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New potential therapeutic target identified for Crohn’s disease

New research has shed light on how known genetic risk factors can contribute to Crohn’s disease and treatment response, opening the door to new treatment approaches. Crohn’s disease is a form of inflammatory bowel disease in which the digestive tract is marked by lesions of damaging inflammation. It can start at any age, causing lifelong episodes of cramping, diarrhea, and malnutrition. Medications that block a major component of the inflammatory response called tumor necrosis factor (TNF) are effective for many people, but in some cases the disease does not respond to these drugs. Among the scores of genetic variations that have been linked to a higher risk for developing Crohn’s disease, changes in a gene called NOD2 that impair its function have been found to be a major risk factor. Exactly how these NOD2 genetic variations could contribute to Crohn’s disease has been unclear, however, which has been a major roadblock for developing new therapies.

Researchers set out to answer this question by analyzing intestinal samples from a well-characterized group of male and female children with Crohn’s disease. They found that genetic variations inhibiting NOD2 function were linked to changes in fibroblasts (cells that make up connective tissue) and immune cells in Crohn’s disease lesions. Specifically, these cell types showed signs that they were “activated” and producing factors involved in inflammation. Importantly, activated immune cells and fibroblasts have also been found in lesions from people with refractory Crohn’s disease that is resistant to anti-TNF therapy, suggesting that these activated cells provide an additional route to inflammation that is independent of TNF-mediated inflammation. Using cultured cells and a zebrafish model that effectively mimics human Crohn’s disease, the researchers identified a protein known as gp130 that plays a critical role in activating these cells when NOD2 is impaired. Data from women and men with Crohn’s disease that did not respond well to anti-TNF therapy showed high levels of intestinal proteins in the cellular pathway used by gp130. Additionally, the researchers found that treating zebrafish or cultured cells with a gp130-blocking drug inhibits activation of inflammatory cells. More research is needed to determine if blocking gp130 will similarly reduce cellular activation in human intestinal lesions. However, this study suggests that drugs targeting gp130, when used in conjunction with anti-TNF therapy, might be effective treatments for people with Crohn’s disease resulting from NOD2 risk variants.

Nayar S, Morrison JK, Giri M,…Cho JH. A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease . Nature 593: 275-281, 2021.

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Mirikizumab: A promising breakthrough in Crohn's disease treatment

Muaaz aslam.

1 Department of Medicine, Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College, Lahore Punjab, Pakistan

Mohammad Haris Ali

Hamza irfan, associated data.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Introduction

Crohn's disease (CD) is a chronic, progressive inflammatory bowel disorder characterized by persistent inflammation and noncontiguous “skip lesions” throughout the gastrointestinal tract. With a prevalence of 100–300 cases per 100,000 individuals, CD is most common in Western Europe and North America. Symptoms include abdominal pain, diarrhea, fever, weight loss, and anemia, with severe cases leading to complications such as perianal abscesses and cutaneous fistulas. Treatment involves pharmaceutical interventions, bowel rest, and sometimes surgery, with biological therapies like ustekinumab and mirikizumab gaining prominence.

Clinical Trials

The VIVID‐1 trial assessed mirikizumab in patients with moderately to severely active CD. By Week 12, mirikizumab significantly outperformed placebo in clinical response (45.4% vs. 19.6%, p  < 0.000001). By Week 52, it showed higher clinical remission rates (54.1% vs. 19.6%) and demonstrated non‐inferiority to ustekinumab in clinical remission ( p  = 0.51). The SEQUENCE study compared risankizumab to ustekinumab, with risankizumab showing superior reductions in inflammatory markers and higher biologic remission rates at Weeks 8, 24, and 48. Both treatments had similar safety profiles, with common adverse events including COVID‐19, anemia, and headache.

Mirikizumab, based on the VIVID‐1 trial outcomes, is a promising addition to CD therapy. It demonstrated significant clinical responses and remission rates, warranting further research on its long‐term efficacy and safety. Updating professional guidelines and addressing affordability will ensure broader access and improved management of CD.

1. CORRESPONDENCE

Crohn's disease (CD) is an inflammatory bowel disorder known for its chronic and progressive nature, characterized by persistent inflammation throughout various regions of the gastrointestinal tract. This ailment has exhibited a rising incidence on a global scale. It presents as a distinctive pattern of noncontiguous lesions, commonly referred to as “skip lesions,” affecting multiple parts of the gastrointestinal tract, spanning from the oral cavity to the anus. The etiology of CD is multifactorial and arises from a complex interplay involving genetic susceptibility, environmental elements, and the composition of the intestinal microbiota. These factors collectively contribute to an abnormal mucosal immune response and compromised epithelial barrier function. 1

This condition is most prevalent in Western Europe and North America, with an estimated prevalence of 100–300 cases per 100,000 individuals. 2 CD patients typically present with several clinical symptoms, including abdominal pain localized predominantly in the right lower quadrant, often accompanied by concomitant flatulence, bloating, and diarrhea. The symptoms are further characterized by the presence of fever, progressive weight loss, and anemia. In severe cases, patients may exhibit complications such as perianal abscesses and the formation of cutaneous fistulas. Furthermore, CD is associated with a spectrum of extraintestinal manifestations, such as episcleritis, uveitis, stomatitis, and the presence of aphthous ulcers. Hepatic involvement may manifest as hepatic steatosis, while gallstones, nephrolithiasis, hydronephrosis, and urinary tract infections represent urological manifestations. Joint‐related pathologies, including arthritis and ankylosing spondylitis, are also encountered in association with CD. It is noteworthy that the majority of cases are diagnosed in individuals aged between their 20s and 40s. 3 , 4

Current treatment strategies for CD include pharmaceutical interventions, measures to provide the bowel with essential rest, and, in certain cases, surgical intervention. Pharmaceutical interventions involve administering a range of medications, including corticosteroids, aminosalicylates, immunomodulators, and biological therapies. Notably, biological therapies targeting specific components of the immune system, such as anti‐interleukin‐12 (IL‐12) and interleukin‐23 (IL‐23) therapy (e.g., ustekinumab), have gained prominence in the management of CD. 5 Over time, there has been an immense increase in the utilization of biological therapies, 6 reflecting their efficacy and the evolving landscape of treatment options for this inflammatory disorder. Ustekinumab is a monoclonal antibody therapy designed to treat various immune‐mediated conditions, primarily psoriasis and psoriatic arthritis. It works by targeting the p40 subunit of IL‐12 and IL‐23 and has been indicated for use in the treatment of moderate to severe CD.

On the other hand, Mirikizumab, another biological therapy, is a humanized immunoglobulin G4 anti‐human IL‐23p19 monoclonal antibody. This particular monoclonal antibody targets the p19 subunit of IL‐23, a cytokine that plays an important role in the pathogenesis of ulcerative colitis (UC) and CD. IL‐23 is known to promote a Th‐17 cell‐related immune response, which, in turn, produces a pro‐inflammatory effect. 7 Other p19 inhibitors such as tildrakizumab, guselkumab, and risankizumab have been examined for other inflammatory diseases such as psoriasis and rheumatoid arthritis, showcasing favorable safety profile. 8 By targeting IL‐23, both mirikizumab and ustekinumab have the potential to modulate and mitigate these inflammatory responses, making them promising options for the treatment of both CD and UC. Hence, further head‐to‐head trials comparing the safety and efficacy of these two drugs must be planned.

