MODELING THE TRANSITION TO THE FOURTH EPIDEMIOLOGIC STAGE OF INFLAMMATORY BOWEL DISEASE: PREVALENCE EQUILIBRIUM
Authors: Windsor Joseph , Hracs Lindsay , Cummings Michael , Gorospe Julia , Buie Michael , Quan Joshua , Markovinovic Ante , Caplan Lea , Goddard Quinn , Williamson Tyler , Abbey Yvonne , Abreu Maria , Ali Raja , Abdullah Murdani , Altuwaijri Mansour , Ahuja Vineet , Balderramo Domingo , Banerjee Rupa , Benchimol Eric , Bernstein Charles , Brunet-Mas Eduard , Burisch Johan , Dotan Iris , Dutta Usha , El Ouali Sara , Forbes Angela , Gearry Richard , Dao Viet Hang , Hartono Juanda , Hilmi Ida , Julian-Banos Fabian , Kaibullayeva Jamilya , Kelly Paul , Kotze Paulo , Lakatos Peter , Lees Charlie , Limsrivilai Julajak , Loftus Edward , Ludvigsson Jonas , Mak Joyce , Ng Ka Kei , Olen Ola , Panaccione Remo , Paudel Mukesh , Quaresma Abel , Rubin David , Simadibrata Marcellus , Sun Yang , Suzuki Hidekazu , Toro Martin , Turner Dan , Vergara Beatriz Iade , Wei Shu-Chen , Yamamoto-Furusho Jesus , Yang Kuk-Kyun , Ng Siew , Coward Stephanie , Kaplan Gilaad 
Published: January 2024

Abstract

BACKGROUND
A theoretical framework for population-level transition across four epidemiologic stages has been proposed for inflammatory bowel disease (IBD): 1. Emergence (low incidence/prevalence); 2. Acceleration in Incidence (rapid rising incidence); 3. Compounding Prevalence (stabilizing incidence, rapid rising prevalence); and 4. Prevalence Equilibrium (decelerated prevalence), which no region has entered yet. Many regions of the early-industrialized world (North America, Europe, Oceania) are currently in stage 3.

AIM
To model the transition to the 4th epidemiologic stage of IBD based on real-world data.

METHODS
Transition to stage 4 involves deceleration of prevalence after a period of rapid increase. Age-specific, population-based incidence and prevalence data from Canada (2007–2014, &gt;97% of population) were used to model changing prevalence using a partial differential equation (PDE) derived from a compartment model (Figure 1). The PDE is built on an average historical incidence value (2007–2014) and accounts for changing population age distributions over time.
The PDE prevalence output was internally validated by comparing observed historical prevalence values with model outputs. After validation, the model was used to forecast future age-stratified prevalence and provide an estimate for when the transition to stage 4 is expected. Although incidence is predicted to stabilize in stage 3, the PDE was run on five scenarios to account for variability in future incidence values; therefore, we modeled annual incidence increases of 2% and 1%, stable incidence, and annual incidence decreases of 1% and 2%.

RESULTS
Internal validation of the model compared observed to predicted prevalence values in 2014: The observed prevalence was 0.677%; the model output was 0.678%. The model predicts gradual prevalence deceleration across 2020–2043 (Figure 2). In 2043, prevalence is modeled to range between 1.101% and 1.293% across incidence scenarios (−2% to 2%). Assuming a stable incidence, as predicted by stage 3, the increase in prevalence slows from a difference in annual percent change of 0.021% in 2020 to 0.011% in 2043, signalling transition towards stage 4 (Figure 2).

DISCUSSION
Stage 3 (Compounding Prevalence) is characterized by a stabilizing incidence trend, and rapid growth in prevalence. Without a growing incidence rate, the IBD population continues to age until mortality approximates incidence, thereby allowing prevalence to stabilize (Stage 4). Understanding the markers of epidemiologic transition and predicting the future population distribution (age, prevalence) of IBD allows healthcare administrators to anticipate the future needs of gastroenterology clinics to continue offering timely, high-quality care and prepare for an aging IBD population with complications from long-standing disease, age-related comorbidities, and polypharmacy.

Figure 1 Compartment model that feeds the partial differential equation. The compartment model has three states: healthy (H), diseased (S), and dead (D); the i = incidence; r = remission, and m0 = mortality rates are dependent on age (a) and time (i), where as m1 = mortality rate is dependent on age, time, and possibly duration of disease (d).

Figure 2 Modeled time-dependent prevalence of IBD in Canada for 2%, 1%, 0%, −1%, and −2% change in annual incidence (2015–2043).