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`Advancing Inflammatory Bowel Disease Management

CE / CME

Advancing Inflammatory Bowel Disease Management With Precision Medicine and Emerging Data

Physician Assistants/Physician Associates: 0.75 AAPA Category 1 CME credit

Nurse Practitioners/Nurses: 0.75 Nursing contact hour

Physicians: maximum of 0.75 AMA PRA Category 1 Credit™

Released: May 08, 2025

Expiration: May 07, 2026

Jordan E. Axelrad
Jordan E. Axelrad, MD, MPH, FACG
CME/CE Information

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TL1A in Inflammatory Bowel Disease

In wrapping up on the IBD therapeutics pipeline, the final is TL1A blockade. This includes an exciting new class of agents that are likely to be extremely helpful for our patients.

TL1A is an inflammatory cytokine that is part of the TNF superfamily. It causes inflammation, fibrosis, and disruption in the epithelium. Furthermore, TL1A expression is elevated in patients with IBD. This target was discovered via the genetic polymorphisms in the TNF superfamily gene that were associated with IBD susceptibility. So, this is an inflammatory cytokine that not only has a genetic basis, but also has a direct involvement in inflammation and fibrosis, which is important in IBD, especially in CD.30 

Click here to view a video on the interaction of TL1A with the DR3 receptor.

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Tulisokibart: Humanized Monoclonal TL1A Antibody

One of the investigational TL1A inhibitors is tulisokibart, a monoclonal antibody. There are several studies looking at this agent in IBD.

First is the phase IIa APOLLO-CD trial, which enrolled patients with moderate to severe CD and insufficient response, loss of response, or intolerance with prior treatment. Patients were given intravenous tulisokibart 1000 mg on Day 1 and 500 mg at Weeks 2, 6, and 10 within a 12-week induction period. Responders were then randomized into 2 maintenance arms: tulisokibart 250 mg vs 100 mg every 4 weeks from Week 14 to 170.31

Next is the phase II ARTEMIS-UC trial that enrolled patients with moderate to severe UC and insufficient response, loss of response, or intolerance with prior treatment (NCT04996797). However, this trial was placebo controlled, as patients were randomized to receive intravenous tulisokibart 1000 mg on Day 1 and 500 mg at Weeks 2, 6, and 10 or placebo within a 12-week induction period. Responders were then rerandomized to 2 maintenance arms: tulisokibart 250 mg vs 100 mg every 4 weeks from Week 14 to 170.32

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APOLLO-CD: Tulisokibart Efficacy and Safety

In APOLLO-CD, there were significant improvements in clinical and endoscopic outcomes for both doses of tulisokibart at Weeks 12 and 50. There may be a small dose-dependent effect because of slightly higher improvements seen with 250 mg vs 100 mg.

Adverse events (AEs) were generally grade 1/2 and comparable to what I have seen with many of our other IBD therapies, including upper respiratory tract infections and urinary tract infections. Of importance, minimal serious AEs were reported because anti-TNF agents could be associated serious safety concerns. This open-label study reported good safety and outcomes at Weeks 12 and 50.31

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ARTEMIS-UC: Tulisokibart Efficacy and Safety

Turning to the ARTEMIS-UC study, there was a nice dose-dependent effect in symptomatic, histologic, and mucosal improvement and mucosal healing with tulisokibart vs placebo. The low placebo rates indicate that this was a sicker group of patients who were enrolled in the trial.

Like APOLLO-CD, there were minimal serious AEs reported, and the most common AEs were URTIs. Of importance, tulisokibart was significantly more effective than placebo in achieving important outcomes in UC, including mucosal healing.32

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TUSCANY-2: RO7790121 for Moderate to Severe UC

Looking at another TL1A inhibitor in the pipeline, the phase IIb TUSCANY-2 trial evaluated RO7790121. Like ARTEMIS-UC, this trial enrolled patients with moderate to severe UC and randomized them to RO7790121 50 mg, 150 mg, or 450 mg vs placebo for a 12-week induction period. Then patients received only RO7790121 50 mg, 150 mg, or 450 mg during a 40-week maintenance period. As shown on the slide, clinical responses were significantly greater in patients who were given this TL1A inhibitor vs placebo. In looking at the maintenance and induction periods, there was consistence in that those who were treated with RO7790121 were significantly more likely to achieve clinical response in both induction and maintenance compared with placebo.

Regarding safety, there were some reported treatment-emergent AEs, but none were serious. And again, these were similar to the safety of our other IBD biologics.33

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RELIEVE UCCD: Duvakitug (TEV-48574) for UC and CD

The last TL1A inhibitor to discuss is duvakitug (previously known as TEV-48574). This was studied in the phase IIb RELIEVE UCCD trial, which was a unique trial because it incorporated both patients with CD and UC (NCT05499130). Patients were randomized to receive subcutaneous duvakitug 450 mg or 900 mg (after a 2250-mg loading dose) every 2 weeks or placebo. Its endpoints included endoscopic response, clinical remission, clinical response, and safety. What is different here is that this was only an induction trial, so we only have data from 14 weeks of treatment.34,35

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RELIEVE UCCD: Outcomes at Week 14

As expected and consistent with other TL1A inhibitors, treatment with duvakitug led to significantly improved outcomes vs placebo for both CD and UC. Of note, among patients with CD who did not have prior advanced therapy exposure, there was not a major dose effect vs those with prior advanced. Furthermore, this dose effect was less clear in patients with UC, but the higher dose of duvakitug provided better clinical benefit among all patients.34,35

Click here to listen about clinical trial data on emerging TL1A blockers.

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Key Takeaways

In summary, early aggressive therapy is important in patients with IBD, particularly for those with CD, to reduce long-term disease complications like stricture, fistula, and progression. Assessing for response or disease activity is necessary to ensure that patients are meeting goals via the treat-to-target approach to care. There are several tools at our disposal to measure disease activity, such as noninvasive biomarkers like FCP and CRP, which should be assessed more frequently for patients early in their disease course and at therapy initiation. Once patients are doing well in maintenance, biomarkers can be monitored at longer intervals but should continue to be used to prevent disease relapse. Furthermore, biomarkers can correlate with other measures of IBD disease activity, which is a critical component of the treat-to-target strategy. Then HCPs should use all this information to adjust therapy to help patients achieve mucosal healing.

In conclusion, TL1A is an emerging and promising treatment target in IBD. It plays a key role in inflammation and fibrosis. We reviewed 3 investigational agents that are TL1A inhibitors and how they may be useful for our patients with CD or UC. TL1A is an interesting treatment target that may soon be an integral part of our treatment paradigm.

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