INTRODUCTION:Sickle cell disease (SCD) is an inherited disorder characterized by polymerization of deoxygenated hemoglobin and microvascular obstruction. Generalized, it affects millions of people over 85% from low-and-middle-income countries. The cardinal feature is generalized pain referred to as vaso-occlusive crises (VOC), multi-organ damage and premature death.). SCD is the most prevalent inherited reduced life-threatening disorders in the world and over 85% of world's 400,000 annual births occur low-and-middle-income countries. In the UK with about 250 annual births (1:200 livebirths, and over 14,00 living with the disorder. For decades span. Since 1998 Hydroxyurea remained the only disease modifying therapy until the FDA approved L-glutamine (2017), Crizanlizumab and Voxelotor (2019) and gene therapies (Exa-cel and Lovo-cel, 2023).
AREAS COVERED:A literature review, we discuss established and new treatment. We provide an in-depth review of key clinical trials from 2013-2023. However, for pragmatic purposes we have approached this review in line with the different mechanisms of action, considering the possible options for search was performed in Pubmed Central using the search terms [sickle cell disease] or [sickle cell anemia] and the known treatments, i.e. Hydroxycarbamide/Hydroxyurea, L-Glutamine, Voxelotor, Crizanlizumab, Mitapivat, Etopivat, gene therapy, hematopoietic stem cell transplantation, and combination therapy. Clinical trials performed in the last 10 years (November 2013 - November 2023) were selected.
EXPERT OPINION:In our opinion section, we recommend the consideration for combination therapies for specific complications such as VOCs, pain and renal impairment as well as personalized medicine based on disease phenotype and patient patience characteristics. Following the wake of recent approval of gene therapy for SCD, more curative option is now a reality, the challenge is addressing how to address the issues such as for access, affordability and shared decision- making with families.