Abstract Background A subset of patients with ulcerative colitis (UC) experience a persistently mild disease course, maintaining long-term remission with 5-aminosalicylates (5-ASA) alone and without corticosteroids or therapy escalation. This “very mild” phenotype remains poorly defined. Identifying its determinants could refine disease stratification and guide more individualized management. Methods We conducted a retrospective cohort study including patients with an established diagnosis of UC followed in our IBD unit between 1975-2025. Very mild UC was defined as disease controlled with oral and/or topical 5-ASA for 2 years with no need for corticosteroids, immunomodulators, biologics, hospitalizations or surgery. Clinical and endoscopic characteristics at diagnosis were compared with patients who required treatment escalation. Multivariable logistic regression identified baseline factors associated with a persistently mild course. Results We identified 745 patients, of which 192 (25.8%) met criteria for very mild UC. There were 395 (52.9%) men with median age at diagnosis of 37 (IQR 27-51). Disease extent at diagnosis was: proctitis 211 (28.3%), left-sided colitis 279 (37.4%), and extensive 249 (33.4%). Differences were observed in patients with very mild UC, showing older disease of onset 42 (IQR 32-53) vs 36 (IQR 26-50), p 0.001; shorter disease distribution E1+E2 (86.3% vs 59.4%, p 0.001) and lower endoscopic activity at diagnosis (Mayo 1: 49 (31.6%) vs 58 (13.6%), p 0.001). Independent predictors of not maintaining a very mild UC course included left-sided (OR 1.720; 95% CI 1.060-2.790; p = 0.028) or extensive colitis (OR 5.266; 95% CI 2.739–10.124; p 0.001) and higher endoscopic activity (OR 2.014; 95% CI 1.398-2.901; p 0.001). Conversely, older age at diagnosis increased the likelihood of a very mild course (OR 0.979 per year; 95% CI 0.965–0.993; p = 0.004), whilst smoking habit, EIMS and sex were not. In the sensitivity analysis restricted to 10 years of follow-up, disease extent and endoscopic activity remained significant predictors, while age at diagnosis did not retain statistical significance Conclusion Approximately one in four UC patients maintain sustained remission with 5-ASA monotherapy alone. A “very mild” disease phenotype is characterized by older age at onset, limited extent, and mild endoscopic activity at diagnosis. Recognizing this stable subgroup may help avoid overtreatment and improve long-term risk stratification. Conflict of interest: Mr. Mirabent Moreno, Carlos: No conflict of interest Yazdani, Sara: No conflict of interest Valdivia Krag, Carlos: No conflict of interest Benítez Cantero, José Manuel: José Manuel Benítez has served as an speaker, consultant and advisory member or has recieved grants or honoraria for scientific activities and presentations from Dr Falk Pharma, Faes Farma, Ferring, Shire Pharmaceuticals, Chiesi, Tillots Pharma, MSD, Abbvie, Takeda, Janssen, Gilead, Pfizer, Adacyte, Galápagos, Lilly and Alfasigma Marin Pedrosa, Sandra: NO Soto Escribano, Pilar: No conflict of interest Iglesias Flores, Eva: has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Janssen, Takeda, Gillead, Celgene, Pfizer, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, and Adacyte, Gros, Beatriz: Beatriz Gros has served as a speaker for Abbvie, Johnson and Johnson, Takeda, Roche, Gilead, Pfizer and Galapagos and has served as an advisor for Roche, Gilead, Abbvie, Galapagos and Takeda
Moreno et al. (Thu,) studied this question.