Beyond Anti-TNF: An Evolving IBD Treatment Landscape, With Victor Chedid, MD, MS

The field of inflammatory bowel disease (IBD) is in the midst of a significant period of change. New therapeutic targets are advancing through clinical trials, treatment goals are being redefined, and the question of sequencing therapies is becoming both more nuanced and more pressing.

Victor Chedid, MD, MS, aan assistant professor of medicine and director of the IBD Pride Clinic at Mayo Clinic, spoke with HCPLive at Digestive Disease Week (DDW) 2026 about what he sees as some of the most meaningful shifts in IBD care, along with their meaning for clinicians managing patients with moderate-to-severe disease.

A Toolbox That Looks Different Than It Did a Few Years Ago

Historically, anti-tumor necrosis factor (anti-TNF) agents were once the primary option for patients who needed advanced IBD therapy. Now, interleukin-23 inhibitors are approved and widely used, while agents targeting additional pathways, including TL1A, are in development, with early data suggesting potential anti-fibrotic effects in addition to anti-inflammatory activity.

That last point may be particularly relevant for patients with Crohn's disease who have developed stricturing complications. Prior IBD therapies have largely focused on controlling inflammation. Therefore, an agent that could also address fibrosis would represent a meaningfully different type of intervention.

"The toolbox for the providers taking care of people with IBD has grown dramatically over the past few years," Chedid said. "We've seen a lot of novel therapeutics and agents that are on the market that go beyond just the older anti-TNF, we're seeing agents that target interleukin-23, we're seeing targets of anti-TL1A antibodies that have potential for anti-fibrotic [activity], which is very exciting. We've not seen anti-fibrotics in the IBD toolbox before."

Meanwhile, Chedid has witnessed the expansion of drug delivery options over the years. Subcutaneous formulations, auto-injectors, on-body devices, and oral small molecules are now available or in development, giving patients and clinicians more flexibility when it comes to treatment preferences and practical adherence considerations.

The Shift Toward Deep Remission — and What That Requires

One of the more significant conceptual changes in IBD management is the move away from symptomatic response as a sufficient endpoint. According to the 2025 American Gastroenterological Association (AGA) clinical practice guideline for moderate-to-severe Crohn's disease, the goal of treatment should be deep remission, meaning mucosal and histologic healing, not just the resolution of symptoms.

This has practical implications for how clinicians monitor patients, explains Chedid. Non-invasive markers like fecal calprotectin and C-reactive protein are being increasingly used as ongoing indicators of mucosal activity, alongside more timely endoscopic reassessment to confirm whether treatment targets are being met.

It also has implications for when to start high-efficacy therapy. The updated AGA guidance moves away from the step-up approach, initiating advanced biologics only after simpler therapies have failed, in favor of earlier use of high-efficacy agents.

"Early use of high efficacy therapies has shown more and more benefit for patients with IBD," Chedid said. "We got to think of the right drug at the right time."

Sequencing in an Era of Multiple Options

With more approved agents available, clinicians are now navigating decisions that did not exist a decade ago. Choosing among therapies with different mechanisms, deliveries, safety profiles, and cost considerations requires a structured approach, one accounting for disease phenotype, comorbidities, patient preference, and practical access.

Therapeutic drug monitoring (TDM), measuring trough drug levels prior to the next dose, is one tool that can help individualize biologic dosing. Beyond its clinical utility, Chedid noted that TDM data can also support insurance appeals for dose escalation, a practical consideration in real-world practice.

Combination Therapy: Early Data, but Worth Watching

One area generating interest and still in early stages is the concept of combining biologic agents with different mechanisms of action. Data presented at DDW from the phase 2b DUET-CD trial examined JNJ-78934804 (JNJ-4804), a fixed-dose co-antibody combining an IL-23 inhibitor (guselkumab) and an anti-TNF agent (golimumab), in 693 patients with moderate-to-severe Crohn's disease who had inadequate response to at least one prior systemic therapy. Investigators described the results as promising, particularly in the most treatment-refractory subgroup, but phase 3 trials and FDA review would be necessary before such an approach could be considered for broader use.

"This exciting phase of thinking about combination therapies, seeing them in clinical trials and in the pipelines — that's an exciting future," Chedid said, while noting that the data remain preliminary. "Mind you, it's a phase 2 trial still, so it's not going to be applicable to the general public quite yet."

Looking Ahead: Matching the Right Therapy to the Right Patient

Clinicians are working toward a more precise understanding of which patients are likely to respond to which therapies before treatment begins. Multi-omic profiling, integrating genomic data with endoscopic, radiologic, and laboratory phenotyping, may eventually provide that kind of predictive information, though that application remains largely in development.

For now, Chedid emphasized that decision-making should be grounded in a combination of clinical evidence, careful disease characterization, and shared decision-making with the patient. This includes factoring in disease severity along with lifestyle, delivery preference, and individual treatment goals.

"We're asking: what is the mechanism of action of the drug, what is the phenotype the patient is experiencing, what are the comorbidities?" he said. "All of that falls into the shared decision making."

Editor’s Note: Chedid reports relevant disclosures with Pfizer and Takeda.

References

1. Scott FI, Ananthakrishnan AN, Click B, et al. AGA living clinical practice guideline on the pharmacologic management of moderate-to-severe Crohn's disease. Gastroenterology. 2025;169(7):1397-1448. doi:10.1053/j.gastro.2025.09.038

2. Sands BE, et al. Efficacy and safety of the first co-antibody therapy, JNJ-78934804, in patients with moderately to severely active Crohn's disease refractory to systemic therapies [abstract 979f]. Presented at: Digestive Disease Week 2026; May 2-5, 2026; Chicago, IL.