Table 32:
Evidence profile for roxadustat as an alternative to ESA for DD-CKD patients
Population: Anemia in dialysis-dependent chronic kidney disease Intervention: Roxadustat Comparator: ESA (epoetin alpha/darbepoetin alpha) | |||||
Outcome Time frame |
Study results and measurements | Absolute effect estimates |
Certainty of the evidence |
Plain language summary | |
ESA (epoetin alpha/darbepoetin alpha) | Roxadustat | ||||
All-cause mortality from 6 to 52 weeks |
Odds ratio: 1.11 (CI 95% 0.76–1.62) Based on data from 1715 participants in six studies |
82 per 1000 |
90 per 1000 |
Low Due to serious risk of bias, due to serious imprecision1 |
We are uncertain whether roxadustat (any dose) increases all-cause mortality from 6 to 52 weeks. |
Difference: 8 more per 1000 (CI 95% 18 fewer–44 more) | |||||
All-cause mortality from 108 to 209 weeks |
Odds ratio: 1.13 (CI 95% 0.96–1.33) Based on data from 3974 participants in three studies |
171 per 1000 |
189 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision2 |
We are uncertain whether roxadustat (any dose) increases all-cause mortality from 108 to 209 weeks. |
Difference: 18 more per 1000 (CI 95% 6 fewer–44 more) | |||||
Need for iron supplementation from 6 to 52 weeks |
Odds ratio: 0.57 (CI 95% 0.16–2.05) Based on data from 1215 participants in three studies |
793 per 1000 |
685 per 1000 |
Very low Due to serious risk of bias, due to serious inconsistency, due to serious imprecision3 |
We are uncertain whether roxadustat (any dose) decreases the need for iron supplementation from 6 to 52 weeks. |
Difference: 107 fewer per 1000 (CI 95% 413 fewer–94 more) | |||||
Need for ESA from 6 to 52 weeks |
Odds ratio: 13.38 (CI 95% 0.75–238.31) Based on data from 916 participants in two studies |
0 per 1000 |
0 per 1000 |
Very low Due to very serious risk of bias, due to very serious imprecision4 |
We are uncertain whether roxadustat (any dose) increases the need for ESA from 6 to 52 weeks. |
Difference: 0 fewer per 1000 (CI 95% 0–0) | |||||
Need for iron supplementation from 52 to 208 weeks |
Odds ratio: 0.56 (CI 95% 0.13–2.46) Based on data from 2940 participants in two studies |
288 per 1000 |
184 per 1000 |
Very low Due to very serious risk of bias, due to serious inconsistency, due to serious imprecision5 |
We are uncertain whether roxadustat (any dose) decreases need for iron supplementation from 52 to 208 weeks. |
Difference: 103 fewer per 1000 (CI 95% 238 fewer–211 more) | |||||
Need for ESA up to 208 weeks |
Odds ratio: 20.29 (CI 95% 4.89–84.25) Based on data from 2106 participants in one study |
2 per 1000 |
39 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision6 |
We are uncertain whether roxadustat increases need for ESA up to 208 weeks. |
Difference: 37 more per 1000 (CI 95% 8 more–142 more) | |||||
Treatment emergent adverse events from 6 to 52 weeks |
Odds ratio: 1.45 (CI 95% 1.08–1.96) Based on data from 1715 participants in six studies |
786 per 1000 |
841 per 1000 |
Moderate Due to serious risk of bias7 |
Roxadustat (any dose) may increase treatment emergent adverse events from 6 to 52 weeks. |
Difference: 56 more per 1000 (CI 95% 13 more–92 more) | |||||
Treatment emergent adverse events from 108 to 209 weeks |
Odds ratio: 1.05 (CI 95% 0.85–1.28) Based on data from 2935 participants in two studies |
849 per 1000 |
855 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision8 |
We are uncertain whether roxadustat (any dose) increases or decreases treatment emergent adverse events from 108 to 209 weeks. |
Difference: 6 more per 1000 (CI 95% 22 fewer–29 more) | |||||
Patients requiring blood transfusion 6–52 weeks | Odds ratio: 0.58 (CI 95% 0.42–0.82) Based on data from 821 participants in two studies |
202 per 1000 |
128 per 1000 |
Very low Due to very serious risk of bias, due to serious imprecision9 |
We are uncertain whether roxadustat (any dose) decreases patients requiring blood transfusion from 6 to 52 weeks. |
Difference: 74 fewer per 1000 (CI 95% 106 fewer–30 fewer) | |||||
Patients requiring blood transfusion from 58 to 108 weeks |
Odds ratio: 0.87 (CI 95% 0.65–1.17) Based on data from 1869 participants in two studies |
93 per 1000 |
82 per 1000 |
Very low Due to serious risk of bias, due to serious inconsistency, due to serious imprecision10 |
We are uncertain whether roxadustat (any dose) decreases patients requiring blood transfusion from 58 to 108 weeks. |
Difference: 11 fewer per 1000 (CI 95% 31 fewer–14 more) | |||||
Change in hemoglobin levels from baseline from 6 to 52 weeks |
Measured by: Scale: High better Based on data from 5553 participants in nine studies |
