12 research outputs found
IBD BioResource: an open-access platform of 25 000 patients to accelerate research in Crohn's and Colitis.
No full textAn alliance of clinicians, academics, research nurses, funders, coordinators, programmers and, most importantly, patients has come together in the UK to deliver a powerful new platform to accelerate Crohn’s and colitis research – the Inflammatory Bowel Disease (IBD) BioResource. As part of the NIHR BioResource for translational research, 25,000 patients in over 90 hospitals UK-wide have signed up since we launched in January 2016 (Fig 1). All have detailed phenotypes databased including Montreal classification1, treatment response history (updated annually), surgical history and comorbidities (IBD BioResource panel descriptive, Clinical data collection sheet and Health and Lifestyle questionnaire). Serum, plasma and DNA samples are banked; and genome-wide genetic profiling undertaken. Participants’ data and samples can be studied, and they themselves surveyed or recalled for resampling or downstream studies (see Fig 2). Critically such studies can be lead by any UK or overseas investigator whether from the worlds of clinical research, pharmacovigilance, science or industry
Factors associated with family planning status and voluntary childlessness in women of childbearing age with inflammatory bowel diseases
No full text© 2023 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/jcm12134267Background: Women with Inflammatory Bowel Diseases (IBD) have fewer children and stay childless more often. The decision-making process around family planning choices remains incompletely understood. Methods: We examined family status in women who at recruitment to the UK IBD Bioresource had not had children yet via an electronic survey. The primary outcome was the proportion of women with voluntary childlessness. Secondary outcomes were factors associated with family planning status. Results: Of 326 responders, 10.7% had either given birth, were currently pregnant or were currently trying to conceive; 12.6% were planning to conceive within 12 months; 54.4% were contemplating conception in the distant future (vague plans); and 22.3% were voluntarily childless. Factors associated with family planning status fell into three areas: general background (age, household income, perceived support to raise a child), relationship status (sexual orientation, being single, not cohabiting, perception of being ‘in the right relationship to raise a child’, perception of a good sex life) and the expression of having a child as a goal in life. On binary logistics regression analysis with voluntary childlessness versus vague family plans as the outcomes of choice, having a household income of <£30,000 (p = 0.046), not seeing a child as a life goal (p < 0.0001) and identifying as lesbian or bisexual (p = 0.047) were independent predictors of voluntary childlessness. Conclusions: Clinicians should consider sexual orientation, income, younger age, current relationship and lack of expression of having a child as a life goal as important factors for family planning when providing care. Pre-pregnancy advice should be made widely available for women with IBD
A large-scale comparison of clinical outcomes to IBD therapies in White and South Asian ethnicities
No full textBackground
While ethnic differences in IBD phenotype are recognised, the comparative efficacy and safety of common IBD therapies across ethnically diverse populations remain uncertain. This multicentre cohort study aimed to compare the efficacy and safety of these therapies between White (WH) and South Asian (SA) IBD cohorts.
Methods
Demographic, phenotypic and outcome data from the UK IBD BioResource were utilised
(BioResource inception date: 1st January 2016; data lock for analysis: 12 39 th May 2023). The primary outcome was treatment response (defined as treatment persistence free of discontinuation or failure) to 5-aminosalicylates (5-ASAs), thiopurines and anti-TNFs. The secondary outcome was the occurrence of treatment-related adverse events (AEs). Ethnic differences in treatment response were evaluated using propensity score weighting and Cox proportional hazards regression. AE occurrence was assessed through logistic regression analysis.
Findings
In total 26,530 patients were included [51.2% females; median age at diagnosis 30 years (IQR 21-43); 96.1% WH, 3.9% SA].
SA were diagnosed at a younger age, began treatment younger than WH, and demonstrated
baseline phenotypic differences including more perianal disease in CD. However, no significant
differences in treatment response between WH and SA were identified in either CD (reference
group WH; thiopurines, HR 0.82 (95% CI 0.53-1.27), p=0.37; anti-TNFs, HR 1.07 (95% CI 0.34-3.37), p=0.91] or UC [thiopurines, HR 0.98 (95% CI 0.95-1.02), p=0.36; anti-TNFs, HR 0.98 (95% CI 0.92-1.04), p=0.54]. SA were at significantly increased risk of pancreatitis [HR 2.34 (95% CI 1.37-3.75), p=0.001] and leucopenia [HR 1.76 (95% CI 1.02-2.84), p=0.03] with thiopurines, and renal dysfunction with anti-TNFs [HR 4.75 (95% CI 1.55-12.07), p=0.002].
