David T. Rubin, MD is a professor of medicine at the University of Chicago, director of the Inflammatory Bowel Disease Center, and chair of the International Organization for the Study of IBD (IOIBD).

David Rubin, MD

Patients with moderately to severely active 

 and non-passable intestinal stenosis at baseline had improvement to passable or no stenosis with guselkumab, with gains growing from week 48 to week 96. These post hoc results from the phase 3 GALAXI 2 and 3 and GRAVITI studies were presented at the 

American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting

Translational analyses also showed guselkumab reduced inflammatory and fibrosis-associated fibroblast gene activity in the ileum, while ustekinumab showed limited changes.¹ David Rubin, MD, of the University of Chicago Medicine Inflammatory Bowel Disease Center, told 

 narrowing in CD is not always fibrotic, and recognizing the difference matters for treatment.

“The distinction between a stenosis that’s not fibrotic or is only partially fibrotic, and a stenosis that is too fibrotic to respond to anti-inflammatory therapy is very important,” said Rubin.

Can Guselkumab Reverse Stenosis in Crohn’s Disease? With David Rubin, MD

Intestinal Stenosis Burden in Crohn’s Disease

Intestinal stenosis can cause obstructive symptoms including cramping, pain, nausea, and vomiting, and often leads to dilation or surgery. Evidence on whether biologics can improve stenosis remains limited.¹

Guselkumab, a dual-acting interleukin-23p19 subunit inhibitor, received US Food and Drug Administration approval for moderately to severely active CD in March 2025. It was the first IL-23 inhibitor approved with both intravenous (IV) and subcutaneous (SC) induction options.⁴

GALAXI and GRAVITI Stenosis Analysis Design

GALAXI 2 and 3 evaluated guselkumab 200 mg IV induction, and GRAVITI evaluated 400 mg SC induction, each at weeks 0, 4, and 8.²,³ Maintenance was 100 mg SC every 8 weeks or 200 mg SC every 4 weeks, and GALAXI also included an ustekinumab arm. Patients with symptomatic stenoses or stenoses requiring surgery were excluded from enrollment.¹

Stenosis status was graded using the narrowing component of the Simple Endoscopic Score for Crohn’s Disease (SES-CD), with a score of 3 indicating a non-passable narrowing. Across the pooled studies, 315 of 1103 patients (28.6%) randomized to active treatment had non-passable stenosis at baseline.¹ Rubin noted stenosis is already captured in the SES-CD, so the analysis relied on data collected routinely in the trials.

Stenosis Improvement With Guselkumab Through Week 96

In GALAXI, 33.5% of guselkumab-treated patients with non-passable stenosis at baseline improved to passable or no stenosis by week 12.¹ By week 48, 43.9% of patients receiving guselkumab 100 mg and 41.9% receiving 200 mg had improved, rising to 47.6% and 51.5%, respectively, at week 96.

Complete resolution to no stenosis at week 96 occurred in 38.1% and 44.1% of patients in the 100 mg and 200 mg groups, respectively.¹ Patients receiving ustekinumab also improved, with 38.9% reaching passable or no stenosis at week 96.

In GRAVITI, non-passable stenosis persisted at week 96 in 40.0% of patients receiving guselkumab 100 mg and 51.7% receiving 200 mg.¹ Rubin added few patients developed new stenoses after treatment, countering a long-held concern healing might cause new narrowing.

Fibroblast Biology Changes Linked to Stenosis Improvement

RNA sequencing of ileal biopsies from a GALAXI subset showed improvement in ileal stenosis was associated with reductions in fibrosis-associated and inflammatory fibroblast gene modules.¹ Guselkumab significantly reduced inflammatory fibroblast activity by week 12, followed by further reductions in fibrosis-related biology by week 48. It also increased gene modules linked to epithelial- and mucosa-supporting fibroblasts.

Ustekinumab showed no significant changes in ileal fibroblast biology.¹ Rubin said the biomarker work is preliminary but may eventually help identify which patients with stenosis are likely to respond to medical therapy.

“We don’t want to just give people who are obstructed or partially obstructed medical therapy and hope it’s going to work,” said Rubin.

Editors’ note: Rubin reports relevant disclosures with AbbVie, Abivax, Bristol Myers Squibb, Celltrion, Eli Lilly, Genentech, J&J, and others.

