Introduction

Celiac disease (CeD) is a chronic, immune-mediated, systemic disorder characterized by inflammation of the small intestine and antibody formation in response to gluten ingestion. A gluten-free diet (GFD) has major limitations but is the only current treatment for CeD.

Aims & Methods

This US prospective observational study (Virtual Celiac Symptoms Study, NCT05309330) was conducted from July 25, 2022 to March 04, 2023 and aimed to assess experience with a GFD and celiac-related symptoms in patients with CeD. Eligible participants were aged ≥12 years, had a CeD diagnosis for ≥1 year confirmed via self-reported biopsy and serology (or serology only for participants diagnosed at age <18 years), were on a GFD for ≥6 months and reported CeD-related symptoms in the past 3 months. Participants were recruited with the assistance of the Celiac Disease Foundation via digital advertisements and data were collected using an electronic patient-reported outcomes platform. Study participants were followed up for 12 weeks and CeD-related symptoms and gluten exposure were assessed daily. Quality of life and healthcare resource utilization were also assessed. This analysis focuses on the adult participants’ perception of their disease experience at study initiation.

Results

The baseline questionnaires were completed by 338 adult participants. The median age was 37 years (range 18–71), 88% were female and 99% were White. CeD-related symptoms were reported by 58% of participants in the past week. When questioned about occurrence of CeD symptoms, 23% reported “Chronic/ongoing CeD symptoms even when I don't think I've been exposed to gluten”, 37% reported “CeD symptoms only while I am exposed to gluten or within a few days after exposure to gluten” and 36% reported “Chronic/ongoing CeD symptoms, but they are worse when I get exposed to gluten”. The most commonly reported symptoms were bloating (83%), tiredness (81%), abdominal pain (77%) and diarrhea (71%). All participants were following a GFD; 21% reported “never eating gluten accidentally or on purpose” and 71% reported “rarely eating gluten accidentally”. In total, 84% of participants reported that they were likely/extremely likely to experience CeD symptoms after gluten exposure. Symptom intensity was described as moderate or severe by 71% of participants, and 11% reported hospitalization or emergency department care due to CeD in the past year.

Conclusion

Despite high levels of reported adherence to a GFD, many patients still report CeD-related symptoms, especially in response to perceived gluten exposure. Symptoms were often reported as severe and over 10% reported a CeD-related hospitalization or emergency department visit in the past year. This ongoing study highlights the requirement for further understanding of persistent/recurrent symptoms and an unmet need for additional treatments for patients with CeD on a GFD.

Disclosure

LMM and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. JRM, SSe and SSu are employees of Analysis Group, Inc., which received research support from Takeda Development Center Americas, Inc. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda Development Center Americas, Inc. EL and DA serve as consultants for Takeda Pharmaceuticals.
Funding statement: This study was sponsored by Takeda Development Center Americas, Inc. Medical writing support was provided by Christina Nikolakopoulou, PhD, of Oxford PharmaGenesis, Oxford, UK and was funded by Takeda Pharmaceuticals.

Introduction

Initial reports suggested a high mortality associated with peri-operative COVID-19 infection resulting in delayed surgery and a global change in surgical pathways. The impact of COVID-19 variants and vaccinations on surgical outcomes is yet to be described.

Aims & Methods

We aimed to define the risk of COVID-19 infection in the 30 days following surgery and the associated mortality. With the approval of NHS England we identified all registered adult patients in an OpenSAFELY-TPP primary care general practice within England whilst having an abdominal, obstetric, orthopaedic, thoracic or vascular procedure defined using OPCS codes between 01/02/2020 and 01/03/2022.COVID vaccinations and COVID waves were defined. Crude 30 day risks were calculated using Kaplan Meier curves. A competing risks Cox proportional survival analysis was used to adjust the cumulative risk of COVID-19 infection by the competing risk of death and subsequent non COVID-19 emergency readmissions.
Primary care records managed by the GP software provider TPP were linked to ONS death data, Hospital Episodes Statistics, and Second Generation Surveillance System Public Health England test data through OpenSAFELY. All data were linked, stored and analysed securely within the OpenSAFELY platform: https://opensafely.org/. Data include pseudonymised data such as coded diagnoses, medications and physiological parameters. No free text data are included. All code is shared openly for review and re-use under MIT open license https://github.com/opensafely/PostOpCovid. Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared.
This study was approved by the Health Research Authority [REC reference 21/EE/0278] by the East of England Research Ethics Committee.

