Late-breaking clinical science at DDW2026

Evan S. Dellon, from the University of North Carolina School of Medicine, presented 24-week results from the randomized, placebo-controlled REMOdeling with Dupilumab in Eosinophilic Esophagitis Long-term (REMODEL) trial. The study included 69 patients with active EoE and PPI resistance who were randomized 2:1 to receive dupilumab 300 mg weekly or placebo for 24 weeks, then continued to an open-label extension (OLE). The primary endpoint was the absolute change from baseline in the esophageal distensibility plateau at 24 weeks, measured by endoluminal functional imaging probe (EndoFLIP). This endpoint has been associated with endoscopic severity and the need for dilation. At 24 weeks, there was an absolute change of 1.28 from baseline in the treated group (n=41/46) compared to no change in the placebo group (n=22/23). The improvement with treatment was better in those with more severe disease, and narrowing worsened in the placebo group. Treatment also led to significant improvements in the EREFS total score and the inflammatory and fibrostenotic subscores, as well as histologic severity by grade and extent of disease. Dupilumab was well-tolerated, and the most common TEAEs were non-severe, self-limiting, and similar between the groups. Data from 104 week OLE will provide more insights into durability of effect.

Anouk G. Overdevest, MD, of Amsterdam UMC Locatie AMC, presented results from the multi-center randomized controlled COBRA trial examining the need for antibiotic treatment after acute cholangitis with adequate biliary drainage. Acute cholangitis can occur with bile flow obstruction and is associated with bacterial growth; treatment involves mechanical clearance of the obstruction followed by antibiotic treatment. Current guidelines recommend 4-7 days of antibiotics; however, development of microbial resistance with prolonged antibiotic use is associated with worse outcomes. Observational data suggests that for patients with adequate clearance of the bile duct, fewer days of antibiotic treatment are sufficient after acute cholangitis. The trial enrolled patients with acute cholangitis with distal obstruction who underwent biliary drainage and had no fever within 24 hours of the procedure. Patients were stratified by benign vs. malignant disease and randomized 1:1 to 1 day of antibiotics or 4-7 days of antibiotics, consistent with guidelines. The primary endpoint was clinical cure, defined as symptom-free by day 14 without relapse or death by day 30. The non-inferiority margin was an absolute risk difference greater than -7.5% between the groups. Of 745 screened patients, 433 were randomized to 1 day (n=218) or 4-7 days (n=215) of antibiotic treatment. The majority of patients were male with a median age of 75 years and moderate-to-severe acute cholangitis, and more than 35% had gram negative bacteriema. In the intent-to-treat analysis, 95.1% in the 1-day group achieved clinical cure versus 93.7% in the 4-7 day group. The difference was 1.5%, or within the non-inferiority threshold. Similar results were seen in the per-protocol group, by etiology and by gram negative bacteriemia. Both groups had a similarly low mortality rates and hospital stays, and approximately 10% in each group experienced relapse. A 1-day course of antibiotics may be sufficient for the treatment of acute cholangitis with adequate drainage and no fever (source control). For patients with continued fever (suggesting inadequate source control), longer antibiotic treatment would be necessary.