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

Ms Freedman is a freelance medical editor and writer in New Jersey. Dr Burke, section editor for Journal Club, is chairman of the Department of Pediatrics at Saint Agnes Hospital, Baltimore, Maryland. The editors have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.