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.
