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.