
Chief of the Digestive Disease Institute
Cleveland Clinic, Ohio
The first paper in The Regueiro Report this month has generated significant attention among providers who treat inflammatory bowel disease, and for good reason. It is one of the most important papers about the epidemiology of IBD to appear for several years, perhaps even decades, and I suspect it will be highly cited in years to come.
When I was in medical school, the prevailing idea was that IBD occurred only in certain parts of the world, such as North America and Northern Europe, and was much less common in other parts of the world, such as Asia and Africa. But in the last 25 years or so, IBD rates have spiked in many parts of the world in a way that can’t be explained by genetic evolution, which likely would take generations to manifest.
Instead, there may be something environmental that sparks immune-mediated diseases such as IBD. While our tools for diagnosis have improved with time, the spike in IBD shown in this paper is too large to be explained solely by better detection tools. The paper focuses on IBD, but it also serves as a potential bellwether for similar surges in other immune-mediated diseases.
The authors used large language modeling to analyze more than 500 studies from more than 80 global regions and proposed that IBD generally evolves in four distinct stages, from emergence with low incidence, to increasing incidence and low prevalence, to increasing prevalence with decreasing incidence, to stabilization. The first three stages have empirical evidence, while the fourth stage of a stable incidence rate is more theoretical.
As IBD incidence grows, prevalence rates throughout the world are much higher than previously appreciated. To me, this shows that, contrary to what we once believed, IBD is not a rare disease.
A key question is, with the quick rise in IBD across the world, is there a way to reverse this trend? This paper did not answer this question. I think the importance of this study in defining the evolution of IBD and better describing epidemiological trends highlights the role of early detection. We know that earlier diagnosis and treatment and, possibly, lifestyle changes improve outcomes and lower the risk for future IBD complications.
To be clear, most people who present to the doctor with abdominal pain or diarrhea do not have IBD. However, given the increase in IBD incidence and prevalence, IBD should be on the list of possibilities to consider and test for in people presenting with gastrointestinal symptoms.
The other study I discuss this month found that patients with IBD in deep remission for at least six months could successfully de-escalate from an anti–tumor necrosis factor therapy to an immunomodulator alone. The investigators showed that patients who stopped an anti-TNF therapy but continued an immunomodulator had one-year remission rates that were similar to rates in patients who continued both anti-TNF therapy and an immunomodulator.
However, people who stopped taking an anti-TNF had higher fecal calprotectin levels than their counterparts who maintained an anti-TNF medication. In addition, this paper only looked at data at one year, causing me concern about long-term remission. In my practice, I typically continue the advanced therapy, such as anti-TNF biologic therapy, as long as the patient is tolerating the medicine and maintaining remission. Also, if a patient is on combination therapy of an immunomodulator with an anti-TNF, I usually de-escalate the immunomodulator and continue the anti-TNF, with therapeutic drug monitoring.
That said, in certain parts of the world, payment for long-term biologic therapy could be a challenge, and this study provides reassurance that some patients may successfully stop an anti-TNF therapy and continue with just an immunomodulator. It is important to monitor the patients who de-escalate off an anti-TNF, assessing for recurrent inflammation using fecal calprotectin levels, as was suggested in this study.
Global Evolution of Inflammatory Bowel Disease Across Epidemiologic Stages
Nature. Published online April 30, 2025. doi:10.1038/s41586-025-08940-0
The authors analyzed data from 1920 to 2024 regarding IBD incidence and prevalence, using 522 population-based studies from 82 global regions. They proposed a four-stage model of IBD incidence and prevalence in a given region: stage 1, emergence, in which there is a low but detectable incidence and prevalence; stage 2, acceleration in incidence, with rapidly growing incidence and low prevalence; stage 3, compounding prevalence, in which prevalence increases as incidence decreases; and stage 4, prevalence equilibrium. The fourth stage is theoretical and the other three are empirical.
The United States, Canada, much of Northern Europe and Australia are in stage 3, while countries as diverse as Mexico, Russia, Malaysia and China, along with most of South America, are in stage 2. There are no data available for some parts of the world, including India and much of Africa. The parts of Africa with data are in stage 1.
Withdrawal of Anti-TNF Therapy In IBD Patients in Remission
Gut 2025;74:387-396
Adults with Crohn’s disease or ulcerative colitis in remission for at least six months were randomized to maintain anti-TNF therapy (n=70) or to stop it (n=70).
After one year, there were similar clinical remission rates in people who maintained anti-TNF therapy (59/70 [84%]; 95% CI, 74%-92%) and those who stopped it (53/70 [76%]; 95% CI, 64%-85%). A higher proportion of people had elevated fecal calprotectin (>250 mcg/g) in the group that stopped taking an anti-TNF medication (P=0.01).
This article is from the July 2025 print issue.