Barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families: Report from a U.S. regional collaborative

Abstract

Sickle cell disease (SCD) is an inherited blood disorder that affects about 100,000 people in the U.S., primarily Blacks/African-Americans. A multitude of complications negatively impacts quality of life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD, but is underutilized. Negative and uninformed perceptions of hydroxyurea and barriers to its use hinder adherence and promotion of the medication. As the largest real-world study to date that assessed hydroxyurea use for children and adults with SCD, we gathered and analyzed perspectives of providers, individuals with SCD, and families. Participants provided information about socio-demographics, hospital and emergency admissions for pain, number of severe pain episodes interfering with daily activities, medication adherence, and barriers to hydroxyurea. Providers reported on indications for hydroxyurea, reasons not prescribed, and current laboratory values. We found that hydroxyurea use was reported in over half of eligible patients from this large geographic region in the U.S., representing a range of sickle cell specialty clinical settings and practices. Provider and patient/caregiver reports about hydroxyurea use were consistent with one another; adults 26 years and older were least likely to be on hydroxyurea; and the likelihood of being on hydroxyurea decreased with one or more barriers. Using the intentional and unintentional medication nonadherence framework, we found that, even for patients on hydroxyurea, challenges to taking the medicine at the right time and forgetting were crucial unintentional barriers to adherence. Intentional barriers such as worry about side effects and “tried and it did not work” were important barriers for young adults and adults. For providers, diagnoses other than HgbSS or HgbS-β0 thalassemia were associated with lower odds of prescribing, consistent with evidence-based guidelines. Our results support strengthening provider understanding and confidence in implementing existing SCD guidelines, and the importance of shared decision making. Our findings can assist providers in understanding choices and decisions of families; guide individualized clinical discussions regarding hydroxyurea therapy; and help with developing tailored interventions to address barriers. Addressing barriers to hydroxyurea use can inform strategies to minimize similar barriers in the use of emerging and combination therapies for SCD.

Sickle cell disease in Australia: a snapshot from the Australian Haemoglobinopathy Registry

“…Induction of fetal haemoglobin (HbF) with hydroxyurea is one of the mainstays of therapy and is received by 57.5% of paediatric and 49.7% of adult patients in the registry. This is comparable to the United States (US), where a multisite study ( n = 412) published in 2022 and analysing data from 2015 to 2017 reported hydroxyurea use in 56.3% of participants overall 12 . Landmark trials support its use, demonstrating a reduction in SCD‐related morbidity 13 and a significant improvement in survival 14 .…”

“…This is comparable to the United States (US), where a multisite study (n = 412) published in 2022 and analysing data from 2015 to 2017 reported hydroxyurea use in 56.3% of participants overall. 12 Landmark trials support its use, demonstrating a reduction in SCD-related morbidity 13 and a significant improvement in survival. 14 Recent UK guidelines recommend offering hydroxyurea to all paediatric patients aged 9-42 months with genotype HbSS/ Sbeta 0 and after the age of 42 months to patients of all ages in view of the reduction in mortality.…”

Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study

“…A U.S. regional collaborative report on barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families found providers and patient/caregiver reports about hydroxyurea use were inconsistent with one another; adults 26 years and older were least likely to be on hydroxyurea; and the likelihood of being on hydroxyurea decreased with one or more barriers, they also found that, even for patients on hydroxyurea, challenges to taking the medicine at the right time and forgetting were crucial unintentional barriers to adherence. Intentional barriers such as worry about side effects and “tried and it did not work” were important barriers for young adults and adults [ 16 ].…”

Managing the Cerebrovascular Complications of Sickle Cell Disease: Current Perspectives

“…Because hydroxyurea is given at home, it is essential that the patient and family understand the need for strict adherence and also that the care team is aware of social factors that may complicate the patient's ability to obtain and take their medication. [66][67][68] Continued TCD monitoring is necessary. Hydroxyurea appears to be safe for long-term use, but study of its secondary effects, such as infertility, is ongoing.…”