Table 8:
Evidence profile for enarodustat as an alternative to ESA for anemia in NDD-CKD patients
Population: Anemia in non-dialysis-dependent chronic kidney disease Intervention: Enarodustat (any dose) Comparator: Darbepoetin alpha | |||||
Outcome Time frame |
Study results and measurements | Absolute effect estimates | Certainty of the Evidence | Plain language summary | |
Darbepoetin alpha | Enarodustat (any dose) | ||||
All-cause mortality up to 26 weeks in ESA-naïve and ESA-conditioned patients |
Odds ratio: 0.34 (CI 95% 0.01–8.35) Based on data from 216 participants in one study |
9 per 1000 |
3 per 1000 |
Very low Due to very serious risk of bias, due to very serious indirectness, due to very serious imprecision1 |
We are uncertain whether enarodustat (any dose) decreases all-cause mortality up to 26 weeks in ESA-naïve and ESA-conditioned patients. |
Difference: 6 fewer per 1000 (CI 95% 9 fewer–61 more) | |||||
Adverse events up to 26 weeks in ESA-naïve and ESA-conditioned patients |
Odds ratio: 0.40 (CI 95% 0.21–0.75) Based on data from 216 participants in one study |
826 per 1000 |
655 per 1000 |
Very low Due to very serious risk of bias, due to very serious indirectness2 |
We are uncertain whether enarodustat (any dose) decreases adverse events up to 26 weeks in ESA-naïve and ESA-conditioned patients. |
Difference: 171 fewer per 1000 (CI 95% 327 fewer–45 fewer) | |||||
Adverse events up to 26 weeks in ESA-naïve patients |
Odds ratio: 0.40 (CI 95% 0.15–1.10) Based on data from 102 participants in one study |
865 per 1000 |
719 per 1000 |
Very low Due to very serious risk of bias, due to very serious indirectness, due to very serious imprecision3 |
We are uncertain whether enarodustat (any dose) decreases adverse events up to 26 weeks in ESA-naïve patients. |
Difference: 146 fewer per 1000 (CI 95% 375 fewer–11 more) | |||||
Adverse events up to 26 weeks in ESA-conditioned patients |
Odds ratio: 0.39 (CI 95% 0.17–0.90) Based on data from 114 participants in one study |
789 per 1000 |
593 per 1000 |
Very low Due to very serious risk of bias, due to very serious indirectness, due to serious imprecision4 |
We are uncertain whether enarodustat (any dose) decreases adverse events up to 26 weeks in ESA-conditioned patients. |
Difference: 196 fewer per 1000 (CI 95% 400 fewer–18 fewer) | |||||
Incidences of MACE and MACE plus | No studies were found that viewed incidences of MACE and MACE plus. | ||||
Need for iron supplementation | No studies were found that viewed the need for iron supplementation. | ||||
Need for ESA | No studies were found that viewed the need for ESA. | ||||
Progression to end-stage kidney disease | No studies were found that viewed the progression to end-stage kidney disease. | ||||
Patients requiring blood transfusio | No studies were found that viewed patients requiring blood transfusion. | ||||
Health-related QoL | No studies were found that viewed health-related QoL. | ||||
Fatigue | No studies were found that viewed fatigue. | ||||
Change in hemoglobin levels from baseline up to 24 weeks | Measured by: Scale: High better Based on data from 193 participants in one study | Mean | Mean |
Very low Due to very serious risk of bias, due to very serious indirectness, due to serious imprecision5 |
We are uncertain whether enarodustat (any dose) has little or no difference on change in hemoglobin levels from baseline up to 24 weeks. |
Difference: MD 0.09 lower(CI 95% 0.08 lower–0.26 lower) |
Risk of Bias: very serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias, incomplete data and/or large loss to follow-up, missing intention-to-treat analysis; Indirectness: very serious. The included study was from only one country and was downgraded for lack of directness by two levels; Imprecision: very serious. Low number of patients, only data from one study, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Missing intention-to-treat analysis, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias, incomplete data and/or large loss to follow-up; Indirectness: very serious. The included study was from only one country and was downgraded for lack of directness by two levels; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias, incomplete data and/or large loss to follow-up, missing intention-to-treat analysis; Indirectness: very serious. The included study was from only one country and was downgraded for lack of directness by two levels; Imprecision: very serious. Low number of patients, only data from one study, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias, incomplete data and/or large loss to follow-up, missing intention-to-treat analysis; Indirectness: very serious. The included study was from only one country and was downgraded for lack of directness by two levels; Imprecision: serious. Low number of patients, only data from one study; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias, incomplete data and/or large loss to follow-up, missing intention-to-treat analysis; Indirectness: very serious. The included study was from only one country and was downgraded for lack of directness by two levels; Imprecision: serious. Low number of patients, only data from one study; Publication bias: not serious. Mostly commercially funded studies. ESA: Eythropoiesis-stimulating agents, NDD: Nondialysis dependent, CKD: Chronic kidney disease, CI: Confidence interval, MACE: Major adverse cardiovascular events, QoL: Quality of life.