In the VIVID‐1 trial, mirikizumab demonstrated robust efficacy in patients with moderately to severely active CD. By Week 12, significantly more patients achieved clinical response with mirikizumab compared to placebo (45.4% vs. 19.6%, p  < 0.000001). By Week 52, mirikizumab also showed substantial clinical remission rates (54.1% vs. 19.6% with placebo) and displayed noninferiority to ustekinumab for clinical remission, though it did not achieve superior endoscopic response ( p  = 0.51). Moreover, a higher proportion of patients on mirikizumab achieved combined clinical and endoscopic responses at Week 52 compared to placebo (38% vs. 9%, p  < 0.000001). The safety profile was consistent with known effects, including common adverse events like COVID‐19, anemia, and headache. In contrast, the SEQUENCE study compared risankizumab to ustekinumab in CD management. Risankizumab demonstrated superior efficacy in reducing inflammatory markers over ustekinumab. By Week 8, risankizumab achieved greater reductions in fecal calprotectin (−1014.0 vs. −650.2) and high sensitivity C‐reactive protein (−10.6 vs. −5.5) compared to ustekinumab. Furthermore, a higher proportion of patients achieved biologic remission with risankizumab at Week 8 (26.3% vs. 21.9%), Week 24 (42.8% vs. 24.9%, p  < 0.0001), and Week 48 (46.3% vs. 27.5%, p  < 0.0001) compared to ustekinumab. 9

The safety profiles for both treatments were similar, with no new safety concerns reported. In comparison, while mirikizumab demonstrated superior clinical response rates and a noninferiority to ustekinumab in clinical remission, risankizumab showed stronger efficacy in reducing inflammatory markers and achieving biological remission. Both therapies underline promising avenues for managing CD, each with distinct strengths in clinical endpoints and safety profiles. Mirikizumab not only met the predetermined co‐primary endpoints but also exhibited favorable results across all secondary outcomes at the 52‐week time point in contrast to the placebo‐treated group. Among patients administered mirikizumab, the most frequently observed treatment‐emergent adverse events encompassed COVID‐19, anemia, headache, arthralgia, and infections of the respiratory tract. 10

Based on the positive outcomes observed in the Phase 3 VIVID‐1 trial, mirikizumab emerges as a promising addition to the therapeutic landscape for CD. Further research is imperative to assess its long‐term efficacy and safety, while patient education, individualized treatment plans, and a multidisciplinary approach should guide its use. Rigorous monitoring and comparative studies are essential, and professional guidelines should be updated to incorporate mirikizumab, ensuring equitable access. Efforts to address affordability will facilitate widespread adoption of this innovative therapy, ultimately enhancing the management of CD and the well‐being of affected individuals.

AUTHOR CONTRIBUTIONS

Muaaz Aslam : Conceptualization; writing—original draft; writing—review and editing; validation; project administration; supervision; data curation; resources. Mohammad Haris Ali : Conceptualization; writing—review and editing; writing—original draft; project administration; visualization; validation; data curation; methodology. Hamza Irfan : Conceptualization; writing—original draft; writing—review and editing; validation; project administration; data curation; supervision; resources.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

TRANSPARENCY STATEMENT

The lead author Hamza Irfan affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Aslam M, Ali MH, Irfan H. Mirikizumab: a promising breakthrough in Crohn's disease treatment . Health Sci Rep . 2024; 7 :e2294. 10.1002/hsr2.2294 [ CrossRef ] [ Google Scholar ]

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Current status, challenges, and future directions in crohn’s disease.

• List of Contributions
• Scheurlen, K.M.; A Parks, M.; Macleod, A.; Galandiuk, S. Unmet Challenges in Patients with Crohn’s Disease. J. Clin. Med.   2023 , 12 , 5595.
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• Rosiou, K.; Selinger, C.P. Obstetric Considerations in Pregnant Women with Crohn’s Disease. J. Clin. Med.   2023 , 12 , 684.
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• Zhang, E.; Christensen, B.; Macrae, F.A.; Leong, R. The Effects of the COVID Pandemic on Patients with IBD: Lessons Learned and Future Directions. J. Clin. Med.   2022 , 11 , 7002.
• Yang, C.T.; Yen, H.H.; Chen, Y.Y.; Su, P.Y.; Huang, S.P. Radiation Exposure among Patients with Inflammatory Bowel Disease: A Single-Medical-Center Retrospective Analysis in Taiwan. J. Clin. Med.   2022 , 11 , 5050.
• Sharip, M.T.; Nishad, N.; Pillay, L.; Goordyal, N.; Goerge, S.; Subramanian, S. Ustekinumab or Vedolizumab after Failure of Anti-TNF Agents in Crohn’s Disease: A Review of Comparative Effectiveness Studies. J. Clin. Med.   2024 , 13 , 2187.

Author Contributions

Conflicts of interest.

• Lamb, C.A.; Kennedy, N.A.; Raine, T.; Hendy, P.A.; Smith, P.J.; Limdi, J.K.; Hayee, B.; Lomer, M.C.E.; Parkes, G.C.; Selinger, C.; et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019 , 68 (Suppl. S3), s1–s106. [ Google Scholar ] [ CrossRef ] [ PubMed ]
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Share and Cite

Selinger, C.; van der Meulen, A. Current Status, Challenges, and Future Directions in Crohn’s Disease. J. Clin. Med. 2024 , 13 , 4699. https://doi.org/10.3390/jcm13164699

Selinger C, van der Meulen A. Current Status, Challenges, and Future Directions in Crohn’s Disease. Journal of Clinical Medicine . 2024; 13(16):4699. https://doi.org/10.3390/jcm13164699

Selinger, Christian, and Andrea van der Meulen. 2024. "Current Status, Challenges, and Future Directions in Crohn’s Disease" Journal of Clinical Medicine 13, no. 16: 4699. https://doi.org/10.3390/jcm13164699

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How comparative studies can inform treatment decisions for Crohn's disease

Affiliations.

• 1 Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.
• 2 IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
• 3 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
• PMID: 39132872
• DOI: 10.1080/14712598.2024.2389985

Introduction: As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing.

Areas covered: Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions.

Expert opinion: There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.

Keywords: anti-IL23p19; anti-TNF alpha; randomized controlled trials; real-life evidence; therapeutic algorithm; upadacitinib; ustekinumab; vedolizumab.

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Major cause of inflammatory bowel disease discovered

• Date created: 5 June 2024
• Category Tag:
• Immune System Health and Ageing
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Researchers at the Francis Crick Institute, working with UCL and Imperial College London, have discovered a new biological pathway that is a principal driver of inflammatory bowel disease (IBD) and related conditions, and which can be targeted using existing drugs.

About 5% of the world’s population, and one in ten people in the UK , are currently affected by an autoimmune disease, such as IBD, the umbrella term for Crohn’s disease and ulcerative colitis. These diseases are also becoming more common, with over half a million people living with IBD in the UK as of 2022 , nearly double the 300,000 previously estimated.

Despite increasing prevalence, current treatments do not work in every patient and attempts to develop new drugs often fail due to our incomplete understanding of what causes IBD.

Christophe Bourges, Senior Laboratory Research Scientist at the Francis Crick Institute, discusses the identification of a major genetic driver for inflammatory bowel disease.

Macrophages, a major type of immune cell. Credit: Christina Stankey.

In research published in Nature today, scientists at the Crick journeyed into a ‘gene desert’ – an area of DNA that doesn’t code for proteins – which has previously been linked to IBD and several other autoimmune diseases.

They found that this gene desert contains an ‘enhancer’, a section of DNA that is like a volume dial for nearby genes, able to crank up the amount of proteins they make. The team discovered that this particular enhancer was only active in macrophages, a type of immune cell known to be important in IBD, and boosted a gene called ETS2 , with higher levels correlating with a higher risk of disease.  

Using genetic editing, the scientists showed that ETS2 was essential for almost all inflammatory functions in macrophages, including several that directly contribute to tissue damage in IBD. Strikingly, simply increasing the amount of ETS2 in resting macrophages turned them into inflammatory cells that closely resembled those from IBD patients.

The team also discovered that many other genes previously linked to IBD are part of the ETS2 pathway, providing further evidence that it is a major cause of IBD.

ETS2 as a treatment target

Specific drugs that block ETS2 don’t exist, so the team searched for drugs that might indirectly reduce its activity. They found that MEK inhibitors, drugs already prescribed for other non-inflammatory conditions, were predicted to switch off the inflammatory effects of ETS2 .

The researchers then put this to the test, and discovered that these drugs not only reduced inflammation in macrophages, but also in gut samples from patients with IBD.

As MEK inhibitors can have side effects in other organs, the researchers are now working with LifeArc to find ways to deliver MEK inhibitors directly to macrophages.

Volunteer participants from the NIHR BioResource, with and without IBD, provided blood samples that contributed to this research. The research was funded by Crohn’s and Colitis UK, the Wellcome Trust, MRC and Cancer Research UK, and the researchers worked with collaborators across the UK and Europe.

Image of an inflammatory liver disease, which often occurs at the same time as IBD, with ETS2 target genes (yellow and cyan) expressed at the site of liver damage. Credit: Christina Stankey.

Why have we evolved to carry a genetic variant linked to chronic inflammation.

The unusual thing about the disease variant in the ETS2 enhancer is that it is very common, with approximately 95% of people with IBD carrying one or two copies of it.

