To treat of not to treat – prospection and prognosis in IBD

Fernando Gomollón, MD, PhD

Daniel Gilbert starts his amazing book “Stumbling in happiness” with a key sentence: “The human being is the only animal who thinks about the future” (1), a specific property called “prospection”. Later on, he states: “We want to know what is likely to happen so that we can do something”. This sentence symbolizes our key thoughts in our encounters with inflammatory bowel disease (IBD) patients, especially early on . Let us further analyze our reasoning in the typical clinical situation. First, both Crohn’s disease (CD) and Ulcerative Colitis (UC) are currently considered “progressive diseases, leading to bowel damage and disability”(2–4), as also stated in the paper by Jacobsen et al in this issue of CGH (5). In fact, in almost every IBDfocused meeting, someone displays the classic progression slide, showing evolution from health to severe complications throughout the years. So, we could safely assume that “what is likely to happen” is a complicated course with tough consequences in the life of our patients. Second, accumulating data suggest that currently available treatments significantly improve prognosis, especially if used in the early stages of the disease. Three very recently published papers seem to consolidate this established argument in adults(6,7) and, most interestingly, in children(8). Therefore, we know what is likely to happen, and we can, and probably should, do something. In this case, such action entails the early use of “advanced therapies”(6) or, in some scenarios, early surgery(9), not missing the “window of opportunity”. However, heterogeneity is a well-known feature of IBD – which creates a much more complex scenario. In a seminal paper with data extracted from extensive experience at a daily clinic during more than three decades, Jacques Cosnes et al(10) observed that a group of CD patients had a very benign course. In fact many patients with mild disease had almost uneventful long-term evolution(10). In a small, but very detailed more recent study, Yanai et al observed an “indolent course” in one third of the patients(11). Many UC patients do well for many years while receiving only mesalazine, or even no treatment at all(4). And, finally, we often see some patients’ activity and severity fluctuate through time, which has been called the “rolling” phenotype(12). In reality, Journal Pre-proof our knowledge on natural history is limited as much high quality data come from reference centers, which do not use the same definitions and/or are derived from relatively small samples. In this issue of CGH, Jacobsen et al try to obtain high-quality data on the long-term prognosis of mild-onset IBD, making a detailed analysis of a population-based cohort in North Denmark (NorDIBD)(5). They had two key goals: analyzing the progression of mild disease in the long-term and looking for clues associated with prognosis as age at diagnosis, sex, IBD subtype, and number of years with persistent mild IBD. Of 4,607 total patients in the database (66.6% UC), 2,315 (1,937 UC and 378 CD) matched the definition of mild-onset during the first year of follow-up and were analyzed. After 20 years, 33.1% of mid-onset UC had advanced to moderate-severe UC, while progression was much more common in CD: 66.9% of mild-onset patients progressed to moderate-severe (p<.001 when compared with UC). This confirms that progression is more common in CD(2), but only progression-free time after diagnosis and a younger age at diagnosis were modest predictors of disease course. So, at the individual patient level, prognosis remains elusive with the available data.

LEGGI TUTTO https://doi.org/10.1016/j.cgh.2025.01.013