Understanding Glucocorticoid Toxicity: The Impact of Glucocorticoid Regimens on Toxicities, Clinical Outcomes, and Quality-of-Life in Vasculitis

Massachusetts General Hospital, Boston MA

Investigators

Abstract

Candidate: Naomi J. Patel (previously Serling-Boyd) is an Instructor in Medicine at Harvard Medical School (HMS) and a rheumatologist at Massachusetts General Hospital (MGH). After receiving her undergraduate degree in Biochemistry (summa cum laude) and MD at the University of California, Los Angeles, she completed her internal medicine residency and chief residency at Stanford prior to rheumatology fellowship at MGH. During her fellowship, she began patient-oriented research focused on vasculitis; this and other work has resulted in 18 peer-reviewed first author publications in top-tier rheumatology journals (e.g., Ann Rheum Dis, Lancet Rheum). Her goal is to become an independent clinical investigator and leader in patient-oriented research in vasculitis, glucocorticoid (GC) toxicity, clinical epidemiology, and simulation modeling. Mentorship, Training Activities, and Environment: Dr. Patel will conduct the proposed study at MGH under an outstanding mentorship team. Hyon Choi, MD, DrPH (Primary Mentor) is a Professor of Medicine at HMS, world-renowned MGH investigator in gout and other rheumatic diseases, and a highly regarded epidemiologist with continuous NIH funding and numerous prior K mentee awardees. Zachary Wallace, MD, MSc (Co-Mentor) is a rheumatologist and clinical epidemiologist at MGH where he Co-Directs the Rheumatology and Allergy Clinical Epidemiology Research Center as well as the Rheumatology Vasculitis Program. He developed the ANCA-associated vasculitis (AAV) simulation model (AAV-Sim) that will be expanded in this proposal. Emily Hyle, MD, MSc (Co-Mentor) is an MGH infectious disease physician with expertise in decision science, simulation modeling, and cost-effectiveness. Dr. Patel will also benefit from key collaborators with expertise in GC toxicity, vasculitis, health state utilities, simulation modeling, & advanced epidemiologic methods (e.g., causal inference). Dr. Patel will pursue coursework in advanced epidemiologic methods & cost-effectiveness. Research: Despite the advent of various biologic and other steroid-sparing medications, GCs (e.g., prednisone) remain the cornerstone of care for many rheumatic diseases despite their numerous toxicities. The central goal of this project is to assess the impact of different GC regimens on GC toxicity in order to ultimately reduce toxicity. To achieve this, Dr. Patel will use well-phenotyped data sources and advanced methods to evaluate the effect of time to GC discontinuation on toxicity (Aim 1). She will use quality-of-life data to derive patient-centered health state utilities associated with metabolic GC toxicities (Aim 2). Last, she will expand an existing simulation model (AAV-Sim) by incorporating metabolic and other GC toxicities using a novel instrument (the Glucocorticoid Toxicity Index-Metabolic Domains) and project the cost-effectiveness of different GC treatment regimens in AAV (Aim 3). The completion of this proposal and the associated training will provide Dr. Patel with the experience needed to become an independent clinical investigator with expertise in vasculitis, assessment and modeling of GC toxicity, and cost-effectiveness analysis.