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    Crizanlizumab helps prevent pain crises in sickle cell disease

    In patients with sickle cell disease, therapy with crizanlizumab, an antibody against the adhesion molecule P-selectin, resulted in a significantly lower rate of sickle cell-related pain crises than placebo, a trial in 198 patients aged from 16 to 65 years showed.

    Participants were divided into 2 treatment groups and 1 placebo group: 1 treatment group received low-dose crizanlizumab (2.5 mg per kg of body weight) and the other high-dose crizanlizumab (5.0 mg per kg). In both groups, crizanlizumab was administered intravenously 14 times during a 52-week period.

    At the end of the treatment period, the median crisis rate per year was 45.3% lower in the high-dose crizanlizumab group than in the placebo group (1.63 vs 2.98, respectively). In addition, the median times to the first and second crises were 2 to 3 times as long in patients’ receiving high-dose crizanlizumab as in those receiving placebo. Low-dose crizanlizumab also was effective, but less so than high-dose; the low dose was associated with a 32.6% lower crisis rate per year compared with placebo. A total of 36% of patients in the high-dose group, 18% in the low-dose group, and 17% of the placebo group had no crises during the treatment period.

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    Trial participants included patients who were receiving concomitant hydroxyurea as well as those who were not. Compared with placebo, high-dose crizanlizumab was associated with a 32.1% lower annual crisis rate in those receiving hydroxyurea and a 50% lower rate among those who were not receiving hydroxyurea. The overall incidence of adverse events was similar in all 3 groups (Ataga KI, et al. N Engl J Med. 2017;376[5]:429-439).

    Thoughts from Dr Burke

    It has become clear that the problem in sickle cell anemia is not just sickling; it’s also the vascular injury from inflammation. In the words of Martin Steinberg, MD, in an editorial accompanying the article, “Polymer-induced erythrocyte injury has downstream effects that include hemolysis, leukocyte-platelet-erythrocyte-endothelial interactions, inflammation, and oxidant-induced tissue damage.” P-selectin has a key role in that cascade. As an intravenous chronic medication with some adverse effects, crizanlizumab may not be a treatment that is ready for prime time. Watch for more on this approach, however: combining therapies that enhance fetal hemoglobin production to reduce sickling and hemolysis along with treatments that inhibit effects of inflammation by blocking P-selectin. —Michael G Burke, MD

    Marian Freedman
    Marian Freedman is a freelance writer.


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