How High Should You Go? Buprenorphine Dosing in the ANCHOR Investigation

Background
In people who use drugs(PWUD) with opioid use disorder(OUD), buprenorphine is a vital treatment to decrease opioid use and overdose. FDA prescribing information for buprenorphine advises dosing up to 24mg/day, however doses of buprenorphine up to 32mg have been shown to be safe and effective(1). Further, treatment retention increases linearly with higher doses of buprenorphine up to 32mg and doses over 16mg are associated with decreased opioid use(2,3). However, 32mg dosing is not recommended in SAMHSA guidelines and is often not supported by insurance. We aimed to understand the outcomes associated with buprenorphine dosing of 32mg/day relative to 24mg/day.

Methods
ANCHOR is a single center study of PWUD with HCV, OUD, and opioid misuse within 3months, who were treated for HCV and offered buprenorphine. Patients initiating buprenorphine were induced on 16mg/day and uptitrated to 32mg/day as needed. Patient-endorsed drug use, mode of drug use and urine drug screens(UDS) were collected at first visit post-dosage increase, and after two weeks on increased dose. For analysis, the cohort was divided into individuals stabilized on 24mg(24mg-cohort) and 32mg(32mg-cohort). Comparisons were made looking at drug use factors of both cohorts at 24mg dosing, and within the 32mg-cohort alone, comparing visits on 24mg vs visits on 32mg. Fisher’s exact test were used for statistical analysis.

Results
73 participants initiated buprenorphine treatment. Patients were predominantly male(54,74%) and Black(71,96%), injected daily(46,63%), had a mean OUD-DSM5 score of 9.4. The average age at which opioid use was initiated was 21.4 years.

Over the course of median 64weeks of buprenorphine treatment(IQR197-785), one(1.3%)patient remained on 16mg, 18(25%)patients stabilized on 24mg(24mg-cohort), and 54(74%)patients stabilized on 32mg(32mg-cohort). Stabilizing on 32mg was not significantly associated with housing status, baseline IDU frequency, previous MOUD treatment, hazardous alcohol use, co-morbid mental illness, or age of opioid initiation(p> 0.05 for all).

When comparing 24mg and 32mg-cohort patients at visits receiving 24mg/day, 32mg-cohort patients were more likely to endorse drug use(p=0.04), despite also being more likely to have buprenorphine present in UDS(p=0.004). There was no statistically significant association between mode of drug use(p=0.44), or UDS positive for opioids(p=0.20).


When looking only at the 32mg-cohort patients, and comparing factors at visits while on 32mg vs 24mg, patients were less likely to endorse prior week drug use(p=0.04) or being triggered to use by cravings(p=0.017) or withdrawal(p=0.017) while on 32mg. There was no significant association between dose strength and presence of buprenorphine in UDS(p=0.31) or UDS positive for opioids(p=0.65).

Conclusion
Higher buprenorphine doses have been associated with better retention and outcomes(1,3). In our cohort, patients who stabilized on 32mg were more likely to endorse drug use while on 24mg compared to those stabilized on 24mg. After increasing to 32mg dosing, these patients were less likely to endorse drug use, triggers of craving and withdrawal. These data indicate that there are some patients who benefit from 32mg/day of buprenorphine. Consideration should be given to modifying treatment guidelines and insurance policies to facilitate higher dosing in these patients.

References: 1. Comer, Sandra D et al. “Buprenorphine/naloxone reduces the reinforcing and subjective effects of heroin in heroin-dependent volunteers.” Psychopharmacology vol. 181,4 (2005): 664-75. doi:10.1007/s00213-005-0023-6
2. Hser, Yih-Ing et al. “Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial.” Addiction (Abingdon, England) vol. 109,1 (2014): 79-87. doi:10.1111/add.12333
3. Fareed, Ayman et al. “Treatment outcome for flexible dosing buprenorphine maintenance treatment.” The American journal of drug and alcohol abuse vol. 38,2 (2012): 155-60. doi:10.3109/00952990.2011.643988