David Rubin, MD

Optimizing What We Have: Closing the Gap Between IBD Therapies and Patient Outcomes

 treatment armamentarium that now exceeds a dozen approved advanced therapies, outcomes for patients with Crohn's disease and ulcerative colitis remain far short of what the field should be achieving.

The problem, according to David Rubin, MD, Joseph B. Kirsner Professor of Medicine, chief of Gastroenterology, Hepatology and Nutrition, and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, may be less about what clinicians have available and more about how they are using it. Speaking at Digestive Disease Week (DDW) 2026 in Chicago, IL, Rubin made the case that rigorous optimization of existing therapies, not just the next pipeline agent, is where the greatest near-term gains lie.

Treat Early to Change the Disease Trajectory

A central theme of Rubin’s discussion is the growing body of evidence supporting early intervention. Traditional clinical trials often enroll patients with long-standing disease, frequently 7 to 10 years in duration, who have already cycled through multiple therapies. As a result, reported remission rates of 20-30% may underestimate what is achievable in earlier disease.

“We've learned that we can achieve 80% remission rates in Crohn's disease when we treat earlier,” Rubin said.

These findings, supported by emerging real-world and trial data, suggest that early use of advanced therapies may fundamentally alter disease course. This paradigm shift aligns with broader trends in IBD management, where early disease control is increasingly viewed as critical to preventing irreversible bowel damage.

Optimizing Existing Therapies Before Seeking New Ones

While innovation continues across the IBD pipeline, Rubin emphasized that substantial gains can still be made by optimizing current therapies. One common pitfall is inadequate induction dosing, particularly when intravenous induction and subcutaneous maintenance require separate authorization processes.

“If you don’t induce properly, you’re not going to gain control of a hot inflammatory bowel,” he noted.

Therapeutic drug monitoring also plays a role, though its evidence base remains strongest for anti-TNF agents. In patients losing response, dose optimization may be appropriate, but Rubin advised limiting attempts to recapture response. If efficacy is not regained after several cycles, switching to a different mechanism of action is often more effective than cycling within the same class.

A Structured Approach to Loss of Response

Rubin outlined a practical framework for evaluating patients who are not responding to therapy. First, clinicians must confirm active inflammation, as symptoms alone may reflect alternative processes such as strictures, bile acid diarrhea, or motility disorders. Next, infection, particularly Clostridioides difficile, must be ruled out.

Only then should attention turn to the therapy itself. “Where is the drug?” Rubin asked, highlighting factors such as adherence, drug clearance, and delivery challenges. For example, patients with high inflammatory burden or low albumin may experience increased biologic clearance, while those with altered gastrointestinal anatomy may have impaired absorption of oral agents.

Proactive Monitoring and Treat-to-Target Strategies

Another key message is the need to shift from reactive to proactive care. Treat-to-target strategies, supported by biomarkers like fecal calprotectin and C-reactive protein, as well as endoscopy and intestinal ultrasound, are increasingly recognized as essential for optimizing outcomes.

Of note, Rubin stressed that the goal is not perfection, but meaningful disease control and improved quality of life. Overreliance on corticosteroids, for example, remains a persistent issue despite evidence that many patients can achieve remission without them.

With appropriate early treatment, proactive monitoring, and thoughtful optimization, Rubin believes outcomes in IBD can improve significantly, even without new therapies.

“If we have informed clinicians, we have a motivated patient population, we have access to the available therapies, and we optimize those therapies properly, we'll end up with most patients achieving remission with what we already have,” he said. “Innovations are needed and we still want to find cures, but what we have now, if we do it with the best approach that we've learned, we can do a lot better for many people.”

Editors’ note: Rubin reports relevant disclosures with AbbVie, Abivax SA, Bristol-Myers Squibb, Celltrion, Eli Lilly & Co., Genentech (Roche) Inc., Johnson & Johnson, Merck & Co., and others.

Early Biologic Treatment for Inflammatory Bowel Disease: Drugs. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2024 Oct. https://www.ncbi.nlm.nih.gov/books/NBK609613/ 

Appiah JK, Hayat U, Garg N, et al. Emerging Therapies in Inflammatory Bowel Disease: A Comprehensive Review. 

