Drug safety in thalassemia: lessons from the present and directions for the future.

IntroductionBeta-thalassemia is an autosomal recessive hereditary anemia characterized by reduced or absent β-globin chain synthesis, affecting about 60,000 people per year. The only curative treatment is hematopoietic stem cell transplantation but this is risky and expensive. Management for β-thalassemia major includes regular blood transfusions followed by iron chelating therapy and drug targeting ineffective erythropoiesis.Areas covered:The safety of currently licenced drugs for the management of β-thalassemia is reviewed in detail, using evidence from clinical trials and observational research. Such drugs include the iron chelators and the erythrocyte maturation agent luspatercept. The safety of emerging treatment, such as hydroxyurea and thalidomide is also reviewed.Expert opinionBeta-thalassemia is a rare disease, and as such, it is not surprising that there are limited studies investigating the safety of drugs used in this disease. Indeed, although observational studies are the main source of drug safety information in a real-world setting, only eleven studies were identified for iron-chelators and none of these estimated the risk of a given safety outcome but provided only event frequencies. Future work should aim to better leverage existing sources of real-world data, including electronic medical records, administrative healthcare databases and registries to investigate drug safety in thalassemia.