Table 18:
Evidence to decision table for vadadustat as an alternative to ESA for anemia in NDD-CKD patients
Benefits and harms | Small net benefit or little difference between alternatives | |
Vadadustat reduced adverse events for up to 52 weeks by 21/1000 as compared to darbepoetin alpha. However, evidence on this was uncertain. All GDG members (not including patients) find such a cut-off acceptable for using HIF-PHIs. Similarly, vadadustat reduced adverse events beyond 52 weeks in ESA-naïve patients by 8/1000 as compared to darbepoetin alpha. However, evidence on this was uncertain. Almost 41% of GDG members (not including patients) find such a cut-off acceptable for using HIF-PHIs. Vadadustat decreased all-cause mortality for up to 52 weeks by 5/1000 as compared to darbepoetin alpha. Evidence on this was uncertain. About 14% of GDG members (not including patients) would find such a scenario acceptable for using HIF-PHIs. Vadadustat had little or no difference on all-cause mortality beyond 52 weeks in ESA-conditioned patients. However, evidence on this was uncertain. About 14% of GDG members (not including patients) find such a scenario acceptable to switch to HIF-PHIs. Vadadustat had little or no difference on all-cause mortality beyond 52 weeks. However, evidence on this was uncertain. About 14% of GDG members (not including patients) find such a scenario acceptable to switch to HIF-PHIs. Vadadustat had little or no difference in hemoglobin levels from baseline up to 52 weeks as compared to darbepoetin alpha. However, evidence on this was uncertain. All GDG members (not including patients) find such a scenario acceptable to switch to HIF-PHIs In the group that received vadadustat, there were 13/1000 more adverse events beyond 52 weeks for ESA-conditioned patients as compared to darbepoetin alpha. Evidence on this was uncertain. About 97% of GDG members (not including patients) would find such a scenario unacceptable. Vadadustat increased incidences of MACE beyond 52 weeks by 16/1000 as compared to darbepoetin alpha. Evidence on this was uncertain. All GDG members (not including patients) find such a scenario unacceptable to switch to HIF-PHIs. Vadadustat increased incidences of MACE plus beyond 52 weeks by 7/1000 as compared to darbepoetin alpha. Evidence on this was uncertain. About 81% GDG members (not including patients) find such a scenario unacceptable to switch to HIF-PHIs. Vadadustat increases the incidence of all-cause mortality beyond 52 weeks in ESA-naïve patients by 12/1000 as 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 vadadustat, there were 50/1000 more patients who needed oral iron supplementation up to 52 weeks as compared to darbepoetin alpha. Evidence on this was uncertain. All GDG members (not including patients) find such a scenario unacceptable to switch to HIF-PHIs. There were no included studies that examined health-related QoL, fatigue, need for blood transfusion, progression to end-stage kidney disease, or need for ESA as outcomes. Overall, the panel judged that the anticipated benefits and anticipated harm were both moderate when comparing vadadustat to darbepoetin alpha, noting that there was very low certainty in the evidence base. | ||
Certainty of the evidence | Very low [Table 17] | |
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. Our recommendation reflects a belief that patients and caregivers prefer oral drugs over subcutaneous injections for those who are not DD. However, the GDG also inferred that the informed patient might be reluctant to use vadadustat due to the very low certainty of evidence and the lack of evidence on QoL and fatigue, which are of importance to patients. | ||
Resources | No important issues with the recommended alternative | |
Vadadustat is currently not available in India, so it is not possible to compare the cost. It is administered orally, thereby requiring minimal resources as compared to darbepoetin alpha which is injectable and requires refrigeration prior to administration. The ease of administration and easy storage for vadadustat can reduce the additional resource requirements. | ||
Equity | No important issues with the recommended alternative | |
Vadadustat does not need refrigeration (cold chain) as compared to darbepoetin alpha. It is thus more useful in remote areas with irregular supply of electricity and in equity groups, who might not have refrigeration in their homes. Furthermore, as darbepoetin alpha requires injection, a certain level of health literacy may be needed on how to self-administer the treatment. | ||
Acceptability | No important issues with the recommended alternative | |
Vadadustat has a preferable route of administration for patients; patients either must self-administer ESA injections or make a hospital visit for the injection. However, ESAs have weekly/fortnightly dose requirements, whereas vadadustat should be taken daily or on alternate days. Both these factors can impact compliance and treatment adherence. ESAs may also be easier to supervise than vadadustat due to the differences in dose frequency requirements. Overall, for NDD patients, the oral nature of vadadustat was thought to be more acceptable by the GDG. | ||
Feasibility | Intervention is likely difficult to implement | |
Vadadustat can be orally administered and does not require cold chain, unlike darbepoetin alpha, which is relatively easy to administer and store. In addition, vadadustat may increase accessibility, particularly for non-dialysis patients, as it does not require hospital visitation or self-injection. As vadadustat is not yet approved in India or any other South Asian country, the treatment is not feasible at the current time. |
HIF PHI: Hypoxia-inducible factor prolyl hydroxylase inhibitor, ESA: Eythropoiesis-stimulating agents, NDD: Nondialysis dependent, CKD: Chronic kidney disease, MACE: Major adverse cardiovascular events, GDG: Guideline development group