sickle cell disease article

Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease

Ataga KI¹, Kutlar A¹, Kanter J¹, Liles D¹, Cancado R¹, Friedrisch J¹, Guthrie TH¹, Knight-Madden J¹, Alvarez OA¹, Gordeuk VR¹, Gualandro S¹, Colella MP¹, Smith WR¹, Rollins SA¹, Stocker JW¹, Rother RP¹.

N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3.

Summary of the article:

• Sickle cell disease is characterized as the presence of the HbS, chronic hemolysis, recurrent pain episodes, multi-organ dysfunction, and early death. Many patients who receive hydroxyurea therapy continue to have crisis, end-organ damage, and a decreased life expectancy.
• The study is conducted on the safety and efficacy of crizanlizumab, which is a monoclonal antibody targeted towards P-selectin. It is indicated for the prevention of vaso-occlusive crisis in patients with sickle cell. There is no potential conflict of interest relevant to this article.
• It is a double-blind, randomized, placebo-controlled, phase 2 trial.
• 198 patients were assigned to receive low dose crizanlizumab (2.5 mg/kg), high dose crizanlizumab (5/0 mg/kg), or placebo, administered intravenously 14 times over a period of 52 weeks.
• Results:
• The median rate of crisis per year was 1.63 with high dose vs 2.98 with placebo (indicating 45% lower rate with high dose, p=0.01)
• The median time to the first crisis was significantly longer with high dose than with placebo (4.07 vs 1.38 months, p=0.001), as was the median time to the second crisis (10.32 vs 5.09 months, p=0.02)
• The median rate of uncomplicated crisis per year was 1.08 with high dose as compared with 2.91 with placebo (indicating a 62.9% lower rate with high dose, p=0.02)
• Conclusions: in patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crisis than placebo.

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