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. 2025 Feb 25;35(2):129–167. doi: 10.25259/ijn_389_23

Table 27:

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

Benefits and harms Small net benefit or little difference between alternatives

Enarodustat lowered the hemoglobin levels from baseline up to 24 weeks by 12/1000 compared to darbepoetin alpha. However, evidence on this was uncertain. All GDG members (not including patients) find such a scenario unacceptable to switch to HIF-PHIs.

In the group that received enarodustat, there was 36/1000 more risk of adverse events up to 26 weeks compared to darbepoetin alpha. Evidence on this was uncertain. All GDG members (not including patients) would find such a scenario unacceptable.

Enarodustat increased the need for oral iron supplementation up to 24 weeks as compared to darbepoetin alpha by 82/1000. Evidence on this was uncertain. All GDG members (not including patients) would find such a scenario unacceptable.

There were no patients who experienced all-cause mortality up to 26 weeks; thus it is uncertain to determine whether enarodustat made a difference as compared to darbepoetin alpha.

None of the included studies measured health-related QoL, fatigue, incidences of MACE and MACE plus, need for blood, and ESA as outcomes.

Overall, compared to darbepoetin alpha, the panel judged desirable anticipated effects for enarodustat to be trivial and harm to be moderate, noting that there was very low certainty in the evidence base. There is substantial concern regarding the lack of robust evidence on cardiovascular safety in DD-CKD patients with anemia.

Certainty of the evidence Very low [Table 26]
Values and preferences Substantial variability is expected or uncertain
Empirical examinations of patients’ values and preferences from South Asia are not available. This section is based on unstructured interactions with individual patients and caregivers and discussions with panel members. Subcutaneous ESA administration is challenging due to its invasive nature, its use has a learning curve, and there are logistic issues (refrigeration). Use of HIF-PHIs might have concerns around pill burden and adherence in some patients. However, some patients might prefer injections because of the need to limit fluid intake.
Resources Important issues or potential issues not investigated
Enarodustat is currently not available in India, so it is not possible to compare the cost at this time. Although it does not need refrigeration and can be administered orally (unlike darbepoetin alpha), this may not be of added benefit for DD patients as they would already be undertaking regular hospital visits for dialysis. In this case, they can receive the intervention during hospital visits, which is unlikely to require extra resources from the patient
Equity Important issues or potential issues not investigated
Although enarodustat does not need refrigeration and can be administered orally (unlike darbepoetin alpha), this is less likely to decrease equity for DD patients, as they would already have regular hospital visits for dialysis purposes. In this case, it would put minimal additional strain to have darbepoetin alpha administered.
Acceptability Important issues or potential issues not investigated
There are no qualitative studies on preference of South Asian patients with DD-CKD with respect to the acceptability of HIF-PHIs. Patients with hemodialysis might get ESAs intravenously, thus not requiring additional pricks through subcutaneous routes. However, there are concerns around polypharmacy on the use of HIF-PHIs.
Feasibility Intervention is likely difficult to implement
There are no formal studies on facilitators and barriers to the use of HIF-PHIs in South Asia. The panel adjudged that enarodustat, although preferred because of its oral route of administration, is not licensed by the national drug regulators in India or any other South Asian country. As such, it is probably not feasible.

DD: Dialysis-Dependent, CKD: Chronic kidney disease, ESA: Eythropoiesis-stimulating agents, MACE: Major adverse cardiovascular events, HIF PHI: Hypoxia-inducible factor prolyl hydroxylase inhibitor