Comparative effectiveness research in Hispanic patients with inflammatory bowel diseases

PROJECT SUMMARY/ABSTRACT Despite rising incidence and prevalence of inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, in Hispanic population in the United States, there is limited understanding of the natural history and treatment outcomes for this vulnerable population, who are vastly underrepresented in clinical trials. The principal investigator’s (PI) long-term goal is to inform evidence-based management of IBD in Hispanic population, using large-scale epidemiologic studies and novel comparative effectiveness research using real world data. The overall objectives of this proposal are to understand patterns and drivers of disease and treatment outcomes in Hispanic patients with IBD, specifically focusing on social and structural determinants (SDoH) and biological determinants of health. The central hypothesis is that Hispanic patients experience a complicated IBD course with high disease burden and inferior treatment outcomes, driven primarily by adverse SDoH, rather than biological differences in treatment effectiveness. The rationale for this proposal is that a comprehensive epidemiological assessment of the natural history, social and biological predictors of outcomes and real-world comparative effectiveness and safety of targeted immunomodulator (TIM) therapies in Hispanic patients with IBD will directly and decisively inform management of IBD in a timely manner in this population just as the disease is at an inflection point in the US. The central hypothesis will be tested by pursuing three specific aims: (1) characterize natural history and treatment outcomes, and compare the effectiveness and safety of TIMs, in Hispanic patients with IBD using large-scale epidemiologic studies and novel target trial emulation methodology; (2) understand impact of area-level SDoH and patient-level social risk factors on adverse disease and treatment outcomes in Hispanic patients; and (3) understand the impact of specific genetic (HLA-DQA1*05 variants) and tissue transcriptomic (oncostatin M) factors on treatment outcomes with TIMs in Hispanic patients with IBD. The context for this proposal is a contemporary, electronic health record-based registry of patients with IBD seen at 7 large health systems in California with ~14,000 Hispanic patients that the investigator team have developed, a large commercial insurance claims database (OptumLabs Data Warehouse, ~18,000 Hispanic patients with IBD), and robust infrastructure of an established Cedars Genetics Research Center and biorepositories at UCSD. These large cohorts allow for efficient and cost-effective large-scale analysis in this health disparity population. The research proposed in this application is innovative, utilizing tools of applied clinical informatics, innovative causal inference methodology and combined evaluation of biological and non-biological determinants of health, to conduct the largest study on Hispanic patients with IBD in the United States. The proposed research is significant because it is expected to fill a key evidence gap in understanding the natural history and treatment outcomes in Hispanic patients with IBD, providing timely information on evidence-based management.