Results

We identified 1,213,890 patients within the study period who underwent at least one surgical procedure. Following surgery 11,950 (0.9%) patients developed COVID-19 infection within 30 days. Post-operative COVID infections were greatest in wave 4 with 2.5% of patients having a post-operative infection. Adjusting for all factors post-operative COVID infection risk was 4.9 (aHR 4.88 95% CI 4.65-5.12) fold greater in the fourth wave compared to the first wave.
Within 90 days of surgery there were 820 (0.06%) deaths. A recent COVID infection increased crude morality to 1.42%, and a post-operative COVID infection increased crude mortality to 1.82%. The risk of death reduced following a first and second vaccination (aHR 0.11 95% CI 0.09-0.13). A recent COVID infection (7-42 days prior to admission) increased mortality 4 fold (aHR 3.84 95% CI 3.31-4.45) and a post-operative COVID infection increased mortality 8 fold (aHR 8.49 95% CI 7.6-9.48) compared to those without a COVID-19 infection. This increased 90 day mortality risk was highest in the second wave following a post-operative COVID infection, but then decreased to the non-covid baseline for both emergency and elective procedures in the 3^rd and 4^th waves.

Conclusion

The risk of post-operative COVID infection is low but has increased as strains have been become more transmissible. The absolute risk of death following peri-operative COVID-19 infection is greater than those who have not had infection however this risk has become attenuated during the latter waves of the pandemic.

Acknowledgements: We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and the NHS England Transformation Directorate.

Disclosure

None to declare

Introduction

Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement.

Aims & Methods

We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was evaluated. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components).

Results

At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve this composite endpoint because they did not achieve pMCS remission; whereas 5.0%, 10.1% and 6.0% did not do so because they did not achieve IBDQ remission, biomarker remission or endoscopic improvement, respectively. Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions, with or without histological remission.

Conclusion

CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

Table. NTB with exclusion of different components of the CDC4-150 endpoint.

Disclosure

We thank Katrien Van Beneden for her contribution to conceptualization, investigation and data interpretation.
The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA). Galapagos NV (Mechelen, Belgium) was a collaborator for the SELECTION trial and funded this analysis.
Medical writing support for the development of this abstract was provided by Hannah Stephens, PhD, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.
VV and AO are employees of Alfasigma S.p.A at the time of abstract submission
SS has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos/Gilead Sciences, I-Mab, Janssen Pharmaceuticals, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma and UCB.
BGF has received grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; and personal fees from Ablynx, ActoGeniX, Akebia Therapeutics, Inc., Allergan, Atlantic Pharmaceuticals, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, Eli Lilly, enGene, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, gIcare Pharma, Gilead Sciences, Given Imaging, Gossamer Bio, GSK, Inception IBD, Inc., Ironwood Pharmaceuticals, Japan Tobacco Company, Kyowa Hakko Kirin Co. Ltd, Lexicon Pharmaceuticals, Lycera, Mesoblast, Millennium Pharmaceuticals, MSD, Nestlé, Nextbiotix, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus, Protagonist, Qu Biologics, Q32 Bio (formerly AdMIRx, Inc.), Salix Pharmaceuticals, Shire, Sienna Biopharmaceuticals, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts Pharma, UCB, Vertex Pharmaceuticals, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand Pharma and Zyngenia.
SV receives financial support for research from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Bior Therapeutics (formerly Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cytoki Pharma, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech-Roche, Gilead Sciences, GSK, Hospira, IMIDomics, Janssen Pharmaceuticals, Johnson & Johnson, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, VectivBio, Ventyx Biosciences and Zealand Pharma.
SD reports personal fees from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen Pharmaceuticals, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor Pharma.
MF is an employee and shareholder of Galapagos NV.
VV and AO are former employees and shareholders of Galapagos NV, and employees of Alfasigma. S.p.A.
LP-B has received consulting fees from Abivax, AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, CONNECT Biopharma, Cytoki Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance Biopharma, Thermo Fisher Scientific, TiGenix, Tillotts Pharma, VectivBio, Ventyx, Viatris, Vifor Pharma and Ysopia; grants from Celltrion, Fresenius Kabi and Takeda; and speaking fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Celltrion, Eli Lilly, Ferring Pharmaceutics, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Medac, MSD, Pfizer, Sandoz, Takeda, Tillotts Pharma, Viatris and Vifor Pharma.

Introduction

Making an Inflammatory Bowel Disease (IBD) diagnosis can be challenging as symptoms may mimic more common conditions such as irritable bowel syndrome or haemorrhoids. This can lead to delays in IBD diagnosis, which can be associated with the need for more complex treatment or surgery.

