Dr Sands reviews the results of the DUET-CD study of combination therapy with guselkumab and golimumab in patients with Crohn's disease, which showed a significant increase in efficacy for the combination versus either drug independently.

Bruce Sands, MD, is chief of the Division of Gastroenterology at Mount Sinai in New York and Professor of Medicine at the Icahn School of Medicine at Mount Sinai.

DUET-CD Phase IIb: Golimumab + Guselkumab Combination Therapy in Refractory Crohn’s Disease Shows Additive Efficacy Over 48 Weeks

• At DDW 2026, Dr Bruce Sands presented results from the 48-week DUET-CD phase IIb study evaluating coformulated golimumab plus guselkumab combination therapy in Crohn’s disease versus either monotherapy in patients who had failed ≥1 systemic therapy mechanism of action, including many with multiple prior mechanism failures.
• In the overall DUET-CD population, the high-dose golimumab/guselkumab combination was superior to golimumab monotherapy and numerically superior, but not statistically significant, versus guselkumab monotherapy. Approximately 82% of patients who had failed one therapy class had previously failed a TNF blocker, and guselkumab showed strong activity in this subgroup. Endpoints included clinical remission by CDAI and endoscopic response by SES-CD.
• In the subgroup with failure of ≥2 systemic therapy classes, the high-dose combination demonstrated near-doubled efficacy versus monotherapies, including stronger effects on stringent outcomes such as endoscopic remission and deep remission (combined CDAI clinical remission plus endoscopic remission). No additional safety signal was observed versus known golimumab or guselkumab safety profiles despite dual active therapy exposure.

I'm Bruce Sands. I'm Chief of the Division of Gastroenterology at Mount Sinai in New York and Professor of Medicine at the Icahn School of Medicine at Mount Sinai. And I'm here at DDW 2026 in Chicago and very excited about my imminent presentation on the results for the DUET-CD study.

So DUET-CD comes from the concept of combination therapy and IBD. If you remember, we've been doing combination therapy for a long time based on the SONIC study, which is a combination of azathioprine and inflixmab, showing that when you put those two things together, that combination is better than monotherapy. But now we're reaching a plateauing of efficacy with any of our individual therapies, and we're looking for ways to overcome that plateauing.

There might be a few different ways in which we could do that. If we had precision medicine approaches, maybe we could do a biomarker test and identify a subset of patients who would have a remarkable response to one mechanism of action or another. But we really don't have that. Maybe we'd identify a new mechanism of action that might have transformative efficacy. We've been trying to identify that MOA for a long time, but we don't yet have that. So combination therapy may be the third way that we get there. And the idea is,obviously, inflammatory bowel disease is complex in its pathogenesis. There are many different pathways. We know that a patient who has one therapy, when they go on to the next therapy, they're less likely to respond. And every time you move on, you get lesser and lesser efficacy.

And so we're looking to move beyond that. We have a precedent for this in the VEGA study. VEGA was a phase 2A study which looked at the combination of golimumab, which is approved for treatment of ulcerative colitis, and guselkumab, which is an anti-IL-23 antibody that is also approved for treatment of ulcerative colitis. And in relatively treatment-naive patients with ulcerative colitis that was moderately to severely active, you saw a rough doubling of the efficacy when you put these 2 things together over either monotherapy.

So the DUET studies are an extension of this now. Moving to phase IIb, the idea was to look at more treatment refractory patient populations. And in fact, for both DUET-UC and DUET-CD, these patients who were enrolled had to have failed at least one mechanism of a systemic therapy—systemic therapy is the new designation for what we used to call advanced therapies —had to have failed at least one, but many had failed many. And we're talking about mechanism of action. They could have failed multiple agents within the same mechanism of action—for example, 2 or 3 anti-TNF antibodies could have been failed within that one class.

So a different population. And for the Crohn study, DUET-CD, of course, we had no phase IIa study in Crohn's disease at all. So the intention of this study was an exploration of this concept of combination therapy to see what the combination could do and to compare it to either of the monotherapy components.

And long story short, the overall study, if you looked at the overall population, about half of the patients had failed one systemic mechanism of action. And the other half had failed 1 or more mechanisms of action of systemic therapies. In the overall population, the comparison of the highest dose of the combination was dose ranging with the low, medium, and high dose combination—a fixed combination, though, in each of those dose levels. And these were coformulated, put in the same syringe, so administered together, not separate syringes.

What you saw is that the combination of the high dose was certainly superior to golimumab. When it came to the comparison of the combination to guselkumab, that was numerically superior to guselkumab, but was not statistically significant. And I think the reason for that is 82% of the patients who had failed one class of agents had failed a TNF blocker. And we know from the GALAXI studies that actually you have very high success rate, with the guselkumab in patients who had failed in anti-TNF, so that makes sense.

However, if you went on to analyze the data according to patients, the roughly half of patients who had failed 2 or more classes of advanced therapies or systemic therapies, there you saw a real difference. With that comparison of the high dose of the combination, you saw roughly additive efficacy of what you saw for each of the monotherapies, or in fact, a rough doubling of the efficacy of them. And so this was very meaningful for us because this is a very difficult group of patients to treat, a very needy patient population. I would estimate that something like 15 to 20% of our patients end up that way, and probably that number is rising as we use more and more advanced therapies.

If you looked—and I should say that the endpoints here were both clinical remission by the CDAI and endoscopic response by the SES-CD, so that was sort of additive benefit—if you looked at even more stringent outcomes, things like endoscopic remission or the holy grail of deep remission, a patient who achieves both clinical remission by CDAI and endoscopic remission, there those outcomes for the combination seem to be beyond additive in efficacy. They really seem to show some synergy, in fact. And that's what we expected from the preclinical rationale, actually.

So I think this is very meaningful. It means that when a patient with Crohn's disease has failed 2 mechanisms of systemic therapies, we shouldn't cast about and keep going

for one after the other monotherapy. The concept would be that now would be the time then to go for this combination therapy when it's available in the market.

And the last thing that I'll say is, do we have good safety when we combine two active agents? And the good news is that we don't see any additional safety signal. We see basically the same signal that we see for the anti-TNF, golimumab, and guselkumab. So no increase in safety concern. And that's very important for our patients.

So this was a long-term study, 48 weeks, a very meaningful result, even though it missed its primary analysis.