Abstract
Introduction Hydroxyurea (HU) has been shown to reduce hospitalizations, pain crises, mortality, and several long-term complications among individuals with sickle cell disease (SCD). Therefore, education, acceptance and adherence to HU therapy is essential in improving outcomes for our patients. The World Health Organization (WHO) defines adherence as “the extent to which the person's behavior (including medication taking) corresponds with agreed recommendations from a healthcare provider.” Currently, a standard definition of being “on hydroxyurea” is defined as 2 prescriptions filled in a 6-month period. Refill adherence assumes that prescription-refilling patterns correspond to the patient's medication-taking behavior and has been considered an acceptable estimate of adherence. However, in our practice, we did not feel this definition captured whether the patient was adherent as, despite being prescribed HU therapy, some patients did not report full adherence, nor did their laboratory results align with adherence.
Goals Our specific goals for this study were to: 1) Define HU adherence, 2) Increase the number of patients who were fully adherent to HU by 10% over a 12-month period (definitions created in step 1), through standardized HU education and counseling from our multidisciplinary SCD team.
Methods We created a database of all patients followed in our large, urban pediatric sickle cell clinic and determined how many patients were eligible for HU therapy. We defined eligibility if the patient had genotypes HbSS, HbSβ0 or HbSD-Los Angeles and was not on chronic transfusion therapy. Through weekly team meetings with our clinical team, we created shared definitions for HU adherence including: “Fully adherent,” “Working on adherence,” “Not taking,” “Declining,” “Too young” or “Other.” If patients were still considering HU therapy, had missed appointments so adherence could not be assessed, were pregnant or breastfeeding or had just started HU therapy within the past 2 months, they were placed in the “Other” category. Our team created Smart phrases in our electronic medical record (EMR) that were specific for providers, social workers, and psychologists to capture education related to HU provided, barriers to HU identified and what the team member did to address those barriers. These phrases also included patient reported adherence for the past 7 days. We set up a yearly disease modifying therapy education session with all multidisciplinary sickle cell team members to ensure they were aware of indications, benefits and risks related to HU therapy for SCD. Every 4 months during the first year (beginning November 2022), 2 providers reviewed the EMR and categorized all HU eligible patients using our predefined HU adherence definitions. This review took place every 6 months from December 2022 until February 2025.
Results We initially noted that >90% of HU eligible patients had a HU prescription filled in their EMR within 6 months prior to study initiation. The HU definitions we created through provider and team members' consensus included: criteria for absolute neutrophil counts (ANC) at baseline, mean corpuscular volume (MCV) if patient did not have concurrent thalassemia trait, HbF levels in addition to changes in HbF levels over time and patient reported adherence over the past 7 days. Based on these definitions, 92 patients in our practice were HU eligible and only 29.3% of them were “Fully adherent” to HU therapy with 15.2% “Working on adherence”, 33.7% “Not taking, 9.8% “Declining”, 7.6% “Too young” and 4.3% “Other” in Nov 2022. In the 12 months following, we improved our fully adherent patients to 39.1%. During our last review in Feb 2025, our fully adherent patients has increased to 44% (improvement by 14.7% from Nov 2022) with 80% of our medical records showing documentation about HU counseling.
Conclusions We conclude that standardizing definitions of HU adherence, improving team-based counseling to our patients and families, and standardizing documentation about HU counseling in the EMR led to measurable improvements in HU adherence in our clinic. We plan to continue tracking HU adherence through this process in our clinics, expanding the adherence project as well, to other key disease-modifying therapies that can significantly improve our patients' outcomes.
