Safety and efficacy of a prescription digital therapeutic as an adjunct to buprenorphine for treatment of opioid use disorder.
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ABSTRACT: Objectives
To evaluate the safety and efficacy of a digital therapeutic in treatment-seeking individuals with opioid use disorder (OUD) in an analysis of randomized clinical trial (RCT) data (ClinicalTrials.gov identifier: NCT00929253).Methods
Secondary analysis of an RCT including 170 adults meeting DSM-IV criteria for OUD. Participants were randomized to 12-weeks of treatment-as-usual (TAU) or TAU plus a digital therapeutic providing 67 digital, interactive educational modules based on the Community Reinforcement Approach. TAU consisted of buprenorphine maintenance therapy, 30 min biweekly clinician interaction, and abstinence-based contingency management. Primary endpoints were treatment retention and abstinence (negative urine drug screen) during weeks 9-12 of treatment. Safety was assessed by evaluating adverse events.Results
Participants randomized to TAU plus a digital therapeutic had significantly greater odds of opioid abstinence during weeks 9-12 compared to TAU: 77.3 versus 62.1%, respectively (p=.02), OR 2.08, 95% CI 1.10-3.95. The risk of patients leaving treatment was significantly lower in the digital therapeutic group (HR 0.49, 95% CI 0.26-0.92). No significant difference was observed in the rate of adverse events between groups (p=.42).Conclusions
A prescription digital therapeutic (PDT) in combination with buprenorphine therapy improves clinically significant patient outcomes including abstinence from illicit opioids and retention in treatment compared with treatment as usual.
SUBMITTER: Maricich YA
PROVIDER: S-EPMC8666102 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHome-based (unsupervised) buprenorphine initiation is considered safe and effective, yet many patients report barriers to successful treatment initiation. Prescription digital therapeutics (PDTs) are software-based disease treatments regulated by the US Food and Drug Administration (FDA). The reSET-O PDT was authorized by the FDA in 2018 and delivers behavioral treatment for individuals receiving buprenorphine for opioid use disorder (OUD). A prototype PDT (PEAR-002b) designed for use with reSET-O was developed to assist in unsupervised buprenorphine initiation.ObjectiveThe primary objective of this pilot study is to evaluate the acceptability of PEAR-002b in individuals with OUD who use it to support buprenorphine initiation, their unsupervised buprenorphine initiation success rate, and their medication adherence.MethodsTen adults with OUD will be recruited for acceptability and feasibility testing. Outcomes will be assessed using week-1 visit attendance, participant interviews and satisfaction surveys, and urine drug screening (UDS). Three tools will be used in the study: PEAR-002b, reSET-O, and EmbracePlus. PEAR-002b includes a new set of features designed for use with reSET-O. The mechanism of action for the combined PEAR-002b and reSET-O treatment is a program of medication dosing support during week 1 of the initiation phase, cognitive behavioral therapy, and contingency management. During the medication initiation phase, participants are guided through a process to support proper medication use. PEAR-002b advises them when to take their buprenorphine based on provider inputs (eg, starting dose), self-reported substance use, and self-reported withdrawal symptoms. This study also administers the EmbracePlus device, a medical-grade smartwatch, to pilot methods for collecting physiologic data (eg, heart rate and skin conductance) and evaluate the device's potential for use along with PDTs that are designed to improve OUD treatment initiation. Home buprenorphine initiation success will be summarized as the proportion of participants attending the post-buprenorphine initiation visit (week 1) and the proportion of participants who experience buprenorphine initiation-related adverse events (eg, precipitated withdrawal). Acceptability of PEAR-002b will be evaluated based on individual participants' ratings of ease of use, satisfaction, perceived helpfulness, and likelihood of recommending PEAR-002b. Medication adherence will be evaluated by participant self-report data and confirmed by UDS. UDS data will be summarized as the mean of individual participants' proportion of total urine samples testing positive for buprenorphine or norbuprenorphine over the 4-week study.ResultsThis project was funded in September 2019. As of September 2022, participant enrollment is ongoing.ConclusionsThis is the first study to our knowledge to develop a PDT that assists with unsupervised buprenorphine initiation with the intent to better support patients and prescribers during this early phase of treatment. This pilot study will assess the acceptability and utility of a digital therapeutic to assist individuals with OUD with unsupervised buprenorphine initiation.Trial registrationClinicalTrials.gov NCT05412966; https://clinicaltrials.gov/ct2/show/NCT05412966.International registered report identifier (irrid)PRR1-10.2196/43122.
