatment of anaemia in chronic kidney disease patients on dialysis in a phase 3 randomised, double-blind, active-comparator conversion study. Nephrol Dial Transplant. 35(issue supplement 3). doi: 10.1093/ndt/gfaa140.MO002 Presented at the European Renal Association-European Dialysis and Transplant Association 2020 virtual congress, June 6 to 9. Abstract MO002.