Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial

• Published in: JAMA network open 2024-06, Vol.7 (6), p.e2417377
• Main Authors: Nunes, Edward V, Comer, Sandra D, Lofwall, Michelle R, Walsh, Sharon L, Peterson, Stefan, Tiberg, Fredrik, Hjelmstrom, Peter, Budilovsky-Kelley, Natalie R
• Format: Article
• Language: English
• Subjects: Administration, Sublingual; Adult; Analgesics, Opioid - administration & dosage; Buprenorphine - administration & dosage; Buprenorphine, Naloxone Drug Combination - administration & dosage; Buprenorphine, Naloxone Drug Combination - therapeutic use; Clinical trials; Delayed-Action Preparations; Double-Blind Method; Drug overdose; Drug withdrawal; Female; Fentanyl; Fentanyl - administration & dosage; Fentanyl - therapeutic use; Humans; Injections, Subcutaneous; Male; Middle Aged; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - therapeutic use; Narcotics; Online Only; Opiate Substitution Treatment - methods; Opioid-Related Disorders - drug therapy; Original Investigation; Substance Use and Addiction; Substance use disorder; Treatment Outcome; Urine
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2024.17377

Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited. To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use. Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023. Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone. Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales. Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving s