Factors of Interest in Extended-Release Buprenorphine



Opioid use dysfunction (OUD) is the official time period for opioid dependancy. OUD is liable for an essential burden of illness, partially resulting from overdose, viral an infection similar to HIV or HCV, or extreme psychosocial penalties.1 Methadone and buprenorphine are the commonest medicines for opioid use dysfunction (MOUD) used within the pharmacotherapy of opioid use dysfunction (OUD). MOUDs permit to considerably enhance the outcomes of uncontrolled opioid use, in addition to restoration and high quality of life amongst OUD topics.2 Nonetheless, MOUDs even have some particular drawbacks. Methadone might considerably improve the dangers of overdose, specifically throughout its initiation section and if supervision is inadequate.3 Sublingual buprenorphine might be misused if diverted for injection or intranasal use, which can result in particular issues similar to injection abscess, trauma, endocarditis.1 Moreover, the present types of buprenorphine- and methadone-based therapies require day by day consumption, which can be a supply of constraints, stigma and inconvenience.4

For all these causes, new formulations of extended-release buprenorphine (XR-BUP) have not too long ago been developed and commercialized, providing a one-week, one-month, or six-month remedy protection to OUD topics, by means of subcutaneous depot or implant formulations.5 Two depot types, ie Buvidal® (Camurus®, Sweden) and Sublocade® (Indivior®, USA), have been accredited in several international locations. Moreover, an implant, Sixmo®, has been accredited within the USA and in Europe. The efficacy of Buvidal® (one-week or one-month) has been explored in a double-blind double-dummy randomized medical trial evaluating Buvidal® versus sublingual buprenorphine/naloxone, throughout 24 weeks and amongst 428 topics. This examine discovered that Buvidal® was not inferior to sublingual buprenorphine/naloxone for supporting the cessation of non-therapeutic opioid use (35.1% and 28.4%, respectively).6 In different examine conducting throughout 48 weeks in 227 topics, 82.8% of the individuals who had switched from sublingual buprenorphine to Buvidal® maintained the cessation of non-therapeutic use of opioids.7 Regarding Sublocade® (one-month), its efficacy has been investigated versus placebo for six months in 489 topics. The principle evaluation criterion was reporting no opioid use and displaying a adverse urine display on the finish of the examine interval (42.7% with Sublocade® versus 5.0% with placebo).8 Lastly, three efficacy research have been performed on the implants (6-months formulation) in 627 topics.9–11 Efficacy was outlined as a adverse urine display on the finish of the examine interval, ie 24 weeks for 287 sufferers (31% efficacy for the implant, versus 13% for placebo and 33% for sublingual buprenorphine); 16 weeks for 163 sufferers (40% efficacy for the implant versus 28% for placebo); and 6 months for 177 topics (roughly 96% have been adverse for heroin within the group receiving the energetic implant, versus 88% within the group receiving energetic sublingual buprenorphine). These new remedy choices goal to enhance remedy protection, but in addition the discount of withdrawal and craving, and the consolation and comfort options amongst treatment-seeking sufferers with OUD. Surveys amongst folks utilizing opioids or treatment-seeking OUD topics have revealed that these new formulations elevate curiosity for the explanations listed above. Nonetheless, interviewees expressed some issues: these new formulations might be perceived as coercive or as decreasing the power to cease MOUD and resume leisure opioid use, relying on particular person preferences and remedy goals.12–14

OUD is especially prevalent amongst incarcerated individuals. Although no prevalence charge has been estimated, it has been discovered that roughly one-third of people with OUD are incarcerated yearly.15 For these people, incarceration can represent a possibility to provoke remedy.16 In contrast with incarcerated topics with OUD who’re untreated, those that obtain a MOUD present vital reductions of their total opioid use throughout incarceration, in addition to within the frequency of their injection behaviors, jail infractions, and suicide and total mortality threat in jail.17,18 Furthermore, handled topics are much less prone to expertise an overdose after jail launch. Consequently, it has been deemed essential to scale up OUD remedy and prevention methods inside a continuum of initiatives happening earlier than, throughout, and after incarceration.18 Nonetheless, the entry to MOUDs stays globally inadequate in jail. This may be defined by an absence of sources and applicable providers, in addition to adverse perceptions amongst jail medical groups and penitentiary employees associated to stigma, uncertainty of the effectiveness of MOUDs, and apprehension associated to issues of safety, similar to overdose, diversion, or misuse of MOUDs.19 Boundaries might also come from the topics’ surroundings, as MOUD diversion is essential in jail,20 which might result in bullying and violence, and thus stop inmates with OUD from looking for remedy.21 Justice-involved populations are largely disconnected from care, and providing on-demand, versatile, and de-stigmatizing remedy could also be a primary step in connecting high-risk populations with the healthcare system and interventions that scale back dangers of overdose and associated harms.22,23