Pontus Skoglund and Leo Speidel in the Ancient Genomics Laboratory at the Crick, which studies ancient DNA, worked with James to shed light on when this genetic variant first appeared, showing that it’s incredibly old, at least 500,000 to one million years old, and was even present in Neanderthals and other archaic humans.

They found that the reason this variant remains so common is because switching on ETS2 appears to be an important part of the early response to bacterial infection. Before antibiotics, this may have had a protective effect during infections, which is probably why so many of us still carry the risk variant today, and why it is even more common in regions with high rates of infectious diseases.

James Lee quote

James lee, group leader of the genetic mechanisms of disease laboratory at the crick, and consultant gastroenterologist at the royal free hospital and ucl, who led the research, said:.

“IBD usually develops in young people and can cause severe symptoms that disrupt education, relationships, family life and employment. Better treatments are urgently needed.

“Using genetics as a starting point, we’ve uncovered a pathway that appears to play a major role in IBD and other inflammatory diseases. Excitingly, we’ve shown that this can be targeted therapeutically, and we’re now working on how to ensure this approach is safe and effective for treating people in the future."

Christina quote

Christina stankey, phd student at the crick, and first author along with christophe bourges and lea-maxie haag, said:.

“IBD and other autoimmune conditions are really complex, with multiple genetic and environmental risk factors, so to find one of the central pathways, and show how this can be switched off with an existing drug, is a massive step forwards.”

Ruth Wakeman quote

Ruth wakeman, director of services, advocacy and evidence at crohn's & colitis uk, said:.

"Every year, more than 25,000 people are told that they have Inflammatory Bowel Disease. Crohn's and Colitis are complex, lifelong conditions for which there is no cure, but research like this is helping us to answer some of the big questions about what causes them. The more we can understand about Inflammatory Bowel Disease, the more likely we are to be able to help patients live well with these conditions. This research is a really exciting step towards the possibility of a world free from Crohn's and Colitis one day."

Making a difference for people living with IBD

Lauren golightly is 27 years old and was diagnosed with crohn’s disease in 2018 after experiencing stomach cramps, blood in her poo and irregular bowel habits. she said:.

"Crohn’s has had a huge impact on my life. I’ve had a rocky road since diagnosis, with many hospital admissions, several different medications and even surgery to have a temporary stoma bag. One of the hardest things about having Inflammatory Bowel Disease ( IBD) is the uncertainty around it. I still experience flare-ups and can still spend quite a bit of time in hospital. Learning about this research is so exciting and encouraging. I am hopeful this could potentially make a difference for myself and so many other hundreds of thousands of people living with IBD.”

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Latest Crohn's Research

Crohn's disease can be a frustrating cycle of diarrhea, belly cramps, and constipation. There's still a lot we don't know about this long-lasting inflammatory disease. But for the 3 million Americans living with Crohn's, the latest research sends a message of hope. Scientists are getting a better understanding of what triggers Crohn's disease and how diet can make it worse (or better). They're also studying new ways to find, track, and treat it.

Predicting and Preventing Crohn's Disease

In their search for ways to prevent Crohn's, researchers have looked at everything from diet to things in the environment.

A typical "Western" diet, high in calories, saturated fat , and sugar, increases inflammation in your gut. And inflammation could trigger bowel diseases. This type of diet also throws off the gut microbiome. That's is a careful balance of bacteria and other tiny organisms found in your intestines.

A Harvard University study found that people who ate lots of foods linked to inflammation were at higher risk of getting Crohn's. These foods include processed meat, sweets, and refined grains like white bread.

Early research hints that fructose, a type of sugar often found in sweetened drinks and processed foods, might be a problem. A study in mice found that a high-fructose diet could make symptoms of inflammatory bowel diseases ( IBD ) like Crohn's worse.

But a Mediterranean diet, high in fruits, vegetables, beans, and nuts, could have the opposite effect. It may reduce inflammation and improve Crohn's symptoms . One small study offered a possible environmental clue why Crohn's and other types of IBD are on the rise. Researchers analyzed the baby teeth of 30 adults in Portugal, where there's a tradition of saving these teeth. Those whose teeth showed they'd been exposed to lead, copper, zinc, and chromium soon before and after birth were more likely to have Crohn's.

Another study indicated that blood tests could someday show who's likely to get Crohn's, years before symptoms show up.

Researchers found 51 characteristics (called biomarkers) in blood that were 76% accurate at predicting whether someone would get Crohn's, 5 years before their diagnosis. Understanding the body processes that lead to Crohn's could help scientists find ways to prevent or delay it.  

Expanding Treatment Options

There's still no cure for Crohn's. But researchers are looking at lots of new drugs, especially anti-inflammatory biologics. These are complicated mixtures grown in a lab. They stop proteins in your body from creating inflammation.

Some drugs they're studying focus on your T-cells, white blood cells that are an important part of your immune system . Others stimulate your natural immunity or use prebiotics to change your gut bacteria. Prebiotics are plant fibers that help healthy bacteria grow.

Other researchers have focused on ways to treat Crohn's. In an approach called "tight control," doctors treat both Crohn's symptoms and the inflammation that causes them. One study showed that doing this early on helped heal the intestinal linings of people with Crohn's.

Some people in this study achieved what doctors call "deep remission ." That means they felt well and had no signs of disease activity.

Researchers looked at the same people again 3 years later. In those who'd reached deep remission, Crohn's disease was much less likely to have gotten worse. This was true even if they didn't use the tight control method.

Other Findings

Scientists recently learned more about why abdominal fat sometimes gets into the intestines of people with Crohn's. This process is called "creeping fat." It can lead to intestinal scars that require surgery.

Researchers found that creeping fat happens when bacteria called Clostridium innocuum leak from the small intestine, which has been damaged by Crohn's. They think the fat wraps around your intestine to keep the bacteria from getting into your bloodstream, where it could do harm. But the creeping fat itself ends up causing problems.

This finding could someday lead to new therapies that target C. innocuum. They might prevent creeping fat or reduce its damage.  

Researchers are also looking at a possible way to predict and track Crohn's flare-ups . They're testing a wearable device that monitors biomarkers in your sweat. You wear it around your wrist like a watch. Scientists hope the device could help people gain more control over this unpredictable condition.

Crohn's Disease Statistics

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Volume 18, Issue 8, August 2024

Epigenetic fingerprints in ibd: from methylation patterns to clinical implications.

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Navigating Postoperative Management in Crohn’s Disease: Insights from the PORCSE Study

Original articles, peripheral blood dna methylation signatures and response to tofacitinib in moderate-to-severe ulcerative colitis.

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Whole Blood DNA Methylation Changes Are Associated with Anti-TNF Drug Concentration in Patients with Crohn’s Disease

Prophylactic versus endoscopy-driven treatment of crohn’s postoperative recurrence: a retrospective, multicentric, european study [porcse study], accuracy of information given by chatgpt for patients with inflammatory bowel disease in relation to ecco guidelines, pragmatic trial design to compare real-world effectiveness of different treatments for inflammatory bowel diseases: the practice-ibd european consensus, specific antibiotics increase the risk of flare-ups in patients with inflammatory bowel disease: results from a danish nationwide population-based nested case-control study, the epidemiology of inflammatory bowel diseases during the covid-19 pandemic: comparison of two nationwide cohorts, outcomes in adult inflammatory bowel disease clinical trials: assessment of similarity among participants with adolescent-onset and adult-onset disease, does combined medical and surgical treatment improve perianal fistula outcomes in patients with crohn’s disease a systematic review and meta-analysis, efficacy and safety of etrasimod in patients with moderately to severely active isolated proctitis: results from the phase 3 elevate uc clinical programme.

Histological Outcomes and JAK-STAT Signalling in Ulcerative Colitis Patients Treated with Tofacitinib

Intestinal adipocytes transdifferentiate into myofibroblast-like cells and contribute to fibrosis in crohn’s disease, spatial single cell profiling using imaging mass cytometry: inflammatory versus penetrating crohn’s disease.

