Publications by authors named "Frank M Ruemmele"
Gut-homing and intestinal TIGITCD38 memory T cells acquire an IL-12-induced, ex-Th17 pathogenic phenotype in a subgroup of Crohn's disease patients with a severe disease course.
Mucosal Immunol
November 2024
Article Synopsis
- CD4 memory T cell reactivation is linked to chronic inflammatory bowel disease (IBD), affecting conditions like Crohn's disease (CD) and ulcerative colitis, with unclear differences in T cell regulation among patients.
- In a study of pediatric IBD patients, a specific subgroup of therapy-naïve CD patients showed higher frequencies of a particular inflammatory T cell type (TIGITCD38T) associated with severe disease and elevated IFN-γ levels.
- The research identified IL-12 as a key driver of this inflammatory response, with increased IL-12 signaling linked to the transformation of T cells into more pathogenic forms, correlating with worsened intestinal inflammation.
Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn's disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10-12 weeks' induction therapy.
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- The study aimed to create a method for reporting rare and severe adverse events in children with inflammatory bowel disease (IBD) to establish incidence rates, compare different regions, and benchmark against overall children’s adverse event rates.
- Researchers utilized data from the PIBD-SETQuality Safety Registry, which collected information on ten specified adverse events among children under 19 diagnosed with IBD, reported by pediatric gastroenterologists.
- The registry gathered monthly reports from doctors participating in a network, focusing only on recent events and excluding events that didn’t meet specific criteria or involved unverified IBD diagnoses.
Efficacy of infliximab after loss of response of/intolerance to adalimumab in pediatric Crohn's disease: A retrospective multicenter cohort study of the "GETAID pédiatrique".
J Pediatr Gastroenterol Nutr
May 2024
Article Synopsis
- Infliximab (IFX) is evaluated as a second-line treatment for pediatric Crohn's disease (CD) patients who experience loss of response (LOR) or intolerance to adalimumab (ADA) after one year of therapy.
- A study involving 32 patients showed that 84.4% continued with IFX after 12 months, with 68.7% achieving corticosteroid-free clinical remission.
- Key finding indicates that absence of perianal disease at the start of IFX correlates with better remission outcomes, suggesting IFX is a viable option when ADA fails.
Improved Clinical Outcomes With Early Anti-Tumour Necrosis Factor Alpha Therapy in Children With Newly Diagnosed Crohn's Disease: Real-world Data from the International Prospective PIBD-SETQuality Inception Cohort Study.
J Crohns Colitis
May 2024
Article Synopsis
- The study assessed the impact of early anti-TNF treatment for children diagnosed with Crohn's disease, focusing on high-risk individuals.
- It involved tracking the health outcomes of 331 children over 2 years, comparing those who started anti-TNF therapy within 90 days of diagnosis to those who did not.
- Results showed that early anti-TNF users had significantly better rates of achieving remission and mild/inactive disease at one year, especially among high-risk patients.
Background: Several studies have proposed models to predict disease outcomes in paediatric ulcerative colitis (UC), notably PROTECT, Schechter and PIBD-ahead, but none has been validated by external cohorts AIM: To explore these models in a prospective multicentre inception cohort METHODS: Children newly diagnosed with UC in 17 centres were followed at disease onset and 3 and 12 months thereafter, as well as at last visit. Outcomes included steroid-free remission (SFR) and acute severe colitis (ASC).
Results: Of the 223 included children, 74 (34%), 97 (43%) and 52 (23%) presented with mild, moderate and severe disease, respectively.
A critical review of adalimumab for the treatment of moderate-to-severe active ulcerative colitis in children.
Expert Rev Gastroenterol Hepatol
January 2023
Article Synopsis
- Anti-tumor necrosis factor (TNF) antibodies, especially adalimumab (ADA), are important for treating inflammatory bowel disease (IBD) in children and adolescents, but there’s less research on ADA compared to infliximab for ulcerative colitis (UC).
- Recent studies, including the ENVISION I trial, show ADA is effective in inducing and maintaining remission in pediatric UC patients, with response rates even higher than in adults.
- More research is needed to optimize ADA treatment for children, but current evidence supports its use as a first-line therapy, as many adolescents prefer subcutaneous administration for convenience.
Article Synopsis
- ECCO and ESPGHAN recommend early use of anti-TNF biologics, like adalimumab (ADA), for pediatric patients with Crohn's Disease who show signs of poor outcomes; this study compares early "Top-Down" treatment versus conventional "Step-Up" management.
- The study involved 120 patients treated with ADA from 2008 to 2019, with the Top-Down group showing a significantly higher remission rate (73% at 24 months) compared to the Step-Up group (51%).
- Results indicate that early ADA treatment is more effective for maintaining relapse-free remission and is often used as a monotherapy, without serious adverse events reported
Article Synopsis
- There are only two approved advanced treatment options for children with inflammatory bowel disease (IBD), despite new drugs for adults being available.
- A virtual meeting involving various stakeholders was held to discuss improving the approval process for pediatric IBD drug development.
- Collaborative actions among clinical experts, patient groups, pharmaceutical companies, and regulators are essential to speed up the approval of new medications for children with IBD.
Article Synopsis
- Scientists discovered that changes in a gene called UNC45A can lead to a health problem that includes diarrhea, deafness, and fragile bones.
- They studied 6 patients and found that their UNC45A gene wasn't working properly, causing issues in their intestines.
- The research showed that UNC45A helps other proteins, like myosin VB, work correctly, and when this gene is missing, it can lead to serious problems in how the intestines are formed and function.
