Buprenorphine & Sickle Cell: How Pediatric and Adult Providers Differ in Prescribing Habits and Evolving Pain Management Styles

Background:

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusion, tissue hypoxia, and infarction. Pain is the leading reason for emergency visits and hospitalization. Both acute and chronic pain are markers of increased morbidity and decreased quality of life. Pain management in SCD is heterogenous among SCD providers. Full opioid agonists have been the mainstay of therapy; however, they can lead to dose-dependent adverse effects.

Case studies have explored the use of buprenorphine, a partial opioid agonist originally developed to treat pain and later FDA approved for opioid use disorder (OUD), for pain in SCD with promising results. Until 2023, an X-waiver was required to prescribe buprenorphine for OUD. Data on SCD providers' awareness and prescribing habits of buprenorphine is limited. The goal of this study was to assess the prescribing habits of buprenorphine among SCD providers.

Methods:

In this cross-sectional study, physicians and advanced practice providers caring for children or adults with SCD in the United States were recruited via email and SCD-focused listservs to complete a Qualtrics-designed survey. 52 providers were surveyed, and respondents who completed <50% of the survey were excluded. Data analysis included descriptive and inferential statistics using STATA.

Results:

The majority (84%) were physicians and 96% of providers were associated with a sickle cell center. Providers saw a median of 150 patients annually. 56% of respondents were adult providers, 32% were pediatric providers, and 12% provided care for both. Of the physicians, 40.5% were pediatric hematology/oncology trained and 31% adult trained.

Most providers (61.5%) managed SCD-related pain themselves; however, a majority (51.9%) had never prescribed buprenorphine. Pediatric-only providers (31.2%) were less likely to manage SCD pain themselves as compared to adult providers (p =0.008). Most pediatric providers (93.8%) had never prescribed buprenorphine (p= 0.001). Of those, the most common barriers to prescribing were: discomfort with the dosing (88%), uncertainty of side effects (48%) and efficacy (40%).

Providers who initiated buprenorphine themselves (48.1%) saw more patients annually (248 vs 100, p= 0.011). Over half of the providers surveyed (54%) strongly preferred to receive education on how to initiate buprenorphine themselves. Most common barriers to prescribing were: patient reluctance (88%), discomfort with dosing (54%), and the patient's high amount daily prescribed opioids (52%). There was no relationship to the repeal of the X-waiver for first-time prescribers. Only 12 providers had obtained an X-waiver, none were pediatric-only providers (p=0.024).

Overall, all providers were least comfortable prescribing buprenorphine compared with other opioids. The median rating for buprenorphine was 1.5, 4.8 for morphine, and 5.0 for oxycodone (0 = least comfortable to 5 = most comfortable). Pediatric-only providers were less comfortable with buprenorphine compared with adult providers (p<0.001).

Conclusion:

In this study we found that most SCD providers manage SCD-related pain themselves. However, they are uncomfortable with prescribing buprenorphine and the majority have never prescribed buprenorphine, despite its potential as a safe intervention for chronic pain in SCD. Irrespective of prescribing history, discomfort with dosing and uncertainty of side effects were barriers, highlighting an opportunity for training and education. There was a significant difference in prescribing patterns and comfort levels between pediatric-only and adult providers, which may be attributed to the worsening of acute and chronic pain as persons with SCD age. Additionally, buprenorphine is FDA approved for ≥16 years of age. Providers who managed a higher volume of patients were more likely to independently initiate buprenorphine.

The emerging interest in buprenorphine for pain management in SCD suggests that SCD providers are seeking novel modalities to manage SCD-related pain, evidenced by the rise of other non-full opioid agonists such as ketamine, intravenous lidocaine, and cannabinoids. Like buprenorphine, these therapies are not discussed in pain management guidelines. This study underscores the need for SCD-directed buprenorphine education to enhance implementation and optimize pain management in this debilitating disease.

Van Doren:Pfizer/GBT: Ended employment in the past 24 months, Speakers Bureau; Sobi: Ended employment in the past 24 months, Speakers Bureau; Daiichi Sankyo: Ended employment in the past 24 months, Speakers Bureau; Sanofi: Ended employment in the past 24 months, Speakers Bureau; Pharmacosmos, Inc: Consultancy, Honoraria.