Very early onset inflammatory bowel disease (VEO-IBD) with interleukin-10 receptor-A (IL-10RA) defects is characterised by severe and unmanageable intestinal inflammation, perianal lesions, and a high mortality rate, with the onset of the disease occurring at a very early age. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective treatments for VEO-IBD patients with IL-10 signaling deficiency. The objective of this study was to evaluate the clinical effectiveness of allo-HSCT in the treatment of children with VEO-IBD and IL-10RA deficiency, and to provide further clinical insights. A retrospective analysis and summary of the clinical data of seven patients with VEO-IBD and IL-10RA deficiency from January 2021 to December 2023 was performed. These patients subsequently underwent allo-HSCT after receiving a reduced-intensity conditioning regimen followed by a cyclosporine-based regimen for the prevention of graft versus host disease (GVHD). Hematopoietic reconstruction was performed on seven children with VEO-IBD combined with IL-10RA deficiency. Four patients developed grade I-II GVHD, while three patients developed grade III-IV GVHD after undergoing allo-HSCT. At a median follow-up of 518 days after allo-HSCT (range: 210-1072 days), six patients were alive, while one patient died 16 months after the procedure because of chronic GVHD and severe infections. The 3-year cumulative overall survival (OS) probability rate was 80.0% (95% CI: 44.7-100.0). All VEO-IBD patients demonstrated weight gain following HSCT, with substantial improvements observed in severe malnutrition and growth retardation associated with IL-10RA deficiency post-transplantation. Allo-HSCT is thus identified as the optimal curative therapy for VEO-IBD patients with IL10-RA deficiency. The importance of early multidisciplinary intervention and co-management of VEO-IBD is paramount in improving HSCT outcomes.

Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT); however, peritransplantation intestinal inflammation may increase the risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GVHD in pediatric patients with IEI-associated IBD has not been studied. Here we describe a cohort of pediatric patients with IEI-associated IBD treated with vedolizumab before and during allogeneic HSCT. The study involved a retrospective chart review of pediatric patients with IEI-associated IBD treated with vedolizumab at 6 weeks, 4 weeks, and 1 week before undergoing HSCT. The conditioning regimen consisted of treosulfan, fludarabine, and cyclophosphamide with rabbit antithymocyte globulin, and GVHD prophylaxis included tacrolimus and steroids. Eleven patients (6 females) with a median age of 5 years (range, 0.4 to 14 years) with diverse IEI were included. IBD symptoms were characterized by abdominal pain, loose stools, and blood in stools. Four patients had developed a perianal fistula, and 1 patient had a rectal prolapse. One patient had both a gastrostomy tube and a jejunal tube in situ. Treatment of IBD before HSCT included steroids in 11 patients, anakinra in 2, infliximab in 4, sulfasalazine in 2, mesalazine in 2, and vedolizumab. IBD symptoms were considered controlled in the absence of abdominal pain, loose stools, or blood in stools. Graft sources for HSCT were unrelated donor cord in 5 patients (2 with a 5/8 HLA match, 2 with a 7/8 match, and 1 with a 6/8 match), peripheral blood stem cells in 5 patients (2 haploidentical, 1 with a 9/10 HLA match, and 2 with a 10/10 match), and bone marrow in 1 patient (10/10 matched sibling donor). The median number of vedolizumab infusions was 4 (range, 3 to 12) before HSCT and 1 (range, 1 to 3) after HSCT, and all were reported to be uneventful. All patients had engrafted. Acute GVHD occurred in 4 patients and was limited to grade I skin GVHD only. Chronic GVHD occurred in 1 patient and again was limited to the skin. There was no gut GVHD. Three patients experienced cytomegalovirus viremia, and 2 patients had Epstein-Barr virus viremia. At the time of this report, all patients were alive with no evidence of IBD at a median follow-up of 15 months (range, 3 to 39 months). Administration of vedolizumab pre- and post-HSCT in pediatric patients with IEI-associated IBD is well tolerated and associated with a low rate of gut GVHD. These findings provide a platform for the prospective study and use of vedolizumab for GVHD prophylaxis in pediatric patients with known intestinal inflammation as a pre-HSCT comorbidity.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with increasing incidence, such as Crohn's disease and ulcerative colitis. The accurate etiology and pathogenesis of IBD remain unclear, and it is generally believed that it is related to genetic susceptibility, gut microbiota, environmental factors, immunological abnormalities, and potentially other factors. Currently, the mainstream therapeutic drugs are amino salicylic acid agents, corticosteroids, immunomodulators, and biological agents, but the remission rates do not surpass 30-60% of patients in a real-life setting. As a consequence, there are many studies focusing on emerging drugs and bioactive ingredients that have higher efficacy and long-term safety for achieving complete deep healing. This article begins with a review of the latest, systematic, and credible summaries of the pathogenesis of IBD. In addition, we provide a summary of the current treatments and drugs for IBD. Finally, we focus on the therapeutic effects of emerging drugs such as microRNAs and lncRNAs, nanoparticles-mediated drugs and natural products on IBD and their mechanisms of action.

Inflammatory bowel disease (IBD) is a complex disease with variability in genetic, environmental, and lifestyle factors affecting disease presentation and course. Precision medicine has the potential to play a crucial role in managing IBD by tailoring treatment plans based on the heterogeneity of clinical and temporal variability of patients. Precision medicine is a population-based approach to managing IBD by integrating environmental, genomic, epigenomic, transcriptomic, proteomic, and metabolomic factors. It is a recent and rapidly developing medicine. The widespread adoption of precision medicine worldwide has the potential to result in the early detection of diseases, optimal utilization of healthcare resources, enhanced patient outcomes, and, ultimately, improved quality of life for individuals with IBD. Though precision medicine is promising in terms of better quality of patient care, inadequacies exist in the ongoing research. There is discordance in study conduct, and data collection, utilization, interpretation, and analysis. This review aims to describe the current literature on precision medicine, its multiomics approach, and future directions for its application in IBD.

The article by Moser et al. details the outcomes of 11 patients with inflammatory bowel disease (IBD) as the main manifestation of their immune deficiency syndrome who are treated with allogeneic transplantation. The authors report low rates of complications (including graft-versus-host disease) and resolution of symptoms. Here we outline whether allogeneic transplantation should be considered more broadly for IBD. Commentary on: Moser et al. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol 2023;200:595-607.