"Crizanlizumab in Sickle Cell Disease". The New England Journal of Medicine. 2016.
Links to original sources: Wiki Journal Post Full Journal Article
Does crizanlizumab, an antibody against P-selectin, reduce the rate of sickle cell–related pain crises in patients with sickle cell disease?
Crizanlizumab significantly decreased the frequency of sickle cell–related pain crises compared to placebo and showed a low rate of adverse effects in patients with sickle cell disease.
Sickle cell–related pain crises significantly impact quality of life and contribute to morbidity in patients with sickle cell disease. Crizanlizumab, a P-selectin inhibitor, was theorized to reduce cell adhesion and subsequent vaso-occlusion, potentially decreasing the incidence of pain crises. The phase 2 SUSTAIN trial found that high-dose crizanlizumab reduced the annual rate of pain crises by 45.3% in the treatment group compared to placebo.
As of the last update, there is no specific mention of crizanlizumab in current guidelines for the treatment of sickle cell disease.
Multicenter, double-blind, randomized, placebo-controlled, phase 2 trial. N=198 patients with sickle cell disease. Intervention groups: low-dose crizanlizumab (2.5 mg/kg), high-dose crizanlizumab (5.0 mg/kg), vs. placebo. 52 weeks of intravenous treatment followed by a 6-week follow-up. Primary outcome: Sickle cell–related pain crises rate.
Inclusion Criteria: Patients 16-65 years old with sickle cell disease experiencing 2-10 pain crises in the previous 12 months. Exclusion Criteria: Long-term red-cell transfusion therapy.
High-dose crizanlizumab (5.0 mg/kg), low-dose crizanlizumab (2.5 mg/kg), or placebo given intravenously.
Primary Outcomes: Annual rate of pain crises was 1.63 with high-dose crizanlizumab vs. 2.98 with placebo (45.3% lower rate with high-dose, P=0.01). Secondary Outcomes: - Median time to first crisis: 4.07 months with high-dose vs. 1.38 months with placebo (P=0.001). - Median time to second crisis: 10.32 months with high-dose vs. 5.09 months with placebo (P=0.02). - A nonsignificant reduction in the median rate of days hospitalized (P=0.45). - A 62.9% lower rate in annual uncomplicated crises (P=0.02). - No significant effect on the acute chest syndrome.
- Long-term safety and immunogenicity require further monitoring. - No significant changes were observed in markers of hemolysis. - The impact on patients with genotypes other than HbSS needs further investigation.
Funded by Selexys Pharmaceuticals, NIH, and FDA. Authors disclosed financial relationships with Selexys and other pharmaceutical companies.
Additional information about SUSTAIN can be found at ClinicalTrials.gov number NCT01895361 and in the full text of the article at NEJM.org.