Thalassemia is an inherited blood disorders resulting from a defect in the gene coding for hemoglobin, the substance in our red blood cells responsible for carrying oxygen to our organs. For a patient to have a clinically significant form of thalassemia, they need to inherit one copy of this defective gene form each parent. Accordingly, thalassemia may be more common in families who carry this defective gene and have a high rate of consanguineous marriages.
Today, thalassemia is most prevalent in the area extending from the Middle East and North Africa (MENA) region towards central and Southeast Asia due to evolutionary links and genomic alterations that conferred resistance to malaria for historic inhabitants of these regions. The disease is also becoming more and more common in large multiethnic cities in the US and Europe due to recent migrations. In the UAE, there is an estimated 1000-1500 patients identified with different forms of thalassemia and we have recently established a new thalassemia longitudinal cohort through a collaborative effort between key treatment centers with support of the Department of Health – Abu Dhabi to better understand clinical profiles and needs of patients in the Emirate and the country.
We categorize thalassemia into two main forms. Patients with transfusion-dependent thalassemia (TDT) are those who get diagnosed in very early childhood with severe anemia and who eventually require regular (monthly) blood transfusion therapy for survival. Regular transfusions, however, lead to accumulation of extra iron in the body which requires chronic use of iron chelation therapy to prevent iron overload in the heart and liver leading to their failure. Iron chelation therapy is not necessarily always effective, and it can be associated with several side effects and poor adherence. Thus, as much as conventional treatments are widely available and very well-orchestrated across the UAE and MENA region, the burden of lifelong treatment on the patient and healthcare system remains a big unmet need.
Bone marrow transplantation can be done in a subset of patients and may achieve disease cure, and we are lucky to have several facilities with evolving bone marrow transplant capabilities in the UAE. More recently, other innovative curative therapies also became available, including approaches that aim to edit the patients’ genes (gene editing) or to insert new genes (gene therapy), to replace the function of the faulty gene that these patients carry. These approaches have shown promise in recent global clinical trials leading to their regulatory approvals in the US and Europe, and we are working to make them available for patients in the UAE through various channels, considering they require very specialized facilities for implementation and they do come at a high cost.
The other form of thalassemia, non-transfusion-dependent thalassemia (NTDT) has also received much attention in the last decade. Through several studies from the Middle East and UAE, we were able to reshape understanding of disease burden in NTDT patients. We discovered that even though their anaemia is not severe enough to prompt regular transfusion at first diagnosis, it can be associated with significant complications and lead to significant morbidity and early mortality if left untreated.
Thus, the search for novel drugs that can ‘modify’ the disease continues, and several agents are being developed to reduce transfusion requirements in TDT patients and improve anemia in NTDT patients by supporting the bone marrow to produce healthier red blood cells on its own. It is worth noting that we have conducted several studies in the UAE that were highly recognized globally and published in top-tier medical journals, as they were able to clarify the optimal levels of anemia and safe iron levels that patients need for them to be at lower risks of morbidity and mortality, and these helped inform the optimal design of clinical trials of such novel disease-modifying agents.
One such drug is luspatercept, a subcutaneous injection given every 3 weeks which has shown effectiveness in reducing transfusion requirement by at least 33% in adults with TDT and in improving hemoglobin level by at least 1 gram in patients with NTDT and has been recently approved for these indications in various parts of the world including the UAE.
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A newer oral agent, mitapivat, was also shown more recently to successfully reduce transfusion requirement by at least 50% in adults with TDT and to increase hemoglobin level by at least 1 gram with associated improvement in fatigue symptoms in patients with NTDT, through initial data from two ongoing global phase 3 trials, ENERGIZE and ENERGIZE-T, which we are very proud to be part of and run at Burjeel Medical City with the support of the Department of Health – Abu Dhabi, allowing our patients to get early access to such innovative medicines. These results have been featured during a plenary presentation at the European Haematology Association Congress in Madrid last June of this year.
We are also honoured to be involved in the development of the recent international management guidelines published by the Thalassaemia International Federation (TIF) to help disseminate best practices and novel approaches to management to healthcare providers all over the world. Our region has made major contributions to advancing knowledge and developing new treatments that helped reshape disease prospect and patient outcomes, but several unmet needs continue to persist which can only be addressed through local and international collaborations between all stakeholders involved in the patient journey.
The views expressed in this article are the author’s own and do not necessarily reflect MedEdge MEA’s editorial stance.