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• Published: 02 April 2020

Crohn’s disease

• Giulia Roda 1 ,
• Siew Chien Ng 2 ,
• Paulo Gustavo Kotze 3 ,
• Marjorie Argollo 1 ,
• Remo Panaccione 4 ,
• Antonino Spinelli 5 , 6 ,
• Arthur Kaser 7 ,
• Laurent Peyrin-Biroulet 8 &
• Silvio Danese 1 , 6  

Nature Reviews Disease Primers volume  6 , Article number:  22 ( 2020 ) Cite this article

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• Crohn's disease
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An Author Correction to this article was published on 19 June 2020

An Author Correction to this article was published on 20 May 2020

A Publisher Correction to this article was published on 06 April 2020

This article has been updated

Crohn’s disease is an inflammatory bowel disease that is characterized by chronic inflammation of any part of the gastrointestinal tract, has a progressive and destructive course and is increasing in incidence worldwide. Several factors have been implicated in the cause of Crohn’s disease, including a dysregulated immune system, an altered microbiota, genetic susceptibility and environmental factors, but the cause of the disease remains unknown. The onset of the disease at a young age in most cases necessitates prompt but long-term treatment to prevent disease flares and disease progression with intestinal complications. Thus, earlier, more aggressive treatment with biologic therapies or novel small molecules could profoundly change the natural history of the disease and decrease complications and the need for hospitalization and surgery. Although less invasive biomarkers are in development, diagnosis still relies on endoscopy and histological assessment of biopsy specimens. Crohn’s disease is a complex disease, and treatment should be personalized to address the underlying pathogenetic mechanism. In the future, disease management might rely on severity scores that incorporate prognostic factors, bowel damage assessment and non-invasive close monitoring of disease activity to reduce the severity of complications.

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Location is important: differentiation between ileal and colonic Crohn’s disease

Microscopic colitis

Ulcerative colitis

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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06 april 2020.

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Acknowledgements

Work in the laboratory of A.K. is supported by the Wellcome Trust (Senior Investigator Award 106260/Z/14/Z) and the European Research Council (Consolidator Grant 648889).

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Authors and affiliations.

IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center – IRCCS –, Rozzano, Italy

Giulia Roda, Marjorie Argollo & Silvio Danese

Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China

Siew Chien Ng

Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil

Paulo Gustavo Kotze

Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada

Remo Panaccione

Humanitas Clinical and Research Center – IRCCS –, Rozzano, Italy

Antonino Spinelli

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

Antonino Spinelli & Silvio Danese

Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

Arthur Kaser

Department of Gastroenterology, University Hospital of Nancy, Nancy, France

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Contributions

Introduction (G.R., L.P.-B. and S.D.); Epidemiology (S.C.N.); Mechanisms/pathophysiology (A.K.); Diagnosis, screening and prevention (P.G.K. and M.A.); Management (R.P.); Quality of life (G.R., A.S., L.P.-B. and S.D.); Outlook (G.R., A.S., L.P.-B. and S.D.).

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Correspondence to Silvio Danese .

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S.D. has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Merck Sharp & Dohme, UCB Pharma, Ferring, Cellerix, Takeda Pharmaceutical Company, Nycomed, Pharmacosmos, Actelion, Alpha Wasserman, Genentech, Grünenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, Johnson & Johnson and Nikkiso Europe GmbH. L.P.-B. has received consulting fees from AbbVie, Amgen, Biogaran, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Ferring, Genentech, HAC Pharma, Hospira, Index Pharmaceuticals, Janssen, Lilly, Merck, Mitsubishi, Norgine, Pfizer, Pharmacosmos, Pilege, Sandoz, Takeda, Therakos, Tillotts, UCB Pharma and Vifor and lecture fees from AbbVie, Ferring, HAC Pharma, Janssen, Merck, Mitsubishi, Norgine, Takeda, Therakos, Tillotts and Vifor. A.S. has acted as a consultant or speaker for Ethicon, Olympus, Frankenman, Transenterix (not active), Tigenyx, Pfizer, Takeda and Sandoz. P.G.K has been a lecturer for AbbVie, Janssen, Pfizer and Takeda and is a member of the advisory board of AbbVie, Pfizer and Takeda. A.K. has served as an adviser to Boehringer Ingelheim, Ferring, Genentech, GlaxoSmithKline, Gilead, Hospira, Janssen, Pfizer, and VHSquared. R.P. has received consultant and/or lecture fees from AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc., Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Millennium Pharmaceuticals (now Takeda Oncology), Ocera Therapeutics Inc., Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Laboratories, Schering-Plough Corporation, Synta Pharmaceuticals Corp., Teva, UCB Pharma and Warner Chilcott. S.C.N. has received consulting and speaker fees from AbbVie, Ferring, Janssen, Menarini and Takeda, has served as a scientific advisory board member for AbbVie, Ferring and Takeda and has received research grants from AbbVie, Ferring and Janssen. The other authors declare no competing interests.

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Roda, G., Chien Ng, S., Kotze, P.G. et al. Crohn’s disease. Nat Rev Dis Primers 6 , 22 (2020). https://doi.org/10.1038/s41572-020-0156-2

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• All Resources Ask the Expert: Your Crohn’s Questions Answered

New Crohn’s Disease Medications and Other Treatment Research

• There’s promising research on new treatment options for Crohn’s disease.
• Potential treatments now in clinical trials include fecal transplant and new classes of medications.
• The U.S. Food and Drug Administration (FDA) recently approved several new biologic drugs and the first oral drug to treat Crohn’s disease.

When you live with inflammatory bowel disease (IBD) like Crohn’s disease, it can feel like you’ve tried everything to manage your condition. As one MyCrohnsAndColitisTeam member shared, “I’m running out of treatment options.”

Keeping up with research and the latest advances in treatments can help you and your doctor find new options for the treatment of Crohn’s and to improve your quality of life. Research on IBD is ongoing in several areas, from understanding the causes of IBD to running clinical trials that test new treatments.

Promising Animal Studies

Developing new treatments often starts with scientists using lab-grown cells or animals to study genetic factors or environmental triggers that may influence why someone develops Crohn’s. They might also begin research after noticing something common among people living with a particular condition.

For example, a recent study looked at nine families of people with Crohn’s disease. The findings showed that a fungus called Candida tropicalis was more abundant in the people with Crohn’s compared with their relatives who didn’t have the condition. Scientists then examined mice with C. tropicalis infections and found differences in their gastrointestinal bacteria and immune systems that made the infected mice likely to develop intestinal inflammation. More studies will be needed to assess the strength of the association between C. tropicalis fungal infection and Crohn’s disease.

Another new area of research involves zebrafish with mutations (changes) in a gene called NOD2. Around 10 percent of people with Crohn’s disease have changes in the NOD2 gene and are more likely to be diagnosed with Crohn’s before age 18. Scientists studied zebrafish with the same genetic change and found that a medication called bazedoxifene (Conbriza) calmed overactive immune cells in the fish. Bazedoxifene is already approved to treat menopausal symptoms in humans. Scientists are hopeful that this drug could someday help people with Crohn’s disease and NOD2 gene mutations.

Active Clinical Trials

Before being used in a medical clinic, treatments must go through clinical trials to evaluate possible side effects and adverse events and show that the drugs are safe and effective. Although taking a drug that hasn’t been approved by the FDA comes with certain risks, clinical trials offer the earliest opportunity for people to receive a new medication.

Following are just a few of the recent and ongoing clinical trials for new treatments for Crohn’s disease.

Fecal Transplants

In a fecal transplant, a person with Crohn’s disease is given “good” bacteria from someone else’s digestive system to help improve symptoms. The transplant can be given orally or performed using an endoscope, a thin, tubelike instrument.

One team member asked, “I want to know if anyone has done a fecal transplant and how it worked for them. Was it helpful? Did it decrease your symptoms?”

In reply, a member said that they’d had one for a Clostridioides difficile infection and saw an ”immediate improvement.” ”I’ve been C. difficile-free for nine months, and I feel like it also helped my Crohn’s symptoms beyond my regular treatments,” they wrote.

Another member added, “Studies are looking at the fecal microbiome transplant as a treatment for colitis itself (not just for C. difficile). I’m interested to see where that goes.”

Several studies are or will be recruiting volunteers for further study of fecal transplants for Crohn’s disease.

Medications

Most of these clinical trials are investigating medications. For example, the Cultivate trial is studying etrasimod, a once-a-day pill that is a selective sphingosine 1-phosphate (S1P) receptor modulator. S1P receptor modulators are medications that reduce immune reactions and are currently used to treat multiple sclerosis, which, like Crohn’s, is an autoimmune disease. Cultivate is looking into whether etrasimod may help people with active Crohn’s disease who are resistant to other types of Crohn’s medications.

