P0393Evolution of definitions of refractory and difficult-to-treat Inflammatory Bowel Disease: a systematic review

Abstract Background A subgroup of patients with inflammatory bowel disease (IBD) experience active disease and symptoms and impaired quality of life despite appropriate interventions. The International Organization for the Study of IBD (IOIBD) proposed the definition of difficult-to-treat IBD (DTT-IBD)1 as a multidimensional concept incorporating treatment or surgical failure, and psychological burden. However, the terms and criteria used to describe these patients in the literature remain variable. Methods A systematic review of PubMed, Embase, and the Cochrane Database of Systematic Reviews (up to September 2025) was conducted. Studies that defined DTT-IBD, refractory (RF) IBD, or similar were included. Of 1,373 references identified, 1,029 were screened, 100 underwent full-text review, and 36 were included in accordance with PRISMA 2020 methodology (Figure 1). Results Publications spanned 2006 to 2025, with an increase in definitions after 2023 (2024 n = 8; 2025 n = 10) (Table 1). Nine studies included mixed IBD, of which 5 used the IOIBD DTT-IBD definition and 4 used the term RF-IBD. Fourteen studies included definitions of RF-Crohn’s disease (CD) (1 DTT; 13 RF), and 5 for RF-ulcerative colitis (UC). Both RF pouchitis and RF perianal CD were defined in 4 studies each. Populations included 2 pediatric-only studies, 1 combining pediatric and geriatric patients, 2 young-adult cohorts (10–30 years), and the remainder adults. Study designs included 11 retrospective and 5 prospective cohorts; 10 clinical trials; 1 cross-sectional cohort; 2 narrative reviews; 6 scoping/systematic reviews/meta-analyses; and the 2023 IOIBD consensus. RF IBD was most often defined as failure or loss of response to ≥ 2 advanced therapies; some studies used symptom-based definitions without mandatory objective inflammation. DTT-IBD additionally incorporates comorbidities or psychosocial factors. Five studies published in 2024–2025 adopted the IOIBD definition, 3 from the Italian group that led the consensus. No clinical trial has used the DTT-IBD definition; instead, “refractory” criteria are used (6 RF-CD, 2 RF-UC, 2 RF-perianal CD). No separate publications focused just on psychosocial comorbidities or recurrent surgeries in RF or DTT-IBD were identified. Conclusion Definitions of DTT-IBD and RF-IBD remain heterogeneous, particularly before the IOIBD consensus. Although clarity is increasing, adoption remains incomplete, and trials have not yet implemented DTT-IBD. Implementation of IOIBD criteria is needed to standardize reporting, facilitate comparisons, and support earlier, strategic management of complex IBD. Reference: 1. Parigi TL, D’Amico F, Abreu MT, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. doi:10.1016/S2468-1253(23)00154-1 Conflict of interest: Dr. Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda Speaker fees: Abbvie, AstraZeneca, Bayer, Johnson & Johnson, Ferring, Sandoz Thomas, Mithun: No conflict of interest Patel, Sameet Tariq: No conflict of interest Jena, Anuraag: None Sharma, Vishal: None Sebastian, Shaji: Grant: Takeda, Tillots pharma, Biogen, Pfizer, Abbvie, Johnson & Johnson, Olympus -Odin Vision Personal Fees: Tillots, Johnson & Johnson, Olympus Odin Vision, AbbVie, Takeda, Merck, Pharmacosmos, Amgen, Eli Lilly, BMS, Odin Vision Non-financial Support: Tillots, Takeda, AbbVie, Celltrion, Johnson & Johnson, Eli Lilly, Alphasigma, Ferring Pharma