Adverse Event Rates Higher in the Early Post-RBC Transfusion Period

Treatment-emergent adverse events (TEAEs) occur at higher rates within the first 2 weeks of red blood cell (RBC) transfusion than during the period afterward, investigators reported at Kidney Week 2020 Reimagined, the virtual conference sponsored by the American Society of Nephrology.

RBC transfusion was associated with higher rates of TEAEs within 14 days in roxadustat trials involving nondialysis, prevalent dialysis, and incident dialysis patients, Robert Provenzano, MD, of Wayne State University in Detroit, Michigan, reported. RBCl transfusion is often “a necessary evil” and is common in the United States, he said by way of background. Nephrologists try to avoid transfusion in patients with chronic kidney disease, he said, because transfusion increases the risk of sensitization to human leukocyte antigens and panel reactive antibodies, delaying the time to kidney transplantation.

In pooled data from the 3 roxadustat trials of nondialysis-dependent (NDD-CKD) patients – OLYMPUS, ANDES, ALPS involving nearly 3700 patients – the rate of intravascular volume-related TEAEs, such as heart failure, pulmonary edema, and respiratory failure, for roxadustat-treated patients and placebo recipients was 11.25 and 9.03 times higher within the first 2 weeks after transfusion than during the follow-up period after 2 weeks (on-treatment period plus 28 days), respectively. The incidence rates per 100 patient-exposure years during these periods were 147.1 vs 13.1 for roxadustat and 121.1 vs 13.4 for placebo, respectively. The rate of any TEAEs was 18.44 and 9.98 times higher within the first 14 days, respectively, possibly due to the comorbidity burden of the population, Dr Provenzano stated. The incidence rates per 100 patient-exposure years were 992.8 vs 53.8 for roxadustat and 790.3 vs 79.2 for placebo, respectively.

Among the dialysis-dependent (DD-CKD) patients in the ROCKIES, SIERRAS, and HIMALAYAS trials, the rate of volume-related TEAEs was 12.06 and 9.77 times higher and the rate of any TEAEs was 21.43 and 18.46 higher within the initial 2 weeks of transfusion than during the follow-up period for roxadustat- and epoetin alfa-treated patients, respectively. For volume-related TEAEs, the incidence rates per 100 patient-exposure years were 151.7 vs 12.6 for roxadustat and 143.1 vs 14.6 for placebo, respectively. For any TEAEs, the corresponding incidence rates were 1061.9 vs 49.6 for roxadustat and 838.1 vs 45.4 for placebo, respectively.

Looking at incident dialysis patients only, the same pattern emerged. The rate of volume-related TEAEs was 15.39 and 10.47 times higher and the rate of any TEAEs was 16.67 and 13.96 times higher within the first 2 weeks of transfusion for roxadustat and epoetin-treated patients, respectively. For volume-related TEAEs, the incidence rates per 100 patientexposure years were 184.5 vs 12.0 for roxadustat and 141.2 vs 13.5 for placebo, respectively. For any TEAEs, the corresponding incidence rates were 959.2 vs 57.5 for roxadustat and 800.2 vs 57.3 for placebo, respectively.

“Avoiding transfusions through consistent management of anemia should reduce AE risk, as well as healthcare resource utilization,” Dr Provenzano said.

Disclosure: These trials were supported by Fibrogen, AstraZeneca, and Astellas Pharma. Please see the original references for a full list of authors’ disclosures.

Reference

Provenzano R, Pollock CA, Pecoits-Filho R, et al. Adverse event rates are higher post-transfusion vs. overall follow-up and independent of background anemia treatment in patients with CKD. Presented at: Kidney Week 2020 Reimagined, October 19-25, 2020. Poster TH-OR09.