Reinisch W, Afzali A, Bassiri H, et al. Changes in intestinal stenosis among patients with moderately to severely active Crohn’s disease treated with guselkumab: results from the phase 3 GALAXI and GRAVITI studies. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

Panaccione R, Feagan BG, Afzali A, et al. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn’s disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials. Lancet. 2025;406(10501):358-375. doi:10.1016/S0140-6736(25)00681-6

Hart A, Panaccione R, Steinwurz F, et al. Efficacy and safety of guselkumab subcutaneous induction and maintenance in participants with moderately to severely active Crohn’s disease: results from the phase 3 GRAVITI study. Gastroenterology. 2025;169(2):308-325. doi:10.1053/j.gastro.2025.02.033

U.S. FDA approves Tremfya (guselkumab), the first and only IL-23 inhibitor offering both subcutaneous and intravenous induction options for adult patients with moderately to severely active Crohn’s disease. News release. Johnson & Johnson. March 20, 2025. Accessed October 19, 2026. 

https://www.jnj.com/media-center/press-releases/u-s-fda-approves-tremfya-guselkumab-the-first-and-only-il-23-inhibitor-offering-both-subcutaneous-and-intravenous-induction-options-for-adult-patients-with-moderately-to-severely-active-crohns-disease

Videos

David Rubin, MD, discusses GALAXI and GRAVITI data showing guselkumab improved non-passable intestinal stenosis in Crohn’s disease through 2 years.

Guselkumab and Intestinal Stenosis in Crohn’s Disease, With David Rubin, MD

Most patients with moderately to severely active 

 who reached histologic remission on guselkumab maintained it through 3 years, according to a post hoc analysis of the QUASAR long-term extension (LTE). The findings were presented at the 

Among patients in histologic remission at the start of maintenance, 75.9% receiving guselkumab 100 mg every 8 weeks and 81.3% receiving 200 mg every 4 weeks remained in histologic remission at maintenance week 140.

Although histologic outcomes are frequently reported in UC trials, long-term changes over multiple years have not been well characterized.

David Rubin, MD, of the University of Chicago Medicine Inflammatory Bowel Disease Center, told 

 the analysis shows histologic remission is achievable in most responders and relatively stable once reached.

Guselkumab in Ulcerative Colitis: Is Histologic Remission Durable?

QUASAR Long-Term Extension Design and Histologic Assessment

QUASAR enrolled adults with a modified Mayo score of 5 to 9, a rectal bleeding subscore ≥ 1, and an endoscopic subscore of 2 or 3.

 Patients in clinical response 12 weeks after intravenous guselkumab induction were randomly assigned in a 1:1:1 ratio to subcutaneous guselkumab 100 mg every 8 weeks, 200 mg every 4 weeks, or placebo. In the primary maintenance analysis, clinical remission at week 44 was achieved by 45% and 50% of patients receiving guselkumab, respectively, vs 19% with placebo.

Patients receiving 100 mg who lost response between maintenance weeks 8 and 32 received a blinded dose adjustment to 200 mg every 4 weeks. Biopsies were collected at induction baseline and at maintenance weeks 0, 44, 92, and 140, and scored using the Geboes system. The analysis included 137 patients in the 100-mg group and 130 in the 200-mg group with evaluations at every time point.

Histologic remission was defined as the absence of neutrophils in the lamina propria and epithelium, with no crypt destruction, erosions, ulcerations, or granulation tissue. In the LTE randomized population, 38.7% and 41.9% of patients had a prior inadequate response or intolerance to advanced therapy.

Histologic Improvement Through 3 Years of Guselkumab

At induction baseline, 91.9% of patients in the 100-mg group and 86.1% in the 200-mg group had Geboes scores of 3.2 to 5.4. After 12 weeks of intravenous induction, 62.7% and 63.9%, respectively, had Geboes scores of 0.0 to 3.1. This proportion rose to 76.6% and 83.9% at maintenance week 44 and held at 79.6% and 83.1% at week 140.

The proportion of patients with the most severe Geboes scores of 5.3 or 5.4 fell from 28.4% and 26.1% at induction baseline to 5.8% and 6.9% at maintenance week 0, reaching 3.6% and 2.3% at week 140.

At the start of maintenance, 56.4% (79/140) of patients receiving 100 mg and 57.3% (75/131) receiving 200 mg were in histologic remission. Of these, 75.9% (60/79) and 81.3% (61/75) remained in remission at week 140, and 53.2% (42/79) and 61.3% (46/75) were in remission at every maintenance time point.

“If you had histological remission at the end of 1 year, you were likely to still be there at the ends of 2 and 3 years,” Rubin explained.

He noted most gains occurred within the first year of treatment, with little additional improvement afterward. He added the 200-mg dose appeared numerically more effective, although the analysis was not powered to compare doses.

