DDW 2026
Dual‑mechanism therapy shows promise beyond monotherapy in refractory IBD
Clinical takeaway: In patients with moderate to severe IBD refractory to multiple biologics or oral agents, a fixed‑dose combination targeting both TNF and IL‑23 pathways achieved higher remission rates than anti‑TNF therapy alone, with a comparable safety profile—supporting combination biologic strategies for the most treatment‑resistant cases.
Patients with inflammatory bowel disease (IBD) who fail successive therapies often face diminishing benefits and limited options. New data presented at Digestive Disease Week (DDW) 2026 suggest that targeting two inflammatory pathways simultaneously may help overcome this plateau.
“In some patients, the immune system essentially finds a way around single therapies,” said Maria T. Abreu, MD of Cedars-Sinai and lead study author. “By targeting two pathways at once, we may be able to ’outsmart’ the immune system and achieve better outcomes.”
Results from two parallel phase 2b trials—DUET‑CD (N=693) and DUET‑UC (N=572)—evaluated JNJ‑78934804 (JNJ‑4804), a fixed‑dose co‑antibody combining guselkumab (anti‑IL‑23) and golimumab (anti‑TNF). Participants had moderate‑to‑severely active Crohn’s disease or ulcerative colitis and had failed at least one prior therapy; about half had failed two or more systemic treatments.
At 48 weeks, high‑dose JNJ‑4804 significantly outperformed golimumab alone across key endpoints, including clinical remission and endoscopic response. Benefits were most pronounced in the most treatment‑resistant subgroup: among patients with ≥2 prior treatment failures, remission rates were >20 percentage points higher than guselkumab and ~40 points higher than placebo in Crohn’s disease, with similar advantages observed in ulcerative colitis. In UC, gains also extended to endoscopic improvement and histologic remission.
Safety was comparable to monotherapy, with uncommon serious adverse events, largely gastrointestinal. Investigators described the results as potentially transformational and noted the therapy is poised to advance to phase 3 trials.
“Despite many treatment advances for Crohn’s disease over the past two decades, many patients do not achieve long-term disease control with the currently available options, even after trying multiple monotherapies with different classes,” said Bruce E. Sands, MD, MS, of Icahn School of Medicine and Mount Sinai Health System. “The results from DUET-CD are particularly promising because they show meaningful clinical and endoscopic improvements in patients who have exhausted existing options.”
Sources:
Sands BE. Digestive Disease Week 2026 Abstract 979f. Efficacy and safety of the first co‑antibody therapy, JNJ‑78934804, in patients with moderately to severely active Crohn’s disease refractory to systemic therapies
Abreu MT. Digestive Disease Week 2026 Abstract 1058b. Efficacy and safety of the first co‑antibody therapy, JNJ‑78934804, in patients with moderately to severely active ulcerative colitis refractory to systemic therapies