BACKGROUND: Agonist therapy reduces cravings and relapse risk during recovery from opioid dependence. Fewer relapses equate to reduced societal consequences such as illicit drug use, disease transmission, criminal activity, mortality, and harm to community members. Sublingual buprenorphine+naloxone (SL-BPN), the standard-of-care in outpatient opioid dependence treatment, lacks intrinsic safeguards from diversion and non-adherence. Investigational subdermally implanted buprenorphine (BI, Probuphine) was more effective than SL-BPN in Phase-3 clinical trials, including a large double-blind, double-dummy trial in stable opioid-dependent patients. The extent that these clinical benefits translate into meaningful societal benefits has not been previously quantified. This model assessed the benefits of SD-BP from a societal perspective.
METHODS: Using Phase 3 clinical trial data of BI versus SL-BPN, a Markov model simulated monthly progression of nationally-representative cohorts through five health-states for six months: on agonist therapy (1) with and (2) without illicit drug use, discontinued therapy (3) with and (4) without illicit drug use, and (5) death. Each cycle applied health-state- and time-dependent risks of: opioid diversion and misuse, illicit drug use, accidental pediatric exposure, detox program entry, and death (suicide / drug-related non-suicide). Cohorts were derived from state-specific, patient-level agonist treatment utilization data. Model robustness was assessed by univariate and probabilistic sensitivity analyses.
RESULTS: BI was associated with an overall 45% reduction in treatment failure (i.e., 40,845 fewer patients relapsing) over 6 months of treatment. Modeled reductions in societal-level consequences were: opioid diversion and misuse (-92%), illicit drug use (-45%), accidental pediatric exposure (-98%), detox program entry (-80%), and drug-related death/suicide (-24%). A State-wise comparison demonstrated the greatest benefits for Pennsylvania and the fewest benefits for Idaho.
CONCLUSIONS: The incremental benefits of investigational BI versus SL-BPN include improved morbidity and mortality and improved societal-level outcomes - including reduced pediatric exposures - when outcomes were modeled over six months. Benefits were largely driven by the relative difficulty of diverting an implantable formulation. Patient-level benefits including improved morbidity and mortality may be driven by the increased adherence and pharmacokinetic profile of the implants. While these results need to be confirmed either in subsequent prospective clinical trials and/or large, real-world datasets, it can be conservatively concluded that BI treatment used for stable opioid dependent patients will likely have a positive societal benefit beyond the current standard of care.