Division on Substance Use Disorders, New York State Psychiatric Institute, New York.
Columbia University Irving Medical Center Department of Psychiatry, New York, New York.
JAMA Netw Open. 2024 Jun 3;7(6):e2417377. 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.
DESIGN, SETTING, AND PARTICIPANTS: 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 sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.
In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.
ClinicalTrials.gov Identifier: NCT02651584.
重要性：芬太尼加剧了阿片类药物使用障碍（OUD）和阿片类药物过量流行。关于在使用芬太尼的患者中使用丁丙诺啡的药物治疗 OUD 的有效性的数据有限。
目的：评估舌下或缓释注射剂型丁丙诺啡治疗有或无芬太尼使用的 OUD 患者的疗效。
设计、地点和参与者：这是一项在美国 35 个门诊地点进行的 24 周、随机、双盲临床试验的事后分析，于 2015 年 12 月至 2016 年 11 月进行，使用舌下丁丙诺啡-纳洛酮与缓释皮下注射丁丙诺啡（CAM2038）治疗 OUD 患者，根据基线时尿液中是否存在芬太尼或去甲芬太尼将患者分为亚组。在 12 周时进行每周和每月的皮下丁丙诺啡与每日舌下丁丙诺啡-纳洛酮治疗，然后在第 13 至 24 周之间进行 6 次随访。从 2022 年 3 月到 2023 年 8 月，对数据进行了意向治疗分析。
干预措施：每周和每月皮下丁丙诺啡与每日舌下丁丙诺啡-纳洛酮。
主要结局和测量：治疗保留率、尿液中任何阿片类药物检测阴性的百分比（缺失值被假定为阳性）、尿液中芬太尼或去甲芬太尼检测阴性的百分比（缺失值未被假定）、阿片类药物戒断量表和视觉模拟渴望量表的评分。
结果：在 428 名参与者中，有 123 名（皮下丁丙诺啡组，n=64；舌下丁丙诺啡-纳洛酮组，n=59；平均[SD]年龄，39.1[10.8]岁；75 名男性[61.0%]）有基线芬太尼使用证据，305 名（皮下丁丙诺啡组，n=149；丁丙诺啡-纳洛酮组，n=156；平均[SD]年龄，38.1[11.1]岁；188 名男性[61.6%]）无基线芬太尼使用证据。芬太尼阳性亚组（60.2%[74 名患者]）和芬太尼阴性亚组（56.7%[173 名患者]）的研究完成率相似。在芬太尼阳性亚组中，接受皮下丁丙诺啡治疗的患者中尿液中任何阿片类药物检测阴性的平均百分比为 28.5%，接受丁丙诺啡-纳洛酮治疗的患者为 18.8%（差异，9.6%；95%CI，-3.0%至 22.3%）；在芬太尼阴性亚组中，接受皮下丁丙诺啡治疗的患者中尿液中任何阿片类药物检测阴性的平均百分比为 36.7%，接受丁丙诺啡-纳洛酮治疗的患者为 30.6%（差异，6.1%；95%CI，-1.9%至 14.1%），主要与基线芬太尼状态和治疗组相关。在芬太尼阳性亚组中，接受皮下丁丙诺啡治疗的患者在研究期间尿液中芬太尼检测阴性的平均百分比为 74.6%，接受舌下丁丙诺啡-纳洛酮治疗的患者为 61.9%（差异，12.7%；95%CI，9.6%至 15.9%）。在所有组中，阿片类药物戒断和渴望评分在治疗开始后迅速下降。
结论和相关性：在这项关于舌下与缓释注射丁丙诺啡治疗 OUD 的随机临床试验的事后分析中，丁丙诺啡似乎对有基线芬太尼使用的患者有效。与芬太尼阴性亚组相比，有芬太尼使用的患者在试验期间的阿片类药物阴性尿液样本较少。这些发现表明，皮下丁丙诺啡制剂可能更有效地减少芬太尼的使用。
试验注册：ClinicalTrials.gov 标识符：NCT02651584。