. 2025;14(17):6119. Published 2025 Aug 29. doi:10.3390/jcm14176119

Videos

Despite a growing armamentarium of approved IBD therapies, outcomes remain suboptimal. Rubin explains how earlier treatment and smarter optimization can close the gap.

Closing the Gap Between IBD Therapies and Patient Outcomes, With David Rubin, MD

Guselkumab Subcutaneous Induction Advances Ulcerative Colitis Care, With David Rubin, MD

 took an important step forward with the US Food and Drug Administration’s approval of a subcutaneous (SC) induction regimen for guselkumab (Tremfya).

The September 19, 2025, decision makes guselkumab the first and only IL-23 inhibitor to offer both intravenous (IV) and SC induction options in inflammatory bowel disease (IBD) and was based on results from the phase 3 ASTRO trial, which employed a treat-through design to evaluate the efficacy and safety of guselkumab SC induction therapy in adults with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy and advanced therapies.

“Having subcutaneous induction of guselkumab for ulcerative colitis has two important implications. The first one is for patients, and the sense of making this a bit more convenient for them to be able to either have it done in the doctor's office in a short period of time, or learning how to do it and doing it themselves, which most of our patients do,” David Rubin, MD, a professor of medicine and director of the IBD Center at the University of Chicago and chair of the International Organization for the Study of IBD, explained to 

. “The second one that I think is important, that we should really understand, is the simplification of preauthorization for the drug from insurance companies.”

In ASTRO, patients were randomly assigned in a 1:1:1 ratio to receive guselkumab 400 mg SC induction at Weeks 0, 4 and 8 followed by guselkumab 200 mg SC every 4 weeks (q4w); or guselkumab 400 mg SC induction at Weeks 0, 4 and 8, followed by guselkumab 100 mg SC every 8 weeks (q8w); or placebo. In the trial, all multiplicity-controlled primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with guselkumab compared to placebo across all clinical and endoscopic measures. Among these was early symptomatic response, with guselkumab separating from placebo as early as 2 weeks and sustained through week 24.

Additionally, significantly greater proportions of patients treated with guselkumab 400 mg SC q4w achieved clinical remission (26% vs 7%; 

<.001) and endoscopic improvement (36% vs 12%; 

<.001) at week 12 versus those treated with placebo. Of note, results were consistent with the FDA-approved 200mg IV induction regimen, which previously achieved clinical remission (23% vs 8%; 

<.001) and endoscopic improvement (27% vs 11%; 

<.001) versus those treated with placebo.

“The data in ASTRO are interesting and important, because the subcutaneous loading in ASTRO at week 12 looks just like the IV loading from QUASAR at week 12,” Rubin explained. “In other words, as much as people may have thought that a subcutaneous loading phase might be a weaker delivery or a lower dose or some other adjustment that's not going to be as effective as what was seen with IV, it actually looks the same. In fact, arguably, some of the numbers even look better.”

Looking at data for guselkumab from various studies in IV and SC across both Crohn’s disease and UC, Rubin also points to the importance of remission at week 12, which he says has consistently predicted more success in maintenance. He additionally highlights guselkumab’s consistent benefit across various subgroups for both SC and IV induction in UC as well as its safety and tolerability.

“I've often said that the sign of progress in our field is when we start thinking about convenience,” Rubin said. “In addition to the general mechanism, when you think about convenience as the next thing you're going to talk about to patients and to ourselves and our staff, it really means that we've started to make some progress, because we've gotten past understanding that, yes, this mechanism works, and now we can start talking about how we deliver it in a more tolerable way, or how we get it to the patient with less hassle.”

Editors’ note: Relevant disclosures for 

include Takeda, AbbVie, Abivax SA, Bristol Myers Squibb, Celltrion, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi, Takeda, and others.

Brooks A. FDA Approves Guselkumab (Tremfya) Subcutaneous Induction Regimen for Ulcerative Colitis. 

. September 19, 2025. Accessed September 26, 2025. 

https://www.hcplive.com/view/fda-approves-guselkumab-tremfya-subcutaneous-induction-regimen-for-ulcerative-colitis

Rubin reflects on the FDA approval of a SC induction regimen for guselkumab (Tremfya) in UC and explains the significance of having both IV and SC induction options in IBD.