Are you interested in participating in clinical trials? ClinicalTrials.gov has more than 200 listings of clinical trials for Crohn’s disease that are currently recruiting. You can search using your location, age, gender, the type of trial, and more to find trials that may be a good fit for you. Sometimes, your care team may suggest you enroll in a clinical trial. Always follow up with your health care providers if you are looking for other treatment options, including clinical trials.

New Treatment Strategies and Drug Approvals

Several new treatments and related management strategies are available now.

Lifestyle Changes

Following special diets as a strategy for managing Crohn’s disease is a common topic, and there are many eating plans to choose from.

For example, one team member asked, “SCD, IBD-AID, FODMAP, anti-inflammatory, GAPS, paleo — I’m wondering whether anyone with IBD has tried these diets, and if so, what happened?”

A review of seven studies involving the Crohn’s disease exclusion diet (CDED) was recently published. CDED focuses on fresh, whole foods and excludes foods that can negatively affect the intestines, such as gluten, dairy, animal fat, and processed products. Although the studies involving the CDED differed to some extent, the review found that, in general, the diet was associated with remission from Crohn’s disease symptoms.

Read more about what foods to eat — and to avoid — with Crohn’s disease .

The FDA recently approved new drugs in various categories to treat Crohn’s disease. Drugs are approved based on the safety and effectiveness they demonstrated in clinical trials.

Until recently, the biologic infliximab-dyyb (sold under the brand name Inflectra ) needed to be administered via an intravenous infusion at a clinic. In October 2023, the FDA approved a version of infliximab sold under the brand name Zymfentra for subcutaneous (under the skin) injection. Both versions work by blocking an inflammatory molecule called tumor necrosis factor, so infliximab is known as an anti-TNF drug.

One newer biologic, risankizumab-rzaa ( Skyrizi ), is an inhibitor of a cytokine called interleukin (IL)-23 — the drug blocks this inflammatory molecule. It was approved in June 2022 to treat Crohn’s disease. IL-23 inhibitors now in clinical trials include guselkumab and mirikizumab.

A related treatment, ustekinumab ( Stelara ), also reduces disease activity by lowering inflammation. Ustekinumab is a human monoclonal antibody (a laboratory-made protein) that blocks signals from both IL-23 and IL-12. It’s FDA-approved for adults with Crohn’s disease. Now clinical trials are seeing if it’s safe for children with Crohn’s disease.

Kinase inhibitor

In May 2023, upadacitinib ( Rinvoq ) became the first drug in a class called Janus kinase (JAK) inhibitors to be FDA-approved for treatment of moderately to severely active Crohn’s disease. It’s also the first oral drug to receive approval to treat Crohn’s. JAK inhibitors are known as “small molecules” and are available to your body when taken by mouth, whereas biologics must be injected.

Speak With Your Treatment Team

Always speak with your gastroenterology care team before you adjust your treatment plan. Be honest about your symptoms and concerns so that your doctor can discuss your options and find the most effective treatment to help you reach remission from Crohn’s . Your gastroenterologist should also be aware of clinical trials for Crohn’s disease treatments. They can advise you when a clinical trial may be the best option for your treatment.

Get tips for making the most out of your appointment with your Crohn’s specialist.

Talk With Others Who Understand

On MyCrohnsAndColitisTeam , you’ll meet other people with inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. Here, more than 178,000 members who understand life with IBD come together to share support, advice, and stories from their daily lives.

Are you interested in recent advances in the treatment of Crohn’s disease? Have you asked your health care provider about clinical trials? Share your experiences and thoughts in the comments below or by posting on MyCrohnsAndColitisTeam.

• Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease — American Society for Microbiology
• Candida Tropicalis Infection Modulates the Gut Microbiome and Confers Enhanced Susceptibility to Colitis in Mice — Cellular and Molecular Gastroenterology and Hepatology
• Mutation Spectrum of NOD2 Reveals Recessive Inheritance as a Main Driver of Early Onset Crohn’s Disease — Scientific Reports
• A Myeloid–Stromal Niche and GP130 Rescue in NOD2-Driven Crohn’s Disease — Nature
• Gp130 Blockade To NOD Off Crohn’s Disease — Trends in Immunology
• Fecal Microbiota Transplantation for Induction of Remission in Crohn’s Disease: A Systematic Review and Meta-Analysis — International Journal of Colorectal Disease
• A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn’s Disease (Cultivate) — ClinicalTrials.gov
• Clinical Trial Resources — Crohn’s & Colitis Foundation
• Effects of Crohn’s Disease Exclusion Diet on Remission: A Systematic Review — Therapeutic Advances in Gastroenterology
• IBD-AID Diet — UMass Chan Medical School
• Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn’s Disease — Gastroenterology
• FDA Approves Risankizumab-Rzaa for Moderately to Severely Active Crohn Disease — Pharmacy Times
• Investigational Drugs in Phase I and Phase II Clinical Trials Targeting Interleukin 23 (IL23) for the Treatment of Crohn’s Disease — Expert Opinion on Investigational Drugs
• A Study of Guselkumab in Participants With Moderately to Severely Active Crohn’s Disease — ClinicalTrials.gov
• A Study of Mirikizumab (LY3074828) in Participants With Crohn’s Disease (VIVID-1) — ClinicalTrials.gov
• A Long-Term Extension Study of Ustekinumab in Pediatric Participants (United) — ClinicalTrials.gov
• A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn’s Disease Who Have Inadequately Responded to or Are Intolerant to Conventional and/or Biologic Therapies (U-Excel) — ClinicalTrials.gov
• Janus Kinase Inhibitors (JAK Inhibitors) — Crohn’s & Colitis Foundation
• AGA Recommends Early Use of Biologics in Patients With Moderate-to-Severe Crohn’s Disease — American Gastroenterological Association
• FDA Approves Subcutaneous Infliximab for IBD — Gastroenterology & Endoscopy News
• FDA Approves First Oral Treatment for Moderately to Severely Active Crohn’s Disease — U.S. Food and Drug Administration
• Will Biologics Surpass Small Molecules in the Pharmaceutical Race? — BioPharmaTrend.com

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Related questions.

• How much caffeine can I have with Crohn's or colitis? See answer
• Can I take Ozempic and GLP-1 agonists with Crohn's or colitis? See answer
• How do biologics work in treating Crohn's or colitis, and what are their side effects? See answer
• What are foods and drinks to avoid with Crohn's or colitis? See answer

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Thank you do much for information. I'll be seeing my gastro Dr on Tuesday to fine out what are some of my options. Hope you have a good night

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Study may have solved a mystery surrounding Crohn’s disease

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A new study may have solved a mystery surrounding Crohn's disease, a type of inflammatory bowel disease in which immune defenses meant to attack invading microbes instead mistakenly target the body's own digestive tract. Norovirus, a common infection that causes vomiting and diarrhea, is one of several viruses and bacteria thought to trigger disease onset in people with Crohn's disease, but the field does not know why.

One clue emerged when past studies found that a certain genetic change (mutation) is present in most people with the condition. This mutation makes gut lining cells more vulnerable to damage. The mystery deepened again, however, when it was learned that half of all Americans have this same risk-conferring genetic mutation, but fewer than half a million develop Crohn's disease.

Published online October 5 in the journal Nature , the new work in mice and in human tissue revealed for the first time that in healthy individuals, immune defenders called T cells secrete a protein called apoptosis inhibitor 5 (API5), which signals the immune system to halt the attack on gut lining cells. This protein adds an extra layer of protection against immune damage, so even those with the mutation can have a healthy gut. However, the researchers also found that norovirus infection blocks T cell secretion of API5 in mice bred to have a rodent form of Crohn's disease, killing gut lining cells in the process.

Led by researchers at NYU Grossman School of Medicine, the work supports the theory that API5 protects most people with the mutation against the disease until a second trigger, such as norovirus infection, pushes some across the disease threshold.

In experiments centered on mice genetically modified to have the mutation linked to Crohn's disease in humans, mice that received an injection of API5 survived, while half of the untreated group died. This confirmed the idea that the protein protects gut cells, say the study authors. In human tissue, the investigators found that those with Crohn's disease had between 5- and 10-fold fewer API5-producing T cells in their gut tissue than those without the illness.

