UPPER gastrointestinal involvement (UGI) in Crohn’s disease (CD) does not confer intrinsic resistance to biologic therapy despite its more aggressive disease course. However, the findings suggested that UGI in CD remains associated with increased long-term risk of intestinal surgery even with biologic treatment, according to a new retrospective cohort study presented at UEG Week 2026.
It is not currently known whether UGI in Crohn’s disease confers intrinsic resistance to biologic therapy. As a result, researchers assessed the effectiveness of biologic treatment in patients with UGI and evaluated their risk of intestinal surgery despite biologic therapy.
The retrospective cohort study analysed data from 9,524 biologic-treated patients with CD enrolled in the ENEIDA multicentre registry between 2015 and 2025. UGI was classified according to the Montreal classification, using the L4 phenotype, and the analysis included patients with ileal or ileocolonic disease.
The primary outcome was biologic treatment persistence, measured by the time until treatment discontinuation because of primary nonresponse or loss of response. The secondary outcome was time to intestinal resection. Researchers used statistical weighting to account for differences between patients with and without UGI, with adjusted models used to assess treatment persistence and intestinal resection risk. Additional analyses examined different UGI subtypes and potential interactions between UGI phenotype and biologic class.
The median follow-up was 81 months. Following weighting and adjustment for biologic class, UGI was not associated with a significant reduction in biologic treatment persistence (hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 0.96–1.10). Reasons for discontinuation due to lack of effectiveness were also comparable between patients with and without UGI.
However, UGI was independently associated with an increased risk of intestinal resection (HR: 1.19; 95% CI: 1.04–1.36). Subgroup analysis showed that this association was primarily driven by patients with combined L4a and L4b involvement (HR: 1.47; 95% CI: 1.15–1.88). Neither isolated L4a involvement nor isolated L4b involvement was significantly associated with surgery.
Biologic class was also independently associated with treatment persistence and intestinal resection. Ustekinumab showed the greatest treatment durability and a lower risk of intestinal resection across the overall cohort. However, researchers found no significant interaction between biologic class and UGI phenotype.
Overall, the findings indicated that upper gastrointestinal involvement in Crohn’s disease was not associated with reduced biologic treatment persistence. However, it remained associated with an increased long-term risk of intestinal resection despite biologic therapy. These results suggest that the L4 phenotype may identify patients at greater risk of surgery rather than those with an intrinsically reduced response to biologic treatment.
Giordano A et al. Upper gastrointestinal Crohn’s disease does not confer intrinsic biologic resistance but remains associated with increased intestinal surgery despite biologic therapy. Abstract OP004. UEG Congress, 17-20 October 2026.
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