Latest professional opinions and nationwide tips have identified the curiosity of utilizing XR-BUP in jail4,24 to higher guarantee remedy protection and discretion, in addition to consolation of sufferers prepared to obtain these new types of MOUD.4 Nonetheless, till not too long ago, the surveys investigating the curiosity for XR-BUP didn’t embody incarcerated topics. Within the latest AMBRE examine performed in France in 366 treatment-seeking topics with OUD, roughly one-third of the recruited pattern consisted of incarcerated folks.25 This examine discovered no distinction within the variety of folks fascinated by being handled with XR-BUP between incarcerated and non-incarcerated individuals. Nonetheless, respondents that reported experiencing conditions wherein taking their MOUD was impractical have been considerably extra fascinated by XR-BUP. Nonetheless, the primary sequence of analyses didn’t evaluate the explanations for which XR-BUP could be thought of as an possibility between incarcerated and non-incarcerated topics. Put up-hoc analyses have been thus required to look at this extra query.

Sufferers and Strategies

This examine is reported based on the “Strengthening the reporting of observational research in epidemiology” (STROBE) assertion.26

Research Design and Inhabitants

The “AMBRE” examine was a cross-sectional survey performed in 366 sufferers, recruited in 68 French dependancy services prescribing MOUDs. Amongst them, 6 have been jail medical facilities. The survey happened between December 2, 2018 and Could 31, 2019. Amongst them, 6 have been jail medical facilities. The survey happened between 12/02/2018 and 05/31/2019. Inclusion standards have been as follows: 1) being aged 18 years or extra; 2) initiating or being at the moment handled with a MOUD; 3) offering written consent for taking part within the survey; and 4) being able to finishing a self-administered questionnaire. Different options of the survey might be discovered within the mum or dad publication.25

Research Questionnaire

The questionnaire (obtainable in Supplemental Materials) was constructed by the authors and pre-tested on a small group of treatment-seeking OUD topics, so as to make sure the acceptability and reproducibility of the collected knowledge. It aimed to discover: 1) the principle sociodemographic options and medical historical past of individuals, in addition to traits concerning their use of MOUD; 2) the individuals’ goals with respect to their OUD remedy; and three) the perceptions of individuals concerning the handy or problematic features of MOUD of their day by day life. Contributors needed to reply questions of a self-questionnaire, however they could possibly be helped by a doctor or a nurse if required. After this primary sequence of questions, a fast standardized textual content, included within the questionnaire sheet and obtainable within the Supplemental Materials, described what weekly and month-to-month XR-BUP include. After studying this textual content, individuals have been requested to evaluate their potential curiosity in such formulations of MOUD, utilizing a 1–10 Likert scale. A final sequence of questions explored why individuals would select XR-BUP formulations, and what they might count on.

Knowledge Transformation and Evaluation

Within the current examine, solely the next objects of the questionnaire have been built-in within the analyses: 1) sociodemographic options of individuals; 2) kind of present MOUD (ie, buprenorphine or methadone); and three) attainable elements of alternative for altering their present temper for XR-BUP (as investigated in Q38). To simplify the evaluation course of and the interpretation of the outcomes, the solutions to questions providing a number of reply choices have been binarized. Solutions to the totally different questions included in Q38 (eg, “In your opinion, what are the essential elements that would lead you to decide on this new remedy?”) have been binarized as follows: “crucial” and “essential” have been merged into “essential”, whereas “not crucial” and “not essential in any respect” have been regrouped into “not essential”. The 4 reply choices to Q40 (ie “On a private degree, would you be ready to vary your present remedy so as to take this new remedy?”) have been additionally binarized as follows: “Sure, undoubtedly”, and “Sure, probably”, have been merged into “Sure”, whereas “I can not say at the moment”, “No, most likely not”, and “No, actually not”, have been outlined as “No, or have no idea”.