Our findings offer new insight into the key role that apoptosis inhibitor 5 plays in Crohn's disease. This molecule may provide a new target for treating this chronic autoimmune illness, which has proven difficult to manage over the long term." Yu Matsuzawa-Ishimoto, MD, PhD, Study Lead Author and Gastroenterologist

Dr. Matsuzawa-Ishimoto, a postdoctoral research fellow at NYU Langone Health, notes that current therapies, which work by suppressing the immune system, put patients at high risk for infection and often become less effective after a few years of use. A treatment method targeting API5, he adds, might avert those issues.

In another set of experiments, the investigators created organ-like structures out of tissue collected from humans who tested positive for the mutation. Notably, these structures were made only of gut lining cells. Then, the research team dropped API5 into these "mini guts" and found that this treatment protected gut lining cells. In addition, adding API5-producing T cells also protected the gut lining.

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"The results of our investigation help explain why the genetic links to Crohn's disease are much broader than the actual number of people who have the disease," says study co-senior author and biochemist Shohei Koide, PhD. Dr. Koide is a professor in the Department of Biochemistry and Molecular Pharmacology and a member of the Perlmutter Cancer Center at NYU Langone.

"Our study suggests that when norovirus infects those with a weakened ability to produce apoptosis inhibitor 5, it tips the balance toward a full-blown autoimmune disease ," adds study co-senior author and microbiologist Ken H. Cadwell, PhD, the Recanati Family Professor of Microbiology at NYU Langone.

Dr. Cadwell cautions that while the study authors derived API5 protein from human tissue rather than rodents, it remains unclear whether the injection treatment can be safely administered in humans.

The research team next plans to explore the long-term effects of API5 injections to better understand whether the prospective treatment can effectively manage Crohn's disease, which can flare up repeatedly over a long period.

Funding for the study was provided by National Institutes of Health grants R0IL123340, R0IDK093668, R0IAI140754, R0IAI121244, R0IAI130945, R0IDK124336, and R0IDK088199. Further funding was provided by the Howard Hughes Medical Institute, the Kenneth Rainin Foundation, the Crohn's & Colitis Foundation, and the Takeda-Columbia-NYU Alliance.

Dr. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and Abbvie, and has served as a consultant for Puretech Health, which develops microbiome therapies, as well as GentiBio and Synedgen. Dr. Koide has received research support from Argenx BVBA, Black Diamond Therapeutics, and Puretech Health, and has served as a consultant for Black Diamond Therapeutics. NYU Langone has patents pending (10,722,600, 62/935,035, and 63/157,225) for therapies developed from this treatment approach, from which Dr. Cadwell, Dr. Koide, Dr. Matsuzawa-Ishimoto, and NYU Langone may benefit financially. The terms and conditions of these relationships are being managed in accordance with the policies of NYU Langone.

NYU Langone

Matsuzawa-Ishimoto, Y., et al. (2022) The γδ IEL effector API5 masks genetic susceptibility to Paneth cell death. Nature. doi.org/10.1038/s41586-022-05259-y .

Posted in: Medical Science News | Medical Research News | Medical Condition News

Tags: Apoptosis , Autoimmune Disease , B Cell , Bacteria , Biochemistry , Cancer , Cell , Chronic , Crohn’s Disease , Crohn's Disease , Diarrhea , Genetic , Genetic Engineering , Immune System , Inflammatory Bowel Disease , Medical School , Medicine , Microbiology , Microbiome , Molecule , Mutation , Norovirus , Pharmacology , Protein , Research , Therapeutics , Vomiting

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• What is Crohn's disease? A Mayo Clinic expert explains

Learn more about Crohn's disease from gastroenterologist William Faubion, M.D.

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William A. Faubion, Jr., M.D., Gastroenterology, Mayo Clinic: I'm Dr. Bill Faubion, a gastroenterologist at Mayo Clinic. In this video, we'll cover the basics of Crohn's disease. What it is? Who gets it? The symptoms, diagnosis and treatment. Whether you're looking for answers for yourself or someone you love, we're here to give you the best information available. Crohn's disease is an inflammatory bowel disease that causes chronic inflammation of the GI tract, which extends from your stomach all the way down to your anus. Different areas of the GI tract can be affected in different people, and it often spreads into the deeper layers of the bowel. It's estimated that over half a million Americans are living with Crohn's disease. It can be painful and debilitating, occasionally leading to severe complications, as well as emotionally stressful. And while there is no cure, once you've been diagnosed, treatment can help you get back to a more normal and comfortable life.

Who gets it?

There are a lot of particulars that figure into or aggravate Crohn's disease, but the exact cause is still unknown. It may involve an abnormal immune response against some microorganism in which your tissues are also attacked. Genetics might also play a role. And it's true that you're at higher risk if a first-degree relative has it. But that's really only seen in about 20% of cases. There is a correlation with age. Although it can show up at any stage of life, most people are diagnosed before 30. Ethnicity is a risk factor. Whites have the highest risk, especially among people of Ashkenazi Jewish descent. However, incidence is increasing among black people in North America and the UK. Non-steroidal anti-inflammatory medications or NSAIDS... they don't cause Crohn's disease, but they are known to trigger inflammation of the bowel and make it worse. They include common over-the-counter painkillers like ibuprofen, naproxen sodium, diclofenac sodium, and others. So if you've been diagnosed with Crohn's, make sure you talk to your doctor about what medications should be avoided. Many of these elements are out of our hands, but smoking is the most important controllable risk factor for developing Crohn's disease. It also leads to more severe disease and increased need for surgery. So if you smoke and you're diagnosed, now is a good time to quit.

What are the symptoms?

Crohn's disease can affect any area in the GI tract, but it's mostly found in the large and the small intestine. It can also be confined to one area or found in multiple segments. Symptoms can range in severity and it can depend on the area of the GI tract that's affected. You also may experience periods of remission when you have no symptoms or issues at all. The symptoms can come on gradually, but they can also show up suddenly. And these can include diarrhea, fever, fatigue, abdominal pain and cramping, blood in your stool, mouth sores, reduced appetite and weight loss. If your Crohn's disease has caused fistulas or inflamed tunnels in the skin near the anal area, you may notice pain or drainage. And in more severe cases, you may have inflammation of the eyes, skin, joints, liver or bile ducts, kidney stones, and anemia. In children, it can delay growth and development. Over time, Crohn's disease can lead to other complications, including bowel obstruction, ulcers, fistulas, anal fissures, malnutrition, and other health problems. It can also increase your risk for blood clots and colon cancer. Having these symptoms doesn't automatically mean you have Crohn's. But if you're experiencing anything that concerns you, it's a good idea to make an appointment with your doctor.

How is it diagnosed?

There's no single test for Crohn's disease, and it has similar symptoms to a lot of other conditions, so it can take a little time to get a diagnosis. First, your doctor is going to consider your medical history. Then your doctor may want to run a variety of tests or procedures. And at some point, your general practitioner may want to refer you to a specialist called a gastroenterologist like myself. A blood test can check for anemia and check for signs of infection. A stool study can test if there's blood present or rule out certain pathogens. A colonoscopy may be needed. This also allows your doctor to view your entire colon and the very end of the ileum using an endoscope, a small camera mounted on a thin flexible tube. They can take tissue samples for a biopsy at the same time. And the presence of granulomas or clusters of inflammatory cells, can essentially confirm the diagnosis. A CT scan might be ordered for a better look at the bowel and all of the surrounding tissues; or an MRI , which is especially good for evaluating fistulas around the anus or the small intestine. A capsule endoscopy can be done. Here you actually swallow the camera about the size of a large vitamin and it takes images of your digestive tract as it travels through. And a balloon-assisted enteroscopy may be done to get further into the bowel than a standard endoscope can if abnormalities have been found that need further investigation.

How is it treated?

Your doctor can work with you to find therapies that alleviate your symptoms. One of the main goals is to reduce the inflammation that produces painful and disruptive issues. Another is to limit complications over the long-term. There is currently no cure, but many treatments can provide a lot of relief, and in some cases, even long-term remission. These may include anti-inflammatory drugs like corticosteroids, immune system suppressants, and antibiotics. Certain biologics, which target proteins made by the immune system, can help. Antidiarrheals, pain relievers, and supplements can help counter other symptoms. Nutritional therapy and a special diet may be recommended. And in some cases where other measures aren't effective, surgery may be required. And that's to remove the damaged tissue. Some of these therapies may have side effects themselves. So be sure and review the risks and benefits with your doctor.

