Increasing Mortality of Inflammatory Bowel Disease in Women: A Population-Based Time-Trend Analysis Using the Global Burden of Diseases Database, 1990-2019

Introduction: Patients with Inflammatory Bowel Disease (IBD) are at increased risk of death compared to the general population. However, limited data exist regarding changes in mortality rates with the introduction of biological medications in the US. The aim of this study was to conduct a time-trend analysis of age and gender-specific IBD mortality rates in the US using the Global Burden Diseases (GBD) 2019 database. Methods: Data was obtained from the GBD 2019 database, an international database covering most IBD diagnosed cases in the US. IBD incidence rates, age-adjusted to the standard US population, were calculated using SEER*Stat software (v.8.4.0.1, National Cancer Institute “NCI”) and were stratified by gender, as reported in the database. Time-trends were estimated as annual percentage change (APC) and average APC (AAPC) using Joinpoint Regression Software (v.4.9.0.1, NCI) utilizing Monte Carlo permutation analysis to generate the simplest trend. Pairwise comparison was conducted between gender-specific trends using the tests of parallelism and coincidence. Age-specific trends were also assessed in 2 age sub-groups: younger adults aged 15-49 years and older adults aged 50-74 years. A 2-sided P-value cut-off of 0.05 was utilized for statistical significance. Results: In the GBD dataset, 121,138 deaths were attributed to IBD in the US between 1990-2019. Overall, IBD mortality rates have been increasing at similar rates in both older and younger adults (AAPC=1.4 vs. 1.5; AAPC difference=0.1, P= 0.41). However, mortality rates have been significantly increasing at a higher rate in women (75,776 deaths) than men (45,362 deaths) (AAPC= 1.7 vs. 1.3; AAPC difference=0.4, P< 0.001), suggesting that the increase in IBD mortality rates arises from women. Gender-specific trends were not identical (P< 0.001) nor parallel (P< 0.001), suggesting that IBD incidence rates are different and increasing at a greater rate in women compared to men (Figure 1, Table 1). Conclusion: Our results suggest that IBD mortality rates have been increasing in the US over the last 3 decades, and this increase appears to be predominantly driven by increasing deaths in women rather than men. Future studies are warranted to investigate and address risk factors associated with the increased mortality rates in women.Figure 1.: Trend Analysis of IBD Age-Standardized Mortality Rate with (A) Age and (B) Gender Variations Between 1990-2019. Table 1. - Trend analysis of Inflammatory Bowel Disease Age-Standardized Mortality Rate With Gender and Age Variations from 1990 to 2019 Mortality Trendsa Gender/age-specific AAPC difference (95% CI) Pairwise comparison P-values Time period APC (95% CI) AAPC (95% CI) Gender/age-specific AAPC difference Coincidenceb Parallelismc Gender Male 1990-1998 1.4 (1.3 to 1.6) 1.3 (1.2 to 1.4) 0.4 (0.1-0.6) < 0.001 < 0.001 < 0.001 1998-2002 3.5 (2.8 to 4.1) 2002-2008 1.9 (1.6 to 2.2) 2008-2019 0.1 (0.0 to 0.2) Female 1990-1997 1.7 (1.3 to 2.0) 1.7 (1.4 to 1.9) 1997-2001 5.3 (4.1 to 6.6) 2001-2006 2.8 (2.0 to 3.5) 2006-2011 1.2 (0.4 to 2.0) 2011-2019 −0.5 (−0.8 to −0.2) Age 50-74 years 1990-1998 1.0 (0.9 to 1.2) 1.5 (1.3 to 1.6) −0.1 (−0.3-0.1) 0.414 < 0.001 < 0.001 1998-2001 3.4 (1.8 to 4.9) 2001-2019 1.3 (1.3 to 1.4) 15-49 years 1990-1998 2.1 (1.9 to 2.2) 1.4 (1.2 to 1.5) 1998-2002 4.6 (3.8 to 5.4) 2002-2007 1.4 (0.9 to 1.8) 2007-2017 0.3 (0.2 to 0.5) 2017-2019 −2.7 (−4.2 to −1.2) a Time-trends were computed using Joinpoint Regression Program (v4.9.0.1, NCI) with 5 maximum joinpoints allowed (6-line segments). b Tests whether gender and age-specific trends were identical. A significant P-value indicates that the trends were not identical (i.e., they had different incidence rates and coincidence was rejected). c Tests whether gender and age-specific trends were parallel. A significant P-value indicates that the trends were not parallel (i.e., parallelism was rejected).