Table 29:
Evidence profile for molidustat as an alternative to ESA for DD-CKD patients
Population: Anemia in dialysis-dependent chronic kidney disease Intervention: Molidustat Comparator: ESA (epoetin alpha/epoetin beta/darbepoetin alpha) | |||||
Outcome Time frame |
Study results and measurements | Absolute effect estimates | Certainty of the evidence | Plain language summary | |
ESA (epoetin alpha/epoetin beta/darbepoetin alpha) | Molidustat | ||||
Need for iron supplementation (oral) up to 52 weeks |
Odds ratio: 3.45 (CI 95% 0.99–12.05) Based on data from 229 participants in one study |
39 per 1000 |
122 per 1000 |
Very low Due to serious risk of bias, due to serious indirectness, due to very serious imprecision1 |
We are uncertain whether molidustat (any dose) increases the need for iron supplementation (oral) up to 52 weeks. |
Difference: 84 more per 1000 (CI 95% 0–289 more) | |||||
All-cause mortality up to 52 weeks | Odds ratio: 0.56 (CI 95% 0.10–3.04) Based on data from 428 participants in two studies |
17 per 1000 |
9 per 1000 |
Very low Due to serious risk of bias, due to very serious imprecision2 |
We are uncertain whether molidustat (any dose) decreases all-cause mortality up to 52 weeks. |
Difference: 7 fewer per 1000 (CI 95% 15 fewer–33 more) | |||||
Need for ESA up to 52 weeks |
Odds ratio: 8.15 (CI 95% 1.06–62.93) Based on data from 229 participants in one study |
13 per 1000 |
96 per 1000 |
Very low Due to serious risk of bias, due to serious indirectness, due to very serious imprecision3 |
We are uncertain whether molidustat (any dose) increases the need for ESA up to 52 weeks. |
Difference: 84 more per 1000 (CI 95% 1 more–440 more) | |||||
Need for iron supplementation (IV) up to 52 weeks |
Odds ratio: 0.96 (CI 95% 0.54–1.69) Based on data from 229 participants in one study |
632 per 1000 |
622 per 1000 |
Very low Due to serious risk of bias, due to serious indirectness, due to very serious imprecision4 |
We are uncertain whether molidustat (any dose) decreases the need for iron supplementation (IV) up to 52 weeks. |
Difference: 10 fewer per 1000 (CI 95% 151 fewer–112 more) | |||||
Incidences of MACE up to 52 weeks | Odds ratio: 1.25 (CI 95% 0.24–6.60) Based on data from 229 participants in one study |
26 per 1000 |
32 per 1000 |
Very low Due to serious risk of bias, due to serious indirectness, due to very serious imprecision5 |
We are uncertain whether molidustat (any dose) increases incidences of MACE up to 52 weeks. |
Difference: 6 more per 1000 (CI 95% 20 fewer–124 more) | |||||
Treatment emergent adverse event up to 52 weeks |
Odds ratio: 1.24 (CI 95% 0.62–2.45) Based on data from 428 participants in two studies |
881 per 1000 |
901 per 1000 |
Very low Due to serious risk of bias, due to very serious imprecision6 |
We are uncertain whether molidustat increases treatment emergent adverse event up to 52 weeks. |
Difference: 21 more per 1000 (CI 95% 60 fewer–67 more) | |||||
Patients requiring blood transfusion up to 20 weeks |
Odds ratio: 1.47 (CI 95% 0.34–6.38) Based on data from 199 participants in one study |
48 per 1000 |
69 per 1000 |
Very low Due to very serious risk of bias, due to very serious imprecision7 |
We are uncertain whether molidustat (any dose) increases patients requiring blood transfusion up to 20 weeks. |
Difference: 21 more per 1000 (CI 95% 31 fewer–195 more) | |||||
Change in hemoglobin levels from baseline up to 36 weeks |
Measured by: Scale: High better Based on data from 379 participants in two studies |
Mean |
Mean |
Low due to serious risk of bias, due to serious imprecision8 |
We are uncertain whether molidustat (any dose) lowered the hemoglobin levels from baseline up to 36 weeks. |
Difference: 0.17 lower (MD) (CI 95% 0.43 lower–0.10 higher) | |||||
QoL | No studies were found that viewed QoL. | ||||
Fatigue | No studies were found that viewed fatigue. |
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. Wide confidence intervals, low number of patients, only data from one study, 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. Missing intention-to-treat analysis; Imprecision: very serious. Wide confidence intervals, low number of patients, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0). 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. Only data from one study, low number of patients, 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. 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. Wide confidence intervals, low number of patients, only data from one study, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0). 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. Wide confidence intervals, low number of patients, only data from one study, 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. Missing intention-to-treat analysis; Imprecision: very serious. Wide confidence intervals, low number of patients, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0). 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. Low number of patients, only data from one study, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: serious. Missing intention-to-treat analysis; 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, CI: Confidence interval, MD: Mean difference, QoL: Quality of life