Crohn's disease can be physically and emotionally challenging, but there are things that can help. Although there's no firm evidence that any particular foods cause Crohn's disease, certain things seem to aggravate flare-ups. So a food diary can help you identify personal triggers. Beyond that, limit dairy products, eating smaller meals, stay hydrated, and try to avoid caffeine, alcohol, and carbonation. Consider multivitamins if you're concerned about weight loss. Or if your diet has become too limited, talk to a registered dietitian. And again, if you smoke, you should stop. It's important to take care of your mental health too. Find ways to manage stress, like exercise, breathing, relaxation techniques or biofeedback. Some symptoms like abdominal pain, gas, and diarrhea... they can cause anxiety and frustration. They can make it difficult to go out in public for any amount of time. It can feel limiting and isolating and lead to depression. So learn as much as you can about Crohn's. Staying informed can help a lot in feeling like you're in control of your condition. Talk to a therapist, especially one familiar with inflammatory bowel disease. Your doctor can give you some recommendations. And you might want to find a support group of people going through the same thing that you are. Crohn's disease is a complex disease. But having expert medical care and developing a treatment strategy can make it more manageable and even help you get back to the freedom of your normal life. Meanwhile, significant advances continue to be made in understanding and treating the disease, getting us closer to curing it or preventing it entirely. If you'd like to learn more about Crohn's disease, here are other related videos or visit mayoclinic.org. We wish you well.

Digestive system

In Crohn's disease, any part of your small or large intestine can be involved. It may involve multiple segments, or it may be continuous. Crohn's disease most commonly affects the last part of the small intestine (ileum) and parts of the colon.

Gastroenterology & GI Surgery Blog

Crohn's disease is a type of inflammatory bowel disease (IBD). It causes swelling of the tissues (inflammation) in your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition.

Inflammation caused by Crohn's disease can involve different areas of the digestive tract in different people, most commonly the small intestine. This inflammation often spreads into the deeper layers of the bowel.

Crohn's disease can be both painful and debilitating, and sometimes may lead to life-threatening complications.

There's no known cure for Crohn's disease, but therapies can greatly reduce its signs and symptoms and even bring about long-term remission and healing of inflammation. With treatment, many people with Crohn's disease are able to function well.

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In Crohn's disease, any part of your small or large intestine can be involved. It may involve multiple segments, or it may be continuous. In some people, the disease is only in the colon, which is part of the large intestine.

Signs and symptoms of Crohn's disease can range from mild to severe. They usually develop gradually, but sometimes will come on suddenly, without warning. You may also have periods of time when you have no signs or symptoms (remission).

When the disease is active, symptoms typically include:

• Abdominal pain and cramping
• Blood in your stool
• Mouth sores
• Reduced appetite and weight loss
• Pain or drainage near or around the anus due to inflammation from a tunnel into the skin (fistula)

Other signs and symptoms

People with severe Crohn's disease may also experience symptoms outside of the intestinal tract, including:

• Inflammation of skin, eyes and joints
• Inflammation of the liver or bile ducts
• Kidney stones
• Iron deficiency (anemia)
• Delayed growth or sexual development, in children

When to see a doctor

See your doctor if you have persistent changes in your bowel habits or if you have any of the signs and symptoms of Crohn's disease, such as:

• Abdominal pain
• Nausea and vomiting
• Diarrhea lasting more than two weeks
• Unexplained weight loss
• Fever in addition to any of the above symptoms

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The exact cause of Crohn's disease remains unknown. Previously, diet and stress were suspected, but now doctors know that these factors may aggravate, but don't cause, Crohn's disease. Several factors likely play a role in its development.

• Immune system. It's possible that a virus or bacterium may trigger Crohn's disease; however, scientists have yet to identify such a trigger. When your immune system tries to fight off an invading microorganism or environmental triggers, an atypical immune response causes the immune system to attack the cells in the digestive tract, too.
• Heredity. Crohn's disease is more common in people who have family members with the disease, so genes may play a role in making people more likely to have it. However, most people with Crohn's disease do not have a family history of the disease.

Risk factors

Risk factors for Crohn's disease may include:

• Age. Crohn's disease can occur at any age, but you're likely to develop the condition when you're young. Most people who develop Crohn's disease are diagnosed before they're around 30 years old.
• Ethnicity. Although Crohn's disease can affect any ethnic group, whites have the highest risk, especially people of Eastern European (Ashkenazi) Jewish descent. However, the incidence of Crohn's disease is increasing among Black people who live in North America and the United Kingdom. Crohn's disease is also being increasingly seen in the Middle Eastern population and among migrants to the United States.
• Family history. You're at higher risk if you have a first-degree relative, such as a parent, sibling or child, with the disease. As many as 1 in 5 people with Crohn's disease has a family member with the disease.
• Cigarette smoking. Cigarette smoking is the most important controllable risk factor for developing Crohn's disease. Smoking also leads to more-severe disease and a greater risk of having surgery. If you smoke, it's important to stop.
• Nonsteroidal anti-inflammatory medications. These include ibuprofen (Advil, Motrin IB, others), naproxen sodium (Aleve), diclofenac sodium and others. While they do not cause Crohn's disease, they can lead to inflammation of the bowel that makes Crohn's disease worse.

Complications

Crohn's disease may lead to one or more of the following complications:

• Bowel obstruction. Crohn's disease can affect the entire thickness of the intestinal wall. Over time, parts of the bowel can scar and narrow, which may block the flow of digestive contents, often known as a stricture. You may require surgery to widen the stricture or sometimes to remove the diseased portion of your bowel.
• Ulcers. Chronic inflammation can lead to open sores (ulcers) anywhere in your digestive tract, including your mouth and anus, and in the genital area (perineum).

Fistulas. Sometimes ulcers can extend completely through the intestinal wall, creating a fistula — an abnormal connection between different body parts. Fistulas can develop between your intestine and your skin, or between your intestine and another organ. Fistulas near or around the anal area (perianal) are the most common kind.

When fistulas develop inside the abdomen, it may lead to infections and abscesses, which are collections of pus. These can be life-threatening if not treated. Fistulas may form between loops of bowel, in the bladder or vagina, or through the skin, causing continuous drainage of bowel contents to your skin.

• Anal fissure. This is a small tear in the tissue that lines the anus or in the skin around the anus where infections can occur. It's often associated with painful bowel movements and may lead to a perianal fistula.
• Malnutrition. Diarrhea, abdominal pain and cramping may make it difficult for you to eat or for your intestine to absorb enough nutrients to keep you nourished. It's also common to develop anemia due to low iron or vitamin B-12 caused by the disease.
• Colon cancer. Having Crohn's disease that affects your colon increases your risk of colon cancer. General colon cancer screening guidelines for people without Crohn's disease call for a colonoscopy at least every 10 years beginning at age 45. In people with Crohn's disease affecting a large part of the colon, a colonoscopy to screen for colon cancer is recommended about 8 years after disease onset and generally is performed every 1 to 2 years afterward. Ask your doctor whether you need to have this test done sooner and more frequently.
• Skin disorders. Many people with Crohn's disease may also develop a condition called hidradenitis suppurativa. This skin disorder involves deep nodules, tunnels and abscesses in the armpits, groin, under the breasts, and in the perianal or genital area.
• Other health problems. Crohn's disease can also cause problems in other parts of the body. Among these problems are low iron (anemia), osteoporosis, arthritis, and gallbladder or liver disease.

Medication risks. Certain Crohn's disease drugs that act by blocking functions of the immune system are associated with a small risk of developing cancers such as lymphoma and skin cancers. They also increase the risk of infections.

Corticosteroids can be associated with a risk of osteoporosis, bone fractures, cataracts, glaucoma, diabetes and high blood pressure, among other conditions. Work with your doctor to determine risks and benefits of medications.

• Blood clots. Crohn's disease increases the risk of blood clots in veins and arteries.

