Patients report greater satisfaction with weekly, monthly buprenorphine

People with opioid dependence reported being more satisfied—and more compliant—with weekly or monthly depot buprenorphine versus sublingual buprenorphine, researchers reported.

In an open-label, 24-week randomized trial done at six outpatient clinical sites in Australia, the self-reported global satisfaction score was significantly higher for the depot group compared with the sublingual group at a mean TSQM (Treatment Satisfaction Questionnaire for Medication v1.4) score of 82.5 versus 74.3, for a difference of 8.2 (95% CI 1.7-14.6, P=0.01), according to Fredrik Tiberg, PhD, of Camurus in Lund, Sweden, and co-authors (TQSM ranges from 0-100 with higher score indicating greater satisfaction).

Improved outcomes were also seen for multiple secondary endpoints post-treatment with extended-release (ER) depot buprenorphine, including Treatment Burden Questionnaire (TBQ) global score, quality of life (QoL), patient satisfaction, and treatment retention, they reported in JAMA Network Open.

While there were some adverse events (AEs) with ER treatment, none of the participants withdrew from the buprenorphine because of those AEs, the authors added. Camurus makes Buvidal, a weekly/monthly buprenorphine injectable, which is approved for use in Australia and other countries. In the U.S., FDA review of the agent—called Brixadi and licensed to Braeburn of Plymouth Meeting, Pennsylvania—is pending.

Previous research has shown the value of weekly and monthly, flexible-dose depot buprenorphine formulations, versus SL buprenorphine for illicit opioid use treatment, but no trial has “compared patient-reported outcomes (PROs) between the two treatment approaches,” Tiberg’s group explained.

In an invited commentary accompanying the study, Wilson M. Compton, MD, MPE, and Nora D. Volkow, MD, both of the National Institute on Drug Abuse in Bethesda, Maryland, praised the authors for using “PROs instead of drug abstinence as the primary outcome… and [for] using a comparative effectiveness design… the practice-based nature of the study, in which real-world settings with few exclusion criteria were used to recruit participants, suggests the likely generalizability of findings.”

But they pointed out a caveat: Would the results be the same outside the Australian health system, particularly in the U.S.?

“Specifically, treatment included observed dosing of oral buprenorphine, although participants were allowed to take as many as six doses per week without supervision, and included at least weekly clinical visits, whereas in the United States, monthly appointments are typical… Does more frequent follow-up for oral medication in Australia relate to its lesser acceptability?” Compton and Volkow wrote.

Nonetheless, they offered two take-home messages from the study: The importance of including PROs in clinical trials, and that “ER formulations might help to improve long-term retention and… be a valuable tool to help combat the current opioid epidemic and reduce its associated mortality.”

For the trial, 119 participants (58.8% men; mean age 44.4; 85% White) were enrolled and randomized to either depot buprenorphine (50.4%) or sublingual buprenorphine (49.6%). All patients had been pre-treated with sublingual buprenorphine. Exclusion criteria were severe respiratory and hepatic insufficiency, as well as untreated psychiatric conditions, among others.

“Weekly and monthly depot buprenorphine were administered at trial sites as [subcutaneous] injections according to clinician and individual participant choice of dosing strength, dosing frequency, and injection site,” the authors explained. Maximum doses for the injectable version were 32 mg per week and 160 mg per month. The maximum dose for the oral version (buprenorphine with naloxone) was 32 mg daily.

Scheduled visits were mandatory scheduled visits, while urinary drug screenings (UDS) took place on day 1, week 0 (baseline) and at weeks 4, 8, 12, 16, 20, and 24. Psychosocial interventions were provided as needed regardless of the scheduled visits. Participants in the sublingual buprenorphine group could receive their dose at the trial clinic or at a nominated community pharmacy, attending between daily to weekly, and were allowed up to six unsupervised doses/week.

The authors reported improvements for key secondary outcomes including:

The authors conceded that “there were no improvements in either the depot buprenorphine or SL buprenorphine group of the recovery measures using SURE.” However, while “SURE has been validated against other PROs, its sensitivity to change over time has not been previously examined, and we propose further secondary analysis of this instrument.”

As for sticking with the assigned treatment, 88.3% in the depot group completed the study as did 93.3% of the oral group. One participant in the latter group withdrew consent and did not receive study treatment.

Tiberg’s group found in a post hoc analysis of the TSQM global satisfaction score that the number of participants with a score of ≥80 was higher in the depot buprenorphine group (53.3% versus 33.9%) at week 24, and that the number-needed-to-treat to achieve the threshold of ≥80 was 5.1 (95% CI 2.8 to 61.1), which highlights the “magnitude of the improvements in the treatment-related PROs in the depot buprenorphine group.”

Finally, for AEs, the authors reported that treatment-related ones were higher in the depot group versus the sublingual group (90% vs 83.1%), and that they were mainly injection site reactions of mild intensity. There was one incident of suicidal ideation potentially related to the injectable, but “the dose was increased, and the event resolved,” according to Tiberg and co-authors.

Treatment-related AEs in the oral group were two events of intentional overdose, one case of pneumonia, and one of alcohol dependence, but “[n]one of these events were considered related to the drug, and all events resolved without sequelae,” they stated.

Study limitations included the fact that TSQM may not have captured all principal effects of the medications used to treat addiction, such as effect on craving of substances. Also, pharmacy dosing fees were covered during the trial which may have influenced satisfaction. Finally, results may be different in patients who are new to treatment of opioid dependence.

  1. The mean Treatment Satisfaction Questionnaire for Medication global score was significantly higher in people with opioid use disorder receiving depot buprenorphine than in the group receiving sublingual buprenorphine in a 24-week, open-label trial.

  2. Extended-release buprenorphine formulations may help improve long-term retention and serve as a valuable tool to combat the current opioid epidemic, while patient-reported outcomes should be included in clinical trials. Be aware the buprenophine is still pending approval in the U.S.

Shalmali Pal, Contributing Writer, BreakingMED™

The study was funded by Camurus AB. Tiberg and some co-authors are company employees.

Co-authors reported relationships with, and/or support from, GW Pharmaceuticals, Indivior, Mundipharma, Chiesi Pharmaceuticals, Braeburn Pharmaceuticals/Camurus, Sequiris, Gilead, AbbVie, the Australian Medical Research Future Fund Next Generation Fellowship, Lundbeck, AstraZeneca, Camurus, Janssen Pharmaceuticals, Servier, Shire, Cilag, and Viiv.

Compton reported relationships with General Electric, 3M, and Pfizer. Volkow reported no relationships relevant to the contents of this paper to disclose.

Cat ID: 144

Topic ID: 87,144,730,192,144,925