Sickle Cell Disease Management Requires Pharmacist Involvement in Multidisciplinary Care Team

Sickle cell disease, a genetic disorder impacting hemoglobin that causes red blood cells to “sickle” and block blood flow to the body, can be one of the most difficult hematologic conditions to manage due to its chronic and unpredictable nature. The disease is characterized by sudden and intense vaso-occlusive crises, also called sickle cell crises, that cause strong, acute pain. Other complications, including the burden of lifelong pain and a higher risk of stroke, infections, and kidney disease, are all possible in patients with sickle cell disease.^1-3

Thousands of individuals in the US and millions worldwide are affected by sickle cell disease. But the disease has been shown to have a higher incidence in Black individuals; according to the National Heart, Lung, and Blood Institute, 9 out of 10 individuals with sickle cell disease are of African ancestry or identify as Black. Owing to the severe and variable nature of the disease, in addition to the disproportionate impact that sickle cell disease has on many communities, it is critical for pharmacists, as part of a patient’s multidisciplinary care team, to be well-versed in the management of the condition.^1-3

Red blood cells in patients with sickle cell disease present with a trademark "sickle" shape. | Image Credit: © extender_01 - stock.adobe.com

Management of Sickle Cell Crisis-Related Pain

Pharmacists have an especially integral role due to their expertise in optimizing treatment regimens and selecting appropriate medications for patients based on their specific requirements. Often, pharmacists see dozens of patients that each have their own unique aspects and conditions that require tailored, individualized regimens. This makes them the ideal candidate for ensuring accurate dosing and selection of treatments for the symptoms of sickle cell disease.^2,3

Unpredictable, serious pain crises are the hallmark of sickle cell disease complications. Data indicates that sickle cell crises are the leading cause of emergency department (ED) visits for adults with sickle cell disease, accounting for 90% of inpatient hospitalizations and 85% of all acute medical care. Pharmacists typically have a presence during these ED or medical care encounters and can prescribe appropriate therapies for pain management and relief of a sickle cell crisis. Patients with sickle cell disease may have developed a tolerance to common pain relief therapies, requiring that pharmacists adjust the dosing and routes of administration of therapies as necessary.^2,3

Long-Term Care

Treatment of sickle cell disease goes beyond acute management. It is a lifelong, inherited condition; though there are strategies available to safely live a fulfilling life, and a bone marrow transplant represents a potential curative therapy, there is a lack of long-term treatments to effectively and conveniently manage sickle cell pain crises. Pharmacists should counsel patients on the likelihood of long-term disease management and can ensure a strategy is in place for treatment of acute pain episodes. Acute pain, if serious enough, may require therapy with opioids. Although the first option should always be nonopioid use, if opioids are required, pharmacists are integral to tapering off use to avoid addiction.^2-4

Frequent patient follow-up is necessary for patients with sickle cell disease. Monitoring patients' medication use, including medications prescribed to treat sickle cell crises, is a critical role of pharmacists due to their front-line role in a patient’s care team. Beyond checking for medication adherence and any problems with dosing or administration, pharmacists should always be advocating for regular vaccination against viral diseases due to the higher risk of infection in patients with sickle cell disease. Overall, pharmacists can aid patients with sickle cell disease in creating and sticking to a treatment plan for long-term disease management.^3,4

Mitapivat Presents as a Potential Transformative Treatment

New, convenient therapies for the vaso-occlusive crises that occur with sickle cell disease are needed to ensure optimal treatment that does not require additional patient burden or come with associated risks. One potential option is mitapivat (Pyrukynd; Agios Pharmaceuticals), a pyruvate kinase activator designed to increase adenosine triphosphate levels and decrease red blood cell sickling. The drug has shown promise in clinical trials of patients with sickle cell disease, presenting as a potentially major improvement compared with currently available therapies.⁵

In a double-blind, placebo-controlled, phase 2 clinical trial, patients with sickle cell disease who were treated with mitapivat demonstrated a statistically meaningful improvement in hemoglobin response across both 50 mg and 100 mg dose levels compared with placebo. Furthermore, improvements were observed in annualized rates of sickle cell pain crises and in markers of hemolysis and erythropoiesis for both mitapivat treatment arms compared with placebo, according to investigators.⁵

Importantly, mitapivat was safe and tolerable among participants, with a safety profile like those of other studies. Common treatment-emergent adverse events (TEAEs) included headache, arthralgia, dysmenorrhea, pain, and fatigue. However, no serious TEAEs were attributed to treatment with mitapivat.⁵

“Sickle cell disease is a tremendously burdensome disease that impacts all aspects of patients’ and families’ lives. New therapeutic options—particularly those with convenient and easy administration—are desperately needed for this underserved community,” Modupe Idowu, MD, professor at the University of Texas Health Science Center at Houston, said in a news release. Idowu noted that there are no currently approved oral therapies that address both sickle cell pain crises and chronic anemia, and that mitapivat could potentially address both in a single pill.⁵

Mitapivat is currently being investigated further in the phase 3 RISE UP global, double-blind, randomized, placebo-controlled clinical trial. Investigators have enrolled over 200 patients 16 years or older with sickle cell disease across the world. The primary end points of the trial are hemoglobin response and annualized rate of sickle cell pain crises, and clinical trial results are expected in late 2025. If the trial garners positive data, mitapivat could become a transformative therapy that pharmacists can prescribe to patients struggling with sickle cell disease complications.^5,6

REFERENCES

1. National Heart, Lung, and Blood Institute. Sickle cell disease—What is sickle cell disease? Last Updated September 30, 2024. Accessed Online February 18, 2025. https://www.nhlbi.nih.gov/health/sickle-cell-disease#:~:text=Sickle%20cell%20disease%20%E2%80%94%20also%20called,easily%20through%20the%20blood%20vessels.

2. Weaver SB, Nonyel NP, Rungkitwattanakul D, et al. Roles of pharmacists in the management of sickle cell disease in adults: A narrative review. J Pharm Technol. 2024;40(2):92-99. doi:10.1177/87551225231222437

3. Oliver EL, Bulloch MN. World sickle cell day: The pharmacist’s role in medication management. Pharmacy Times. Published June 19, 2022. Accessed February 18, 2025. https://www.pharmacytimes.com/view/world-sickle-cell-day-the-pharmacist-s-role-in-medication-management

4. National Heart, Lung, and Blood Institute. Sickle cell disease—Living with sickle cell disease. Last Updated August 22, 2024. Accessed Online February 18, 2025. https://www.nhlbi.nih.gov/health/sickle-cell-disease/living-with

5. Agios Therapeutics. Agios presents positive results from phase 2 portion of the RISE UP pivotal study in sickle cell disease at 65^th ASH Annual Meeting and Exposition. News Release. Released December 9, 2023. Accessed February 18, 2025. https://investor.agios.com/news-releases/news-release-details/agios-presents-positive-results-phase-2-portion-rise-pivotal

6. Agios Therapeutics. Agios completes enrollment of phase 3 RISE UP study of mitapivat in sickle cell disease. News Release. Released October 23, 2024. Accessed February 18, 2025. https://investor.agios.com/news-releases/news-release-details/agios-completes-enrollment-phase-3-rise-study-mitapivat-sickle