Crohn's disease care at Mayo Clinic

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• Colorectal cancer screening (PDQ): Health professional version. National Cancer Institute. https://www.cancer.gov/types/colorectal/hp/colorectal-screening-pdq. Accessed July 7, 2022.
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• Ferri FF. Crohn disease. In: Ferri's Clinical Advisor 2020. Elsevier; 2020. https://www.clinicalkey.com. Accessed July 22, 2020.
• Lichtenstein GR, et al. ACG clinical guideline: Management of Crohn's disease in adults. American Journal of Gastroenterology. 2018; doi:10.1038/ajg.2018.27.
• Crohn's disease. American College of Gastroenterology. https://gi.org/topics/crohns-disease/. Accessed July 7, 2022.
• What should I eat? Crohn's & Colitis Foundation. https://www.crohnscolitisfoundation.org/diet-and-nutrition/what-should-i-eat. Accessed July 7, 2022.
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• Ami TR. Allscripts EPSi. Mayo Clinic. April 11, 2022.
• Kane SV (expert opinion). Mayo Clinic. Sept. 12, 2020.
• Khanna S (expert opinion). Mayo Clinic. July 5, 2022.
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August 16, 2024

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Keep your gut healthy and avoid inflammatory disease, says gastroenterologist

by Mayo Clinic News Network

A healthy gut helps lower your risk of developing inflammatory diseases such as inflammatory bowel disease (IBD), a chronic condition that causes inflammation in the digestive tract.

Victor Chedid, M.D., a gastroenterologist and IBD expert at Mayo Clinic in Rochester, offers tips people can take to keep their gut healthy and inflammatory diseases at bay.

Dr. Chedid recommends a four-pronged approach to gut health.

"Paying attention to all these factors is essential for maintaining gut health," Dr. Chedid says.

Maintaining gut health is important, especially when a person is dealing with inflammatory bowel disease . There are two main types of IBD: Crohn's disease and ulcerative colitis.

IBD is a global disease with about 6–8 million cases worldwide. The prevalence of Crohn's disease and ulcerative colitis is on the rise in African countries, the Middle East and the Asia Pacific region.

"That's why we have to increase awareness and make sure that people seek care when they have symptoms so that they can get the diagnosis and care that is appropriate for them," Dr. Chedid says.

There is no cure for IBD, but a variety of treatments exist to help patients achieve remission. These include anti-inflammatory drugs , immune system suppressors, biologics, antibiotics and surgery.

Diarrhea and rectal bleeding are common symptoms, but these symptoms can make people with IBD feel ashamed and hesitant to seek support. Dr. Chedid says families can play a crucial role in helping their loved ones manage IBD.

"It's about being there for them, recognizing that they're not always going to be themselves at all times," Dr. Chedid says. "There will be times when they feel down, are in pain or don't want to eat what you cook. Don't be offended. You just need to be there for them."

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U.S. Unveils Price Limits for 10 Costly or Common Medications

The Biden administration said it would have saved $6 billion had the new prices been in effect last year.

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By Noah Weiland and Rebecca Robbins

Noah Weiland covers federal health policy, and Rebecca Robbins covers the pharmaceutical industry.

The Biden administration on Thursday unveiled the results of landmark drug price negotiations between Medicare and pharmaceutical companies, allowing President Biden and Vice President Kamala Harris to cast themselves as confronting the drug industry on behalf of older Americans at a critical moment in the presidential campaign.

The negotiated prices, which take effect in 2026, are expected to save billions of dollars for Medicare, which is funded by taxpayers. But they will lead to direct out-of-pocket savings for only a subset of the millions of older Americans who take the drugs subject to negotiations.

Other provisions of the law that created the drug negotiation program, such as capping patients’ expenses for insulin and their yearly out-of-pocket drug costs, will do more to save older Americans money at the pharmacy counter.

The 10 drugs subject to negotiations include widely used blood thinners and arthritis medications. Had the new prices been in effect last year, administration officials said, Medicare would have saved $6 billion, which would have reduced its spending on those drugs by 22 percent.

“This is a fight all of us have been fighting for a long time: taking on Big Pharma,” Mr. Biden said at an event in Maryland celebrating the announcement, where he and Ms. Harris had their first joint public appearance since she took over the Democratic presidential ticket.

The negotiations, a longtime aspiration of Democrats, are the first that the federal government has directly conducted with drugmakers on behalf of Medicare beneficiaries. Mr. Biden on Thursday recalled working on legislation as a senator in the 1970s that would have allowed Medicare to negotiate prices directly.

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Which 10 prescription drug prices are dropping in 2026 after negotiations? What we know

Ten widely prescribed and expensive medications used by millions of Americans on Medicare to treat blood clots, cancer, heart disease and diabetes such as Xarelto, Eliquis and Jardiance will be getting a lot cheaper after negotiated discounts with pharmaceutical companies, according to an announcement from the Biden administration Thursday.

List prices will be reduced by 38% to 79%, which means savings of hundreds or even thousands of dollars for 30-day supplies when the negotiated prices take effect in 2026. The Centers for Medicare & Medicaid Services (CMS) estimates that 8.8 million of the 54 million Americans with Medicare Part D were using these medications last year.

The bargaining with the pharmaceutical companies went on for months after the CMS selected 10 high-priced, single-source drugs that didn't have generic or competitor versions to renegotiate under Biden's Inflation Reduction Act of 2022 , The administration says people enrolled in Medicare prescription drug coverage could save an estimated $1.5 billion, and taxpayers are expected to save $6 billion.

“I’ve been waiting for this moment for a long long time,” President Joe Biden said Thursday, during his first policy-oriented appearance with Vice President Kamala Harris since leaving the presidential race. “We pay more for prescription drugs, it’s not hyperbole, than any advanced nation in the world.”

How will the new prescription drug prices affect Florida?

According to health policy research site KFF , nearly 4 million Floridians were enrolled in Medicare Part D in 2023 with 1.4 million enrolled in a stand-alone prescription drug plan and 2.6 million enrolled in the Medicare Advantage drug plan. Over 5 million Floridians were enrolled in Medicare last year, according to data from the Florida Department of Health .

The new prices are set to take effect Jan. 1, 2026. Note that these list prices may not be what you pay. Discounts, coinsurance and copays will affect the final prices.

Over the next two years, another 30 drugs will be selected for negotiated prices beginning in 2027 and 2028.

Which prescription drugs will have their prices reduced?

Here are the drugs set for price reduction in 2026 and the percentage decrease for a 30-day supply:

Januvia , from Merck Sharp Dohme helps patients with diabetes lower their blood sugar. It had a list price of $527 in 2023 for a 30-day supply. As of 2026, the list price will be $113, a 79% savings.

Fiasp, NovoLog

Fiasp, Fiasp FlexTouch, Fiasp PenFill, NovoLog, NovoLog FlexPen, NovoLog PenFill from Novo Nordisk Inc are all insulin or insulin infectors for patients with diabetes. Last year they ran a list price of $495 for 30 days, the new price of $119 is 76% cheaper.

Farxiga from AstraZeneca AB is used to reduce the risks of diabetes, heart failure and chronic kidney disease. List price in 2023 for a 30-day supply was $556, new list price will be $178.50, down 68%.

The Immunex Corporation's Enbrel treats rheumatoid arthritis, psoriasis and psoriatic arthritis. In 2023 the list price for a 30-day supply was a staggering $7,106. The price for 2026 has dropped 67%, to $2,355.

Jardiance from Boehringer Ingelheim is used to reduce the risk of heart failure and chronic kidney disease and lower blood sugar. List price last year was $573, 2026 list price will drop 66% to $197.

Stelara by Janssen Biotech, Inc. is used to treat psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. The 2026 list price will drop 66% from $13,836 for a 30-day supply to $4,695.

Janssen Pharms' Xarelto is prescribed to reduce the risk of stroke and blood clots and treat existing blood clots, and reduce the risk for patients with coronary or peripheral artery disease. In 2023, the list price was $517, in 2026 the price will drop 62% to $197.

Eliquis from Bristol Myers Squibb is also used to prevent and treat blood clots. Last year it was prescribed to nearly 4 million Medicare Plan D patients. List price for a 30-day supply was $521, negotiations brought that down 56% to $231 in 2026.

Entresto from Novartis Pharms Corp used to treat patients with chronic heart failure to reduce the risk of death and hospitalization. Last year the list price for 30 days was $628, in two years it will drop 53% to $295.

Imbruvica from Pharmacyclics LLC is prescribed to treat blood cancers such as chronic lymphocytic leukemia, Waldenström's macroglobulinemia and chronic graft versus host disease. The most expensive on the list, the 2023 list price of $14,934 will drop 38% to $9,319 in 2026.