Table 14:
Evidence profile for roxadustat as an alternative to ESA for anemia in NDD-CKD patients
Population: Anemia in non-dialysis-dependent chronic kidney disease Intervention: Roxadustat (any dose) Comparator: Darbepoetin alpha | |||||
Outcome Time frame |
Study results and measurements | Absolute effect estimates |
Certainty of the evidence |
Plain language summary | |
Darbepoetin alpha | Roxadustat (any dose) | ||||
Treatment emergent adverse events up to 52 weeks in ESA-conditioned patients |
Odds ratio: 1.56 (CI 95% 0.89–2.73) Based on data from 262 participants in one study |
702 per 1000 |
786 per 1000 |
Very low Due to very serious risk of bias, due to serious indirectness, due to very serious imprecision1 |
We are uncertain whether roxadustat (any dose) increases treatment emergent adverse events up to 52 weeks in ESA-conditioned patients. |
Difference: 84 more per 1000 (CI 95% 25 fewer–163 more) | |||||
Treatment emergent adverse events up to 108 weeks in ESA-naïve patients |
Odds ratio: 0.89 (CI 95% 0.50–1.6) Based on data from 616 participants in one study |
925 per 1000 |
916 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision2 |
We are uncertain whether roxadustat (any dose) decreases treatment emergent adverse events up to 108 weeks in ESA-naïve patients. |
Difference: 8 fewer per 1000 (CI 95% 65 fewer–27 more) | |||||
All-cause mortality up to 52 weeks in ESA-conditioned patients |
Odds ratio: 0.33 (CI 95% 0.01–8.19) Based on data from 262 participants in one study |
8 per 1000 |
2 per 1000 |
Very low Due to very serious imprecision, due to serious indirectness3 |
We are uncertain whether roxadustat (any dose) decreases all-cause mortality up to 52 weeks in ESA-conditioned patients. |
Difference: 5 fewer per 1000 (CI 95% 8 fewer–54 more) | |||||
All-cause mortality up to 108 weeks in ESA-naïve patients |
Odds ratio: 0.87 (CI 95% 0.51–1.47) Based on data from 616 participants in one study |
106 per 1000 |
93 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision4 |
We are uncertain whether roxadustat (any dose) decreases all-cause mortality up to 108 weeks in ESA-naïve patients. |
Difference: 12 fewer per 1000 (CI 95% 49 fewer–42 more) | |||||
Incidence of MACE up to 108 weeks in ESA-naïve patients |
Odds ratio: 0.82 (CI 95% 0.51–1.31) Based on data from 616 participants in one study |
140 per 1000 |
117 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision5 |
We are uncertain whether roxadustat (any dose) decreases incidence of MACE up to 108 weeks in ESA-naïve patients. |
Difference: 22 fewer per 1000 (CI 95% 63 fewer–36 more) | |||||
Incidence of MACE plus up to 108 weeks in ESA-naïve patients |
Odds ratio: 0.91 (CI 95% 0.6–1.38) Based on data from 616 participants in one study |
181 per 1000 |
167 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision6 |
We are uncertain whether roxadustat (any dose) decreases incidence of MACE plus up to 108 weeks in ESA-naïve patients. |
Difference: 14 fewer per 1000 (CI 95% 64 fewer–53 more) | |||||
Need for iron supplementation (bivalent oral) up to 36 weeks in ESA-naïve patients |
Odds ratio: 0.78 (CI 95% 0.57–1.07) Based on data from 616 participants in one study3 |
498 per 1000 |
436 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision7 |
We are uncertain whether roxadustat (any dose) decreases need for iron supplementation (bivalent oral) up to 36 weeks in ESA-naïve patients. |
Difference: 62 fewer per 1000 (CI 95% 137 fewer–17 more) | |||||
Need for iron supplementation (IV) up to 36 weeks in ESA-naïve patients |
Odds ratio: 0.46 (CI 95% 0.26–0.81) Based on data from 616 participants in one study |
126 per 1000 |
62 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision8 |
We are uncertain whether roxadustat (any dose) decreases need for iron supplementation (IV) up to 36 weeks in ESA-naïve patients. |
Difference: 64 fewer per 1000 (CI 95% 90 fewer–21 fewer) | |||||
Need for iron supplementation (trivalent oral) up to 36 weeks in ESA-naïve patients |
Odds ratio: 0.67 (CI 95% 0.49–0.93) Based on data from 616 participants in one study7 |
447 per 1000 |
351 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision9 |
We are uncertain whether roxadustat (any dose) decreases the need for iron supplementation (trivalent oral) up to 36 weeks in ESA-naïve patients. |
Difference: 96 fewer per 1000 (CI 95% 163 fewer–18 fewer) | |||||
Need for ESA | No studies were found that viewed a need for ESA. | ||||
Progression to end-stage kidney disease | No studies were found that viewed progression to end-stage kidney disease. | ||||
Patients requiring blood transfusion up to 108 weeks |
Odds ratio: 1.26 (CI 95% 0.75–2.11) Based on data from 614 participants in one study |
96 per 1000 |
118 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision10 |
Roxadustat (any dose) may worsen patients requiring blood transfusion up to 108 weeks. |
Difference: 22 more per 1000 (CI 95% 22 fewer–87 more) | |||||
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 in ESA-conditioned patients | Measured by: Scale: High better Based on data from 262 participants in one study |
Mean |
Mean |
Very low Due to very serious risk of bias, due to serious indirectness, due to very serious imprecision11 |
Roxadustat (any dose) may have little or no difference on hemoglobin levels from baseline up to 24 weeks in ESA-conditioned patients. |
Difference: MD 0.12 lower (CI 95% 0.30 lower–0.06 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, selective outcome reporting, missing intention-to-treat analysis; Indirectness: serious. The included study was from only one non-South Asian country and was downgraded for lack of directness by one level; Imprecision: very serious. Wide confidence intervals, 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. Wide confidence intervals, only data from one study; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Indirectness: serious. The included study was from only one non-South-Asian country and was downgraded for lack of directness by one level; Imprecision: very serious. Wide confidence intervals, 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. Wide confidence intervals, 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. Wide confidence intervals, 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. Wide confidence intervals, 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. 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, incomplete data and/or large loss to follow-up, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. 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, selective outcome reporting, missing intention-to-treat analysis; Indirectness: serious. The included study was from only one non-South Asian country and was downgraded for lack of directness by one level; Imprecision: very serious. Only data from one study, low number of patients; Publication bias: not serious. Mostly commercially funded studies. ESA: Eythropoiesis-stimulating agents, NDD: Nondialysis dependent, CKD: Chronic kidney disease, MACE: Major adverse cardiovascular events, CI: Confidence interval, QoL: Quality of life, MD: Mean difference.