Sara Horst, MD, MPH

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.

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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.

panel discussion on a head-to-head sequence study of rizankizumab vs ustekinumab in the treatment of CD, as well as approaches to choosing first-line treatment.

Sequence Study of Risankizumab vs Ustekinumab in CD

The transcript discusses the findings of the sequence study, focusing on the comparison between two drugs, P41 (referred to as risankizumab) and P19 (referred to as IL (interleukin)-23 therapy). The study aimed to evaluate the efficacy of risankizumab in patients with Crohn's disease who had been exposed to TNF.

The results indicate that risankizumab-exposed patients were more likely to achieve clinical response, clinical remission, and endoscopic improvement compared to those on P40 (risankizumab with IL-12 and IL-23). The transcript emphasizes that the head-to-head comparison provides valuable insights, guiding clinicians in choosing the most effective therapy.

It highlights that risankizumab, along with its biosimilar, is an approved and effective option for Crohn's disease. The discussion touches upon the significance of the sequence study's second primary endpoint, endoscopic remission, and how it could be a pivotal moment in the field.

The conversation also touches on the evolution of clinical trials in Crohn's disease, emphasizing the importance of endoscopic outcomes and the progression from subjective measures to objective proof of efficacy. The participants express optimism about the potential impact of risankizumab, especially when used as a first-line therapy.

Furthermore, the transcript discusses the importance of early intervention in Crohn's disease, suggesting that initiating treatment early is more likely to result in a positive response and prevent further damage. The participants encourage setting higher expectations for patients and discuss the advantages of using risankizumab in biologic treatment-naive patients.

In conclusion, the discussion underscores the positive findings from the sequence study, positioning risankizumab as a promising option for Crohn's disease, particularly in terms of achieving endoscopic remission and improving patient outcomes. The participants stress the need for effective communication with patients about treatment options and the potential long-term benefits of early intervention.

David Rubin, MD, leads the panel discussion on a head-to-head sequence study of rizankizumab vs ustekinumab in the treatment of CD, as well as approaches to choosing first-line treatment.

reviews the use of IL-12 and IL-23 inhibitors in the treatment of CD, highlighting ustekinumab and risankizumab for first-line therapy and beyond.

Role of IL-12/23 Inhibitors and IL-23 Inhibitors in CD

In this discussion, the focus is on IL (interleukin)-23 inhibitors. The conversation explores the effectiveness and confidence surrounding IL-23 inhibitors, particularly anti-P40 antibodies and emerging P19 antibodies. The speaker highlights the dual impact of anti-P40 antibodies on both IL-12 and IL-23, while P19 antibodies specifically target IL-23.

The speaker notes the safety and efficacy of both types of IL-23 inhibitors in treating moderate to severe Crohn's disease. The discussion delves into the unique immunological aspects of IL-23, emphasizing its tissue-specific expression rather than a broad impact on the immune system. The effectiveness of IL-23 inhibitors in addressing skin inflammation is acknowledged, making them a favorable choice for patients with both skin conditions and Crohn's disease.

The conversation incorporates recent head-to-head data comparing P19 and P40 inhibitors in patients previously on anti-TNF (tumor necrosis factor) therapy. The results indicate that P19 inhibitors were approximately 20% more effective across various endpoints, providing valuable insights into the specificity and dosing of IL-23 inhibitors.

The speaker expresses comfort in using IL-23 inhibitors as a first-line therapy for Crohn's disease and considers them a viable second-line option. Furthermore, the potential benefits of IL-23 inhibitors in post-operative Crohn's patients and those with less complex perianal disease are highlighted. The speaker also emphasizes the significance of IL-23 inhibitors as an option during pregnancy, distinguishing them from small molecules.

In summary, the discussion positions IL-23 inhibitors, particularly P19 antibodies, as a significant addition to the treatment arsenal for Crohn's disease. The emerging head-to-head data contributes to a more informed approach to therapy selection, and the speaker underscores the ease of discussing this option with patients. Overall, IL-23 inhibitors are portrayed as a versatile and valuable choice in the evolving landscape of Crohn's disease management.

David Rubin, MD, reviews the use of IL-12 and IL-23 inhibitors in the treatment of CD, highlighting ustekinumab and risankizumab for first-line therapy and beyond.

Sara Horst, MD, MPH

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