| S-EPMC9898828 | biostudies-literature
Project description:OBJECTIVE:Although buprenorphine treatment reduces risk of overdose and death in opioid use disorder, most patients discontinue treatment within a few weeks or months. Adverse health outcomes following buprenorphine discontinuation were compared among patients who were successfully retained beyond 6 months of continuous treatment, a minimum treatment duration recently endorsed by the National Quality Forum. METHODS:A retrospective longitudinal cohort analysis was performed using the MarketScan multistate Medicaid claims database (2013-2017), covering 12 million beneficiaries annually. The sample included adults (18-64 years of age) who received buprenorphine continuously for ?180 days by cohorts retained for 6-9 months, 9-12 months, 12-15 months, and 15-18 months. For outcome assessment in the postdiscontinuation period, patients had to be continuously enrolled in Medicaid for 6 months after buprenorphine discontinuation. Primary adverse outcomes included all-cause emergency department visits, all-cause inpatient hospitalizations, opioid prescriptions, and drug overdose (opioid or non-opioid). RESULTS:Adverse events were common across all cohorts, and almost half of patients (42.1%-49.9%) were seen in the emergency department at least once. Compared with patients retained on buprenorphine for 6-9 months (N=4,126), those retained for 15-18 months (N=931) had significantly lower odds of emergency department visits (odds ratio=0.75, 95% CI=0.65-0.86), inpatient hospitalizations (odds ratio=0.79, 95% CI=0.64-0.99), and filling opioid prescriptions (odds ratio=0.67, 95% CI=0.56-0.80) in the 6 months following discontinuation. Approximately 5% of patients across all cohorts experienced one or more medically treated overdoses. CONCLUSIONS:Risk of acute care service use and overdose were high following buprenorphine discontinuation irrespective of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high.
| S-EPMC7002204 | biostudies-literature
Project description:BackgroundBUP-XR (RBP-6000 or SUBLOCADE) is the first Food and Drug Administration-approved subcutaneously administered monthly extended-release buprenorphine medication for the treatment of moderate or severe opioid use disorder. The primary objective of this phase III study was to assess the long-term safety, tolerability, and efficacy of BUP-XR.MethodsThis open-label multicenter study in adults with moderate or severe opioid use disorder enrolled 257 participants from a previously conducted placebo-controlled, double-blind phase III study (rollover group) and 412 de novo participants not previously treated with BUP-XR. Participants received an initial injection of BUP-XR 300 mg and subsequent monthly 300 mg or 100 mg flexible doses. By study end, participants received up to 12 injections.ResultsOverall, 66.8% of participants reported more than 1 treatment-emergent adverse event (TEAE). Injection-site TEAEs (13.2% of participants) were mostly mild or moderate in severity. There were no clinically meaningful changes in safety assessments. An integrated analysis of the double-blind and open-label study participants showed that the incidence of TEAEs, including injection-site TEAEs, was lower in the second 6 months of treatment versus the first 6 months. After 12 months of treatment, 61.5% of the rollover participants and 75.8% of the de novo participants were abstinent. Retention rates after 12 months were 50.6% for the participants who initiated BUP-XR in the double-blind study and 50.5% for de novo participants.ConclusionsThis study demonstrates that the clinical benefits and acceptable safety profile of BUP-XR demonstrated in the 6-month double-blind study are sustained over a 12-month open-label study, with lower incidence of TEAEs in the second 6 months of treatment.
| S-EPMC7188268 | biostudies-literature
Project description:The authors present 12-month and lifetime prevalence, correlates, psychiatric comorbidity, and treatment of nonmedical prescription opioid use (NMPOU) and DSM-5 NMPOU disorder (NMPOUD).Data were derived from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) (N = 36,309).Prevalences of 12-month and lifetime NMPOU were 4.1% and 11.3%, exceeding rates in the 2001-2002 NESARC (1.8%, 4.7%). Twelve-month and lifetime rates of DSM-5 NMPOUD were 0.9% and 2.1%. NESARC-III DSM-IV NMPOUD rates (0.8%, 2.9%) were greater than those observed in the 2001-2002 NESARC (0.4% and 1.4%). Rates of NMPOU were greater among men, but no sex differential was observed for NMPOUD. Prevalences of NMPOU and NMPOUD were generally greater among 18- to 64-year-old individuals, whites, and Native Americans, and individuals with lower socioeconomic status. Associations were observed between 12-month and lifetime NMPOU and NMPOUD and other drug use disorders, posttraumatic stress disorder, and borderline, schizotypal, and antisocial personality disorders; persistent depression and major depressive disorder (for NMPOU); and bipolar I disorder (for NMPOUD). Only 5.5% and 17.7% of individuals with 12-month NMPOU and NMPOUD were ever treated.NMPOU and NMPOUD have considerably increased over the past decade, are associated with a broad array of risk factors and comorbidities, and largely go untreated in the United States. More information on the determinants, characteristics, and outcomes of NMPOU and NMPOUD is needed to support evidence-based interventions and prevention.