Histology, Endoscopy, and Treatment Targets in UC

The investigators reported histologic improvement trends over time were similar to previously reported endoscopic trends in QUASAR.

 Rubin said Mayo endoscopic scores appeared less healed than histology at corresponding time points, and he outlined possible explanations, including histologic improvement preceding visible mucosal healing.

“My own hypothesis is that it starts with histological improvement,” said Rubin. “That’s where the therapy might be working directly and having an effect, and the mucosa catches up later, and that might be why we’re seeing what we see.”

Rubin said the next step is determining whether treatment decisions should be guided by symptoms, endoscopy, histology, or all 3. He pointed to the VERDICT trial of vedolizumab, being presented at United European Gastroenterology Week, as a complementary study testing whether targeting histologic remission improves outcomes.

Rubin DT, Allegretti JR, Alvarez Y, et al. Histology outcomes over time in patients with moderately to severely active ulcerative colitis treated with guselkumab in the QUASAR long-term extension study. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49. doi:10.1016/S0140-6736(24)01927-5

David Rubin, MD, discusses QUASAR extension data showing most patients in histologic remission on guselkumab stayed there through 3 years of maintenance.

Guselkumab Sustains Histologic Healing in Ulcerative Colitis Over 3 Years

Comprehensive disease control is a familiar phrase in 

 circles by now. Pairing standardized quality-of-life measures with symptom control and endoscopic healing brings the endpoint closer to what patients actually experience. What remains less familiar is the first step: asking patients what the disease is actually taking from them.

David T. Rubin, MD, argues the concept alone will not move outcomes without a method attached to it: specific screening questions, validated instruments, and a therapy choice tied to what the screen turns up. Without it, quality of life stays a talking point rather than a target.

Patients with IBD carry a significantly higher burden of anxiety and depression than the general population. In a 2026 Norwegian cohort, 37.4% of patients with Crohn's disease and 32.1% with 

 screened positive for anxiety, compared with 17.5% among matched controls.¹ Despite this gap, the American Gastroenterological Association's recommendation of annual depression and anxiety screening for every adult with IBD is inconsistently followed in practice.²

Rubin is professor of medicine at the University of Chicago, director of the Inflammatory Bowel Disease Center, and chair of the International Organization for the Study of IBD (IOIBD). He built comprehensive disease control around three sequential tiers of remission: symptomatic relief, biological control of inflammation, and functional remission covering joint, mental, and sexual health. "If you don't ask, you won't know," Rubin said.

Below, Rubin walks through the specific questions and validated tools he uses to surface functional limitations patients rarely volunteer. He also explains why referral infrastructure and visit time work against routine screening, and how comorbid joint or skin disease guides his choice of therapy.

Q&A: IBD screening tools and biologic selection by comorbidity

HCPLive: Can you describe what comprehensive disease control means in inflammatory bowel disease? 

 The topic is comprehensive disease control, sometimes called comprehensive disease management. It's the evolution of our attempt to provide improved quality of life for people living with Crohn's disease and ulcerative colitis.

It's based on the principle that ultimately, what we're trying to do for anybody suffering from anything, frankly, is improve their quality of life. As much as our many treatments for Crohn's and colitis have evolved and multiplied, they're focused on specific clinical trial endpoints centered on the bowel. But we recognize these conditions affect much more than the intestines. To take care of people properly, we need to think about the whole person.

The way I describe it is a more holistic approach to management. Thinking about the whole person means addressing coexisting extraintestinal manifestations, like joint pain or skin inflammation, but also going beyond that to what I've started calling atypical extraintestinal manifestations, or less traditional ones, like mental health disorders. People with inflammatory bowel disease have a higher prevalence of anxiety and depression than those without IBD. Sexual health is affected by bowel conditions, so is sleep quality. Ultimately, what we're trying to do is improve individuals' functioning and quality of life, what I usually describe as an unrestricted, high quality of life.

The way I break this down in my practice is by talking to my patients about three types of remission. This is a chronic inflammatory problem in which the immune system of their gut is trying to do its job when it's not really needed, meaning it's active when, as far as we can tell, there's no threat or infection, and it's chronic, meaning it's not shutting itself off.

So when we talk about remission, the first thing is turning off the inflammation so the patient feels perfect: no pain, no diarrhea, no bleeding, no urgency. Second, we want objective evidence that we're controlling the disease process. That means biological markers of inflammation are normalized, whether that's scopes, stool tests, or blood tests. In children, it's growth and development. Those markers show you've controlled the actual inflammation beyond symptoms. The reason you have to look at both is that 50% of people who feel well or feel better will still be inflamed, and if you're still inflamed despite feeling okay, you will relapse. There'll be progression of the disease to a complication, or there'll be a full relapse of clinical symptoms. So the way I say it to people is: I want you to feel perfect, but I want it to last forever, and that means we have to control the disease process.

