Extended-release subcutaneous buprenorphine administered by healthcare providers may increase opioid
Resident Focus - Volume 14, Issue 4
Since Subutex (buprenorphine) and Suboxone (buprenorphine/naloxone) were FDA approved in 2002, management options for medication-assisted treatment of opioid use disorder have expanded. Buprenorphine agents offer true outpatient, at-home treatment instead of daily-observed dosing in methadone clinics. Concerns with outpatient buprenorphine therapy include variability in the bio-availability of sublingually administered buprenorphine and the potential of at-home self-administered sublingual buprenorphine for diversion, misuse, and abuse (J Addict Med. 2014). The new buprenorphine formulation, depot BupXR (Sublocade) injection, avoids these issues as it is administered monthly in an outpatient clinic (Drug Des Devel Ther. 2017). The study to be reviewed, which is the largest randomized trial to date for this formulation of depot buprenorphine, assesses the efficacy of this new therapy (Lancet 2019).In this double-blind, placebo-controlled phase III trial, 504 adults seeking treatment for opioid use disorder were randomized at 36 centers in 4:4:1:1 fashion to receive two differing BupXR subcutaneous monthly injections or two differing volume-matched placebo injections for 6 months. All patients in all groups had weekly individual counseling. Patients with moderate to severe addiction to other substances such as alcohol, cocaine, or cannabis were excluded, as were patients treated with medication-assisted treatment for opioid use disorder within the last 90 days. All participants had a two-week run-in phase of buprenorphine-naloxone sublingual film use to assess their tolerance and response. Only patients without allergic reaction and with mild withdrawal according to both the Clinical Opiate Withdrawal Scale and Opioid Craving Visual Analogue scale were included in the study. After the run-in phase, patients received monthly subcutaneous injections for six months. For the first two months, patients in the two BupXR groups both received 300 mg to achieve opioid blockade and therapeutic blood levels, and then either received 300 mg or 100 mg monthly by randomized group assignment. The remaining control groups received volume-matched placebo injections of 300 mg or 100 mg but were combined into a single placebo group for the purpose of outcomes analysis. The primary outcome was the percentage of participants who demonstrated weekly abstinence according to self-report and urine samples from weeks 5-24.
Of the combined buprenorphine groups, 63% completed the trial compared to 24% of the placebo group, but the authors included all patients in an intention-to-treat analysis with missed assessments being counted as positive for opioids. Weekly abstinence rates were 41.3% in the BupXR 300 mg group, 42.7% in the BupXR 100 mg group, and 5% in the placebo group (p < 0.0001 and NNT 3 for each BupXR group compared to placebo). The secondary outcome of “treatment success” (defined as ≥ 80%-abstinence) was achieved by 29%, 28%, and 2% for the buprenorphine groups and placebo group respectively (p < 0.0001 and NNT 4 for each BupXR group compared to placebo). Questionnaires demonstrated treatment satisfaction rates of 88% in both BupXR groups versus 46% in placebo group ( p < 0.0001 for each dosing regimen compared to placebo). Employment also rose by 10% for both BupXR groups, whereas it fell by 13% for the placebo group.
This study is elegant in its design by further dividing the treatment and control groups into 4 total groups. In this way, we are able to not only determine the efficacy of the medication, but also compare two different dosing regimens. Also, by analyzing the treatment satisfaction rates in addition to the abstinence rates, we are given more evidence that this therapy will translate well into practice. However, the findings of this study are tempered by several limitations. First, there was significant study discontinuation in all randomized groups, which raises validity concerns. However, it should be noted that studies of populations with substance use disorders typically have high relapse and poor follow-up rates, and the authors treated absent data as treatment failure. Secondly, there is a lack of generalizability as patients with polysubstance abuse, which is common, were not included. Additionally, patients who did not show at least partial response to buprenorphine-naloxone sublingual film in the form of reduced craving and/or withdrawal symptoms during the two run-in weeks of the trial were excluded, potentially further biasing the results towards efficacy.
Despite the limitations, monthly BupXR plus weekly counseling may help increase abstinence compared to placebo in a population of adults with opioid use disorder seeking treatment who had mild withdrawal symptoms with the convenience of monthly dosing. Further studies, including a patient population with more severe withdrawal symptoms and with polysubstance use disorder, and comparison with other abstinence therapies and strategies may help clarify the most precise indications for the use of BupXR in the treatment of patients with opioid use disorders.
For more information, see Opioid abuse and dependence in DynaMed.
Sarah Rooney was born in and lived most of her life in New York, with the exception of 7 years spent in Indonesia. She attended college at Stony Brook University in Long Island, NY, where she majored in Women’s Studies with Specialization in Gender, Sexuality and Public Health. She participated in translational research at Mount Sinai hospital in NYC for a year prior to attending Touro College of Osteopathic Medicine in Harlem, NY. She completed her Family Medicine residency training at United Health Services Wilson hospital in Johnson City, NY in June of 2019.