Aims & Methods

This study aims to quantify the time to diagnosis for IBD and examine associations with patient characteristics and faecal calprotectin (FC) and its impact on surgery and emergency hospital admissions.
A retrospective cohort study was conducted using Clinical Practice Research Datalink (CPRD AURUM) from 1st Jan 2007 to 31st Dec 2019. Adult patients were followed from when they first presented with symptoms, signs, test results or alternative diagnosis potentially related to IBD in primary care in the 3 year period prior to IBD diagnosis. The association between patient level factors and FC with the time to IBD diagnosis were examined using logistic regression analysis. We examined changes in time to IBD diagnosis over the 10 year study period. The association of time to IBD diagnosis with IBD related surgeries and emergency admissions was also examined.

Results

Of 28,092 IBD patients: 60.0% ulcerative colitis (UC) and 40.0% Crohn’s disease (CD). Median age 43(IQR 30-58) years; 51.9% female. Median time to diagnosis 15.6 (IQR 4.3- 28.1) months; UC 13.8 (3.2-27.1) months and CD 17.8 (6.5-29.2) months.
Factors associated with over 12 months to IBD diagnosis: female ((OR 1.64(95%CI 1.56-1.72)); Black (1.45(1.20-1.76)) or Asian ethnicity (1.55(1.40-1.72); older age compared to 18-30 years (>70 1.14(1.03-1.27)); obesity (1.09(1.01-1.17)); smoking (1.13(1.06-1.20)); lower socioeconomic status (1.15 (1.06-1.25)); anxiety (1.15(1.07-1.24)); depression (1.19(1.11-1.28)); non-steroidal anti-inflammatory drugs (NSAIDs) (1.45(1.33-1.59)); loperamide (1.56 (1.31-1.86)) and increasing comorbidity Charlson score >2 (1.46(1.32-1.61)).
Only 11.3% of IBD patients had FC testing. Time to diagnosis from FC date was median 4.0 (IQR 1.8- 8.8) months. Higher FC levels were associated with decreasing time to IBD diagnosis: 500-1000 (0.76 (0.66-0.89)),>1000 (0.61(0.51-0.72)).
No improvement in time to IBD diagnosis was observed over the last 10 years: 2010-2011 (14.4 (3.6 -27.6) months) compared to 2018-2019 median (15.6 (4.8-28.8) months).
Patients with time to diagnosis in highest quartile were at lower risk of surgery within a year of diagnosis (HR 0.91(0.81-1.03) but had more IBD related emergency admissions after diagnosis (IRR 1.06 (1.01-1.11).

Conclusion

Longer times to diagnoses were associated with females, minority ethnicities, increasing age, increasing comorbidity, deprivation, obesity, anxiety, depression, NSAIDs and loperamide use. Faecal calprotectin testing reduced time to diagnoses. Higher number of IBD related emergency admissions were observed in patients with a prolonged time to diagnosis.

Disclosure

No conflict of interest to declare

Introduction

Advances in medical management of Crohn’s disease (CD) have improved disease outcomes; however, significant gaps remain. Approximately 30% of patients experience primary non-response to induction therapy with biologics, and over 40% will experience loss of response. There is an urgent need to identify new adjunct therapies, including diet, that can alter the disease course. Dietary patterns characterized by increased intakes of fibre, fruit, vegetables and decreased intakes of processed foods, sugar and omega-6 fatty acids are linked to a reduced prevalence of CD and decreased biomarkers of intestinal and systemic inflammation; however, the effects upon mucosal inflammation are unknown in patients who have lost response to usual medical treatments. We developed the CD Therapeutic Dietary Intervention (CD-TDI), a novel dietary approach incorporating best practices and current evidence to determine its therapeutic potential in reducing inflammation in patients with active CD who have lost response to their usual therapies.

Aims & Methods

This 13-week RCT aimed to explore the efficacy of the CD-TDI compared with conventional management (CM) to reduce clinical disease activity (Harvey-Bradshaw Index (HBI) <5) and reduce mucosal inflammation, as measured by fecal calprotectin (FCP) in mild-to-moderately active luminal CD. Patients with mild to moderately active disease, determined by endoscopic, cross-sectional imaging or FCP >100 ug/g, on stable medical therapy 8 weeks prior to recruitment were eligible to participate (n=28). Upon randomization, the CD-TDI group (n=16) met virtually with a registered dietitian trained in the CD-TDI protocol weekly for 13 weeks. Participants assigned to CM (n=12) followed their habitual diet and met with the same registered dietitian as participants in the CD-TDI group at week 0 (W0) and week 13 (W13) to capture their dietary recall. FCP, HBI, and C-reactive protein (CRP) were assessed at W0 and W13.