The third type of remission I call functional remission. This is where we say no joint pain, no skin inflammation, no depression or anxiety, your sexual health is restored, and you're able to do everything else you want to do in life: have children, work, go to school, maintain your career, travel without worry. Functional remission is our ultimate goal, but you have to do them in order. You want the bowel symptoms to be better, you want to control the disease process, then you want to make sure you're addressing all these other problems.

So comprehensive disease control is a construct that looks at an endpoint that includes the usual clinical trial endpoints of patient-reported symptoms and disease control related to endoscopy or labs, but it adds a standardized version of quality of life. When you add IBD quality-of-life measures to symptoms and endoscopy or other biomarkers, that's what we're calling CDC.

When you raise the bar, you start to realize that even when you have people whose bowels are perfect, you're not improving their quality of life because you haven't addressed the other issues. It sounds obvious, but the reality is that until you start looking at it and combining it with these other measures, you're not going to get a full picture of what it takes to heal. Healing is different than just treating inflammation.

HCPLive: How are you individualizing treatment options, and are certain patients at higher risk or likely to need more time?

 Those are great questions, and really important ones. The answer is, first, that if you don't ask, you won't know, and it starts by making sure you're not losing sight of your ultimate goal: an improved quality of life. Sometimes both the patient and the clinician can become too focused on bowel symptoms, or bleeding, or anemia. The reality is you end up missing the main picture: the patient may be unable to leave the house, or their hands hurt so they can't type, which is part of their job. There are other pieces to this, so you have to start by knowing you need to ask.

There are different ways to do that. One question you can ask a patient is, "What does having this disease prevent you from doing that you would want to do?" Or, "What are you unable to eat that you would like to enjoy?" You start to learn about somebody's limitations from the disease so you can develop a treatment plan that addresses them.

The other part is incorporating standardized and validated screening tools. If you want to know if somebody is anxious or depressed, there are measures you can use in clinic: a generalized anxiety scoring system, or the health questionnaire called the PHQ-9, which detects depression. If you screen for it, you will find it, and I'd challenge my colleagues to consider doing this, not only because it's in the guidelines for management, but because they'll uncover that many of their patients screen positive even when they had no idea. I've had colleagues say, "I can tell when one of my patients is depressed." I'd challenge that. I think there are a lot of people who are depressed that you'd never be able to tell in a limited clinical encounter.

But the other reason people don't routinely ask is you also have to have a treatment option and the ability to provide care if you identify these issues. Where are you going to refer the patient if they have depression or anxiety? Very few centers like ours have a psychogastroenterologist to refer them to, so we need a system in our clinics if we're going to screen for it, so that we're able to refer people. Or asking about sexual health: we're not taught that in medical school, or we weren't when I was in training. So how do you ask about that?

Meanwhile, who has time? I don't mean that as though it's not important, so why make time? I mean in a busy clinical practice, when you have a 20-minute encounter if you're lucky, most people only get 15, and you're trying to figure out how to talk about a new therapy, the goals of management, when their scope is due, any pre-testing before a new treatment, what their insurance may or may not cover, how you'll follow up on lab results. How do you do all that, and by the way, tell me about your sex life, or fill out this survey and tell me if you're anxious or depressed?

There are some very big system issues preventing us from providing the care people need. Whether we measure it in clinical trials or in post-hoc analyses and call it CDC, the real issue isn't just that we're underestimating the prevalence of these other problems. The issue is we need a different care model to give clinicians the time and resources to manage these conditions properly.

Now, the last part of this is choosing therapies, and this factors into quality of life and a variety of other things. If a patient has inflammatory joint problems coexisting with their IBD, you'd want to choose a treatment likely to cover the joint inflammation too, which means leaning toward an anti-TNF or a JAK inhibitor. If they have coexisting skin problems, whether psoriasis, erythema nodosum, or pyoderma, you might lean toward an IL-23 inhibitor, which is effective for skin and bowel together. You can pick therapies based on knowing about some of these other challenges. A patient with IBD deserves care that tries to address these issues. The reason it's not routinely done, and the reason it's important for HCPLive to discuss and share, is it hasn't been incorporated into practice the way it should be.

Editor’s Note: Rubin reports relevant disclosures with AbbVie, Takeda, Pfizer, Janssen, Bristol Myers Squibb, and others.

