1 minute read
Materia Medica
by TEAM
an ESA for at least six weeks, and had a Hb level between 8-12 g/dL. Additionally, patients had to have adequate iron stores and serum transferrin saturation. The main exclusion criteria included anemia unrelated to CKD, a recent cardiovascular event, or current or recent cancer. Patients were randomized to either oral daprodustat or an injectable ESA (IV epoetin alfa or SQ darbepoetin alfa) groups. Initial doses of daprodustat (4-12 mg) were chosen based on the patient’s previous ESA dose and were adjusted anywhere from 1-24 mg as needed to maintain a Hb range of 10-11 g/dL. The participants were evaluated at least every four weeks for the first year and every 12 weeks thereafter from November 23, 2016, to August 10, 2018. Two primary noninferiority outcomes were assessed and included the mean change in the Hb level from baseline to the average, during weeks 28-52, and the first occurrence of a major cardiovascular event (MACE). Additionally, secondary outcomes included the average monthly dose of IV iron (baseline through week 52), the first occurrence of a MACE, the first occurrence of a MACE or thromboembolic event, and the first occurrence of a MACE or hospitalization for heart failure. All three cardiovascular secondary outcomes were tested for superiority rather than noninferiority.7
The primary outcomes results of the trial are summarized in the figure below. Both primary outcomes met noninferiority criteria, concluding that oral daprodustat was non-inferior to parenteral ESAs in terms of change in Hb concentration from baseline and occurrences of MACEs.7
Advertisement
As for secondary outcomes, none of the cardiovascular outcomes were significantly different between groups: the first occurrence of MACE (hazard ratio, 0.93; 95% CI, 0.811.07), the first occurrence of MACE or a thromboembolic event (hazard ratio, 0.88; 95% CI, 0.78-1.00), the first occurrence of MACE or hospitalization for heart failure (hazard ratio, 0.97; 95% CI, 0.85-1.11). The difference in mean monthly dose of IV iron was also insignificant and showed a decrease of 90.8±3.3 mg in the daprodustat group and 99.9±3.3 mg in the ESA group, for a mean difference of −9.1 mg (95% CI, −18.4 to 0.2 mg). Additionally, no significant differences were found when comparing adverse events between the daprodustat and ESA groups.7
Daprodustat Prescribing Information
Indication and Administration
Daprodustat is approved in the US for anemia due to CKD in adults who have been on dialysis for at least four months. Daprodustat is a once-daily oral tablet taken without regard to food, iron, phosphate binders, or dialysis. Iron status should be monitored during daprodustat therapy and supplemental iron should be administered when serum ferritin is <100 mcg/ mL and/or when serum transferrin saturation is <20%. Liver function tests should be assessed before treatment and if there are concerns for liver disease during treatment. 6
Continued on Page 30
