Table 26:

Evidence profile for enarodustat as an alternative to ESA for DD-CKD patients

Population: Anemia in dialysis-dependent chronic kidney disease Intervention: Enarodustat (any dose) Comparator: Darbepoetin alpha
Outcome Time frame	Study results and measurements	Absolute effect estimates		Certainty of evidence	Plain language summary
		Darbepoetin alpha	Enarodustat any dose
Need for ESA					No studies were found that viewed at the need for ESA.
Incidences of MACE up to 52 weeks					No studies were found that viewed incidences of MACE up to 52 weeks.
Need for iron supplementation (oral) up to 24 weeks	Odds ratio: 1.40 (CI 95% 0.76–2.56) Based on data from 172 participants in one study	384 per 1000	466 per 1000	Very low Due to serious risk of bias, due to serious indirectness, due to very serious imprecision1	We are uncertain whether enarodustat (any dose) increases the need for iron supplementation (oral) up to 24 weeks.
		Difference: 82 more per 1000 (CI 95% 63 fewer–231 more)
Adverse events up to 26 weeks	Odds ratio: 1.34 (CI 95% 0.57–3.15) Based on data from 173 participants in one study	837 per 1000	873 per 1000	Very low Due to serious indirectness, due to very serious imprecision2	We are uncertain whether enarodustat (any dose) increases adverse events up to 26 weeks.
		Difference: 36 more per 1000 (CI 95% 92 fewer–105 more)
Patients requiring blood transfusion					No studies were found that viewed patients requiring blood transfusion.
Change in hemoglobin levels from baseline up to 24 weeks	Measured by: Scale: High better Based on data from 172 participants in one study	Mean	Mean	Low Due to serious indirectness, due to serious imprecision3	Enarodustat (any dose) lowered the hemoglobin levels from baseline up to 24 weeks.
		Difference: MD 0.12 lower (CI 95% -0.33 lower–0.09 higher)
QoL					No studies were found that viewed QoL.
Fatigue					No studies were found that viewed fatigue.
All-cause mortality up to 26 weeks	Based on data from 173 participants in one study	No deaths were reported in either enarodustat any dose or darbepoetin alpha group		Very low Due to serious risk of bias, due to serious indirectness, due to serious imprecision4	There were no patients who experienced all-cause mortality up to 26 weeks, so we were unable to determine whether enarodustat (any dose) made a difference.

Risk of Bias: serious. Missing intention-to-treat analysis; Indirectness: serious. The included study was from only one country which is not in South Asia and was downgraded for lack of directness by one level; Imprecision: very serious. The 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate, only data from one study, low number of patients, wide confidence intervals; Publication bias: not serious. The study is commercially funded. Risk of Bias: not serious. Missing intention-to-treat analysis; Indirectness: serious. The included study was from only one country which is not in South Asia and was downgraded for lack of directness by one level; Imprecision: very serious. The 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate only data from one study, low number of patients, wide confidence intervals; Publication bias: not serious. The study is commercially funded. Risk of Bias: not serious. Missing intention-to-treat analysis; Indirectness: serious. The included study was from only one country which is not in South Asia and was downgraded for lack of directness by one level; Imprecision: serious. Only data from one study, low number of patients, the 95% CI of the included study overlaps line of no effect; Publication bias: not serious. The study is commercially funded.; Risk of Bias: serious. Missing intention-to-treat analysis; Indirectness: serious. The included study was from only one country which is not in South Asia and was downgraded for lack of directness by one level; Imprecision: serious. Low number of patients, only data from one study; Publication bias: not serious. The study is commercially funded. DD: Dialysis-Dependent, CKD: Chronic kidney disease, ESA: Eythropoiesis-stimulating agents, MACE: Major adverse cardiovascular events, CI: Confidence interval, QoL: Quality of life, MD: Mean difference