Discussion
OI, OUD
SECONDARY
Overall, no significant difference in the percentage of opioid abstinence was observed between the 100-mg and 300-mg maintenance doses in non-injecting opioid participants, suggesting that the two dosing regimens performed equally well in this population. Conversely, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements compared with the 100-mg maintenance dose, in terms of both opioid abstinence and treatment retention. Furthermore, the safety profiles of 300-mg and 100-mg maintenance doses were comparable in both populations.The differences in injecting participants’ mean percentage of abstinence between the 2 maintenance dose groups (Table The results of secondary analyses align with our previous exposure–response modeling work conducted on opioid abstinence using the same Phase 3 data [Findings also align with earlier literature demonstrating that higher doses of buprenorphine are needed to block the subjective effects of higher doses of a full agonist such as hydromorphone [From a safety perspective, both maintenance doses of BUP-XR were well tolerated, as previously reported [One plausible explanation for the present findings is that, on average, OI are more opioid-tolerant than non-injecting participants, possibly due to changes in Overall, the current findings have implications for harm reduction approaches in the treatment of OUD across 3 key domains: public health, clinical practice, and patient-centeredness [A potential limitation of this study is that we did not compare BUP-XR 300 mg versus 100 mg during the maintenance dose period in the randomized intent-to-treat population. As a result, the treatment comparison might be subject to the bias introduced by participants’ discontinuation prior to receiving the maintenance dose. We attempted to limit such bias by performing the efficacy comparison via risk adjustment including both baseline and post-randomization variables. Despite these efforts, unmeasured confounders may have influenced the accuracy of efficacy comparison results. To overcome this limitation and confirm the benefit of BUP-XR 300-mg maintenance dose observed in the OI, a clinical study is currently ongoing to compare the efficacy, safety, and tolerability of the 100-mg versus 300-mg BUP-XR maintenance doses in participants with high opioid tolerance, including those who inject opioids and/or use high doses of opioids. In this study, treatment-seeking, high-risk opioid participants are randomized immediately prior to the first maintenance dose and receive twice-longer maintenance treatment than in the Phase 3 study used in the present analysis (8 vs. 4 maintenance doses).