Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease

• Published in: The New England journal of medicine Vol. 376; no. 5; pp. 429 - 439
• Main Authors: Ataga, Kenneth I, Kutlar, Abdullah, Kanter, Julie, Liles, Darla, Cancado, Rodolfo, Friedrisch, João, Guthrie, Troy H, Knight-Madden, Jennifer, Alvarez, Ofelia A, Gordeuk, Victor R, Gualandro, Sandra, Colella, Marina P, Smith, Wally R, Rollins, Scott A, Stocker, Jonathan W, Rother, Russell P
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 02-02-2017
• Subjects: Adolescent; Adult; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - drug therapy; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Arthralgia; Blood platelets; Body weight; Cell interactions; Chest; Diarrhea; Double-Blind Method; Drug Therapy, Combination; Endothelial cells; Endothelium; Female; Hemoglobin; Humans; Hydroxyurea; Hydroxyurea - therapeutic use; Inflammation; Male; Middle Aged; Monoclonal antibodies; Neutrophils; Occlusion; P-selectin; P-Selectin - antagonists & inhibitors; P-Selectin - immunology; Pain; Pain - etiology; Pain - prevention & control; Patients; Pruritus; Quality of Life; Sickle cell disease; Spleen; Transgenic animals; Vomiting; Young Adult; United States > US
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1611770

In this yearlong trial involving patients with sickle cell disease, crizanlizumab, an antibody to P-selectin, was associated with a 45% lower rate of pain crises than placebo and a longer time to their onset. Adverse events included arthralgia, diarrhea, and pruritus.
Sickle cell disease is characterized by the presence of sickle hemoglobin (HbS), chronic hemolysis, recurrent pain episodes (called sickle cell–related pain crises or vaso-occlusive crises), multiorgan dysfunction, and early death. Sickle cell–related pain crises are the primary cause of health care encounters in patients with sickle cell disease.
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These crises result in a decrease in quality of life
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and an increase in the risk of death.
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Crises are thought to be caused by vascular occlusion in the microcirculation, increased inflammation, and alterations in nociception.
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The prevention of crises could minimize or prevent tissue and organ damage and decrease the subsequent . . .