Health-Related Quality of Life and Adherence to Hydroxyurea and Other Disease-Modifying Therapies among Individuals with Sickle Cell Disease: A Systematic Review

Abstract

Background. Sickle cell disease (SCD) is a hemoglobinopathy with increasing global prevalence resulting in pain episodes and multiorgan complications. Complications of SCD have been shown to adversely impact health-related quality of life (HRQOL) comprised of physical, social, and emotional domains; hence, HRQOL measures can serve as an effective evaluator of disease burden. Hydroxyurea (HU) and other disease-modifying therapies have demonstrated to significantly improve clinical outcomes in patients with SCD. Medication adherence is an essential mediator of the clinical benefits of these therapies; low adherence has been shown to increase disease burden and healthcare utilization. This systematic literature review intends to determine the association between adherence to disease-modifying therapies and HRQOL in patients with SCD. Methods. We found a total of 12 articles involving 788 participants, which included both patients with SCD and caregivers/parents. Adherence was measured using self-report instruments, laboratory markers, such as fetal hemoglobin and mean corpuscular volume, and mHealth medication trackers. HRQOL was measured using self-report instruments. Results. All studies demonstrated a correlation between higher HU adherence and better HRQOL scores. Higher HU adherence was associated with lower pain impact, less frequent pain episodes, less fatigue, and improved physical function and mobility, reflecting better physical HRQOL outcomes. Higher adherence was also associated with improved emotional response, decreased anxiety and depressive symptoms, and better social functioning and peer relationships. In addition, our findings indicated that having less frequent barriers to HU adherence was associated with better HRQOL scores. No studies evaluated HRQOL outcomes in relation to adherence to l-glutamine, voxelotor, or crizanlizumab. Conclusions. Optimizing HU adherence has the potential to improve HRQOL in patients with SCD in addition to reducing healthcare utilization and improving treatment satisfaction. Addressing barriers to HU adherence can positively strengthen the relationship between adherence and HRQOL to potentially improve patient outcomes.

Psychiatric comorbidities in adults with sickle cell disease: A narrative review

“…Adherence to care is necessary for treatment success 189 . Improved hydroxyurea adherence is associated with fewer pain episodes, improved functioning, decreased anxiety and depression and better QOL in patients with SCD 189–191 .…”

New Synthetic Isoxazole Derivatives Acting as Potent Inducers of Fetal Hemoglobin in Erythroid Precursor Cells Isolated from β-Thalassemic Patients

“…At present, the only drug approved for γ-globin induction is HU, of which efficacy and safety are still unresolved issues [ 21 , 22 ]. Until now, this drug has been used in thalassemia intermedia and SCD.…”

“…Until now, this drug has been used in thalassemia intermedia and SCD. It acts through multiple mechanisms and performs its cytotoxic activity by accelerating the differentiation process and stimulating cellular stress response pathways, leading to an overall increase in the number of F cells [ 21 , 22 ]. More recently, decitabine [ 23 ] and HQK-1001 [ 24 ] have been proposed as new fetal globin inducers under pre-clinical and clinical development.…”

Intravenous fluid therapy and hospital outcomes for vaso‐occlusive episodes in children, adolescents, and young adults with sickle cell disease

“…3 Factors such as disease severity and non-adherence to disease-modifying therapies, such as hydroxyurea, contribute to the frequency of VOEs. [4][5][6][7] VOEs are the leading cause of emergency department (ED) visits and hospitalizations, and greatly impact the quality of life for individuals with SCD. 8,9 The main strategies for managing a VOE are supportive care with intravenous fluid (IVF) therapy and analgesics coupled with non-pharmacological approaches.…”

“…VOEs can last for several hours to days and, over time, can lead to chronic pain and disability, 2 leading to a significant economic burden across a patient's lifespan 3 . Factors such as disease severity and non‐adherence to disease‐modifying therapies, such as hydroxyurea, contribute to the frequency of VOEs 4–7 . VOEs are the leading cause of emergency department (ED) visits and hospitalizations, and greatly impact the quality of life for individuals with SCD 8,9 .…”