Y-ECCO Literature Review: Almina Jukic

During the early twentieth century, Inflammatory Bowel Diseases (IBDs), such as Crohn’s Disease (CD) and Ulcerative Colitis (UC), were considered to exclusively affect early industrialised regions within North America, Europe and Oceania [1]. By the twenty-first century, however, newly industrialised regions within Africa, Asia and Latin America were reporting a marked increase in IBD incidence, while IBD prevalence continued to rise in early industrialised regions [2–4]. Experimental evidence indicates that the global increase in IBD incidence and prevalence is linked to environmental factors, particularly those associated with Westernisation of lifestyle [5–7]
The geographical and temporal evolution of IBD is stratified into four theoretical epidemiologic stages. Stage 1 (emergence) is characterised by low incidence and prevalence; stage 2 (acceleration in incidence), by growing incidence and low prevalence; and stage 3 (compounding prevalence), by stable or decreasing incidence but continuously rising prevalence [2]. The fourth epidemiologic stage (prevalence equilibrium) has not yet been evidenced and is believed to represent a prevalence plateau as the IBD population ages and incidence remains stable. To date, numerical thresholds defining transitions between these stages have been scarce. In this context, Hracs and colleagues investigated the spatiotemporal dynamics of epidemiologic stages 1–3 and modelled a potential transition to stage 4.

Analyses were performed using real-word data derived from 522 population-based studies on the incidence and prevalence of CD and/or UC, encompassing 82 regions with data collected between 1920 and 2024. Investigations implicate distinct regional and temporal patterns in IBD evolution. Early industrialised regions such as North America, the United Kingdom and Scandinavia exhibited an early increase in IBD incidence after the Second World War. However, since 2000, incidence has remained stable while prevalence has risen steadily, in some cases exceeding 1%. In contrast, newly industrialised regions, such as Japan, South Korea and Brazil, are still experiencing a rising incidence and low prevalence of IBD, a trend which emerged in the early 2000s. Developing regions, especially countries in Africa, continue to exhibit both low incidence and low prevalence. Only a few early industrialised regions currently report an incidence exceeding 40 per 100,000, which resembles a potential epidemiologic threshold. Scandinavia is among the regions with the highest incidence, with the Faroe Islands reporting the highest UC incidence to date: 73.7 per 100,000 in 2011 [8]. Collectively, developing countries correspond to the emergence stage, newly industrialised regions to the acceleration stage and Western regions to the compounding stage.

To classify epidemiologic stages of IBD, the authors implemented a machine-learning approach. Early industrialised regions currently assumed to be experiencing epidemiologic stage 3 were used to derive historical benchmarks for stages 1 and 2. These were validated against epidemiologic trends obtained from regions currently estimated to be in stage 1 or 2, i.e. developing and newly industrialised countries. Classification was finally performed using a supervised random-forest model [9] and benchmarked coalescing ranges for incidence (CR-I) and prevalence (CR-P) were defined for epidemiologic stages 1–3: Emerging IBD is represented by epidemiologic stage 1 with a CR-I of 0.1–1.2 and a CR-P of 1.2–10.5. Epidemiologic stage 2 was defined by rising incidence with a CR of 3.3–10.6 and low prevalence with a CR of 31.2–100.5. The third stage is described by stable incidence (CR: 18.1–34.1) and rising prevalence (CR: 362.9–660.1). Significant changes in the incidence and prevalence of CD and UC were observed across all epidemiologic stages.

Epidemiologic stage 4 was mathematically modelled by applying partial differential equations (PDEs) to forecasts of prevalence trajectories in three regions currently considered to be experiencing stage 3. Using this method, IBD prevalence was modelled for Canada, Denmark and Scotland until 2043. Calculations were based on the assumption that IBD incidence will remain stable over time while prevalence will continue to grow. Assuming a stable yearly incidence, only Canada is projected to reach epidemiologic stage 4 before 2043. If incidence declines by 2% annually, all three regions are predicted to achieve prevalence equilibrium within the modelled timeframe.