Hydroxyurea Adherence Linked to Low Opioid Use in Sickle Cell Patients

Hyeun Ah Kang, PD

Findings from a new study showed a negative correlation between hydroxyurea adherence and risk of receiving a prescription for strong opioids among patients with sickle cell disease.

Current practice guidelines recommend opioid analgesics due to the recurrent pain crises experienced by these patients. However, hydroxyurea has long demonstrated benefit in reducing these crises. Nevertheless, there has been limited research assessing hydroxyurea adherence and opioid use among this population.

Therefore, Hyeun Ah Kang, PhD, School of Pharmacy, University of Texas at El Paso, and Jamie Barner, PhD, Austin College of Pharmacy, University of Texas at Austin, conducted a retrospective database study using Texas Medicaid claims data to further elucidate this link between hydroxyurea and opioid use.

The study population included those with evidence of hydroxyurea use between September 2011-August 2015 and who were aged 2-63 years. Eligible subjects were required to have at least 1 hospitalization or 2 outpatient visits associated with a sickle cell disease diagnosis between the same time period.

Kang and Barner excluded those who were diagnosed with any other indications for hydroxyurea—such as melanoma, resistant chronic myeloid leukemia, etc.

They measured medication adherence to hydroxyurea using the medication possession ratio (MPR), which was defined as the sum of the days of hydroxyurea claims dispensed during the 12 months after the index date (or day 1 of treatment initiation) divided by the 365 days of follow-up.

Thus, they defined medication adherence as ≥80%, where anything less was considered non-adherent.

The outcome sought by the investigators was opioid use during the 1 year following initiation of hydroxyurea.

They assessed a total of 1146 patients with sickle cell disease, with 57.2% being ≤18 years of age. They noted that adherent patients were significantly younger than non-adherent patients (P<.0001). Additionally, about half (50.2%) of the patients were male.

Overall mean MPR was 48.3%, and 19.6% of patients were considered adherent to hyodroxyurea.

About 74.6% had a least 1 vaso-occlusive crisis (VOC) during the 1-year follow-up period. Furthermore, a significantly higher proportion of nonadherent patients (79.8%) experienced VOC than those who were nonadherent (53.3%; P < .0001).

Further, they found that in the 1-year follow-up period, 80.5% of patients had at least 1 opioid prescription. They also noted there were 7.6 opioid prescriptions per patient. About 22.6% of patients had at least 1 strong opioid prescription, with 1.5 strong opioid prescriptions per patient.

According to bivariate analyses, adherent patients had significantly a lower probability of using opioids, strong opioids, and high-dose opioids in comparison with nonadherent patients. (P<.0001 for each).

Additionally, MPR ≥80%—or high adherence—was associated with significantly fewer number of prescriptions for both opioids and strong opioids, lower dose of opioids, and fewer days of prescribed opioids (P<.0001).

Further analyses also revealed that older age was associated with a higher probability of having opioids, strong opioids, and high-dose opioids as well as a greater number of prescriptions for opioids and strong opioids, a higher dose of opioids, and a greater number of days prescribed for opioids (P<.0001).

In their adjusted analyses, only the relationship between hydroxyurea adherence and strong opioids remained. Thus, they noted that—after controlling for other demographic and clinical characteristics—being adherent to hydroxyurea was associated with 50.5% decreased risk of having strong opioids.

“Managing opioid use in this population is important in reducing adverse events associated with long-term use of opioids, including dependence and respiratory depression,” Kang and Barner wrote.

They emphasized the importance of encouraging hydroxyurea among these patients, especially as they transition from pediatric to adult care.

“In addition to providing targeted programs to promote medication adherence among patients with sickle cell disease, psychosocial and behavioral treatment such as relaxation training, operant behavioral strategies, biofeedback, and cognitive coping would also benefit patients to reduce pain episodes and opioid use,” they wrote.

The study, “The association between hydroxyurea adherence and opioid utilization among Texas Medicaid enrollees with sickle cell disease,” was published online in Journal of Managed Care.