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. 2025 May 12:18:17562848251338647.
doi: 10.1177/17562848251338647. eCollection 2025.

Natural history, immunological and genetic characteristics of preclinical inflammatory bowel disease (EARLY): study protocol for a prospective cohort study

Iago Rodríguez-Lago  1 , Urko M Marigorta  2 , Beatriz Mateos  2 , Míriam Mañosa  3   4 , Lucía Márquez-Mosquera  5 , Luis Menchén  6   7 , Francisco Rodríguez-Moranta  8 , Inmaculada Alonso  9 , Mariam Aguas  10 , Horacio Alonso-Galán  11 , Pere Borràs  12 , Beatriz Castro  13 , Eugeni Domènech  4   14 , Rocío Ferreiro-Iglesias  15 , Ruth de Francisco  16 , Francisco Javier García-Alonso  17 , Natalia García  18 , Orlando García-Bosch  19 , Carla Gargallo  20 , Javier P Gisbert  4   21 , Eva Iglesias  22 , Francisco Mesonero  23 , Jone Ortiz de Zárate  24 , Laura Ramos  9 , Empar Sáinz  25 , Pablo Ladrón  26 , Carles Suria  27 , Cristina Suárez Ferrer  28 , Coral Tejido  29 , Pilar Varela  30 , Raquel Vicente  31 , Yamile Zabana  4   12 , Gisela Castany  32 , Eva Rodríguez  32 , Ana Gutiérrez  4   33 , Manuel Barreiro-de Acosta  15
Affiliations

Natural history, immunological and genetic characteristics of preclinical inflammatory bowel disease (EARLY): study protocol for a prospective cohort study

Iago Rodríguez-Lago et al. Therap Adv Gastroenterol. .

Abstract

Background: The period prior to the diagnosis of inflammatory bowel disease (IBD), defined as the preclinical phase, has emerged as a potential target for disease modification strategies. Despite the relevance of an early diagnosis to the prognosis of the disease, only a limited number of patients are diagnosed during this window of opportunity.

Objectives: To determine the risk of developing symptoms after an incidental diagnosis of IBD and to describe the clinical, genetic, and immunological characteristics of IBD during its preclinical phase.

Design: This study protocol describes a prospective, multicenter cohort study in which incidental (i.e., asymptomatic) IBD within the colorectal cancer screening program will be characterized from a clinical and multi-omic perspective and compared with symptomatic patients and healthy non-IBD controls.

Methods: Samples from blood, urine, stool, and intestinal endoscopic biopsies will be obtained at baseline. A second sample set will be obtained after 52 weeks from those who remain asymptomatic; samples will also be obtained in those with new-onset symptoms. Medical treatment will be prescribed in all patients following current guidelines. Follow-up visits will be performed every 6 months for 10 years, and all new-onset symptoms, changes in disease behavior, extraintestinal manifestations, IBD-related medical therapies, or surgeries will be recorded. Two control cohorts will be included: one including recently diagnosed symptomatic IBD patients (<3 months), and another with healthy non-IBD controls after a normal ileocolonoscopy, in whom samples will be obtained at baseline. Samples from patients and controls will undergo genetic, proteomic, transcriptomic, single-cell RNA sequencing, metabolomic, and microbiome analyses, and integration of data between the different omic perspectives will also be performed. The study has been approved by the Basque Country Ethics Committee (PI2021116).

Conclusion: EARLY will generate a unique dataset addressing a previously unexplored area of IBD, with the final aim of describing the prognosis of patients from its earlier phases on the disease and integrating clinical and omic data into useful tools for the long-term prediction of disease outcomes.

Trial registration: NCT05698745.

Keywords: Crohn’s disease; biomarkers; early; natural history; prediction; ulcerative colitis.

