Clinical Impact and Epidemiology of Nonsteroidal Anti-inflammatory Drug Allergies

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for first-line treatment of many conditions ranging from pain to heart disease, but therapeutic use of the entire medication class can be precluded by reported allergy. While NSAIDs represent the second most commonly reported class of drug allergies, it is estimated that <20% of reported NSAID-induced reactions are consistent with allergic hypersensitivity (eg, urticaria, angioedema, anaphylaxis), with the rest representing non-allergic side effects or intolerances (eg, gastrointestinal upset, bleeding, nephrotoxicity). Allergy over-reporting and lack of reaction clarification can lead to unnecessary drug avoidance, and increased use of second line, more costly, and less effective alternative medications, with resultant downstream adverse effects on patient outcomes. The primary objective of this proposal is to determine the impact of reported NSAID allergies on prescribing patterns and clinical outcomes in distinct populations and to define predictors for true NSAID-induced allergic hypersensitivity. The proposed study has three Aims: (1) to assess the impact of reported NSAID allergy on postoperative opioid prescribing and sustained opioid use in a large electronic health record-derived cohort of patients undergoing common surgical procedures; (2) to evaluate differences in aspirin administration and adverse cardiovascular outcomes in patients with acute coronary syndromes with and without reported NSAID allergy; (3) to use a well-defined cohort of subjects who have undergone allergist-observed NSAID drug challenge to determine patient- and drug-specific risk factors for NSAID-induced hypersensitivity. Dr. Li’s research plan will be supported by coursework and training in clinical and epidemiological study design, advanced biostatistical methods for research with large datasets, informatics, patient recruitment, and drug-challenge protocols, and the exceptional scientific environment at the Brigham and Women’s Hospital. She will receive mentorship from Dr. Tanya Laidlaw, an allergy specialist and expert in aspirin- and NSAID-induced hypersensitivity, and Dr. Karen Costenbader, a rheumatologist with extensive experience in investigating risk factors for disease and long-term outcomes in affected patients using large national cohorts and datasets. Dr. Li will obtain additional scientific input and career guidance from a team of three scientific advisors, including Drs. Joshua Boyce, Elena Losina, and Kimberly Blumenthal, who have committed their time, resources and expertise to facilitate her professional development and research goals. This K23 proposal is well-aligned with NIH initiatives to reduce unnecessary opioid prescribing and NIAID support of drug allergy research, and will position the candidate to submit an R01 application during the award period and to establish herself as an independent patient-oriented investigator with a focus on improving the care and health of patients with drug allergies.