| S-EPMC5555044 | biostudies-other
Project description:ImportanceExpanding treatment for opioid addiction has been recognized as an essential component of a comprehensive national response to the opioid epidemic. The Drug Addiction Treatment Act and its amendments attempted to improve access to treatment by involving office-based physicians in the provision of buprenorphine treatment.ObjectivesTo estimate the association of availability of buprenorphine-waivered physicians with buprenorphine treatment use and, secondarily, with prescription opioid use among Medicaid enrollees.Design, setting, and participantsThis economic evaluation study used state-level panel data analysis to estimate the association between the number of buprenorphine-waivered physicians and the Medicaid-covered buprenorphine prescribing rate and opioid prescribing rate among Medicaid fee-for-service and managed care enrollees throughout the United States between January 1, 2011, and December 31, 2016.Main outcomes and measuresBuprenorphine prescribing rate and opioid prescribing rate, measured as the number of buprenorphine prescriptions and opioid prescriptions covered by Medicaid on a quarterly basis per 1000 enrollees.ResultsThe sample included 1059 quarterly observations. Two additional 100-patient-waivered physicians per 1 000 000 residents (approximately a 10% increase) were associated with an increase in the quarterly number of Medicaid-covered buprenorphine prescriptions of 0.46 (95% CI, 0.24-0.67) per 1000 enrollees and a reduction in the quarterly number of opioid prescriptions of 1.01 (95% CI, -1.87 to -0.15) per 1000 enrollees. Furthermore, 5 additional 30-patient-waivered physicians per 1 000 000 residents (approximately a 10% increase) were associated with an increase in the quarterly number of Medicaid-covered buprenorphine prescriptions of 0.37 (95% CI, 0.22-0.52) per 1000 enrollees and a reduction in the quarterly number of opioid prescriptions of 0.96 (95% CI, -1.85 to -0.07) per 1000 enrollees. A 10% increase in the number of buprenorphine-waivered physicians was associated with an approximately 10% increase in the Medicaid-covered buprenorphine prescribing rate and a 1.2% reduction in the opioid prescribing rate.Conclusions and relevanceExpanding capacity for buprenorphine treatment holds the potential to improve access to opioid addiction treatment, which may further reduce prescription opioid use and slow the ongoing opioid epidemic in the United States.
| S-EPMC6324514 | biostudies-literature
Project description:BackgroundBuprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine.MethodsWe examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS).ResultsAmong AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ 2(1) = 4.33, P = .04).ConclusionWe found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.
| S-EPMC7883889 | biostudies-literature
Project description:The impact of agonist dose and of physician, staff and patient engagement on treatment have not been evaluated together in an analysis of treatment for opioid use disorder. Our hypotheses were that greater agonist dose and therapeutic engagement would be associated with reduced illicit opiate use in a time-dependent manner. Publicly-available treatment data from six buprenorphine efficacy and safety trials from the Federally-supported Clinical Trials Network were used to derive treatment variables. Three novel predictors were constructed to capture the time weighted effects of buprenorphine dosage (mg buprenorphine per day), dosing protocol (whether physician could adjust dose), and clinic visits (whether patient attended clinic). We used time-in-trial as a predictor to account for the therapeutic benefits of treatment persistence. The outcome was illicit opiate use defined by self-report or urinalysis. Trial participants (N = 3022 patients with opioid dependence, mean age 36 years, 33% female, 14% Black, 16% Hispanic) were analyzed using a generalized linear mixed model. Treatment variables dose, Odds Ratio (OR) = 0.63 (95% Confidence Interval (95%CI) 0.59-0.67), dosing protocol, OR = 0.70 (95%CI 0.65-0.76), time-in-trial, OR = 0.75 (95%CI 0.71-0.80) and clinic visits, OR = 0.81 (95%CI 0.76-0.87) were significant (p-values < 0.001) protective factors. Treatment implications support higher doses of buprenorphine and greater engagement of patients with providers and clinic staff.
