NICE has approved crizanlizumab for sickle cell crises in patients with sickle cell disease but only as part of a managed access agreement.
The National Institute for Health and Care Excellence (NICE) has given the green light to crizanlizumab for the management of sickle cell crises in people with sickle cell disease.
The term sickle cell disease1 describes a group of inherited red blood cell disorders that affect haemoglobin and, for which, according to the World Health Organization, approximately 5% of the world’s population carries trait genes.2 Sickle cell disease affects around 1 in 500 African American children and 1 in 36,000 Hispanic American children and is characterised by a change in the shape of red blood cells which become more ‘sickle-like”, reducing their flexibility of the cells.3 These sickle-like red blood cells can lead to recurrent and unpredictable blockage of small blood vessels4 producing ischaemic pain, referred to as vaso-occlusion (VOC) or sickle cell crises. In addition, activated and adherent leukocytes are the likely drivers of VOC in collecting venules and this process appears to be initiated by a transmembrane protein, P-selectin.5 Studies have shown that blockage of P-selectin appears to improve blood flow,6 and thus reduce the risk of VOC and sickle cell-related pain crises.
The monoclonal antibody crizanlizumab binds to P-selectin, thereby blocking its action. The approval by NICE was based on data from the SUSTAIN trial.7 This double-blind, randomised, placebo-controlled, Phase II trial, assigned 198 patients to either a low-dose crizanlizumab (2.5mg/kg body weight), a high-dose crizanlizumab (5.0mg/kg), or placebo and which were administered intravenously 14 times over a period of 52 weeks. The primary outcome was the annual rate of sickle cell–related pain crises with high-dose crizanlizumab versus placebo. For the study, this was defined as acute episodes of pain caused by a VOC that resulted in a visit to a medical facility and treatment with pain relief medication. The results showed that the median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (p = 0.01). In addition, the median time to the first crisis was significantly longer with high-dose crizanlizumab 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). In addition, the overall incidence of serious adverse event was comparable across the three arms.
NICE recognised that a limitation of the trial was the absence of longer-term data on crizanlizumab, such as mortality or among those who did not seek medical advice on VOCs. There was also no data on the prolonged treatment benefit and what happens when patients stop taking crizanlizumab.
While the appraisal document8 concluded that “crizanlizumab is not recommended for routine use in the NHS”, the drug could be used where specific criteria are met. Thus, guidance notes that “crizanlizumab is recommended as an option for preventing recurrent sickle cell crises (vaso-occlusive crises) in people aged 16 or over with sickle cell disease only if the conditions in the managed access agreement are followed.”
- Sickle cell disease. NIH. www.nhlbi.nih.gov/health-topics/sickle-cell-disease (accessed November 2021).
- Sickle Cell Disease. World Health Organization. www.afro.who.int/health-topics/sickle-cell-disease (accessed November 2021).
- Borhade MB, Kondamudi NP. Sickle Cell Crisis. [Updated 2021 Sep 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan www.ncbi.nlm.nih.gov/books/NBK526064/
- Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood 2013;122(24):3892–8.
- Lawrence MB, Springer TA. Leukocytes roll on a selection at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991;65(5):859–73.
- Kutlar A et al. A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease. Am J Hematol 2012;87(5):536–9.
- Ataga KI et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med 2017;376(5):429–9.
- NICE. Crizanlizumab for preventing sickle cell crises in sickle cell disease. Final appraisal document. www.nice.org.uk/guidance/ta743/documents/final-appraisal-determination-document (accessed November 2021).