Plain language summary

Study protocol of a study on the natural history, immunological and genetic characteristics of the early phases of inflammatory bowel disease (EARLY) This study focuses on inflammatory bowel disease (IBD) and aims to explore the period before symptoms appear, known as the preclinical phase. Detecting IBD early could improve patient outcomes, but currently, few patients are diagnosed during this phase. The study seeks to determine the risk of developing symptoms after an incidental IBD diagnosis (discovered without symptoms) and to describe the clinical, genetic, and immune characteristics of IBD in this early stage. It involves a prospective, multicenter approach, examining patients who are incidentally diagnosed with IBD during colorectal cancer screening. These patients will be compared to those with symptomatic IBD and healthy individuals without IBD. Researchers will collect samples of blood, urine, stool, and intestinal tissue from participants at the start of the study and again after one year if they remain symptom-free. Additional samples will be taken if symptoms develop. Participants will receive standard medical treatment and have follow-ups every six months for ten years. The study will track new symptoms, changes in disease behavior, extraintestinal symptoms, treatments, and surgeries. Two control groups will be included: one with recently diagnosed symptomatic IBD patients and another with healthy individuals who had normal colonoscopy results. The samples will undergo extensive genetic and molecular analyses to integrate data from different perspectives. The EARLY study will generate a valuable dataset on the early stages of IBD, aiming to understand the prognosis from its earliest phases and to combine clinical and molecular data to predict long-term outcomes.

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Conflict of interest statement

IR-L has received financial support for traveling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. MM has received financial support for traveling and educational activities or has served as a speaker or as an advisory member for Janssen, AbbVie, Lilly, Galapagos, Ferring, Takeda, Pfizer, and Tillots Pharma. LM has received financial support for traveling and educational activities from or has served as an advisory board member for Pfizer, MSD, Takeda, AbbVie, Kern, Janssen, Galapagos, Lilly, Tilllotts Pharma, Ferring, Adacyte, and General Electric. HA has received financial support for traveling and educational activities from or has served as an advisory board member for Janssen, MSD, AbbVie, Takeda, Ferring, Pfizer, and Dr. Falk Pharma. ED has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Samsung, Takeda, Tillotts Pharma. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. EI has received financial support for traveling and educational activities from or has served as an advisory board member for Adacyte, MSD, Takeda, AbbVie, and Janssen. FM has served as a speaker for and received consulting fees from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring, Kern Pharma, Dr. Falk Pharma, Galapagos, Chiesi and Faes Farma. CM has received financial support for traveling and educational activities from or participated in research for AbbVie and Janssen. RFI has received financial support for traveling and educational activities from or has served as an advisory board member for AbbVie, MSD, Takeda, Janssen, Kern, Pfizer, Adacyte, Ferring, Faes, Falk, Palex, Casenrecordati, and Shire. LR has served as a speaker or has received funding for educational activities from MSD, AbbVie, Adacyte, Takeda, Pfizer, Janssen, and Ferring. BS has received financial support for traveling and educational activities from or has served as an advisory board member for AbbVie, Faes, Chiesi, Dr. Falk, MSD, Tillotts Pharma, Kern Pharma, Janssen, Pfizer, and Takeda. YZ has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte, Almirall, Amgen, Dr Falk Pharma, Faes Pharma, Ferring, Janssen, Lilly, MSD, Otsuka, Pfizer, Shire, Takeda, Galapagos, Boehringer Ingelheim, Sanofi, and Tillotts Pharma. AGC has received financial support for traveling and educational activities from or has served as an advisory board member for Pfizer, MSD, Takeda, AbbVie, Kern, Janssen, Fresenius Kabi, Galapagos, Lilly, Ferring, Faes Farma, Chiesi, GSK, and Adacyte. MBA has received financial support for traveling and educational activities from or has served as an advisory board member for Pfizer, MSD, Takeda, AbbVie, Kern, Janssen, Fresenius Kabi, Galapagos, Lilly, BMS, Faes Farma, Chiesi, and Adacyte. The remaining authors have no conflicts of interest to declare. All authors have approved the final version of this manuscript.

Figures

Figure 1.
Figure 1.
Overview of the study visits, samples, and study procedures during the 10-year follow-up and according to the cohort.
See this image and copyright information in PMC

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