New Crohn's data spotlight promising therapies
Beyond drugs, interest is growing in diet-based treatments.
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01/29/2026
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by Doug Brunk
Several important developments in Crohn’s disease treatment have emerged over the past year, offering clinicians new options and patients renewed hope. During the 2026 Crohn’s & Colitis Congress®, a partnership of AGA and the Crohn’s & Colitis Foundation, held in Las Vegas, Ryan C. Ungaro, MD, MS, Associate Professor and of Clinical Research in the Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, highlighted the growing role of IL-23 inhibitors, the impact of disease location on treatment response, and early signals that diet and digital health tools may help guide care.
Three IL-23 inhibitors are now available, with mirikizumab and guselkumab receiving FDA approval within the past year. In large clinical trials, Dr. Ungaro said, mirikizumab significantly improved symptoms and intestinal healing compared with placebo, both in patients who had never used biologics and in those who had failed prior therapies. When directly compared with ustekinumab, mirikizumab achieved similar clinical remission rates at one year, but was not superior in endoscopic outcomes.
Guselkumab also showed strong results. In the GRAVITI and GALAXI trials, patients treated with guselkumab were more likely to achieve clinical remission and endoscopic improvement than those receiving placebo. “Notably, guselkumab performed similarly whether induction therapy was given intravenously or by injection under the skin, offering flexibility in clinical practice,” Dr. Ungaro said. In maintenance studies, guselkumab appeared superior to ustekinumab across several key outcomes.
According to Dr. Ungaro, one common clinical question is whether prior exposure to ustekinumab reduces response to newer IL-23 inhibitors. Trial data presented at the 2025 meeting of the American College of Gastroenterology suggests it does not. Patients who switched from ustekinumab to guselkumab achieved similar response and remission rates as those previously treated with other biologics, supporting IL-23 inhibitors as a viable option even after earlier treatment failure.
Disease location also matters. A large analysis found that most advanced therapies work better in colonic Crohn’s disease than in disease affecting the small intestine. Among available options, IL-23 inhibitors and infliximab appeared to have the strongest effects in ileal disease, while JAK inhibitors showed less benefit in that setting. Infliximab, in particular, demonstrated similar healing rates in both ileal and colonic disease. Dr. Ungaro also cited a review paper on combined advanced targeted therapy in IBD.
New data also support vedolizumab for preventing Crohn’s disease recurrence after surgery. In a randomized trial known as REPREVIO, patients who received vedolizumab shortly after bowel resection had significantly less endoscopic recurrence than those given placebo.
Beyond drugs, Dr. Ungaro said, interest is growing in diet-based therapies. In the ADAPT trial, which was presented at the 2025 European Crohn’s and Colitis Organization Conference in Berlin, 154 patients with mild to moderate Crohn’s disease who followed a low-emulsifier diet were more likely to experience symptom improvement and reductions in fecal calprotectin over eight weeks compared with those on an emulsifier-rich diet. While short-term, the findings provide practical dietary guidance that may complement medical therapy.
“Even looking at the fecal-calprotectin response, there was a significant increased rate of fecal-calprotectin decrease in patients who were on the low emulsifier diet,” Dr. Ungaro added. “It’s intriguing data, [but] I think further longer-term data are needed and it’s always important to involve nutritionists when you’re able to in these discussions.”
Looking ahead, stem cell transplantation is being used for highly refractory disease in specialized centers, wearable devices to predict flares weeks in advance, and even trials aimed at preventing CD in high-risk individuals. For example, the INTERCEPT project, launched in January 2025, is recruiting 10,000 first-degree relatives of people with CD in seven European countries. The goal is to confirm a group of biological markers and develop a blood test score that can identify people who are likely to develop CD and enroll the highest risk individuals in a disease interception trial with vedolizumab.
“This is still in early days, but disease prediction and prevention is very interesting and an exciting area of research,” Dr. Ungaro said.
Dr. Ungaro disclosed that he is an advisor to and consultant for AbbVie, Bristol Myers Squibb, Genentech, Janssen, Lilly, Pfizer, and Takeda. He has also received research funding from the Crohn’s & Colitis Foundation, AbbVie, Boehringer Ingelheim, Pfizer, Prometheus Laboratories, Department of Defense, the National Institutes of Health, and the Helmsley Foundation.
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7 Key Takeaways
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Developed a paper-based colorimetric sensor array for chemical threat detection.
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Can detect 12 chemical agents, including industrial toxins.
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Utilizes dye-loaded silica particles on self-adhesive paper.
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Provides rapid, simultaneous identification through image analysis.
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Future developments include a machine learning-enabled reader device.
The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.