(108) Associations Between Remission from Opioid Use Disorder and Treatment-Relevant Outcomes

Background & Introduction: Recovery from Opioid Use Disorder (OUD) is increasingly considered a multidimensional process that includes factors beyond opioid abstinence1. However, research on OUD treatment most often focuses on abstinence as the primary outcome2. As such, other factors that may contribute to recovery from OUD remain underexplored. For example, measuring changes in DSM-5 symptoms during care3 and considerations for using OUD remission4 (i.e., no DSM-5 symptoms except craving) as markers for treatment progress should be considered. Yet, evidence regarding the utility of these approaches in evaluating treatment success remains scant. Thus, we explored how variables beyond opioid abstinence, such as OUD remission and symptom improvement, are associated with different treatment-relevant outcomes. These findings will provide compelling evidence towards the utility of OUD remission as a recognized treatment outcome.

Methods: The Remission from OUD as a Treatment Endpoint (ROUTE; NCT05860959) Study followed individuals receiving long-acting buprenorphine (BUP-XR) for up to 24 months. Patients were enrolled within 3 months of starting BUP-XR. Here, we analyze the recently completed ROUTE Study that followed participants during their recovery journey. Our objective is to understand the associations between OUD remission and recovery outcomes, thereby providing the first analysis of predictive validity of remission as a treatment outcome5. Demographic and social health measures included age, sex, race, ethnicity, insurance, employment and housing. Treatment outcome measures include OUD remission (i.e., no DSM-5 symptoms except craving) and self reported opioid misuse. Outcome recovery measures include the Opioid Craving Numerical Scale (3 items, 0-30 score), the Subjective Opiate Withdrawal Scale (16 items, 0-64 score), the EuroQol 5-Dimension 5-level quality of life assessment (5 items, 5-25 score), the Pain, Enjoyment of Life, and General Activity scale (3 items, 0-10 score), and employment status (employed or not employed). The association between 3-month (early) OUD remission and outcomes was evaluated using linear and generalized linear models. Results are reported as estimates and odds ratios (OR) with 95% confidence intervals (CIs) and p-values. An alpha less than 0.05 was considered significant.

Results: Participants (n=427) were on average 39.8 years old, predominantly male (56.7%), White (81.7%), non-Hispanic/Latino (85.7%), and unemployed (60.0%). In this sample, 52% presented with no or mild DSM5 symptoms and 81.7% were not currently misusing opioids. Remission rates were at study entry, 6 months and 12 months 41.4%, 63%, and 83% respectively. Individuals entering the study in 3-month remission indicated lower craving (b=-5.48; 95% CI: -7.08, -3.88; p<.001), lower withdrawal (b=-4.79; 95% CI: -6.97, -2.61; p<.001), lower pain (b=-0.62; 95% CI: -1.21, -0.02; p=.041), better quality of life (b=-0.70; 95% CI: -1.36, -0.03; p=.041), and greater rates of employment (OR: 2.62; 95% CI: 1.68, 4.14; p<.001) than those not in remission. Importantly, of those in remission, 2.8% reported misusing opioids; of those not in remission, 28.8% reported misusing opioids.

Conclusion & Discussion: In this real world long-term observational study, we found that OUD remission was associated with multiple recovery dimensions, including quality of life, pain, opioid craving and withdrawal, and employment. Importantly, opioid misuse and OUD remission are not always consistent, and an individual could be abstaining from opioid misuse while not yet in 3-month OUD remission. Despite being viewed as going hand-in-hand with recovery, complete abstinence may be neither sufficient nor necessary. This study comes with limitations. Participants entered the study at different (1) stages of their recovery journey, (2) BUP-XR treatment duration (0-3 months), and (3) prior treatment episodes. Therefore sensitivity analyses will be conducted to better understand the impact of these factors to the remission outcome and associations identified at study entry. Future analyses will explore the longitudinal associations of remission with clinical and functional outcomes. Moreover, we will compare these associations among OUD medications (e.g., sublingual, BUP-XR) in the 3 months prior to study entry to understand if these observed associations are due to remission or medication modality. Taken together, recognizing remission from OUD as a treatment outcome aligns with the rest of medicine in that disease remission is viewed as a reduction and/or elimination of diagnostic symptoms.

References: 1. Craft WH, Shin H, Tegge AN, Keith DR, Athamneh LN, Stein JS, et al. Long‐term recovery from opioid use disorder: recovery subgroups, transition states and their association with substance use, treatment and quality of life. Addiction. 2023 Jan 10;118(5):890–900. Available from: https://dx.doi.org/10.1111/add.16115

2. Kiluk BD, Kleykamp BA, Comer SD, Griffiths RR, Huhn AS, Johnson MW, et al. Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder. JAMA Psychiatry. 2023 Jan 1;80(1):84. Available from: https://dx.doi.org/10.1001/jamapsychiatry.2022.4020

3. Marsden J, Tai B, Ali R, Hu L, Rush AJ, Volkow N. Measurement-based care using DSM-5 for opioid use disorder: can we make opioid medication treatment more effective? Addiction, Jan 4; 114(8), 1346-1353. Available from: https://doi.org/10.1111/add.14546

4. McLellan AT, Volkow ND. Goals for Opioid Use Disorder Medications – Protection, Remission, and Recovery. New England Journal of Medicine, Oct 2; 393(13). Available from: https://doi.org/10.1056/NEJMp2505377

5. Schmidt EM, Gupta S, Bowe T, et al. Predictive Validity of a Quality Measure for Intensive Substance Use Disorder Treatment. Substance Abuse: Official Publication of the Association for Medical Education and Research in Substance Abuse. 2017, 38 (3): 317–323. Available from: https://doi.org/10.1080/08897077.2016.1212779