Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease.

Individuals with sickle cell disease (SCD) are living further into adulthood in high-resource countries. However, despite increased quantity of life, recurrent, acute painful episodes cause significant morbidity for affected individuals. These SCD-related painful episodes, also referred to as vaso-occlusive crises (VOCs), have multifactorial causes, and they often occur as a result of multicellular aggregation and vascular adherence of red blood cells, neutrophils, and platelets, leading to recurrent and unpredictable occlusion of the microcirculation. In addition to severe pain, long-term complications of vaso-occlusion may include damage to muscle and/or bone, in addition to vital organs such as the liver, spleen, kidneys, and brain. Severe pain associated with VOCs also has a substantial detrimental impact on quality of life for individuals with SCD, and is associated with increased health care utilization, financial hardship, and impairments in education and vocation attainment. Previous treatments have targeted primarily SCD symptom management, or were broad nontargeted therapies, and include oral or parenteral hydration, analgesics (including opioids), nonsteroidal anti-inflammatory agents, and various other types of nonpharmacologic pain management strategies to treat the pain associated with VOC. With increased understanding of the pathophysiology of VOCs, there are several new potential therapies that specifically target the pathologic process of vaso-occlusion. These new therapies may reduce cell adhesion and inflammation, leading to decreased incidence of VOCs and prevention of end-organ damage. In this review, we consider the benefits and limitations of current treatments to reduce the occurrence of VOCs in individuals with SCD and the potential impact of emerging treatments on future disease management.
Competing Interests: Conflict of interest statement: IO has received research funding from Health Resources and Services Administration, North Carolina Division of Public Health, and Patient-Centered Outcomes Research Institute; served as a consultant for Cyclerion Therapeutics Inc., Global Blood Therapeutics, Novartis Pharmaceuticals Corp., and Pfizer Inc; participated on advisory boards for Acceleron Biopharma, Forma Therapeutics, Global Blood Therapeutics, Novartis Pharmaceuticals Corp., and Pfizer Inc; participated on the speakers’ bureau for Global Blood Therapeutics, Novartis Pharmaceutics Corp., and Terumo Medical Corporation; and is a member of the Data and Safety Monitoring Board for Micelle BioPharma Inc.; currently serves as Editor in Chief of Hematology News. DM has received research funding from bluebird bio and Global Blood Therapeutics, and served as a consultant for Global Blood Therapeutics, Novartis Pharmaceuticals Corp., and Pfizer Inc. JK has received research funding from Health Resources and Services Administration, Center for Disease Control, and National Institute of Health as well as from bluebird bio and Novartis Pharmaceuticals Corp.; served as a consultant for bluebird bio, Imara Inc., Modus Therapeutics, Novartis Pharmaceuticals Corp., Agios, Beam Therapeutics, and Sanofi; and received honoraria from Bluebird Bio, Global Blood Therapeutics and Terumo Medical Corporation.
(© The Author(s), 2020.)