SOURCE: Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med 2017;376:429-439.
P-selectin is a protein within endothelial cells, megakaryocytes, and platelets that functions during inflammation to enhance adhesion of leukocytes and other cells to the site of inflammation. In sickle cell disease, platelets, erythrocytes, monocytes, and neutrophils can aggregate to compound circulatory flow problems, which lead to painful vaso-occlusive crises symptoms. In animal models of sickle cell anemia, deficiency in P-selectin (and E-selectin) is protective from vaso-occlusive episodes.
Crizanlizumab is a monoclonal antibody that blocks interaction between P-selectin and its receptor. In a double-blind, randomized, placebo-controlled trial of crizanlizumab, subjects (n = 198) who had experienced at least two sickle-cell pain crises within the prior 12 months were in enrolled and followed for one year.
Patients on crizanlizumab enjoyed a 45% reduction in painful crises compared to placebo. Adverse events potentially related to treatment included arthralgia, diarrhea, pruritus, vomiting, and chest pain. Crizanlizumab has been demonstrated to be highly effective in reducing painful crises related to sickle cell disease.
Crizanlizumab has been demonstrated to be highly effective in reducing painful crises related to sickle cell disease.
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