GUIDE-IBD: Biomarker-Informed Therapy Decisions Improve Outcomes with Anti-TNF

Findings from the GUIDE-IBD trial are shedding light on the value of biomarker-informed molecular guidance for improving therapy outcomes in patients with inflammatory bowel disease (IBD).1

Trial data were presented during a late-breaking session at Digestive Disease Week (DDW) 2025 by Florian Tran, MD, a professor of pathophysiology of chronic inflammation at the Christian Albrecht University of Kiel, and highlight greater achievement of disease control compared with standard “best care” in the context of anti-tumor necrosis factor (TNF) therapy.1

Given the central role TNF plays in the pathogenesis of specific immune-mediated inflammatory diseases (IMIDs), anti-TNFs have emerged as popular therapies in several IMIDs, including rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and IBD.2

“Anti-TNF therapies are a cornerstone in the treatment of IBD, yet therapeutic responses vary widely among patients,” Tran and colleagues wrote.1 “Despite extensive biomarker discovery efforts, the clinical utility of defined molecular marker sets remains largely unexplored.”

GUIDE-IBD was designed to assess the efficacy of biomarker-informed therapy decisions by comparing guidance through a molecular therapy board to standard medical “best” care in patients with active IBD initiating anti-TNF therapy. The randomized controlled trial was conducted at 3 German university hospitals and enrolled adult patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) assigned to first-time infliximab therapy.1

Participants were randomly assigned to either molecular medicine care (MMC) or best care, stratified by diagnosis, recruiting center, and baseline corticosteroid use. Molecular assessments were conducted at baseline and weeks 2, 6, 14, and 26, incorporating published mRNA-based biomarkers from peripheral blood and biopsies processed in real-time and provided as a holistic, principal-component description along with infliximab and anti-drug antibody levels. Molecular reports were provided through molecular medicine boards for patients in the MMC group at weeks 2, 14, 26 and 52, while data for patients in the best care group were not communicated.1

The primary endpoint was the patient level combined endpoint “disease control” at week 52, defined as Crohn’s Disease Activity Index <150 and a partial Mayo score <2; as well as endoscopic remission, defined as Simplified Endoscopic Score for CD ≤4, or ≤2 for isolated ileal disease and endoscopic Mayo score ≤1; and biochemical remission, defined as CRP <5 mg/L and fecal calprotectin <250 mg/g.1

Of 102 patients who were randomized between February 2021, and January 2024, 87 patients completed the study with available primary endpoint data to week 52, with 41 patients diagnosed with CD and 46 with UC.1

Upon analysis, disease control was significantly more frequent in the MMC group at week 52 (55%) compared to the best care group (27%), with an absolute difference of 29% (95% CI, 9%–49%; P = .007). Investigators noted combined endoscopic and clinical remission was also greater in the MMC group (61%) versus the best care group (28%; 95% CI, 8%–48%; P = .016).1

“Biomarker-informed molecular guidance significantly improved therapy outcomes, with a higher proportion of patients achieving disease control compared to standard ‘best care’ in the context of anti-TNF therapy,” investigators concluded.1 “These findings support the integration of molecular medicine approaches in therapy boards to optimize treatment strategies in IBD.”

References

1. Tran F, Aden K, Bernardes JP, et al. BIOMARKER-INFORMED THERAPY GUIDANCE IMPROVED CLINICAL OUTCOMES OF ANTI-TNF TREATMENT IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN A MULTI-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE CLINICAL TRIAL (GUIDE-IBD). Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

2. US Pharmacist. Overview of TNF Inhibitors for Treating Inflammatory Bowel Disease. May 14, 2021. Accessed May 6, 2025. https://www.uspharmacist.com/article/overview-of-tnf-inhibitors-for-treating-inflammatory-bowel-disease