News
Anti-TNF therapy for IBD patients is associated with increased risk to Immune Mediated Inflammatory Diseases
Anti-TNFs are primary therapies for several immune-mediated inflammatory diseases (IMIDs). However, case studies have revealed the paradoxical occurrence of IMIDs in patients treated with anti-TNF. The authors in this study conducted 2 nationwide cohort studies comprising all patients with IBD in Denmark (2005–2018) and France (2008–2018). They showed that anti-TNF was associated with an increased risk of rheumatoid arthritis, psoriasis, and hidradenitis suppurativa in both the Danish and the French cohort. Anti-TNF was also associated with an increased risk of the outcomes when compared with azathioprine suggesting that anti-TNF therapy was associated with an increased risk of rheumatoid arthritis, psoriasis, and hidradenitis suppurativa.
Benefits of Proactive Drug Monitoring for Ustekinumab in IBD Patients
A recent study conducted by researchers at Harvard Medical School has identified improved outcomes for patients with inflammatory bowel disease (IBD) receiving ustekinumab therapy alongside proactive therapeutic drug monitoring (TDM).
Ustekinumab, marketed under the brand name Stelara, is funded in Aotearoa New Zealand for individuals with IBD who do not respond to other biologic therapies. This monoclonal antibody treatment targets interleukin pathways to reduce inflammation, however, its long-term effectiveness is not fully established.
This study is the first to explore the role of proactive TDM in optimising ustekinumab treatment. Proactive TDM involves regularly monitoring drug levels in patients which allows clinicians to adjust dosages before clinical symptoms of treatment failure arise. This approach differs from reactive TDM, where drug adjustments are made after a patient experiences a flare-up or shows signs of suboptimal treatment response.
Key findings from the study showed that patients undergoing proactive TDM had higher rates of ustekinumab persistence and fewer IBD-related hospitalisations compared to those who only received reactive TDM. These results were consistent in patients with Crohn’s disease and those that had been previously exposed to other biologics.
These findings highlight the use of proactive TDM as a strategy for maintaining the long-term effectiveness of ustekinumab, to prevent treatment failure and improve patient outcomes. This study builds upon previous research on other biologics like infliximab, adalimumab, and vedolizumab, where proactive TDM has also shown improved drug persistence and reduced risk of treatment failure, surgery, and hospitalisation.
Persistent dysbiosis in pediatric Crohn’s disease patients after resolution of inflammation
A recent study, published in Nature by the University of Virginia school of Medicine, has uncovered that children who achieve clinical remission in Crohn’s disease continue to show signs of microbial dysbiosis which could explain future relapses. This study found lower microbial diversity and notable taxonomic differences, such as decreases in the Lactobacillus and Streptococcus species in the pediatric cohorts’ microbiome. Opposingly, they saw an increase in species such as Oribacterium and Prevotella, which have been previously associated with inflammation. Using flow cytometry, they also noticed an increase in CD4+ T cells which may contribute to the triggering of a future inflammatory flare ups instigated by the increase of pathogenic bacteria. Interestingly, in this study they identified dysbiosis of patients that were in ‘clinical remission’. Previously dysbiosis has been associated with a loss of epithelial integrity. However, in this study, patients had surprisingly strong intestinal epithelial barriers. This contradictory discovery suggests that while current treatments are effective in resolving disease briefly, they may not be targeting the core of the issue.
This study contributes valuable insights into the microbiome involvement in pediatric CD and provides a mechanism behind the cause of disease relapse. This study also highlights the importance of considering the microbiome in CD treatment management even after clinical remission is achieved.
Testin: a new epithelial target to protect leaky guts in CD patients
The causes of the intestinal barrier dysregulation in inflammatory bowel diseases such as Crohn’s disease (CD) and Ulcerative colitis (UC) are unknown. CD is characterised by the persistent chronic inflammation impacting the gastrointestinal tract and is associated with decreased intestinal mucosal barrier integrity.
In a recent publication, researchers have introduced testin as a potential target for IBD patients. The authors show that testin protects the intestinal barrier integrity of mice with Crohn’s disease-like colitis. Their results show that CD patients and TNBS-treated mice have depleted levels of testin (an intercellular linker protein of the epithelium) at baseline compared to healthy controls. Increasing the expression of testin in TNBS-treated mice and LPS intestinal organoids resulted in improved barrier function via the regulation of the tight junction proteins (ZO-1 and Claudin-1). Furthermore, increased expression of testin downregulated the inflammatory cytokines (TNF-α, IL-1β, and IL-6) and suppressed the JNK/P38 downstream signalling pathway to protect the intestinal epithelial barrier. The findings from this study shows a promising new target to improve the intestinal barrier function of CD patients.
