Buprenorphine Is Associated with Lower Home Opioid Use and Acute Care Utilization in Sickle Cell Disease

Introduction: Sickle cell disease (SCD) in an inherited genetic disorder affecting an estimated 100,000 people in the United States. It is associated with unpredictable acute pain, chronic pain, end organ damage, and early death. Pain, the hallmark symptom of SCD, is multifaceted, involving nociceptive pain from vaso-occlusion and bone damage, central and peripheral sensitization, neuropathic pain, and exposomal factors. Acute pain episodes lead to high hospital utilization in SCD and chronic pain accounts for 50% of people with SCD. High hospital utilization in SCD is costly to healthcare systems and is associated with high-dose outpatient opioids and early mortality. While hydroxyurea can reduce vaso-occlusive episodes and lower home opioid use and newer disease modifying agents like crizanlizumab, and l-glutamine reduce pain crises, and voxelotor increases hemoglobin and reduce hemolysis, none effectively modify SCD chronic pain. Chronic SCD pain is treated with full opioid agonists but long-term use of chronic opioid therapy (COT) in SCD is not recommended. Buprenorphine, a partial opioid agonist FDA-approved for pain and primarily used for opioid use disorder (OUD), has shown promise in decreasing hospital utilization and reducing morphine milligram equivalent (MME) dosing in SCD, according to emerging data from small studies and case reports. However, buprenorphine for chronic pain in SCD with concurrent OUD is not well-described in the literature. This study describes the experience of a single center with buprenorphine inductions for SCD chronic pain in individuals with and without OUD. We hypothesized that buprenorphine reduces acute care utilization and opioid MME use in adults with SCD with and without OUD.

Methods: This study was a single-center, retrospective cohort of all individuals with SCD and chronic pain treated with buprenorphine between November 2020 and January 2024. Data was collected from the electronic medical record (EMR). The chart review and extraction included one year of acute care visits before and length of time while on buprenorphine after induction. The charts were cross-checked by another trained reviewer for inter-rater reliability. Descriptive statistics were used to describe the frequency distributions of the data, measures of central tendency, and standard deviation of the variables of interest. Pre- and post-buprenorphine variables between various groups were analyzed using paired t-tests weighted for treatment duration.

Results: The cohort included 13 individuals with SCD, two of whom carried a diagnosis of OUD, with a mean age of 28 years (SD 6.3). Patients had either HbSS (n = 10, 76.9%), HbSC (n = 2, 15.4%), or Sickle β⁰ Thalassemia (n = 1, 7.69%). One individual (7.7%) failed induction and did not continue buprenorphine. The median duration of follow up was 103 days (range 21-1497 days) for a total of 8.3 patient-years of data for those who completed an induction. Buprenorphine use was associated with lower annualized rates of ED visits (7.2 vs 5.9, mean difference -1.3, p <0.001), hospital admissions (8.5 vs 5.6, -2.9, p <0.001), treatment center visits (3.0 vs 2.2, -0.9, p <0.001), and lower rates of home opioid use (189.3 vs 35.6 morphine MME, -153.7, p <0.001). Of the two individuals with OUD, one had 20 acute care visits in the year preceding buprenorphine induction. Following induction, acute care visits decreased to 3 and were due to acute cholecystitis, a subsequent admission for cholecystectomy, and another for withdrawal due to lack of buprenorphine supply at the pharmacy. All full agonist opioids were discontinued for this individual. Another patient with SCD and OUD had 41 acute care visits pre-buprenorphine induction and 19 visits post-buprenorphine, and morphine MME usage decreased by nearly 50% from 392 MME pre-buprenorphine induction to 192 MME post-buprenorphine induction during the treatment period.

Conclusion: Buprenorphine use was significantly associated with reduced acute care utilization and home opioid MME doses. This is the only study to report on patients with SCD and concurrent OUD. This study confirms that buprenorphine is acceptable for SCD chronic pain with and without OUD when full-agonist opioid therapy is not satisfactory. The complex and heterogeneous nature of chronic SCD pain necessitates better phenotyping to understand which subphenotypes benefit most from buprenorphine treatment.