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

Despite an inflammatory bowel disease (IBD) 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.

Rethinking What’s Possible in IBD Care

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.

References

1. 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/

2. Appiah JK, Hayat U, Garg N, et al. Emerging Therapies in Inflammatory Bowel Disease: A Comprehensive Review. J Clin Med. 2025;14(17):6119. Published 2025 Aug 29. doi:10.3390/jcm14176119