The Comparative Effectiveness and Safety of Pharmacotherapies for the Treatment of Opioid Use Disorder in Pregnancy

治疗妊娠期阿片类药物使用障碍的药物疗法的有效性和安全性比较

• 批准号: 10319626
• 负责人: Brian Thomas Bateman
• 金额: $ 68.81万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319626
• 关键词: Affinity; Agonist; Buprenorphine; Cesarean section; Child; Clinical; Congenital Abnormality; Data; Ensure; Epidemiologic Methods; Formulation; Frequencies; General Population; Goals; Guidelines; Injections; International; Low Birth Weight Infant; Measures; Medicaid; Medical Societies; Methadone; Methods; Mothers; Naloxone; Neonatal Abstinence Syndrome; Neurodevelopmental Disorder; Observational Study; Opioid Antagonist; Outcome; Patient Selection; Personal Satisfaction; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Postpartum Period; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prenatal care; Prevalence; Public Health; Randomized Controlled Trials; Recommendation; Relative Risks; Research; Residual state; Risk; Safety; Small for Gestational Age Infant; Stratification; Suboxone; United States National Institutes of Health; Withdrawal Symptom; Woman; adverse outcome; adverse pregnancy outcome; base; beneficiary; buprenorphine treatment; cohort; comparative; comparative effectiveness; comparative safety; congenital anomaly; design; effectiveness outcome; fetal; high dimensionality; high risk; high risk population; illicit opioid; improved; interest; maternal risk; mu opioid receptors; neonatal outcome; neonate; neurodevelopment; opioid agonist therapy; opioid treatment program; opioid use; opioid use disorder; opioid withdrawal; prevent; retention rate; safety outcomes; severe maternal morbidity; social; substance use; treatment comparison

ABSTRACT The frequency of opioid use disorders (OUD) during pregnancy has increased substantially during the past two decades, reflecting the risk observed in the general population. The current recommendation from guideline groups is that pregnant women with OUD be treated with opioid agonist therapy (OAT). OAT has been shown to improve pregnancy outcomes in women with OUD because it prevents opioid withdrawal symptoms that can be disruptive to fetal well-being and to reduce illicit opioid and other substance use. Methadone has historically been the mainstay of OUD treatment during pregnancy. However, in recent years, buprenorphine use has increased and is now used in approximately equal measure with methadone. Methadone and buprenorphine have different pharmacologic effects. The way in which these treatments are administered is also different. Methadone is dispensed under observation via a federally- regulated opioid treatment program. In contrast, buprenorphine is generally dispensed by prescription in a routine office-based setting. Buprenorphine also comes in two formulations, as a monoproduct and in combination with naloxone, an opioid antagonist, which is intended to deter misuse via injection. Comparative safety and effectiveness data for pharmacologic approaches to the treatment of OUD in pregnancy are very limited. The MOTHER trial demonstrated that buprenorphine is associated with less severe neonatal abstinence syndrome compared to methadone. Data regarding the comparative safety of buprenorphine and methadone with respect to other adverse pregnancy outcomes and the impact on long-term neurodevelopment are few and subject to a number of potential biases and limitations. The comparative effectiveness of buprenorphine and methadone with respect to retention in treatment and impact on adequacy of prenatal care has also not been fully defined. For those prescribed buprenorphine in pregnancy, the use of the monoproduct is generally recommended, despite the higher risk for misuse, because there are few data regarding the safety of the combination product which includes naloxone. The overall goal of this study is to utilize state of the art design and analytic epidemiological methods applied to a large cohort of women defined using nationwide Medicaid data to generate the best possible evidence regarding the comparative safety and effectiveness of medications used to treat OUD in pregnancy. Specific methods that we intend to employ include propensity score fine stratification, high-dimensional propensity score adjustment, alternative referents (discontinuer comparisons), and bias analyses to account for potential misclassification of exposure and outcome and residual confounding. The results of the studies are expected to have an important and direct clinical impact guiding clinicians’ and patients’ selection of the best treatment for OUD in order to ensure a good outcome for mothers and their children.

抽象的 怀孕期间阿片类药物使用障碍 (OUD) 的频率在怀孕期间大幅增加 过去二十年，反映了一般人群中观察到的风险。 指南小组建议患有 OUD 的孕妇接受阿片类药物激动剂治疗 (OAT)。 已被证明可以改善患有 OUD 的女性的妊娠结局，因为它可以防止阿片类药物戒断 可能会破坏胎儿健康并减少非法阿片类药物和其他物质使用的症状。 美沙酮历来是妊娠期间 OUD 治疗的主要支柱。 丁丙诺啡的使用有所增加，目前的使用量与美沙酮大致相同。 美沙酮和丁丙诺啡具有不同的药理作用。 治疗的实施方式也不同。美沙酮是在联邦观察下进行分配的。 相比之下，丁丙诺啡通常通过处方进行分配。 常规办公室环境中的丁丙诺啡也有两种配方，一种是单一产品，另一种是在办公室中使用。 与阿片类拮抗剂纳洛酮联合使用，旨在防止通过注射滥用。 治疗妊娠期 OUD 的药物方法的安全性和有效性数据非常丰富 MOTHER 试验表明，丁丙诺啡与新生儿病情较轻有关。 与美沙酮相比的戒断综合症数据。 美沙酮与其他不良妊娠结局以及对长期神经发育的影响 的数量很少，并且受到许多潜在的偏见和限制。 丁丙诺啡和美沙酮对保留治疗及其对产前护理充分性的影响 对于那些在怀孕期间服用丁丙诺啡的人，单一产品的使用也尚未完全确定。 尽管误用风险较高，但通常建议使用，因为有关安全性的数据很少 包括纳洛酮的组合产品。 本研究的总体目标是利用最先进的设计和流行病学分析方法 适用于使用全国医疗补助数据定义的一大群女性，以产生尽可能最佳的结果 有关用于治疗妊娠期 OUD 的药物的相对安全性和有效性的证据。 我们打算采用的具体方法包括倾向评分精细分层、高维 倾向评分调整、替代参照物（中止者比较）和偏差分析以解释 暴露和结果的潜在错误分类以及残余混杂研究的结果是。 预计会对指导和患者选择最佳药物产生重要而直接的临床影响 OUD 治疗，以确保母亲及其孩子获得良好的结果。