Understanding the Association between Sublingual Buprenorphine and Oral Health Outcomes

摘要 阿片类药物使用障碍（OUD）的标准治疗包括使用药物（MOUD），主要是 舌下（SL）丁丙诺啡由于其可及性、有效性和耐受性。最近，食品和 美国药品监督管理局（FDA）发布了一项建议，表明SL丁丙诺啡的使用与口腔疾病有关。 虽然令人信服，但该建议是基于不良事件报告和病例报告，这些报告确实控制了重要的 混杂因素，如行为和生活方式因素，可能会增加OUD个体的风险。更何况， 这些报告是横断面的，提供了有限的进展率和新发 疾病此外，SL丁丙诺啡可能对口腔健康产生不利影响的机制仍然存在 不清楚本项目的长期目标是量化与SL丁丙诺啡相关的不良口腔事件， 促进实施干预措施和实践建议，以减轻口头负担， 服用SL丁丙诺啡的成人并发症。本提案的目的是了解是否以及如何 SL丁丙诺啡增加OUD成人口腔疾病的程度、发作和进展。我们的中央 假设SL丁丙诺啡引起口腔环境的改变（例如，唾液减少 流速/pH/缓冲能力以及微生物组和炎症宿主反应变化）， 和口腔疾病的进展。我们将测试这一假设有三个目标：1）表征基线程度 口腔并发症，并确定接受MOUD的成人的风险因素，2）测试SL丁丙诺啡是否是风险 服用MOUD的成人中口腔疾病发作和进展的因素，以及3）评估SL丁丙诺啡是否 改变唾液的数量，组成，微生物概况或炎症宿主反应在成人服用MOUD。 为了实现这些目标，我们提出了一个前瞻性，多地点，队列研究横跨肯塔基州和北 卡罗莱纳，利用研究人员和临床医生组成的多学科团队来克服所发现的局限性 并扩大我们对SL丁丙诺啡和口腔疾病之间联系的理解。我们将 招募了两个州的372名参与者，这些参与者受到阿片类药物流行的高度影响， 8个月随访期内的临床、影像学、生理和行为信息。本研究 创新，因为它是第一个：进行纵向随访，利用比较MOUD组，并分析 唾液特征，以阐明舌下丁丙诺啡诱导的疾病的机制，并将量化 细菌组成和炎症反应，并与临床发现相关。拟议研究 意义重大，因为它将产生有关口腔疾病相关风险的数据驱动结论 服用SL丁丙诺啡的成人中的程度、发作和进展。这些发现可用于开发 预防性干预措施，以减少口腔疾病的负担，改善这一人群的健康状况。

ABSTRACT The standard treatment for opioid use disorder (OUD) involves the use of medications (MOUD), primarily sublingual (SL) buprenorphine due to its accessibility, efficacy, and tolerability. However, recently the Food and Drug Administration (FDA) published an advisory suggesting SL buprenorphine use is linked to oral disease. While compelling, this advisory is based on adverse event reports and case reports that did control for important confounders such as behavioral and lifestyle factors that may increase the risk in individuals with OUD. More so, these reports were cross-sectional providing limited evidence of rate of progression and incidence of new disease. Additionally, the mechanism by which SL buprenorphine may adversely impact oral health remains unclear. The long-term goal of this project is to quantify adverse oral events associated with SL buprenorphine, facilitating implementation of interventions and practice recommendations to mitigate the burden of oral complications in adults taking SL buprenorphine. The objective of this proposal is to understand if and how SL buprenorphine increases the extent, onset, and progression of oral disease in adults with OUD. Our central hypothesis is that SL buprenorphine causes alterations in the oral environment (e.g., reduction in salivary flow/pH/buffer capacity and microbiome and inflammatory host response changes) that facilitate the incidence and progression of oral disease. We will test this hypothesis with three aims: 1) characterize baseline extent of oral complication and identify risk factors in adults receiving MOUD, 2) test whether SL buprenorphine is a risk factor for oral disease onset and progression in adults taking MOUD, and 3) assess whether SL buprenorphine changes saliva quantity, composition, microbial profile, or inflammatory host response in adults taking MOUD. To accomplish these aims, we propose a prospective, multisite, cohort study across Kentucky and North Carolina, leveraging a multidisciplinary team of researchers and clinicians to overcome the limitations identified in the literature and expand our understanding of the link between SL buprenorphine and oral disease. We will enroll 372 participants across two states that have been highly impacted by the opioid epidemic and evaluate clinical, radiographic, physiologic, and behavioral information over an 8-month follow-up period. This study is innovative as it is the first one to: conduct longitudinal follow-up, utilize a comparison MOUD group, and analyze salivary characteristics to clarify the mechanisms of sublingual buprenorphine-induced disease and will quantify the bacterial composition and inflammatory response and correlate to clinical findings. The proposed research is significant because it will generate data-driven conclusions about the risks associated with oral disease extent, onset, and progression in adults taking SL buprenorphine. These findings can be used to develop preventive interventions to reduce the burden of oral disease and improve health in this population.