Interpretation
Treatment efficacy in similar WH and SA IBD patients recruited to the UK IBD BioResource is unaffected by ethnicity but patients from SA ethnic backgrounds are at increased risk of developing pancreatitis and leucopenia with thiopurines, and renal dysfunction with anti-TNFs. These findings highlight the importance of comprehensive risk assessment and counselling by clinicians, and emphasise the importance of improving ethnic representation in IBD research.
Funding
Bowel Research UK; NIHR Imperial Biomedical Research Centre (BRC); NIHR Cambridge BRC
Clinical response for 12 months or more to the first advanced therapy is associated with a significant decrease in the long-term risk of hospitalisation: A nation-wide analysis of patients from the UK Inflammatory Bowel Disease (IBD) BioResource
No full textBackground and Aims: It is unclear if sustained response to first advanced therapy effects the long-term risk of hospitalisation in patients with inflammatory bowel disease (IBD). We have undertaken a retrospective analysis of clinical outcomes using the National Institute for Health and Care Research (NIHR) IBD BioResource database.Methods: We included adult patients (≥18 years) with Crohn’s disease (CD) or ulcerative colitis (UC) who received treatment with at least one advanced therapy. Treatment response was defined as clinical response or remission for 12 months or longer. The outcome was the incidence of IBD-related long-term risk of hospitalisation, defined as admission for IBD-related surgery or disease exacerbation requiring intravenous corticosteroids over the duration of follow-up. Results: A total of 15531 patients (CD:10024, and UC:5507) were included in the analysis. Overall, 82% of CD patients and 75.2% of UC patients experienced treatment response to their first advanced treatment. Treatment response to the first advanced therapy initiated was significantly associated with a lower long-term risk of hospitalisation in both CD (OR 0.826, 95%CI [0.797-0.857]) and UC (OR 0.975, 95%CI [0.954-0.997]). The median (IQR) time (years) for hospitalisation in CD responders was 2 years (1-4), in CD non-responders was 1.17 years (1-3), p<0.0001, while in UC responders was 1.38 years (0.85-3) and UC non-responders was 1 year (0.65-2), p<0.0019. Conclusions: Treatment response to the first advanced treatment initiated is significantly associated with a lower long-term risk of hospitalisation for IBD. Choosing the best therapy the first time may improve long-term outcomes
Factors associated with chronic abdominal pain in patients with inflammatory bowel disease in remission:A pilot cross-sectional study
No full textBackground: Patients (20%–50%) with inflammatory bowel disease (IBD) experience chronic abdominal pain during remission. The clinical features of IBD patients with abdominal pain during remission remain poorly characterized. This cross-sectional pilot study aimed to assess patient recruitment, adherence, and feedback to optimize questionnaires for future use and to determine the clinical features that distinguish IBD patients in remission with and without abdominal pain. Methods: Online validated questionnaires about disease activity, symptoms, and psychological factors were sent to participants of the UK National Institute for Health and Care Research (NIHR) IBD BioResource, which is a national research platform consisting of re-callable IBD patients designed to expedite research into Crohn's and colitis. Inclusion/exclusion criteria of the IBD BioResource main cohort were applied. Descriptive and inferential statistics were applied to participants in remission. p-values ≤0.01 were considered significant. Key results: A total of 2050 patients were approached; 291 (14.2%) of these agreed to participate. In 35 patients, technical problems, length, and poor understanding of the relevance of some questionnaires affected completion as confirmed by feedback. In total, 244 patients were full responders with 122 (50%) in remission; 33 (27%) of these had chronic abdominal pain. Comparison of those with versus without (n = 89) chronic abdominal pain yielded higher scores in patients with pain for the following: somatization (p < 0.001); gastrointestinal symptoms rating scale score (p = <0.001); highly sensitive person scale (p = 0.007); catastrophizing score (p = 0.010). Trends were observed for azathioprine use (p = 0.021); coping resources inventory health in general (p = 0.046); neuroticism (p = 0.019); and poor sleep (p = 0.03). Conclusions & inferences: Differences in symptoms and psychological characteristics exist between IBD patients in remission with and without abdominal pain. Confirmation of findings in larger studies may facilitate development of personalized chronic pain treatments for IBD patients.</p
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Factors associated with chronic abdominal pain in patients with inflammatory bowel disease in remission: A pilot cross-sectional study.
