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Takeaways in IBD advancements
Advancing Inflammatory Bowel Disease Management: Clinical Takeaways on Emerging Therapies for CD and UC

Released: March 26, 2025

Expiration: March 25, 2026

Jordan E. Axelrad
Jordan E. Axelrad, MD, MPH, FACG
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Key Takeaways
  • Interleukin-23 inhibitors are emerging as the preferred first-line biologic for treating moderate inflammatory bowel disease because they offer durable efficacy.
  • Janus kinase inhibitors provide rapid disease control and are particularly valuable for patients with severe disease and extraintestinal manifestations refractory to anti-TNF therapies.
  • Early studies of TL1A inhibitors show these agents may have antifibrotic and anti-inflammatory potential, making them a promising option for IBD, particularly stricturing Crohn’s disease.

Inflammatory bowel disease (IBD)—which includes Crohn’s disease (CD) and ulcerative colitis (UC)—remains a challenging chronic condition to manage, particularly for patients who do not achieve clinical remission with standard therapies. As our understanding of IBD’s pathophysiology improves, new treatments targeting novel inflammatory pathways emerge and offer hope to those whose disease does not respond or loses an initial response to treatment, including prior biologics.

Targeting Novel Pathways in IBD
Recent data have highlighted the efficacy of interleukin-23 (IL-23), Janus kinase (JAK), and tumor necrosis factor (TNF)–like cytokine 1A (TL1A) inhibitors in patients with persistent disease activity. These therapies represent a new frontier in IBD management, enabling more personalized approaches to care that can consider patients’ disease severity, prior treatment history, and comorbid conditions.

IL-23 Inhibitors
One highly effective treatment class comprises IL-23 inhibitors. These agents target the p19 subunit of IL-23, a proinflammatory cytokine that plays a crucial role in driving the immune response in IBD. Mirikizumab was the first IL-23 inhibitor to be FDA approved to treat moderate to severe UC, with the LUCENT trials demonstrating its superiority over placebo in achieving clinical remission and mucosal healing. This agent was  also recently approved to treat moderate to severe CD, with the VIVID-1 trial showing significant endoscopic response and clinical remission achieved with mirikizumab vs placebo. Further, a head-to-head study in the VIVID-1 trial found mirikizumab to be noninferior to ustekinumab in achieving clinical remission.

Risankizumab is another IL-23 inhibitor that has demonstrated impressive efficacy in CD, particularly in patients previously treated with a biologic. The ADVANCE and MOTIVATE trials confirmed its superiority to placebo, and the SEQUENCE trial showed that risankizumab outperformed ustekinumab in achieving endoscopic remission, deep remission, and mucosal healing. Because of these findings, many healthcare professionals now see risankizumab as the preferred agent vs ustekinumab for treating patients with moderate to severe CD. Risankizumab is also approved to treat moderate to severe UC following positive data from the INSPIRE and COMMAND trials.

In addition, guselkumab is an IL-23 inhibitor that demonstrated positive results in the QUASAR trial for UC and GALAXY-1 trial for CD. The FDA has now approved both subcutaneous and intravenous formulations of guselkumab for induction in adults with moderate to severely active CD, following data from the GRAVITI trial. There are also positive data for subcutaneous induction in adults with moderate to severe active UC. As a class, IL-23 inhibitors offer durable response, favorable safety profiles, and high efficacy in treating IBD, particularly advanced therapy–naive patients. Therefore, these therapies are a promising first-line biologic option for many patients.

JAK Inhibitors
JAK inhibitors offer a targeted, small-molecule approach to IBD management by inhibiting multiple proinflammatory cytokine pathways. Unlike biologics, which are administered via injection or infusion, JAK inhibitors are taken orally, making them a convenient option for many patients. Upadacitinib has rapidly emerged as a preferred option due to its fast onset and robust efficacy. The U-ACHIEVE and U-EXCEED trials demonstrated that upadacitinib was significantly more effective than placebo in achieving clinical remission and mucosal healing in both moderate to severe UC and CD, respectively. Real-world data in UC suggest that upadacitinib induces clinical response rates exceeding 75%, including among patients previously treated with biologics. Its effectiveness in managing extraintestinal manifestations of IBD, such as psoriatic arthritis and ankylosing spondylitis, further enhances upadacitinib’s value as a beneficial therapy.

However, JAK inhibitors do not come without risk. Upadacitinib has a black box warning due to concerns about major cardiovascular events, thrombosis, and malignancy, in particular among previous or current smokers and older patients with 1 or more cardiovascular risk factors. Despite these risks, JAK inhibitors remain a vital treatment option for patients with treatment refractory disease, particularly when rapid symptom control is needed.

TL1A Inhibitors
Another novel and highly promising class of therapy for IBD is TL1A inhibitors. TL1A is a cytokine within the TNF superfamily and plays a role in immune activation, barrier dysfunction, and fibrosis. Therefore, it is an attractive target for patients with both inflammatory and fibrotic complications of IBD. Studies have linked TNFSF15 polymorphisms to IBD susceptibility, suggesting that TL1A inhibition may offer a predictive biomarker for treatment response. Several TL1A inhibitors are currently in phase II and III trials, and early data suggest these agents may offer dual anti-inflammatory and antifibrotic benefits—particularly in stricturing CD. If approved, TL1A inhibitors could reshape the treatment paradigm for patients who have exhausted other biologic options.

Integrating These Agents Into IBD Management
With an increasing number of effective therapies being studied in clinical trials, IBD treatment strategies must be tailored to the individual patient based on their disease severity, treatment history, and comorbidities. While IL-23 inhibitors offer durable response and strong efficacy, making them an excellent option for long-term IBD management, JAK inhibitors provide rapid relief for patients who are refractory to anti-TNF therapies and in need of urgent disease control or with extraintestinal manifestations. Meanwhile, TL1A inhibitors may soon transform current treatment strategies for addressing IBD, pending further validation. Therefore, the key to successfully managing IBD includes early intervention, careful patient selection, and proactive monitoring to ensure patients receive the most effective and appropriate treatment for their disease.

Your Thoughts?
Do you currently use IL-23 inhibitors or JAK inhibitors in your treatment approach for IBD? Share your experiences and perspectives in the comments below.

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