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

ABSTRACT

Introduction: Beta-thalassemia is an autosomal recessive hereditary anemia characterized by reduced or absent β-globin chain synthesis, affecting about 60,000 people peryear. Management for β-thalassemia major includes regular blood transfusions followed by iron chelating therapy and drug targeting ineffective erythropoiesis.

Areas covered: The safety of licensed drugs for the management of β-thalassemia is reviewed, 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 opinion: Beta-thalassemia is arare disease, and 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 areal-world setting, only eleven studies were identified for iron-chelators and none of these estimated the risk of agiven safety outcome. Future work should aim to better leverage existing sources of real-world datato investigate drug safety in thalassemia.

KEYWORDS:

• β-thalassemia
• iron-overload
• chelation therapy
• registries
• clinical studies
• observational studies

Article highlights

• Current management for β-thalassemia includes frequent blood transfusion and iron chelation therapy to prevent iron overload as a result of these transfusions.

• A number of novel therapies to improve outcomes and quality of life in patients with β-thalassemia are emerging. These include therapies that induce HbF, agents that modulate erythropoiesis, and those that modulate iron metabolism.

• Safety data from clinical trials suggest that currently approved drugs to manage iron overload are generally well-tolerated, with the main adverse events being mild.

• Observational studies conducted in a real-world setting also confirm that the currently available drugs used to manage iron-overload are well-tolerated, although the population sizes in these studies are not very large.

• Sources of routinely collected healthcare data, such as electronic medical records and claims databases, are potentially being under-utilized to evaluate the safety of iron chelators in thalassemia.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Additional information

Funding

This paper was funded by the University of Malta research excellence grant (SWITCH).