Study highlights breakthrough in overcoming diminishing returns of sequential IBD therapies

For patients with Crohn's disease or ulcerative colitis who have exhausted other treatment options, a new combination therapy is showing results that offer hope for one of medicine's most treatment-resistant populations, according to findings from two studies to be presented today at Digestive Disease Week® (DDW) 2026.

"Currently in IBD treatment each successive therapy produces diminishing returns, and patients who have failed multiple treatments have very limited options," said Bruce E. Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine, and Chief, Division of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Health System, lead author of the Crohn's disease study.

By combining two mechanisms of action, we're seeing efficacy that appears to be additive - without increasing safety risk."

Bruce E. Sands, Mount Sinai Health System

The findings come from two parallel Phase 2b trials - DUET-Crohn's and DUET-UC - testing JNJ-78934804 (JNJ-4804), a new combination fixed-dose co-antibody therapy designed to target two inflammatory pathways simultaneously. Taken alone, each drug - guselkumab and golimumab - targets a different protein that drives inflammation. Blocking both pathways at once, the combination aims to achieve deeper, more lasting results.

"In some patients, the immune system essentially finds a way around single therapies," said Maria T. Abreu, MD, Executive Director, F. Widjaja IBD Institute at Cedars-Sinai and lead author of the ulcerative colitis study. "By targeting two pathways at once, we may be able to 'outsmart' the immune system and achieve better outcomes."

Both trials enrolled patients with moderate-to-severely active disease who had already failed one or more therapies, including biologics and novel oral agents. For those patients who had failed two or more prior treatments, high-dose JNJ-4804 showed improved outcomes compared with golimumab and similar efficacy to guselkumab across key measures of remission and endoscopic improvement at 48 weeks.

The trials shared the same design. Patients were randomized to receive either a placebo, one of two existing biologics - golimumab, an anti-TNF therapy, or guselkumab, an anti-IL-23 therapy - or JNJ-4804, which combines both, at one of three doses. The Crohn's trial enrolled 693 patients; the UC trial enrolled 572. In both studies, roughly half the patients had already failed two or more systemic therapies - a reality experienced by a significant percentage of individuals with both forms of IBD, noted Sands, a paid consultant for Johnson & Johnson separate from this study.

In the Crohn's disease trial, patients receiving high-dose JNJ-4804 were significantly more likely to achieve clinical remission and endoscopic response at 48 weeks than those receiving golimumab alone. The advantage was clearest in the most treatment-resistant patients - those who had failed two or more prior therapies. In that subgroup, clinical remission rates with high-dose JNJ-4804 were more than 20 percentage points higher than guselkumab in this subgroup, and nearly 40 percentage points higher than placebo.

Results in the ulcerative colitis trial followed a similar pattern. High-dose JNJ-4804 significantly outperformed golimumab on the primary endpoint of clinical remission at 48 weeks, and the combination's advantage was again most pronounced in patients who had failed two or more prior treatments. In that subgroup, clinical remission rates ran more than 20 percentage points higher than guselkumab and nearly 20 percentage points higher than placebo, with similarly meaningful gaps in endoscopic improvement and histologic remission, a measure of healing at the tissue level.

The safety profile of JNJ-4804 was comparable to either monotherapy used alone. Serious adverse events were uncommon across both trials and primarily gastrointestinal in nature. Based on these results, the researchers say the combination is ready to advance to Phase 3 trials. Both studies were sponsored by Johnson & Johnson.