The efficacy and safety of molidustat for anemia in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A systematic review and meta-analysis

Abstract

ObjectiveMolidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. MethodsWe searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. ResultsSix studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P < 0.00001] and ΔHb was also significantly higher for molidustat than for ESAs [MD = 0.25 (95 % CI 0.09 to 0.40), P = 0.002]. For NDD patients, Δhepcidin was significantly lower for molidustat than for placebo [MD = −20.66 (95 % CI: −31.67 to −9.66), P = 0.0002] and Δhepcidin was also significantly lower for molidustat than for ESAs [MD = −24.51 (95 % CI: −29.12 to −19.90), P < 0.00001]. For NDD patients, Δiron was significantly lower for molidustat than for ESAs [MD = −11.85 (95 % CI: −15.52 to −8.18), P < 0.00001], and ΔTSAT was also significantly lower for molidustat than for ESAs [MD = −5.29 (95 % CI: −6.81 to −3.78), P < 0.00001]. For NDD patients, Δferritin was significantly lower for molidustat than for placebo [MD = −90.01 (95 % CI: −134.77 to −45.25), P < 0.00001]. However, for DD-CKD patients, molidustat showed an effect similar to that of ESAs on increasing the Hb level [MD = −0.18 (95 % CI: −0.47 to 0.11), P = 0.23], Δiron level [MD = 3.78 (95 % CI: −7.21 to 14.76), P = 0.5], Δferritin level [MD = 25.03 (95 % CI: −34.69 to 84.75), P = 0.41], and Δhepcidin level [MD = 1.20 (95 % CI: −4.36 to 6.76), P = 0.67]. For DD-CKD patients, compared with the placebo or ESA group, molidustat showed a significantly higher level on ΔTSAT[MD = 3.88 (95 % CI: 2.10 to 5.65), P < 0.0001] and a slightly increased level on ΔTIBC level [MD = 1.08 (95 % CI: −0.07 to 2.23), P = 0.07]. There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups. ConclusionsMoricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence.