We might never know the answer to these specific questions, but we should continue to document realworld findings, particularly regarding the risks and benefits of voxelotor to end-organ function. Building on preclinical models,7 preliminary studies showing preserved or lowered cerebral blood flow,8 together with the results of this study1 and ongoing studies, such as HOPE Kids 2 (NCT04218084), which is investigating the effect of voxelotor on transcranial doppler velocity, are already looking to address cerebrovascular outcomes. Longitudinal studies assessing end-organ damage are surely also needed. Reduced haemoglobin concentrations is a risk factor for sickle cell disease-related morbidity and mortality.9 Howard and colleagues1 show the reliable increase in haemoglobin concentrations, decrease in haemolysis markers, and a lower annualised incidence of acute anaemic episodes in patients with sickle cell disease taking voxelotor compared with those taking placebo. These results suggest that acute anaemic crises could be potentially managed in patients with alloimmunisation or hyperhaemolytic syndrome. The absence of improvement in the incidence of vasoocclusive crises and patient-reported quality of life with voxelotor versus placebo, however, shows that there is still much to learn and optimise with regards to modulators that increase the affinity of haemoglobin for oxygen.
www.thelancet.com/haematology Vol 8 May 2021 e307