Abstract
Background
Inflammatory bowel disease (IBD) progresses through distinct epidemiologic stages: Stage 1 (Emergence), low incidence/prevalence; stage 2 (Acceleration in Incidence), rapid increasing incidence; stage 3 (Compounding Prevalence), stabilizing incidence and increasing prevalence. As IBD emerges in a population, ulcerative colitis (UC) incidence typically exceeds Crohn’s disease (CD) incidence, but over time the UC:CD incidence ratio approximates 1.
Aims
To examine changes in UC:CD incidence ratios across epidemiologic stages.
Methods
Stage classifications were previously determined by machine-learning classifier applied to data from 522 population-based studies of 82 countries (1920–2024). Population-weighted mean incidence (excluding zeros) was used to calculate annual, country-specific UC:CD ratios. Ratios were analyzed using a generalized additive model for location, scale, and shape (GAMLSS), accounting for overdispersion and skewness, with pairwise Wilcoxon rank sum tests and Bonferroni correction for between-stage comparisons. Average annual percent changes (AAPC) with 95% confidence intervals (CI) were calculated for each country within each stage. AAPCs were pooled by meta-analysis within stages. Outliers were defined using the Tukey method and are presented separately.
Results
The GAMLSS model, adjusted for country, showed significant effects of epidemiologic stage on UC:CD incidence ratios (p<0.001), highlighting a progressive shift toward a 1:1 ratio (Figure 1). Significant differences were found between stages: Stage 1: Median: 3.62 (IQR: 3.9 [1.66–5.56]); Stage 2: Median: 1.8 (IQR: 2 [1.12–3.12]); Stage 3: Median: 1.56 (IQR: 1 [1.08–2.08]); all comparisons: p<0.001. Meta-analyses supported these results, decreasing in stages 1 and 2 before stabilizing in stage 3: Stage 1 (13 countries, 1954–2022) AAPC: −4.77 (95%CI: −8.59, −0.95); stage 2 (42 countries, 1952–2022) AAPC: −2.55 (95%CI: −4.04, −1.06); stage 3 (24 countries, 1970–2023) AAPC: −0.12 (95%CI: −0.66, 0.42). Outliers (n=81; 7.8%) were primarily observed in Asia and northern latitudes (Table 1) (eg, China, Faroe Islands).
Conclusions
The UC:CD incidence ratio significantly decreases during stage 1 and 2, then stabilizes in stage 3. Recognising stage-specific changes in the UC and CD incidence may clarify the epidemiologic evolution of IBD and guide research into environmental and diagnostic determinants.
A271 Table 1: UC:CD Incidence Ratio Outliers
|
|
Min | Q1 | Median | Q3 | Max | |
|---|---|---|---|---|---|---|
| Stage 1 (n = 17; 10.3%) | UC Incidence per 100,000 | 0.025 | 0.105 | 0.32 | 0.403 | 5.0 |
| CD Incidence per 100,000 | 0.002 | 0.005 | 0.014 | 0.025 | 0.208 | |
| UC:CD Ratio | 12.2 | 14.8 | 20.3 | 23.8 | 83.0 | |
| Stage 2 (n = 49; 10.96%) | UC Incidence per 100,000 | 0.747 | 3.68 | 5.35 | 7.64 | 21.9 |
| CD Incidence per 100,000 | 0.104 | 0.4 | 0.6 | 0.8 | 2.28 | |
| UC:CD Ratio | 6.22 | 7.62 | 8.66 | 11.4 | 18.3 | |
| Stage 3 (n = 15; 3.53%) | UC Incidence per 100,000 | 10.8 | 14.2 | 22.9 | 43.9 | 73.7 |
| CD Incidence per 100,000 | 2.7 | 3.51 | 4.7 | 7.25 | 10.8 | |
| UC:CD Ratio | 3.63 | 4.08 | 4.78 | 5.49 | 7.02 | |
Funding Agencies
CIHRThe Leona M. and Harry B. Helmsley Charitable Trust; International Organization for the study Inflammatory Bowel Disease (IOIBD)