Objectives: To evaluate the longitudinal evolution of work productivity loss and activity impairment in caregivers of children with inflammatory bowel disease (IBD). We also evaluated the associations between these impairments, IBD-related factors, and caregivers' health-related quality of life (HRQOL) and estimated the indirect costs related to work absenteeism.
Study Design: Since January 2017, children with newly diagnosed IBD were enrolled prospectively in the Pediatric Inflammatory Bowel Disease Network for Safety, Efficacy, Treatment and Quality improvement of care study.
Objective: To describe the ambulatory proton pump inhibitor (PPI) prescription in French children, its trends, and the impact of French (2014) and international (2018) clinical guidelines.
Study Design: We described PPI prescription rates based on national dispensation data in French children (IQVIA's Xponent database, 2009-2019). Using a segmented linear regression, we assessed the impact of clinical guidelines on PPI prescription rates.
Increased Use of Anti-Tumor Necrosis Factor Following the Implementation of the ECCO-ESPGHAN Guidelines and its Impact on the Outcome of Pediatric Crohn's Disease: A Retrospective Single-Center Study.
J Pediatr Gastroenterol Nutr
January 2022
Objectives: The first ECCO-ESPGHAN guidelines for the medical management of pediatric Crohn disease (CD) were published in 2014. Whether their implementation, and the consequent increased use of an upfront anti-tumor necrosis factor therapy, have changed the course of the disease has not been investigated yet. We aimed at comparing the evolution of pediatric CD patients diagnosed and treated before and after 2014.
View Article and Find Full Text PDFBackground And Aims: Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors.
Methods: From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD.
Article Synopsis
- This study evaluated the safety and effectiveness of adalimumab in treating children aged 4-17 with moderate-to-severe ulcerative colitis who were not responding to current medications.
- It involved a double-blind clinical trial across 24 hospitals in 10 countries, where children received either high-dose or standard-dose adalimumab over a period of weeks, with subsequent treatment based on their response.
- The main outcomes measured were the proportion of patients achieving remission at week 8 and week 52, comparing those on adalimumab treatment to external data on adult placebo responses.
FOXP3 deficiency in mice and in patients with immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome results in fatal autoimmunity by altering regulatory T (T) cells. CD4 T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous T-like cells, some very similar to normal T cells, others more distant. Conventional T cells showed no widespread activation or helper T cell bias, but a monomorphic disease signature affected all CD4 T cells.
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- * An international study of 72 CLD patients found that 17% also had IBD, with a notably higher prevalence compared to general European rates, indicating a potential relationship between CLD and IBD.
- * Patients with both CLD and IBD often have growth issues and may require surgical interventions, highlighting the need for attentive management of these patients' health.
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation.
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- The REDUCE-RISK trial aims to compare the effectiveness of different treatments for pediatric low-risk and high-risk Crohn disease, specifically methotrexate, azathioprine, 6-mercaptopurine, and adalimumab.
- A systematic review was conducted to assess existing economic evaluations related to adalimumab treatment for inflammatory bowel diseases in both children and adults, focusing on studies that measure life years gained or quality-adjusted life years.
- The review found 12 relevant studies, none involving children, highlighting the economic viability of adalimumab but pointing out gaps in data about children's school attendance, parental productivity, and quality of life measures in current evaluations.
Article Synopsis
- Identifying monogenic IBD patients is essential for tailored management, and the position statement provides recommendations for using genomics in this evaluation across different age groups.
- A systematic review by pediatric IBD specialists led to recommendations for next-generation DNA sequencing in routine clinical practice, but routine genetic testing is advised only for specific cases based on age of onset and family history.
- A diagnostic algorithm with a gene panel of 75 genes has been developed to assist clinicians, emphasizing the importance of genetic testing before procedures like hematopoietic stem cell transplantation.
Background: We aimed to describe physician practice patterns in holding or continuing IBD therapy in the setting of COVID-19 infection, using the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease [SECURE-IBD] registry.
Methods: IBD medications that were stopped due to COVID-19 were recorded in the SECURE-IBD registry in addition to demographic and clinical data. We conducted descriptive analyses to understand characteristics associated with stopping IBD medications in response to active COVID-19 infection.
Article Synopsis
- The study investigates the safety and effectiveness of TNF-α blockers, specifically infliximab, in treating inflammatory complications in patients with chronic granulomatous disease (CGD).
- Conducted at Necker-Enfants Malades Hospital, the research involved 14 CGD patients, primarily with gastrointestinal and pulmonary issues, treated from 2006 to 2019.
- Results showed a positive response to treatment in most patients, but half experienced infections, though all had favorable outcomes, highlighting the need for careful management of infection risks while using anti-TNF-α therapy.
The coronavirus disease 2019 (COVID-19) pandemic caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents most often with mild clinical symptoms, but the severe forms are of major concern. SARS-CoV-2 enters human cells via the angiotensin-converting enzyme 2 receptor, expressed on epithelial and endothelial cells. Because the highest angiotensin-converting enzyme 2 expression is in the terminal ileum and colon, and up-regulated further during inflammation, and many COVID-19 patients experience gastrointestinal symptoms, longitudinal data are necessary to determine whether inflammatory bowel disease (IBD) patients are at risk for severe or complicated COVID-19.
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- The study aimed to update the ECCO-ESPGHAN guidelines for the medical management of pediatric Crohn's disease by developing 17 clinical questions and conducting a systematic literature search from 1991 to 2019.
- A consensus meeting refined 30 preliminary statements into 22 that achieved over 80% agreement, focusing on identifying high-risk patients and optimizing treatment strategies.
- Key recommendations include using anti-TNF agents for severe cases, exclusive enteral nutrition for low-risk patients, and regular monitoring through faecal calprotectin or imaging to adjust treatments effectively.