Mean | Mean |
Low Due to serious risk of bias, due to serious publication bias11 |
We are uncertain whether roxadustat (any dose) increases change in hemoglobin levels from baseline from 6 to 52 weeks. |
Difference: 0.21 lower (MD) (CI 95% 0.11 lower–0.32 higher) | |||||
QoL assessed by EQ-5D-5L VAS |
Measured by: Scale: High better Based on data from 783 participants in one study |
Mean | Mean |
Very low Due to very serious risk of bias, due to serious imprecision12 |
We are uncertain whether roxadustat (any dose) improves QoL assessed by EQ-5D-5L VAS. |
Difference: 1.42 higher (MD) (CI 95% 1.21 lower–4.04 higher) | |||||
Fatigue measured by FACT—total score at 28 weeks |
Measured by: Scale: High better Based on data from 783 participants in one study |
Mean | Mean |
Very low Due to very serious risk of bias, due to serious imprecision13 |
We are uncertain whether roxadustat (any dose) increases fatigue measured by FACT—total score at 28 weeks. |
Difference: 2.41 higher (MD) (CI 95% 1.68 lower–6.51 higher) | |||||
Incidence of MACE up to 6 weeks | Based on data from 96 participants in one study | No incidence of MACE was reported in either Roxadustat or ESA (epoetin alpha/darbepoetin alpha) group |
Very low Due to very serious risk of bias, due to serious indirectness, due to serious imprecision13 |
There were no participants who experienced MACE up to 6 weeks, so we were unable to determine whether roxadustat (any dose) made a difference. |
Risk of Bias: 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; Imprecision: serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; 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, selective outcome reporting; Imprecision: serious. Wide confidence intervals, wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: 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; Inconsistency: serious. The magnitude of statistical heterogeneity was high with I^2 55 %; Imprecision: serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; 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; Imprecision: very serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate, low number of patients; 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, selective outcome reporting; Inconsistency: serious. The magnitude of statistical heterogeneity was high with I^2: 98%, the confidence interval of some of the studies do not overlap with those of most included studies/the point estimate of some of the included studies; Imprecision: serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; 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, selective outcome reporting; Imprecision: serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: 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; Indirectness: serious. The included study was from countries other than South Asia and was downgraded for lack of directness by one level; 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, selective outcome reporting; Imprecision: serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate, 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; Imprecision: serious. Due to less events (< 400) and inadequate optimal information size (OIS); Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: 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; Inconsistency: serious. The magnitude of statistical heterogeneity was high with I^2:56 %; Imprecision: serious. Wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: 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; Publication bias: serious. Mostly commercially funded studies, asymmetrical funnel plot. 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, selective outcome reporting, missing intention-to-treat analysis; Imprecision: serious. Only data from one study, low number of patients, wide confidence intervals, the 95% CI of the included study overlaps line of no effect; 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, selective outcome reporting; Imprecision: 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. 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: serious. The included study was not from South Asian country 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. Mostly commercially funded studies. DD: Dialysis-Dependent, CKD: Chronic kidney disease, ESA: Eythropoiesis-stimulating agents, MACE: Major adverse cardiovascular events, HIF PHI: Hypoxia-inducible factor prolyl hydroxylase inhibitor, FACT: Functional assessment of cancer therapy (measure of fatigue), CI: Confidence interval, MD: Mean difference