- Current treatments for inflammatory bowel disease (IBD) focus on reducing inflammation and relieving symptoms through therapies such as medications.
- However, some people with IBD, which includes ulcerative colitis and Crohn’s disease, don’t respond to any type of therapy.
- Two new studies found that a combination of two medications may offer better results in treating IBD than using each drug individually, especially in people where other therapies had previously failed.
There is currently no cure for IBD. Current treatments focus on lowering inflammation and symptom relief through the use of medications, lifestyle changes, and surgery, in the hopes of achieving remission.
Unfortunately, not all medications work for everyone with IBD. Past studies show that between one-third to one-half of people with IBD don’t respond to any type of therapy.
Now, two new studies recently presented at Digestive Disease Week® (DDW) 2026 report that a combination of two medications may offer better results in treating IBD than using each drug individually, especially in people where other therapies had previously failed.
The findings of these studies have yet to be published in a peer-reviewed scientific journal.
Scientists conducted two Phase 2b clinical trials sponsored by Johnson & Johnson in tandem — DUET-Crohn’s and DUET-UC — which examined the use of a combination fixed-dose co-antibody therapy known as JNJ-4804 that combined the medications anti-IL-23 therapy guselkumab and an anti-TNF antibody called golimumab.
“We’ve seen an explosion of new kinds of treatments over the last 25 years to treat IBD,” Bruce E. Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine, and chief of the Division of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Health System, and lead author of the Crohn’s disease study, told Medical News Today.
“But unfortunately, while many of these drugs are quite effective, we’re seeing a plateauing of efficacy over time. We need to keep finding new therapies that work better and hopefully are more durable and also have good safety,” he said.
Studying two-drugs-in-one
“Crohn’s disease and ulcerative colitis are very complex immunologic diseases, and there are a lot of different pathways by which the disease occurs. So we think that if we block more than one of these pathways at the same time, we might get [more] additive benefit. So the DUET studies, both Crohn’s and UC, were designed to explore this by comparing a combination of two therapies to either one of those therapies alone.”
— Bruce E. Sands, MD, MS
“Importantly, the study only allowed patients to come into the study that had already been on [at] least one previous advanced systemic therapy mechanism,” added Maria T. Abreu, MD, executive director of the F. Widjaja IBD Institute at Cedars-Sinai, and lead author of the ulcerative colitis study. “So, for example, they could have been previously on anti-TNF, they could have previously been on anti-IL-23, [a]nd they could have been on a multiple of these.”
“Usually the low hanging fruit is to treat patients that have been on nothing,” Abreu explained to MNT. “If they’ve been on nothing, the world is your oyster. Most things help people who have been on nothing. But those patients that have been on previous medications and that medication either lost its mojo, lost its effect, or never had an effect, are more refractory to treatment.”
“It’s actually possible that the immune system changes because now if you suppress only one thing, the immune system tries to find a way around it to continue this inflammatory response,” she said. “And so they were essentially asking for patients to be enrolled that were the most difficult to treat patients.”
Researchers recruited 693 participants for the Crohn’s study and 572 for the UC study. Participants randomly received either a placebo, just golimumab, just guselkumab, or the combination therapy JNJ-4804.
At the conclusion of the UC clinical trial, researchers discovered that for study participants who had previously tried and failed one or more therapies, JNJ-4804 showed improved outcomes when compared with golimumab, as well as similar efficacy to guselkumab across key measures of remission and endoscopic improvement at 48 weeks. While in the CD trial, the highest dose of JNJ-4804 outperformed both individual drugs.
“For patients that have failed two or more mechanisms of action, which we’re getting more and more as we expand our armamentarium, it makes a lot of sense that we’re going to be using combinations of therapy,” Abreu explained.
“Ideally, they will be rational, meaning that the therapies will be complementary in their mechanisms of action and have some thought behind them. And this is really the first foray into that, is using this combination. So I think we’ll be reserving our combination therapies, at least for now, for the patients that are the neediest patients,” she said.
Although the results from these trials are promising, people with IBD may have to wait longer before this therapy becomes readily available as standard treatment.
“I think the significance of these studies is not only the direct results that show that this particular combination of anti-TNF and anti-IL-23, golimumab and guselkumab, is more effective than either one alone in the patients who have failed two or more classes of therapies. It speaks more broadly to the idea that combination therapies are a promising direction for the treatment of people with IBD in general.”
— Bruce E. Sands, MD, MS
“And very importantly, at least for this combination, we hope that in future combinations, there’s no increase in safety events, so there’s no more risk to the combination,” Sands said.
“These were phase 2B studies, so to get approved, this combination will have to enter into phase 3 studies, which are considered the registrational studies that would lead to approval of the drug,” he explained.
“And because they will be large studies and will take a while to conduct, I imagine that we wouldn’t see these approved earlier than two-and-a-half or perhaps three years. But in the meantime, there’s a lot of excitement about that,” he added.
Alyssa Parian, MD, director of the Center for Inflammatory Bowel Disease (CIBD), a comprehensive program offering specialized care for patients with IBD and related colorectal conditions, who was not involved in the study, spoke to MNT about these studies.
“We are already frequently using dual advanced therapy in our practice for patients with severe refractory disease,” Parian said. “These controlled trials help solidify what we are seeing clinically, that these patients have improved response to dual therapy and provide long-term safety data.”
“The concept of a ‘co-antibody’ therapy that targets two inflammatory pathways at once is a significant step forward. Seeing that this approach may be able to ‘outsmart’ the immune system, as Dr. Abreu mentioned, is very exciting. The fact that the combination therapy shows additive efficacy without increasing safety risks is a critical finding.”
— Alyssa Parian, MD
“Long-term monitoring for durability will be critical as there may be concerns that the immune system may continue to find ways around even dual therapies,” Parian added.
MNT also spoke with Ashkan Farhadi, MD, a board certified gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, about these two clinical trials.
Farhadi said it’s very important for researchers to continue to find new treatments for IBD, especially for those people for whom current treatments may not be working. He explained that many times, people with IBD are considered to be a heterogeneous group under one umbrella, but this tells us that maybe they are not one disease.
“They are different diseases that they present very similar, and we call them all the same,” Farhadi continued. “And this is maybe why some of those patients respond beautifully to one medication and the other one does not.”
Some IBD patients don’t respond to treatments
“In general, over the board, we’re having something in a range of 30-50% or sometimes 58% response rates in all these medications. And then you put them in the context that you’re having 20-30% placebo response over the board, we’re having almost 40% of people who are not responding to particular medicine.”
— Ashkan Farhadi, MD
“And if you even switch (their medication), you may not get a response,” he added. “So it’s kind of natural to think that if you just use two medications, you can get a better response. So it’s not that out of touch, if you want to think about it.”
