Treating pain in autoimmune disease: concurrent use of opioids and biologic medication

提案摘要 许多患有自身免疫性疾病的老年人接受生物抗炎疗法（生物制剂）治疗， 控制他们的症状和减缓疾病的发展。虽然使用阿片类药物治疗慢性和神经性 疼痛仍然存在争议，尽管如此，他们可能是常见的处方老年人与自身免疫性 疾病和生物制剂阿片类药物也最常被开给老年人，他们经历了 由于年龄相关变化导致炎症、疼痛和自身免疫性疾病的异常高患病率 比如免疫衰老阿片类药物对免疫系统的影响仍然知之甚少， 与生物制剂一起诱导免疫抑制，导致不良事件风险增加，例如严重 感染，通过药效学药物相互作用。尽管慢性炎症和 自身免疫性疾病的疼痛，同时使用阿片类药物和生物制剂的安全性结果尚未得到证实。 评估。因此，处方医生没有足够的关于同时使用阿片类药物安全性的信息， 生物制剂，并继续这种做法，可能对他们的病人的损害。本次评估大样本 2007年至2019年期间，超过300万患有自身免疫性疾病的老年人参加了医疗保险， 关于阿片类药物和生物制剂同时使用的新的安全性见解，改善个体的治疗结局 自身免疫性疾病这项建议的长远目标是维持长者的健康和福祉， 成人自身免疫性疾病通过优化治疗策略。为了实现这一目标，我们将 确定阿片类药物使用、生物制剂使用以及阿片类药物和生物制剂同时使用的模式和预测因素。 一系列老年人自身免疫性疾病（AIM 1），评估阿片类药物使用对依从性的影响， 在患有自身免疫性疾病的老年人中使用生物制剂（AIM 2），并检查阿片类药物对安全性的影响 老年自身免疫性疾病患者使用生物疗法的结果（AIM 3）。这些拟议 研究将由主要研究者在合作者的支持和指导下完成， 在先进的药物流行病学方法以及阿片类药物和生物制剂研究方面的专业知识。校长 研究人员是由一个合作和跨学科的研究环境，包括世界的支持 布朗大学著名的老年学和卫生保健研究中心和流行病学系 大学公共卫生学院。本申请中详细介绍的培训活动侧重于促进 定量计算技能和发展药物流行病学的深刻背景知识，将 为首席研究员作为独立流行病学家的职业生涯做好准备。

PROPOSAL SUMMARY Many older adults with autoimmune disease are treated with biologic anti-inflammatory therapies (biologics) to control their symptoms and slow disease progression. Although using opioids to treat chronic and neuropathic pain remains controversial, they may nonetheless be commonly prescribed to older adults with autoimmune diseases alongside biologics. Opioids are also most often prescribed to older adults, who experience an inordinately high prevalence of inflammation, pain, and autoimmune conditions due to aging-associated changes like immunosenescence. The effects of opioids on the immune system remain poorly understood and they may induce immunosuppression alongside biologics, leading to increased risk of adverse events, such as severe infection, through pharmacodynamic drug-drug interaction. Despite the coincidence of chronic inflammation and pain in autoimmune disease, the safety outcomes from concurrent opioid and biologic use have not been assessed. Therefore, prescribers do not have enough information on the safety of concurrent use of opioids and biologics, and continue this practice, possibly to their patients’ detriment. This assessment of large sample of over 3 million older adults enrolled in Medicare between 2007 and 2019 with autoimmune disease will produce novel safety insights on the concurrent use of opioids and biologics, improving treatment outcomes for individuals with autoimmune diseases. The long term goal of this proposal is to maintain the health and well-being of older adults with autoimmune diseases through the optimization of treatment strategies. In service of this goal, we will Determine the patterns and predictors of opioid use, biologic use, and concurrent opioid and biologic use across an array of autoimmune diseases among older adults (AIM 1), assess the effects of opioid use on adherence to biologics among older adults with autoimmune diseases (AIM 2), and examine the effects of opioids on safety outcomes among older adults with autoimmune diseases using biologic therapies (AIM 3). These proposed studies will be completed by the principal investigator with support and mentorship from collaborators with deep expertise in advanced pharmacoepidemiology methods and opioid and biologics research. The principal investigator is supported by a collaborative and interdisciplinary research environment that includes the world renowned Center for Gerontology and Health Care Research and Department of Epidemiology at the Brown University School of Public Health. The training activities detailed in this application, focused on advancing quantitative computational skills and developing a deep contextual knowledge of pharmacoepidemiology, will prepare the principal investigator for a career as an independent epidemiologist.