To Örebro University

Background: Substantial variation exists in early inflammatory bowel disease (IBD) disease management. Biomarkers predicting disease trajectories may enable personalised treatment. The NORDTREAT strategy-trial was designed to compare “top-down” treatment with standard clinical care in patients at increased risk of an aggressive IBD course, as defined by the prognostic NORDTREAT protein signature.

Methods: NORDTREAT (NORdic inflammatory bowel disease TREATment; NCT05180175) was a randomised, multicentre, biomarker-strategy design, open-label, controlled trial conducted across 15 Nordic hospitals. Following screening, eligible adult with newly diagnosed IBD were randomised (1:1) to either access or non-access to the protein signature. In the access arm, patients displaying a high-risk profile received “top-down” (anti-TNF +/- immunomodulator) treatment, whereas low-risk patients were excluded. The non-access arm received standard care with stepwise treatment escalation at the investigator’s discretion (“clinical management”). The primary endpoint was corticosteroid-free clinical and endoscopic remission at week 52, with surgery considered treatment failure. Secondary endpoints included endoscopic remission, cumulative corticosteroid exposure, and serious adverse events. Analyses were performed in the intention to treat population.

Results: 313 IBD patients (CD, n = 133 and UC/IBD-unclassified, n = 180) were randomised between February 2022 and March 2024. Median time from diagnosis to enrolment was 7 days. Among access-arm patients (n = 157), 24 (15%) had a high-risk profile. In the non-access arm, 29/156 (19%) patients were found after trial completion to have had a high-risk profile at baseline and of these 16 (55%) received advanced therapy after a median period of 15 days. The primary endpoint was achieved in 10/24 (42%) “top-down” and 8/29 (27%) “clinical management” patients (absolute difference 15%; 95%CI -11-41, p = 0.26). Endoscopic remission rates at week 52 were comparable (53% vs 53%, p = 0.99). Median cumulative cortisone equivalents was 1232 mg in top-down vs 1651 mg in standard care, p = 0.07). Table 1 provides information on serious adverse events. Post-hoc analyses showed numerically higher rates of achieving the primary endpoint in CD, 50% vs 11% (p = 0.09) UC, whereas rates were comparable in UC 36% vs 35% (p = 0.97).

Conclusion: A biomarker-guided “top-down” approach did not increase corticosteroid-free clinical and endoscopic remission at week 52 compared with standard care. However, a possible benefit was seen in CD, suggesting that early “top-down” could improve outcomes in this subgroup of patients even in the era of widespread use of advanced therapies.