RANKL/RANK suppression as a potential new target for the therapy of colon cancer metastases
In a recent publication, researchers have confirmed the role of a TNF receptor superfamily member and its ligand as a driver of Colorectal cancer (CRC) progression and metastasis. Treg-derived RANK and its ligand RANKL were found to cause the production of the chemokine, CCL20 by tumour cells, which would interact with more Tregs, leading to more Tregs being recruited. This positive feedback loop in turn leads to promotion of cancer cell stemness and metastasis. The research conducted in this study was built upon previous findings of RANK/RANKL’s association with CRC. The findings from this study are highly encouraging as they may become an effective drug target to reduce cancer spread, and the disease burden of metastasis.
New colorectal cancer cell-free DNA blood test approved by FDA and used in patients in the United States
Guardant Health, a biotechnology company based in Palo Alto, California, USA, has had one of its blood tests for colon cancer approved by the FDA. Shield is advertised as a, ‘a colon cancer screening option to get excited about’ for patients. The public regards colonoscopies as a screening option not to be excited about. A blood sample is taken and sent to Guardant Health for the Shield test. The test identifies colorectal cancer-specific alterations in cell-free DNA and is for use in colorectal cancer screening in individuals at risk for colorectal cancer aged 45 years or older.
While excellent as a preliminary diagnostic tool, the test has several limitations. Shield has limited detection of Stage I colorectal cancer and has limited effectiveness at detecting precancerous lesions. Shield is effective in detecting Stage II-IV colorectal cancers. Shield is marketed towards the general public who are otherwise healthy. It is not intended for patients with a family history of colorectal or other cancers, or with a previous positive result in the last 6 months. It is also not intended for patients with Inflammatory Bowel Disease, chronic ulcerative colitis, or Crohn’s Disease. While it doesn't replace colonoscopies and is intended as a routine test for otherwise healthy patients, doctors are optimistic about its potential to improve screening rates.
Dr. Arvind Dasari from MD Anderson Cancer Center called the approval a “welcome development” but noted, “We’ll have to wait and see what the impact will be.” Another doctor, Dr. William Grady from Fred Hutchinson Cancer Centre highlighted the importance of screening, saying, “What breaks my heart is that it’s preventable, one of my biggest joys is when I’m doing a colonoscopy and I can take out polyps that, if left alone, would have progressed to cancer.” emphasizing that colonoscopy remains the most accurate method but noting that a blood test is convenient for many people.
Gut microbes – the key to handling stress?
Stress can have huge impacts on our body, suppressing our immune system and increasing our risk of diseases like cancer, as well as mental health issues like anxiety and depression. An exciting new study published in Nature Mental Health shows resilience to stress may lie within our gut.
The latest research from UCLA shows that people who are resilient in the face of stress have unique brain activity and microbial composition in their gut. This study recruited 116 people without mental health diagnoses and evaluated their resilience using a psychological scale. Participants then underwent magnetic resonance imaging (MRI) for brain activity and gave stool samples to assess their gut microbial composition.
The study found that highly resilient people had greater brain activity in areas associated with emotion regulation and mindfulness and lower activity in areas associated with anxiety and depression, as measured by MRI. Within the microbiome of these highly resilient people, they found the presence of gut bacterial signatures associated with anti-inflammatory processes, improved gut barrier function, and increased environmental adaptation.
This research shows an unappreciated link between the gut and the brain, particularly the ability of gut microbes and microbial compounds to influence brain processes, including our response to stress.
Source: https://www.nature.com/articles/s44220-024-00266-6
Blood plasma can be analysed using infrared light to identify Crohn’s disease
A team of researchers in France have demonstrated the use of infrared spectroscopy to detect Crohn’s disease from patient’s plasma with an accuracy of 97 %. Infrared spectroscopy is a non-destructive technique that detects the characteristic absorptions of infrared light (light with longer wavelengths than what we can see) by molecules to give a “spectral fingerprint” relating to molecular composition. In plasma samples this spectral fingerprint gives information on the composition and relative abundance of biomolecules. These biomolecules are present in slightly different levels between Crohn’s disease and control patients. The researchers were able to use this spectral fingerprint with multivariate data analysis techniques to create a classification model to distinguish between Crohn’s disease and control patients. This type of technology needs to be further assessed and developed in larger studies before implementing in clinic, but it is an exciting field to follow and I hope to see it developed to a level that aids the diagnostic pathway for Crohn’s disease in the future.
How does having inflammatory bowel diseases affect your eating and physical activity habits?
A disease flare often makes it difficult to eat well or be as physically active as normal. Research from other countries suggest that people with inflammatory bowel diseases (IBD) like Crohn’s or colitis, eat differently and exercise less compared to people without IBD, but these habits are not known in New Zealand.
