Superior IBD control achieved with biomarker-guided therapy standard care

Biomarker-informed molecular guidance improves anti-TNF therapy outcomes in patients with inflammatory bowel disease (IBD), increasing the likelihood of achieving disease control when compared with standard “best care,” as shown in the GUIDE-IBD trial.

In a cohort of patients with active Crohn’s disease (CD) or ulcerative colitis (UC) who were initiating infliximab therapy, more than half of those who received molecular medicine care achieved the primary endpoint of comprehensive disease control at week 52 compared with a quarter of those who received standard best care (55.3 percent vs 26.5 percent; p=0.0072). [DDW 2025, abstract 987e]

The percentage of patients who achieved combined endoscopic and clinical remission was also greater in the molecular medicine care group than in the standard best care group (60.5 percent vs 32.7 percent; p=0.0163).

“Anti-TNF therapies are a cornerstone in the treatment of IBD, yet therapeutic responses vary widely among patients,” said lead investigator Dr Florian Tran from the University Hospital Schleswig-Holstein in Kiel, Germany.

That being said, Tran pointed out that for all the extensive biomarker discovery efforts, the clinical value of defined molecular marker sets in guiding treatment has been largely unexplored. On the other hand, he noted that changes in the blood observed within 2 weeks of treatment have been shown to predict response to anti-TNF therapy in previous research.

In GUIDE-IBD, Florian and colleagues tested the use of molecular reports, which were provided by a molecular medicine board, for informing therapy decisions including dose adjustments, additional medications, and therapy switches. The reports were based on assessments that combined published mRNA-based biomarkers from peripheral blood and biopsies that were processed in real time and infliximab and anti-drug antibody levels.

The findings from the trial “support the integration of molecular medicine approaches in therapy boards to optimize treatment strategies in IBD,” Tran said.

GUIDE-IBD included 102 adult patients with active Crohn’s disease (47 percent) or ulcerative colitis (53 percent), enrolled from three German clinics between February 2021 and January 2024. They were randomly allocated to the molecular medicine care group (n=48) or the standard best care group (n=54). Molecular reports for patients in the molecular medicine care group were provided at weeks 2, 14, 26 and 52. Conversely, reports for patients in the standard best care group were not shared.

The two groups were similar in terms of demographic and clinical characteristics. Overall, the patients were mostly male, and had a mean BMI of between 23 and 24 kg/m². Mean disease duration was 5–6 years, mean Crohn’s Disease Activity Index (CDAI) score was 237–311, mean Simple Endoscopic Score-Crohn's Disease (SES-CD) was 14–15, mean Partial Mayo Clinic Score (pMCS) was 5.3–5.5, mean Mayo Endoscopic Score (MES) was 2.5, mean C-reactive protein (CRP) level was 14–20 mg/L, and mean faecal calprotectin (fCal) level was 2,369–2,471 mg/g.

A total of 87 patients completed the study with available primary endpoint data to week 52. Comprehensive disease control was defined as a combination of clinical remission (CDAI <150; pMCS ≤1), endoscopic remission (SES-CD ≤4; MES ≤1), and biomarker normalization (CRP <5 mg/L, fCal <250 mg/g).