Abstract Background A subset of newly diagnosed Crohn’s disease (CD) presents with a mild phenotype, yet long-term behaviour varies widely. Identifying patients who will maintain an indolent course versus those who will require treatment escalation is essential for early risk-stratification. Methods We performed a retrospective cohort study including all incident CD diagnoses at a tertiary referral centre (2015–2020). Mild-at-diagnosis CD was defined as no need for surgery, immunomodulators or biologics within 3 months. An indolent course was defined as absence of CD-related surgery, immunomodulators, biologics, hospitalisation, phenotypic progression or CD-related death. Primary outcome was the proportion maintaining indolence; secondary analysis identified predictors using Cox regression. Results Among 257 newly diagnosed patients, 90 met criteria for mild CD (41% women; mean age 49.0 ±14.6 years). Most presented Montreal A3 (71.1%), L1 (63.3%) or L3 (26.7%) phenotypes, with B1 behaviour in 88.9%. At diagnosis, 42.2% received budesonide, 8.9% prednisolone and 30.0% salicylates. Endoscopic activity was mild in 68.9%, while ultrasound and MRI activity were present in 20.0% and 44.4% respectively (Figure 1). After a median follow-up of 87.3 months, 57 patients (63.3%) maintained an indolent course (Figure 2A). Among the 33 who lost indolence, 29 (87.9%) initiated advanced medical therapy (11 adalimumab, 8 azathioprine, 6 infliximab, 2 ustekinumab and 1 methotrexate). Six (18.2%) required surgery (three perianal, two ileocaecal resections, one limited ileal resection), four (12.1%) were hospitalised and one showed phenotypic progression. In univariate analyses, elevated CRP (p = 0.002), faecal calprotectin (p = 0.008), extraintestinal manifestations (p = 0.041), colonic disease (L2; p = 0.024) and intestinal ultrasound activity (p = 0.017) were significantly associated with loss of an indolent course, while upper GI involvement, perianal disease and moderate-to-severe endoscopic activity showed similar non-significant trends (Figure 1). No associations emerged for demographics, family history, disease behaviour or baseline treatments. In multivariable analysis (Figure 2B), CRP, extraintestinal manifestations, L2 location and ultrasound activity remained independently associated. Conclusion A substantial proportion of patients with newly diagnosed mild CD maintained an indolent course for many years. Recognising this low-risk subgroup is crucial to avoid overtreatment, while ensuring timely escalation in patients with higher-risk features. These findings support a risk-stratified approach at diagnosis integrating biochemical and imaging markers, consistent with previous reports 1–4. References: 1. Yanai H, Goren I, Godny L, et al. Early Indolent Course of Crohn’s Disease in Newly Diagnosed Patients Is Not Rare and Possibly Predictable. Clin Gastroenterol Hepatol. 2021;19(8):1564-1572.e5. doi:10.1016/J.CGH.2020.06.0692. 2. Kruis W, Bokemeyer B, Jessen P, et al. Prospective Evaluation of the Prediction Score for a Mild Course of Crohn’s Disease (PreMiCC) in Newly Diagnosed Patients With Crohn’s Disease: The PROGNOS Study. Inflamm Bowel Dis. 2025;31(3):677-685. doi:10.1093/IBD/IZAE0863. 3. Claytor J, Kumar P, Ananthakrishnan AN, Colombel JF, Agrawal M, Ungaro RC. Mild Crohn’s Disease: Definition and Management. Curr Gastroenterol Rep. 2023;25(3):45-51. doi:10.1007/S11894-023-00863-Y4. 4. Elmasry S, Ha C. Evidence-Based Approach to the Management of Mild Crohn’s Disease. Clin Gastroenterol Hepatol. 2024;22(3):480-483. doi:10.1016/J.CGH.2023.11.011 Conflict of interest: Mrs. López Cardona, Julia: No conflict of interest Garcia De La Filia Molina, Irene: No conflict of interest Fernández Fernández, Cristina: No conflict of interest Lobo Bartol, Virginia: No conflict of interest Albillos Martínez, Agustín: No conflict of interest Mesonero Gismero, Francisco: No conflict of interest
Cardona et al. (Thu,) studied this question.