A recent University of Otago research known as the IBD exercise and dietary (IBDeat) study, found that around 69% of people with IBD avoided trigger foods to manage their symptoms. These were mainly gluten (from wheat, barley, rye), dairy products, or high fibre foods including fruits and vegetables. Many people also felt that fatigue, stomach cramps, bowel symptoms, and joint pain were the main challenges to being active.
It is well known that eating a balanced diet and being physically active are the few key steps to maintaining good health. A balanced diet means trying to eat a variety of grain foods, dairy products or fortified plant milks, protein foods, and a rainbow of fruits and vegetables. Although this can be fairly challenging at times for many people with IBD, some studies have shown that it is possible to achieve with proper guidance.
Based on those studies, the IBD Lifestyle Food & Exercise (IBDLiFE) study aims to find out whether providing credible resources and/or support can help people with IBD to make the desired lifestyle changes while managing their symptoms. This research will provide valuable insights to practical lifestyle advice for people with IBD.
Just over half of NZ Patients with Inflammatory Bowel Disease have ‘Good’ Medication Adherence: a look at how well patients take their medication
As former US Surgeon General, Dr C. Everett Koop, said: “Drugs don't work in patients who don't take them.” Hence, it is very important for patients to take their medications as prescribed i.e. practice medication adherence (MA). This is essential particularly for patients with Inflammatory Bowel Disease (IBD) as IBD has no cure; so, it is mainly managed using life-long medication therapy with disease monitoring, besides other interventions.
IBD is a chronic gut disease made up of Crohn’s Disease, Ulcerative Colitis and IBD-unclassified. Patients with IBD may experience periods of active disease with ‘flare-ups’ and ‘quiescent’ periods at other times. They may also have symptoms including (bloody) diarrhoea, urgency, constipation, abdominal pain, weight loss amongst others; all of which limit their quality of life and productivity.
Researchers at the University of Otago, Department of Medicine, investigated the nationwide MA levels of patients with IBD using national pharmacy dispensing claims and hospitalisation data. They found that the average MA over three years, for 4654 patients, was moderately high at 77.4%. Likewise, average MA over five years was also moderately high at 74.9% for 3148 patients. These were measured using a novel formular called daily polypharmacy possession ratio (DPPR) which calculates MA to multiple medications taken at the same time.
The picture was a bit different when they calculated how many patients had ‘good adherence’ i.e. patients whose MA was at least 80%. Only 54% and 51% of patients over three and five years, respectively, met this threshold. These findings suggest that a closer look needs to be paid into the long-term MA patterns and, importantly, the factors impacting how patients with IBD take their medications.
New radiotracer quickly detects gastrointestinal cancer biomarker and helps to identify patients for targeted therapy
Gastrointestinal (GI) cancers occur in the digestive system. It is among the most common types of cancer worldwide. Diagnosis typically involves a combination of endoscopy, imaging (like CT scans and PET scans), biopsies, and blood tests. Treatment options depend on the cancer type and stage and may include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Early detection generally leads to better outcomes, but many GI cancers are diagnosed at an advanced stage, which can complicate treatment and worsen prognosis. A new synthesized PET scan radiotracer, 68Ga-NC-BCH, helps doctors see a protein called Claudin18.2 (an important GI cancer biomarker) that is often found in high amounts in GI cancers. Uptake of 68Ga-NC-BCH is correlated with the amount of Claudin18.2. 68Ga-NC-BCH lets doctors take detailed images in one day, unlike older methods that might take longer and be more invasive. It specifically targets the Claudin18.2 protein. This means doctors can get a clear view of where the cancer is and how much of the protein is in the body. Compared to traditional methods, this new tool is non-invasive and provides quick, accurate results. It can help doctors make better treatment decisions and track how well treatments are working.
Liver transplant added to chemotherapy improves survival in advanced colorectal cancer
The incidence of colorectal cancer continues to rise worldwide. Colorectal cancers originate in the bowel but have the potential to spread or metastasize to other organs. The most common site of spread of colorectal cancer is the liver and to date the most effective treatment for this surgery is to remove the liver, usually in combination with chemotherapy. Unfortunately, only twenty percent of people with liver metastases from colorectal cancer will be able to have surgery to remove the cancer. To date there have been no other treatments that offer a potential cure for people with liver metastases that cannot be surgically removed.
In this clinical trial people with liver metastases from colorectal cancer that are unable to be removed with surgery were randomized to receive either liver transplant and chemotherapy or chemotherapy alone. Promisingly, those patients who underwent liver transplantation had better survival rates compared with those who did not. The combination of liver transplantation and chemotherapy may offer a potential cure to those people who would otherwise have a poor long-term outcome.
Source: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00187-1/fulltext