Crizanlizumab, voxelotor, and L-glutamine for sickle cell disease: effectiveness and value
- Collection:
- Health Policy and Services Research
- Author(s):
- Bradt, Pamela, author Synnott, Patricia G., author Chapman, Rick, author Beinfeld, Molly, author Rind, David M., author Pearson, Steven D., author
- Contributor(s):
- Institute for Clinical and Economic Review, issuing body.
- Publication:
- [Boston, Massachusetts] : Institute for Clinical and Economic Review, March 12, 2020
- Language(s):
- English
- Format:
- Text
- Subject(s):
- Anemia, Sickle Cell -- drug therapy Antibodies, Monoclonal -- therapeutic use Glutamine -- therapeutic use Hemoglobin, Sickle -- antagonists & inhibitors United States
- Genre(s):
- Technical Report
- Abstract:
- Sickle cell disease (SCD) is a broad term referring to a group of inherited disorders carried by the beta (β) allele of the hemoglobin (Hb) gene. It is characterized by abnormal hemoglobin polymerization during deoxygenation resulting in sickle-shaped erythrocytes (red blood cells [RBCs]). The incidence of SCD is estimated at 300,000 to 400,000 live births globally per year. In the United States (US), the current best prevalence estimate is approximately 100,000 individuals with SCD, although comprehensive surveillance and reporting is lacking and the exact number of cases in the US is unknown. Clinical manifestations of SCD derive from at least three different pathophysiologic mechanisms: the loss of deformability of the RBC leading to vascular obstruction and ischemia; a shortened lifespan of the RBC leading to both intravascular and extravascular hemolysis; a sticky RBC surface increasing adherence to the vascular endothelium which can result in vascular obstruction and can contribute to vascular proliferative lesions. Recurrent acute pain crisis, or vaso-occlusive crisis (VOC), is one of the most prevalent manifestations of SCD. Patients also experience significant acute complications such as acute chest syndrome, serious infections, stroke, renal necrosis, and priapism. Chronic complications can emerge across multiple organs and include delayed puberty, avascular necrosis, skin ulcers, chronic pain, neurocognitive impairment, chronic kidney injury, pulmonary hypertension, cardiovascular disease, and can result in early mortality. Resultant health care costs are high, with the total health system economic burden of SCD estimated at $2.98 billion per year in the US with 57% due to inpatient costs, 38% due to outpatient costs, and 5% due to out-of-pocket costs. The impact of SCD on quality of life (QOL) is complex and affects both patients and their caregivers in many ways. In addition to the health-related burden of disease, many other factors further diminish QOL. The lack of treatment options, discrimination, stigma around the need for chronic pain management, disruption of family and social activities, missed school and/or work all combine to make living with SCD very difficult. We heard from both patients and clinicians that the picture of "baseline" or "usual" care for patients with SCD is highly variable. Deep dysfunction in care is driven by poor coordination within provider systems and by barriers to access that arise from a broad range of factors including systemic racism, uninformed clinicians, poverty, and insurance systems poorly designed to coordinate coverage for patients with multi-system chronic conditions. Until recently only three specific interventions were considered helpful for SCD: stem cell transplantation, chronic transfusion with packed RBCs, and hydroxyurea. Chronic transfusion is generally used for primary or secondary stroke prevention; hydroxyurea is used to reduce the number of acute pain crises in those with frequent or severe crises, and in those with a history of ACS or severe anemia.8 Acute pain crisis may be managed with pain medications including opioids, and may require additional inpatient or outpatient treatments including hydration, transfusion, supplemental oxygen, and a variety of other treatments. Within the past several years several new options have gained regulatory approval in the US. L-glutamine (Emmaus) is a precursor of nucleic acids and nucleotides that play a key role in the regulation and prevention of oxidative damage to red blood cells.9 It was approved by the US Food and Drug Administration (FDA) on July 7, 2017 to reduce the acute complications of SCD in adult and pediatric patients 5 years of age and older. Crizanlizumab (Novartis AG), is a humanized monoclonal antibody that binds to P-selectin. P-selectin is expressed on the surface of endothelial cells and platelets and it is thought that blockage could reduce the static adhesion of sickled RBCs thus reducing vaso-occlusion and inflammation. It was approved by the FDA on November 15, 2019 to reduce the frequency of vaso-occlusive crises in adults and pediatric patients ages 16 years and older with SCD. Voxelotor (Global Blood Therapeutics, Inc.) is an HbS polymerization inhibitor that reversibly binds to hemoglobin to stabilize the oxygenated hemoglobin state, thus shifting the oxyhemoglobin dissociation curve. Voxelotor was approved by the FDA on November 25, 2019 for the treatment of SCD in adults and pediatric patients 12 years of age and older.
- Copyright:
- Reproduced with permission of the copyright holder. Further use of the material is subject to CC BY license. (More information)
- Extent:
- 1 online resource (1 PDF file (various pagings))
- Illustrations:
- Illustrations
- NLM Unique ID:
- 101769581 (See catalog record)
- Permanent Link:
- http://resource.nlm.nih.gov/101769581