No full textBACKGROUND: Patients (20%-50%) with inflammatory bowel disease (IBD) experience chronic abdominal pain during remission. The clinical features of IBD patients with abdominal pain during remission remain poorly characterized. This cross-sectional pilot study aimed to assess patient recruitment, adherence, and feedback to optimize questionnaires for future use and to determine the clinical features that distinguish IBD patients in remission with and without abdominal pain. METHODS: Online validated questionnaires about disease activity, symptoms, and psychological factors were sent to participants of the UK National Institute for Health and Care Research (NIHR) IBD BioResource, which is a national research platform consisting of re-callable IBD patients designed to expedite research into Crohn's and colitis. Inclusion/exclusion criteria of the IBD BioResource main cohort were applied. Descriptive and inferential statistics were applied to participants in remission. p-values ≤0.01 were considered significant. KEY RESULTS: A total of 2050 patients were approached; 291 (14.2%) of these agreed to participate. In 35 patients, technical problems, length, and poor understanding of the relevance of some questionnaires affected completion as confirmed by feedback. In total, 244 patients were full responders with 122 (50%) in remission; 33 (27%) of these had chronic abdominal pain. Comparison of those with versus without (n = 89) chronic abdominal pain yielded higher scores in patients with pain for the following: somatization (p < 0.001); gastrointestinal symptoms rating scale score (p = <0.001); highly sensitive person scale (p = 0.007); catastrophizing score (p = 0.010). Trends were observed for azathioprine use (p = 0.021); coping resources inventory health in general (p = 0.046); neuroticism (p = 0.019); and poor sleep (p = 0.03). CONCLUSIONS & INFERENCES: Differences in symptoms and psychological characteristics exist between IBD patients in remission with and without abdominal pain. Confirmation of findings in larger studies may facilitate development of personalized chronic pain treatments for IBD patients
Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility
No full textGenome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn’s disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation
The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn’s Disease Patients in Remission and Individuals Without Gastrointestinal Inflammation
No full textBackground and Aims
Historical and emerging data implicate fungi in Crohn’s disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects.
Methods
Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin <250 μg/g; 47 non-CD subjects were included as comparator groups, including 22 matched household [four NOD2 mutant] and 25 non-household subjects with known NOD2 genotype [14 NOD2 mutant] identified by the NIHR BioResource Cambridge. Faecal mycobiota composition was determined using internal transcribed spacer 1 [ITS1] sequencing and was compared with 16S rRNA gene sequences and volatile organic compounds.
Results
CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray‐Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029].
Conclusions
This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota
The Impact of NOD2 Variants on Fecal Microbiota in Crohn’s Disease and Controls Without Gastrointestinal Disease
No full textFunding was supported by CORE, the Digestive Diseases Foundation and the Wellcome Trust [grant number 097943 to NAK, 093885 to CAL and 098051 to Alan W Walker and Julian Parkhill . Dr. Walker receives core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS). We also acknowledge the NIHR Biomedical Research Centre awards to Addenbrooke’s Hospital/University of Cambridge School of Clinical Medicine and acknowledge the NIHR Newcastle Biomedical Research Centre.Peer reviewe
Genetic risk variants in intestinal inflammatory disorders
No full textPhDThis thesis includes work on the genetics of intestinal inflammatory disorders, concentrating
on coeliac disease and Crohn’s disease. It explores how common genetic variants influence
risk of complex phenotypes including immunological intolerance to gluten (coeliac disease)
and intolerance to therapeutic agents (azathioprine and mercaptopurine) used in the
treatment of intestinal inflammatory diseases. Finally it presents work aiming to move from
genetic associations with complex phenotypes to understanding of how these variants
modulate immunological processes.
Results of a large genome wide association study that identified more than 13 new genetic risk
regions influencing susceptibility to coeliac disease are presented. Results of a genome wide
association study of azathioprine and 6-mercaptopurine-induced pancreatitis in inflammatory
bowel disease-affected individuals are presented. Finally, a cell cytokine release assay for the
prostaglandin EP4 receptor was developed, with a view to investigating how SNPs associated
with Crohn’s disease in the 5p13.1 region influence EP4 receptor signalling and contribute to
disease pathogenesis. This work highlights some of the challenges in moving from SNP-disease
associations identified in GWASs to understanding how genetic variants change biological
processes