| S-EPMC8998781 | biostudies-literature
Project description:Background and aimsreSET-O, an FDA-authorized prescription digital therapeutic (PDT) delivering cognitive behavioral therapy and contingency management to patients with opioid u®se disorder (OUD), may help improve clinical outcomes. One-year differences in healthcare resource utilization (HCRU) and costs post-PDT initiation were evaluated.MethodsRetrospective analysis of healthcare claims data compared all-cause HCRU (across hospital facility encounters [sum of inpatient stays, treat-and-release emergency department [ED] visits, partial hospitalizations, and hospital outpatient department visits] and clinician services [procedure categories]) after PDT initiation (index) between reSET-O patients and controls. Overall and Medicaid-specific differences in HCRU, costs, and buprenorphine adherence were evaluated.FindingsCohorts included 901 reSET-O patients (median age 36 years, 62.4% female, 73.9% Medicaid) and 978 controls (median age 38 years, 51.1% female, 65.4% Medicaid). Compared to the control group, the reSET-O group experienced 12% fewer total unique hospital encounters (non-significant), driven by 28% fewer inpatient stays (IRR 0.72; 95% CI 0.55-0.96; P = 0.02), 56% fewer hospital readmissions [IRR 0.44; 95% CI 0.20-0.93; P = 0.033]), and 7% fewer ED visits (IRR 0.93; 95% CI 0.79-1.09; P = 0.386). Total clinician services increased by 1391 events versus controls. Differences were greater among the Medicaid patients. Adjustment for concomitant baseline substance use and mental health disorders resulted in similar HCRU incidence rate ratios. Changes in all-cause HCRU drove per-patient per-year cost differences of - $2791 versus controls (- $3832 versus Medicaid controls). Adjusted mean medication possession ratio was 0.848 (SE 0.0118) at 12 months for reSET-O patients, which was significantly higher than controls (0.761 [SE 0.0108]; P < 0.001).ConclusionsUse of reSET-O is associated with significant and durable real-world reductions in ED and inpatient (including readmissions) utilization, reduced net costs, and increased clinician services and buprenorphine adherence. Differences in costs versus controls were greatest among Medicaid patients. INFOGRAPHIC.
| S-EPMC9402736 | biostudies-literature
Project description:ImportanceAlthough substantial evidence supports buprenorphine for treatment of opioid use disorder (OUD) in controlled trials, prospective study of patient outcomes in clinical implementation of emergency department (ED) buprenorphine treatment is lacking.ObjectiveTo examine the association between buprenorphine treatment in the ED and follow-up engagement in OUD treatment 1 month later.Design, setting, and participantsThis multisite cohort study was conducted in 7 California EDs participating in a statewide implementation project to improve access to buprenorphine treatment. The study population included ED patients aged at least 18 years identified with OUD between April 1, 2021, and June 30, 2022. Data analysis was performed in October 2023.ExposureAll participants were offered buprenorphine treatment for OUD (either in ED administration, prescription, or both), the uptake of which was examined as the exposure of interest.Main outcomes and measuresThe primary outcome was engagement in OUD treatment 30 days after the ED visit, determined by patient report or clinical documentation. The association of ED buprenorphine treatment with subsequent OUD treatment engagement was estimated using hierarchical generalized linear models.ResultsThis analysis included 464 ED patients with OUD. Their median age was 36.0 (IQR, 29.0-38.7) years, and most were men (343 [73.9%]). With regard to race and ethnicity, 64 patients (13.8%) self-identified as non-Hispanic Black, 183 (39.4%) as Hispanic, and 185 as non-Hispanic White (39.9%). Most patients (396 [85.3%]) had Medicaid insurance, and more than half (262 [57.8%]) had unstable housing. Self-reported fentanyl use (242 [52.2%]) and a comorbid mental health condition (328 [71.5%]) were common. Interest in buprenorphine treatment was high: 398 patients (85.8%) received buprenorphine treatment; 269 (58.0%) were administered buprenorphine in the ED and 339 (73.1%) were prescribed buprenorphine. With regard to OUD treatment engagement at 30 days after the ED visit, 198 participants (49.7%) who received ED buprenorphine treatment remained engaged compared with 15 participants (22.7%) who did not receive ED buprenorphine treatment. An association of ED buprenorphine treatment with subsequent OUD treatment engagement at 30 days was observed (adjusted risk ratio, 1.97 [95% CI, 1.27-3.07]).Conclusions and relevanceThe findings of this cohort study suggest that among patients with OUD presenting to EDs implementing low-threshold access to medications for OUD, buprenorphine treatment was associated with a substantially higher likelihood of follow-up treatment engagement 1 month later. Future research should investigate techniques to optimize both the uptake and effectiveness of buprenorphine initiation in low-threshold settings such as the ED.
| S-EPMC10825722 | biostudies-literature
Project description:ImportanceAgonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone.ObjectiveTo evaluate postrelease outcomes after buprenorphine implementation.Design, setting, and participantsThis cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024.ExposureApril 2019 implementation of buprenorphine during incarceration.Main outcomes and measuresReceipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation.ResultsA total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected.Conclusions and relevanceIn this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.
| S-EPMC10949092 | biostudies-literature