Johansen I, Hagen MC, Løkkeberg ST, et al. Anxiety and depression in newly diagnosed patients with inflammatory bowel disease (the IBSEN III study) compared with the general population in Norway. 

. 2026;20(3):jjag021. doi:10.1093/ecco-jcc/jjag021

Caldera F, Kane S, Hashash JG, et al. AGA Clinical Practice Update on Noncolorectal Cancer Screening and Vaccinations in Patients With Inflammatory Bowel Disease: Expert Review. 

. 2025;23(5). doi:10.1016/j.cgh.2024.12.011

Articles

Comprehensive disease control in IBD extends beyond bowel-centric endpoints by integrating symptom remission, objective inflammatory control, and functional remission encompassing mental, sexual, sleep, and extraintestinal health. Anxiety and depression are substantially more prevalent in Crohn’s disease and ulcerative colitis than in matched controls, yet guideline-recommended annual screening remains inconsistently implemented. Practical execution requires asking targeted limitation-focused questions and applying validated tools (e.g., GAD scales, PHQ-9), coupled to clear treatment and referral pathways. Time constraints and limited behavioral-health infrastructure remain major barriers.

David T. Rubin, MD, on the screening tools, direct questions, and therapy choices behind IBD's three tiers of remission.

Comprehensive Disease Control Starts With Asking, With David T. Rubin, MD

Improving quality of life for patients with inflammatory bowel disease (IBD) starts with a simple but often-skipped step: asking the right questions.

"If you don't ask, you won't know," David T. Rubin, MD,  professor of medicine at the University of Chicago and director of the Inflammatory Bowel Disease Center said in an interview with HCPLive.

Individualizing IBD Care Beyond the Bowel, With David T. Rubin, MD

According to Rubin, clinicians can become so focused on bowel symptoms, bleeding, or anemia that they miss the bigger picture affecting a patient's daily life.

Screening Questions to Identify IBD's Impact on Quality of Life

Rubin suggested 2 direct questions clinicians can use to uncover functional limitations that might otherwise go unspoken: "What does having this disease prevent you from doing that you would want to do?" and "What are you unable to eat that you would like to enjoy?"

"You start to learn more about somebody's limitations from the disease that you can develop a treatment plan that will address them," Rubin said.

Using Validated Screening Tools for Anxiety and Depression in IBD

Beyond open-ended questions, Rubin pointed to validated screening tools, such as a generalized anxiety scoring system and the Patient Health Questionnaire-9 (PHQ-9), as a way to catch what clinical impression alone often misses.

"If you screen for it, you will find it," Rubin said. He pushed back on the idea that experienced clinicians can simply tell when a patient is struggling. "I think that there's a lot of people who are depressed that you would never be able to tell in a limited clinical encounter."

Barriers to Comprehensive IBD Care in Clinical Practice

Rubin was candid about why these conversations don't happen more often, even when clinicians know they should. Referral infrastructure is thin. "Very few centers like ours have a GI psychologist or psychogastroenterologist... that I can refer them to," he said, adding that most clinicians were never trained to ask about sexual health in the first place.

Time is the other constraint. In a 15- to 20-minute visit already covering new therapies, upcoming scopes, insurance coverage, and lab follow-up, Rubin said, there's rarely room left for "tell me about your sex life, or fill out this survey and tell me if you're anxious or depressed."

"There's some very big system issues that are preventing us from providing the care that people need," Rubin said, arguing that the field needs a different care model, not just better awareness, to give clinicians the time and resources to manage these issues properly.

Selecting IBD Therapy Based on Extraintestinal Manifestations

Rubin said knowing about a patient's coexisting conditions can directly shape treatment selection. Patients with inflammatory joint problems alongside their IBD may be better served by an anti-tumor necrosis factor (TNF) therapy or a Janus kinase (JAK) inhibitor, both of which can address joint inflammation as well as bowel disease. Patients with coexisting skin conditions, such as psoriasis, erythema nodosum, or pyoderma, may benefit more from an interleukin-23 (IL-23) inhibitor, which Rubin said is effective for both skin and bowel.

"You can pick therapies based on knowing about some of these other challenges and problems," Rubin said. "The patient with IBD deserves care that tries to address these issues."

Hinnant L, Rios Villacorta N, Chen E, et al. Consensus statement on managing anxiety and depression in individuals with inflammatory bowel disease. 

Holmer AK, Chang S, Malter L. Selecting therapies in moderate to severe inflammatory bowel disease: key factors in decision making. 

David T. Rubin, MD, on the questions, screening tools, and system barriers standing between IBD care and the whole patient.