Introduction

Postoperative recurrence is common in Crohn's disease following ileocecal resection, with varying management strategies employed. This study aimed to compare the efficacy of prophylactic approach (starting thiopurines or biological therapy within 6 months from the surgery) versus reactive one (starting biological therapy after evidence of disease reactivation) in preventing postoperative recurrence.

Aims & Methods

This retrospective, multicenter study included 895 adult patients who underwent ileocecal resection for Crohn's disease across 13 Italian centers (prophylactic strategy: n=196; reactive strategy: n=699). Patients were classified as high-risk (≥1 risk factor: active smoking, prior intestinal resection, penetrating disease, perianal disease, or large resection ≥50 cm) or low-risk. The primary outcome was endoscopic recurrence (Rutgeerts' score ≥i2a) at 6-12 months post-surgery. Secondary outcomes included clinical, biochemical, and radiological recurrence at various time points, as well as long-term outcomes including need for repeat surgery.

Results

The prophylactic biologic therapy group demonstrated significantly lower rates of endoscopic recurrence at 6-12 months compared to the reactive approach (51.54% vs. 64.83%, p=0.007). After adjusting for confounders, including age at surgery and previous biologic exposure, a reactive approach was associated with increased odds of endoscopic recurrence (OR 1.893, 95% CI: 1.225-2.926, p=0.004). The prophylactic strategy also showed lower rates of clinical recurrence (23.08% vs. 36.36%, p=0.002), biochemical recurrence (33.81% vs. 48.89%, p=0.004), and severe endoscopic recurrence (22.31% vs. 32.55%, p=0.028) at 6-12 months. In high-risk patients with a single risk factor, prophylaxis significantly reduced endoscopic recurrence (49.06% vs. 65.75%, p=0.033) and surgical recurrence (2.56% vs. 11.58%, p=0.017). For patients with multiple risk factors, benefits were mainly observed in clinical (29.87% vs. 45.77%, p=0.022) and biochemical recurrence (37.88% vs. 56.32%, p=0.024). In low-risk patients, prophylaxis primarily reduced severe endoscopic recurrence (10.52% vs. 34.48%, p=0.037), but not other outcomes. However, these benefits diminished over time, with no significant differences in all outcomes at 15-36 months or in long-term surgical recurrence rates as compared to patients undergoing the reactive approach in all groups (p=0.438). No significant difference was observed between the two approaches regarding the need for endoscopic dilation during follow-up (p=0.301).

Table 1: Differences in outcomes at 6-12 months between a proactive and reactive strategy approach. Abbreviations: CD: Crohn's Disease, FC: Fecal Calprotectin, HBI: Harvey-Bradshaw Index

Conclusion

A prophylactic strategy significantly reduces short-term postoperative recurrence in Crohn's disease patients following ileocecal resection, with particular benefit in high-risk patients with a single risk factor. However, the protective effects appear to diminish over time. Further research is needed to refine predictive models and validate interventions targeting high-risk populations for sustained benefits.

Introduction

Duvakitug, a human IgG1 monoclonal antibody, inhibits TL1A binding to death receptor 3 (DR3), which drives inflammation in Crohn’s disease (CD). The RELIEVE-UCCD trial (NCT05499130), a 14-week induction study, evaluated duvakitug in ulcerative colitis and CD. This was the first placebo-controlled study of an anti-TL1A in moderately to severely active CD. This subgroup analysis was performed to understand the impact of duvakitug in patients with moderate and severe endoscopic inflammation by assessing Week 14 outcomes in subgroups based on endoscopic disease severity at baseline.

Aims & Methods

Patients with CD (N=138) were randomized (1:1:1) to receive a subcutaneous (SC) loading dose (LD) of duvakitug 2250 mg followed by SC duvakitug 900 mg or duvakitug 450 mg every 2 weeks (q2w), or matching placebo LD followed by placebo q2w. Patients were required to have a simple endoscopic score for Crohn’s disease (SES-CD) ≥6 (≥4 for isolated ileal disease) for study eligibility. In this analysis, endoscopic and patient-reported clinical outcomes were assessed by baseline SES-CD scores of ≤15 (moderate) and >15 (severe).¹ Endpoints included response and remission based on endoscopic assessment (SES-CD) and clinical assessment [2-item Patient Reported Outcome assessment tool (PRO2)] at Week 14. Outcomes were analyzed using descriptive summary statistics.

Results

Among patients with severe endoscopic activity (SES-CD >15) at baseline, endoscopic response was achieved by 36% in the duvakitug 900 mg arm, and 18% in the duvakitug 450 mg arm compared to 8% in the placebo arm. In patients with moderate endoscopic activity (SES-CD ≤15) at baseline, endoscopic response was achieved by 51% in the duvakitug 900 mg arm, and 29% in the duvakitug 450 mg arm compared to 15% in the placebo arm (Table). Greater proportion of patients achieved endoscopic remission, clinical response and remission with both doses of duvakitug compared to placebo in the moderate and severe endoscopic subgroups (Table). The overall adverse event profile was similar across treatment arms by disease severity subgroups.

Table: Week 14 endoscopic and clinical response and remission in CD patients with moderate and severe endoscopic activity at baseline

Conclusion

In CD patients, duvakitug demonstrated efficacy in endoscopic and patient-reported clinical outcomes in both moderate and severe endoscopic activity subgroups in this Phase 2b study. Duvakitug was well tolerated across both subgroups. These findings support further development of duvakitug as a potential treatment option for moderately to severely active CD.

References

1. Moskovitz DN, Daperno M, Van Assche G. Defining and validating cut-offs for the Simple Endoscopic Score for Crohn's Disease. Gastroenterology 2007; 132:S1097.

Disclosure

W.R. has served as a speaker for AbbVie, Celltrion, Ferring, Janssen, Galapagos, Merck Sharp & Dohme, Roche, Pfizer, Sobi and Takeda; as a consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead,
Index Pharma, Janssen, Medahead, Microbiotica, Pfizer, Teva and Takeda; as an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Pfizer and Teva; and have received research funding from AbbVie, Janssen, Sandoz, Sanofi and Takeda.
V.J. has received consulting/advisory board fees from AbbVie, Alimentiv, AnaptyisBio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, Teva, Ventyx and Vividion; and speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Eli Lilly, Fresenius Kabi, Janssen, Pfizer, Shire, Takeda and Tillotts.
B.S. has served as a consultant or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, Viela Bio, and has stock options from Ventyx Biosciences.
S.D. reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor; and reports lecture fees from Abbvie, Amgen, Dr Falk Pharma, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer, and Takeda.
K.A., N.G., B.R-D. are employees of Teva Pharmaceutical Industries Ltd.
P.L. is an employee of Sanofi.
Duvakitug is being developed in partnership by Teva and Sanofi.