Experts in gastroenterology discuss treatment selection in special situations of CD, such as age, women considering pregnancy, extra-intestinal manifestations.

Selecting CD Treatment in Special Scenarios

This is a video synopsis/summary of a panel discussion involving Marla Dubinsky, MD; David Rubin, MD; Miguel Regueiro, MD; Remo Panaccione, MD, FRCPC; and Sara Horst, MD, MPH.

The discussion revolves around advanced therapies for Crohn's disease, focusing on specific scenarios and the choice of treatments. The participants discuss their preferences based on various patient characteristics and conditions.

The conversation begins with considerations for patients previously exposed to anti-TNF (tumor necrosis factor) therapies. Natalizumab is deemed less effective in this population, and risankizumab is suggested as a preferable option over upadacitinib due to similar data outcomes. The need for speed in specific cases, such as those with extra-intestinal manifestations, is highlighted, making upadacitinib an attractive choice.

The panel discusses the importance of personalized medicine, considering factors like inflammatory joint problems, spondyloarthropathy, or other manifestations. Choices are tailored to individual patient profiles, with IL (interleukin)-23-based strategies favored for certain scenarios.

Pregnant women are advised on the importance of disease control, with emphasis on the safety of IL-23 and IL-12/23, alongside traditional anti-TNF options. The potential use of JAK (Janus kinase) inhibitors for quick induction of deeper remission is acknowledged.

The safety profile of JAK inhibitors is addressed, dispelling misconceptions and encouraging broader utilization in IBD (inflammatory bowel disease) management. The discussion concludes with a rapid-fire round where each participant shares their first-line therapy preferences for specific patient scenarios.

In closing, the participants express hope for the future of Crohn's disease management, emphasizing the evolving landscape of precision medicine, advancements in fibrosis treatment, the paradigm shift in disease monitoring, and the promise of combination therapies. The concept of treating Crohn's disease earlier in its course is highlighted as a future goal, providing optimism for improved patient outcomes.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Experts in gastroenterology discuss treatment selection in special situations of CD, such as age, women considering pregnancy, and extra-intestinal manifestations.

Remo Panaccione, MD, FRCPC, provides an overview of the newest oral therapy approved for CD, upadacitinib.

Use of Upadacitinib in Treatment of CD

The discussion shifts to the newest drug for Crohn's disease, upadacitinib, a selective JAK (Janus kinase) 1 inhibitor. The speaker outlines the mechanism of upadacitinib, distinguishing it from other JAK inhibitors and emphasizing its selectivity for JAK1. The drug's impact on the JAK-STAT pathway and its role in modulating gene transcription for pro-inflammatory cytokines are discussed.

Upadacitinib is highlighted for its specificity in targeting JAK1 without significant effects on JAK2, which reduces the risk of off-target effects associated with myelofibrosis and erythropoiesis. The speaker explains that JAK inhibitors act as competitive agonists, binding to the intracellular side of the receptor and competing for STAT activation.

The drug's approval for Crohn's disease is discussed, with a comparison to another treatment mentioned earlier in the conversation. The speaker notes that the data for upadacitinib, an oral small molecule, aligns closely with the effects of the mentioned treatment, administered differently. The discussion emphasizes the drug's effectiveness in achieving clinical and endoscopic remission, with particular attention to its rapid action, possibly quicker than other options.

The speaker shares personal experiences, mentioning that upadacitinib is used as a first-line therapy for Crohn's disease in Canada for about 15% of patients. The drug is frequently used clinical practice, attributed to its quick efficacy and ability to rescue a significant number of patients. The convenience of an oral small molecule is underlined, especially in gastrointestinal diseases, addressing pharmacodynamic challenges associated with monoclonal antibodies in inflamed guts.

In summary, upadacitinib emerges as a remarkable and versatile drug, praised for its selectivity, efficacy, and oral administration. The speaker's experiences and the drug's potential as a first-line therapy contribute to its significance in the evolving landscape of Crohn's disease treatment.

David Rubin, MD

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