The efficacy of voxelotor, 900 mg in patients with sickle cell anaemia: A meta‐analysis of the randomised controlled trials

Abstract Objective Sickle cell anaemia (SCA), an inherited chronic hematological disease affecting hundreds of thousand people worldwide, causes significant morbidity and reduced life expectancy about two or three decades. This study aimed to conduct a meta‐analysis of the efficacy of voxelotor, 900 mg in patients with SCA. Methods The research protocol was registered at the International Register of Prospective Systematic Reviews (PROSPERO), under the registration number: CRD42020147796. ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Conference Abstracts, Google Scholar, Ovid Medline, Scopus, Web of Science, and Wiley Online Library from 2015 through July 25, 2019, and bibliographies of review articles and eligible studies. Eleven eligible studies that evaluated the effectiveness of voxelotor, 900 mg in SCA. Based on pre‐specified inclusion and exclusion criteria, 2 randomized, placebo‐controlled studies were included in the meta‐analysis. Results The primary outcome measured was hemoglobin elevation, assessed in a highly similar fashion in both trials. There was a significant difference between voxelotor and placebo in haemoglobin change from baseline (mean difference [MD]: 0.87, 95% confidence interval [CI]: 0.67‐1.06). Voxelotor also reduced markers of haemolysis, MD: −36.79, 95% CI: (−75.05) to 1.48 for unconjugated bilirubin that changes from baseline; MD: −19.09, 95% CI: (−44.06) to 5.88 for the percentage of reticulocytes that change from baseline and MD: −23.29, 95% CI: (−65.14) to 18.55 for LDH that change from baseline) but the difference was not statistically significant. Conclusions As a conclusion, voxelotor, 900 mg use significantly increased hemoglobin levels which of 1 g/dL elevation predicts a reduced risk of stroke (41%), albuminuria (53%), pulmonary arterial hypertension (57%), and mortality (64%) in recent studies. Voxelotor also reduced markers of hemolysis but failed to reach statistically significance in current evidence. Multicenter, randomized, placebo‐controlled studies are on the way and will provide more evidence to see the potential of disease‐modifying effects of voxelotor.