Categorical parameters are offered because the variety of topics and share (n; %). Every variable of curiosity is offered for incarcerated individuals, non-incarcerated ones, and each teams collectively. Comparisons have been carried out utilizing bivariable checks, ie, chi-squared take a look at or Fisher’s actual take a look at, when applicable. Uncooked odds ratios and their 95% confidence interval (OR [95% CI%) are also displayed.

Subsequently, multivariable regression logistic regression models were built, with the answers to Q40 and Q38 as the dependent variables, incarcerated vs non-incarcerated status as the explanatory variable, and sex, age category, level of education, and housing status, as adjustment variables. Results are provided as raw (ORs) and adjusted (aORs) odds ratios and their 95% confidence interval (95% CI). Subjects with missing values were not integrated in the models. Statistical analyses were performed using the XLSTAT2019 software (https://www.xlstat.com/en/).

Ethical Aspects

In accordance with the French law on clinical research (Loi Jardé), the study protocol was submitted to and approved by the CNIL (#2211988). All participants were informed about the purpose of the study, and that it was conducted in accordance with the Declaration of Helsinki.


From the initial dataset of 366 participants, the data from 317 (ie, 221 non-incarcerated, and 96 incarcerated) interviewees were analyzed. The main sociodemographic and clinical features of the total sample, the responses to the readiness to change their current MOUD for XR-BUP (Q40) and the related factors of interest (Q38), are displayed in Table 1. This table also provides bivariable comparisons of the same parameters between incarcerated and non-incarcerated participants. Table 2 displays the ORs and aORs, and their 95% CI, regarding the comparisons in the different parameters between incarcerated and non-incarcerated participants, before and after adjusting for gender, age category, level of education, and type of MOUD.

Table 1 Bivariable Comparisons in the Features of Incarcerated and Non-Incarcerated Interviewees

Table 2 Raw and Adjusted Comparisons of Factors of Interest for XR-BUP Between Incarcerated and Non-Incarcerated Subjects

Overall, multivariable comparisons found that, relative to non-incarcerated participants, incarcerated participants were readier to try XR-BUP than non-incarcerated ones (aOR= 1.80; 95% CI= 1.04 to 3.13). Significant reasons for a possible switch to XR- BUP were receiving a constant dose of MOUD (aOR= 2.91; 95% CI= 1.21 to 6.98), and taking a form of MOUD more discreet than oral or sublingual forms (aOR= 1.76; 95% CI= 1.01 to 3.10). By contrast, incarcerated subjects granted significantly less interest in the facts that a subcutaneous injection is involved (aOR= 0.24; 95% CI= 0.14 to to 0.43), that XB-BUP could reduce the risk of withdrawal, ie “No longer worrying about feeling ill if I forget my treatment” (aOR= 0.54; 95% CI= 0.29 to 0.99), or that, with XR-BUP, they can “no longer have the option of injecting, snorting or inhaling the MOUD” (aOR= 0.56; 95% CI= 0.34 to 0.94).


Both expert opinions and national guidelines have pointed out that XR-BUP formulations could be of particular interest in prisons, for both convenience and efficacy reasons.4,24 However, because some people with OUD were concerned about the concept of XR-BUP and more precisely with respect to a possible limitation of freedom and coercive treatment,12,13 it was important to address whether incarcerated people with OUD were ready to try XR-BUP or reluctant to receive it, and what could be the factors of interest and the expectations about these new formulations. In the main results of the AMBRE survey, which were previously published in the parent study,25 it was found that a majority of the participants was interested in the principle of XR-BUP, and that the average level of interest was similar in incarcerated and non-incarcerated interviewees. However, we did not explore whether the factors of interest and expectations about XR-BUP were different.