Results

Twenty-eight participants (53% females, age 40 years (IQR:31-55); BMI 27 kg/m² (IQR:24-31)) were enrolled. Medical therapy did not differ between groups, with 54% (15/28) of participants receiving no drug therapy, 29% (8/28) 5-ASA monotherapy, 21% (6/28) biologic therapy, 11% (3/28) corticosteroids or 14% (4/28) immunomodulators. At W0, the FCP, HBI and CRP did not differ significantly between groups. In the CD-TDI group, FCP decreased significantly from 130 ug/g (IQR: 38-411) at W0 to 72 ug/g (IQR:3-153) at W13 (p= 0.01) and significantly differed between the CM group at W13 (p=0.04). In a sub-group analysis (n=11) of participants with FCP >250 ug/g at W0, at W13 the FCP decreased significantly from 632 ug/g (IQR: 356-1013) to 166 ug/g, (IQR:52-701) (p=0.06) within the CD-TDI group, however, this same trend was not observed in the CM (W0:337 ug/g IQR:324-1013 vs. W13:431 ug/g, IQR:46-1770, p=0.69). At W13, between-group differences in the CRP were found between the CD-TDI group (1.0 mg/L, IQR:0.6-2.4) and the CM group (4.5 mg/L, IQR:2.6-13.0) (p=0.002). The CD-TDI group experienced a significant decrease in HBI from W0 to W13 (W0: 3.0, IQR:1.0-5.3; W13: 2.0, IQR:0-3.0; p=0.05), however, this was not observed in the CM group.

Conclusion

At W13, the CD-TDI significantly decreased clinical and biochemical markers of inflammation in patients with mild-to-moderately active CD. This preliminary analysis suggests that CD-TDI could be a potential adjunct management strategy for reducing inflammation in CD. We hope to confirm these promising results with an adequately powered sample.

Introduction

Patients with coeliac disease have well-known increased risks of non-Hodgkin’s lymphoma and small bowel cancer but risks of other digestive cancers remain controversial. The objective of this study was to assess the risks of gastrointestinal cancers in coeliac patients and possible favoring conditions.

Aims & Methods

We performed an exposed-non-exposed cohort study comparing coeliac patients with non-exposed control individuals (with a diagnosis of cutaneous superficial burn or sprained ankle) for risk of malignant gastrointestinal diseases using the French nationwide hospitalization database covering all the inpatient admissions during a 9-years follow-up (2011-2019).

Results

27244 patients with coeliac disease were compared to the same number of non-exposed age and sex matched patients. 104 cases of Enteropathy Associated T cell Lymphoma were recorded in the group of coeliac patients and none in control group. In addition to non-Hodgkin’s lymphoma (OR=4.1 [95% CI 2.8; 6.2]) and small bowel cancer (OR=13.9 [95% CI 7.5; 29.6]), coeliac patients had increased risk of pancreatic cancer (OR=2.4 [95% CI 1.8; 3.3], esophageal cancer (OR=1.7 [95% CI 1.1; 2.8]), gastric cancer (OR=1.5 [95% CI 1.1; 2.2]) and colonic cancer (OR=1.7 [95% CI 1.4; 2.1]) but neither of rectal cancer (OR=1.1 [95% CI 0.8; 1.4]) nor of hepatocellular carcinoma (OR=0.8 [95% CI 0.54; 1.21]). Regarding possible favoring conditions, we also noted an increased risk of pernicious anaemia (OR=11.3 [95%CI 7.3; 18.4]), Crohn’s disease (OR=4.2 [95%CI 3.4; 5.1]), ulcerative colitis (OR=3.3 95%CI 2.7; 4.0]), microscopic colitis (OR=4.5 [95%CI 4.1; 5]) and non-alcoholic chronic pancreatitis (OR=1.7 [95% CI 1.2; 2.3]) in coeliac group. Coeliac patients with non-alcoholic chronic pancreatitis, pernicious anaemia and microscopic colitis had a more increased risk of pancreatic (OR=5.9 [95%CI 1.4;15.9]; p=0.003), gastric ((OR=9 [95%CI 3.1;20.4]; p<0.001) and colonic cancers (OR=1.8 [95%CI 1.3;2.6]; p<0.001), respectively.

Conclusion

In addition to small bowel cancer and lymphoma, coeliac patients have increased risk of pancreatic, gastric and colonic cancers. Coeliac patients have also increased risks of inflammatory and/or autoimmune gastrointestinal diseases which major risks of corresponding digestive cancers. These results argue for an early and regular screening of digestive cancers and inflammatory/autoimmune digestive diseases in coeliac patients.

Disclosure

none