A Review of Treatment Options for the Management of Sickle Cell Disease - Episode 3

SUSTAIN Trial: Reducing Painful Crisis Frequency in SCD

June 1, 2021
Michael R. DeBaun, MD, MPH, Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease

Michael R. DeBaun, MD, MPH, reviews the use of crizanlizumab and its effect on vaso-occlusive crises and opioid use for pain management in patients with sickle cell disease as seen in the SUSTAIN trial.

Michael R. DeBaun, MD, MPH: Unlike voxelotor, where the focus of the therapy is on decreasing polymerization of hemoglobin inside of the red blood cells, crizanlizumab has as its target cell-to-cell interactions that are outside of the red blood cell and specifically P-selectin in endothelial cells and platelets, contributing to the increased adhesiveness of red blood cells in sickle cell disease, which can lead to ischemia and reperfusion injury. This drug, crizanlizumab, directly targets the P-selectin in these cells within the vascular space and vascular cell wall, and results in a decrease in what is believed to be ischemia and reperfusion injury, leading to a decrease in acute vaso-occlusive pain episodes.What’s important to notice is that recently at ASH [the American Society of Hematology meeting], there was an abstract presented that described that the benefit observed in using crizanlizumab, in addition to decreasing the incidence of new vaso-occlusive pain episodes when compared to placebo, is also a decrease in the use of opioids, parenteral and oral opioids. It further bolsters the evidence that this is a very effective therapy for decreasing acute vaso-occlusive pain episodes in individuals with sickle cell disease. I should note that the treatment is not acute. We’re giving the treatment to prevent future episodes but not in the midst of an episode. It is not evident that crizanlizumab will abate the current acute vaso-occlusive pain episode.At ASH, Darla Liles, MD, et al compared 2 different doses of crizanlizumab, a 5 mg/kg dose versus a 7.5 mg/kg dose. Essentially, there were no new safety signals identified; 7.5 was as good as 5 mg/kg, but there was no clinical benefit distinguishable between the 2 doses. 

My reading of the abstract of the preliminary data presented to this point would indicate that the 5 mg/kg dose is just as good as 7.5 mg/kg, although there is no increase in adverse events with a higher dose.Across our sickle cell disease center of excellence, we have approximately 550 individuals with sickle cell disease from infancy through adulthood. We have elected as a standard practice to offer initially to all of our individuals with hemoglobin SS and hemoglobin S beta-zero thalassemia, we offer them hydroxyurea and encourage them to take hydroxyurea as early as 9 months of age as was recommended by the NHLBI [National Heart, Lung, and Blood Institute] guidelines. For our patients with hemoglobin SC disease or hemoglobin S beta-plus thalassemia, who have repetitive pain episodes in childhood for above 16 years of age or as adults, we will offer them as a first therapy for prevention of acute vaso-occlusive pain either L-glutamine or crizanlizumab. 

We describe the pros and cons, the route of administration, and the anticipated benefit. After we do that, almost hands down, I would say 8 out of 10 patients would refer the crizanlizumab over the L-glutamine, primarily because it’s a single dose, once a month after the initial treatment. They are reluctant to take a medication that requires oral administration twice a day. L-glutamine, for the patients who have elected to take it, has very low adherence rates, at least among our adolescents and adults with sickle cell disease, because its taste is not appealing and it’s cumbersome, especially for our active adults, to ensure that they take their medication twice a day.

Transcript Edited for Clarity

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