The first main finding of these post-hoc analyses was that almost two-thirds of incarcerated people with OUD declared themselves ready to change their current MOUD to XR-BUP, versus barely more than one-half of non-incarcerated subjects. This suggests a good level of acceptability of XR-BUP among subjects with OUD in a prison setting. In addition, we found that incarcerated interviewees were not interested in XR-BUP for the same reasons as those outside prison. More specifically, they less expected XR-BUP to help them improve outcomes of OUD, or to reduce safety issues related to MOUD, such as the occurrence of withdrawal, or the potential of misuse. By contrast, practical aspects such as no longer having to take their MOUD every day, or receiving a more discreet treatment, appealed to incarcerated participants. Buprenorphine diversion and misuse are widespread in prison20 and thus recipients of daily medication can be subject to bullying and violence in this environment. This has been reported in France,27 and in some other countries, such as the UK.21 It will thus be important to assess whether the patients treated with a depot or implant form of buprenorphine will be exposed to the same harassment or extortion as those receiving sublingual buprenorphine. This may explain the patterns of responses found in the survey, although this would require further investigation. If the use of XR-BUP makes it possible to reduce diversion and trafficking, and incidentally the violence linked to trafficking in prison, it would be a shame to deprive incarcerated patients of this possibility. In addition, the access to MOUD in a prison setting can be impeded by insufficient time or insufficient training level of both health care and security staffs.28 In this regard, the implementation of XR-BUP could reduce the overall time staff need to provide adequate access to MOUD for people with OUD. Though it would also require an additional, albeit limited, training of physicians and nurses on the injection procedure, the use of XR-BUP might be time-saving on the longer-term, which could facilitate its acceptance by security and health care staffs also.

This survey had some limitations that should be acknowledged. First, the study population was a small sample. Because these types of survey investigate people with illegal behaviors, it is usually very hard to build a “representative” sample of these populations with OUD. Nevertheless, the sample of the survey was consistent with the typical demographics of French people with OUD, including the proportion of males vs females and the proportion of subjects treated with buprenorphine or methadone.27 A similar limitation was that the subjects compared were not paired with others from the second group, which could have generated biases, even if multivariable comparisons were adjusted on important sociodemographic and clinical features. Moreover, because XR-BUP formulations are not yet commercialized in France, this survey explored the intentions and representations of subjects with no practical experience with the products described. Thus, results may vary from those reported here if a comparable study is performed after XR-BUP formulations become available in France. Last, the analyses were not adjusted for multiple comparisons, but some authors deem that such adjustments are not required for exploratory observational studies.29


Our post-hoc analyses found that the motivations for trying XR-BUP were different inside and outside prison. In particular, incarcerated subjects with OUD were more interested in the possible discretion and practicability aspects related to XR-BUP, and less in their potential effectiveness in improving recovery or safety by using long-acting treatment.


The authors thank the survey participants, as well as the investigators who recruited them. They also thank the “KAPPA Santé” team, the CRO that implemented the study and collected the data, as well as Émeline Bréniaux for her help in editing the manuscript for English.


This study was sponsored by Camurus. Camurus contributed to the study design and analysis plan; Camurus played no role in collection of data, nor in the analysis of the manuscript. PH and MK (from Camurus) participated in the discussion and interpretation of the results.

BR received fees for lectures and consultancy from Camurus, Individor, Recordati, and Ethypharm, Accord Health, Lundbeck, HAC Pharma, AbbVie, and Gilead. BT received fees for consultancy from Camurus. JB, GB, and FM received fees for lectures or consultancy from Camurus and Indivior. MK and PH are employed by Camurus, France, and Camurus, Sweden, respectively. FM received fees for lectures or consultancy from Camurus and Indivior. PN received fees for lectures or consultancy from Camurus. GB received fees for lectures or consultancy from Camurus and Indivior. PB reports personal fees from Camurus for Albatros and Encephale congress invitation and financial indemnisation for participation to Ambre study as investigator, during the conduct of the study; Financial indemnisation for Webinar as speaker on “screen addiction” from Ethypharm, outside the submitted work. The authors report no other conflicts of interest in this work.


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