‘Continuous long-term education’ needed amid advances in sickle cell disease treatment
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Sickle cell disease is the most common genetic disorder, affecting approximately 100,000 people in the United States.
The chronic and lifelong disease impacts the entire body due to hemolytic anemia and intravascular inflammation.
Sickled erythrocytes have a much shorter lifespan than normal (15-20 days vs. 120 days).
Pain, often referred to as vaso-occlusive crises, due to impaired oxygen delivery by sickled cells has been noted as the most common cause of acute morbidity. Yet, some patients do not seek treatment for pain, and the underreporting of symptoms overall has been reported in literature.
New and innovative treatment options have been slow to come to the bedside, due in part to lack of appropriate attention and funding. However, exciting breakthroughs in disease management have occurred over the past 2 to 3 years, and a few have become mainstays in the care of patients with sickle cell disease.
These developments have important implications for APPs, who are responsible for assessment of the patient and family as appropriate, ordering and interpreting ancillary labs and tests and providing a diagnosis while developing a treatment plan addressing the clinical situation. There is opportunity for variation within the scope of practice; however, offering and discussing appropriate treatment options is foundational to the role of the APP.
Breakthroughs in management
Vitamin D is a fat-soluble vitamin with significant anti-inflammatory properties. Sickle cell disease is known as a pro-inflammatory state. The monitoring and management of appropriate vitamin D levels is essential for everyone, but especially those with sickle cell disease.
Severe vitamin D deficiency can contribute to chronic pain, osteoporosis, muscle weakness and poor overall growth. A diet high in vitamin D includes fortified dairy products, fatty fish, beef liver and egg yolks, and sunshine is the easiest way to supplement vitamin D.
One of the biggest breakthroughs in sickle cell disease management occurred over 20 years ago, when hydroxyurea received FDA approval. It is now considered standard of care.
Hydroxyurea increases production of fetal hemoglobin, which is able to carry oxygen normally and does not sickle when under stress. In turn, it increases the size, oxygen-carrying capacity and life span of the erythrocyte. These changes at the cellular level are able to reduce the effects of the chronic hemolytic anemia and pain that are associated with sickle cell disease.
L-glutamine oral powder (Endari, Emmaus Medical) is a conditionally essential amino acid that was introduced as a supplemental treatment for patients with sickle cell disease in 2017. Oxidative stress is known to cause sickling. When erythrocytes sickle and break down, glutamine is released and metabolized into an antioxidant. L-glutamine oral powder was found to decrease cell stress and inflammation while increasing oxygen delivery.
Crizanlizumab (Adakveo, Novartis), a monoclonal antibody given as a monthly IV infusion, is designed to decrease the “stickiness” of sickled red blood cells. This drug works by binding P-selectin, which is known to contribute to the adhesive properties of sickled cells. This theoretically decreases the tendency of sickled cells to clump together with each other and with other circulating cells.
The FDA approved the therapy in November 2019 based on results of the randomized phase 2 SUSTAIN study, which showed crizanlizumab reduced the median annual rate of vaso-occlusive crises leading to health care visits by 45.3% compared with placebo (1.63 vs. 2.98, P = .01) among patients with or without hydroxyurea therapy.
Voxelotor (Oxbryta, Global Blood Therapeutics), a hemoglobin S polymerization inhibitor taken daily by mouth, has been shown to decrease sickling of red blood cells and blood viscosity by increasing the affinity of the hemoglobin molecule to oxygen.
In 2019, results of the randomized phase 3 HOPE trial showed significant increases in hemoglobin levels (mean change of 1.1 g/dL after 24 weeks of use) and reduced hemolysis markers among patients with sickle cell disease who received voxelotor. Later that year, FDA approved the agent for patients aged 12 years and older.
Clinical trials are evaluating use of voxelotor by patients aged 2-12 years with sickle cell disease. Preliminary results showed comparable safety and efficacy in this age group, as well.
Gene therapy
Gene therapy is another new frontier in the treatment of sickle cell disease.
In particular, gene editing uses the patient’s own stem cells that have been harvested, genetically modified and then transplanted back into the patient. The modified cells reproduce and repopulate the circulation. This directly addresses the mutation in the beta-globin protein chain of the hemoglobin molecule found in sickle cell disease.
Current clinical trials use a viral vector to insert the corrected globin chain into the harvested stem cells. The use of autologous cells for this therapy drastically increases the treatment availability within this population of patients, compared with only 15% to 20% of patients with sickle cell disease who are matched with an appropriate donor for a traditional hematopoietic stem cell transplant. The significant adverse effects and risks associated with traditional HSCT remain considerations for patients and their families.
Conclusion
APPs often function as the main care provider for their patients.
As such, they are responsible for staying updated about new and innovative treatments that may be available for their patient population. This knowledge must then be interpreted and drilled down to a level easily presented to the patients they manage and treat, as well as to other health care providers on their team.
Availability of and participation opportunities within clinical trials, in particular, should be a priority. Patients and families often are willing to participate in clinical trials while acknowledging their participation may more directly impact the future than the present.
The above research and ongoing clinical trials have shown great promise. Continued work is being done to assess efficacy and long-term use of these treatment options. Caring for this patient population requires continuous long-term education and follow-up for families and staff.
- References:
- AlJama A, et al. Ann Saudi Med. 2018;doi:10.5144/0256-4947.2018.130.
- ASH. State of sickle cell disease 2016 report.Available at: http://www.scdcoalition.org/pdfs/ASH%20State%20of%20Sickle%20Cell%20Disease%202016%20Report.pdf. Accessed July 19, 2021.
- Ataga KI, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1611770.
- Carroll AE. The New York Times. Sickle cell disease still tends to be overlooked. Available at: www.nytimes.com/2019/08/05/upshot/sickle-cell-disease-overlooked.html. Accessed July 19, 2021.
- Goodman MA, et al. Ther Adv Hematol. 2016;doi:10.1177/2040620716653729.
- Heale R. J Am Acad Nurse Pract. 2012;doi:10.1111/j.1745-7599.2012.00737.x.
- Kanter J and Kruse-Jarres R. Blood Rev. 2013;doi:10.1016/j.blre.2013.09.001.
- Lambert LK and Housden LM. Can Oncol Nurs J. 2017 Winter;27(1):107-110.
- Niihara Y, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1715971.
- Platt OS, et al. N Engl J Med. 1991;doi:10.1056/NEJM199107043250103.
- Smith A. PharmaTimes. Novartis’ crizanlizumab granted FDA breakthrough therapy. Available at: www.pharmatimes.com/news/novartis_crizanlizumab_granted_fda_breakthrough_therapy_1274309. Accessed July 19, 2021.
- Vichinsky E, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1903212.
- For more information:
- Robin Pitts, RN, MN, C-FNP, CPHON, is a sickle cell nurse practitioner at Children’s Healthcare of Atlanta. She can be reached at robin.pitts@choa.org.
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