The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease

Abstract

Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapiesare needed. During the last five years the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, there are at least 50 drugs that have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the three drugs (Hydroxyurea, L-Glutamine and Crizanlizumab tmca) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that failed, discontinued or terminated for now and the third category includes 25 drugs that are actively being considered for the treatment of SCD. New therapies targeting multiple pathways in its complex pathophysiology have been achieved or are under continued investigation. The emerging trend seems to be the use of multimodal drugs (i.e. drugs that have different mechanisms of action) to treat SCD similar to the use of multiple chemotherapeutic agents to treat cancer.

What are the key considerations when prescribing pharmacotherapy for sickle cell anemia?

“…Given the benefits of HU that have been elucidated over the past 25 years of its use, all adults with SCA should receive HU as disease modifying-therapy, regardless of SCA severity or complications. The addition of the remaining 3 FDA-approved treatments should be based on clinical and laboratory complications that are still present after HU dosing has been maximized [17,18]. Since nearly two-thirds of patients enrolled in each of the seminal trials for the new agents were being treated with HU, support for utilization of combination therapy for SCA can be found in these studies.…”

Opioids and Sickle Cell Disease: From Opium to the Opioid Epidemic

“…In the United States, there are more than 230,000 hospital admissions related to SCD annually at an economic cost of $2.4 billion [ 2 ]. Acute episodes of pain, also commonly referred to as vaso-occlusive crises (VOCs), are not only the primary presenting morbidity associated with SCD, but also the most common cause of admission to the Emergency Department or Hospital in approximately 95% of cases [ 3 ]. It is estimated that up to 100,000 patients in the USA have SCD [ 2 ].…”

Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem

“…Measures to reduce the morbidity and mortality of sickle cell anemia include prophylactic penicillin therapy and substitute in infants and children, and hydroxyurea (HU), the 30-year old FDA approved drug for SCD, in adults ( Ataga and Desai, 2018 ). Very recently, L-glutamine, Crizanlizumab, and Voxelotor have been approved by the US FDA for their efficacy in reducing acute VOC/year in adult population ( Ballas, 2020 ). However, standardization of SCD management plan is difficult as the classification of sickle patients are not straightforward.…”