Introduction

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

While wide-scale screening for celiac disease (CeD) is increasingly being considered, its overall benefits are not well established.

Aims & Methods

We investigated the general health at diagnosis and long-term outcomes in CeD patients identified through screening in a population-representative cohort. Comprehensive health data from individuals participating in the nationally representative Health 2000 survey (N=6,376) were analyzed using registry data and interviews. Additionally, blood was collected to measure tissue transglutaminase antibodies (TGA) and endomysial antibodies (EmA) if TGA was positive, as well as other laboratory parameters. Altogether, 3254 subjects participated in a follow-up study in 2011. Mortality among subjects in the Health 2000 cohort was evaluated at the 17-year follow-up using the national statistics registry.

Results

Ninety CeD patients were identified in 2000, of whom 54 participated in the follow-up in 2011 while on a gluten-free diet. At diagnosis, patients more often had pre-eclampsia (13% vs. 5%, p=0.016), and lower levels of hemoglobin (median 140 vs 143 g/L, p=0.046), ferritin (29 vs 68 ng/mL, p<0.001), total cholesterol (5.4 vs 5.9 mmol/L, p<0.001), apolipoprotein A1 (1.40 vs 1.57 g/L, p<0.001) and apolipoprotein B (1.16 vs 1.21 g/L, p=0.009) compared to seronegative population. The groups did not differ in age (48 vs 51 years, p=0.159), sex (females 62% vs 56%, p=0.205), BMI (26 vs 26, p=0.567), blood pressure (131/81 mmHg vs 132/82 mmHg, p=0.230), or the presence of other gastrointestinal diseases, cardiovascular and psychiatric diseases, osteoporosis, malignancies, or smoking and alcohol consumption. No significant changes in cholesterol or apolipoprotein levels, mental health, or health care utilization were observed among CeD patients during the 11-year follow-up. The patients had a lower mortality rate compared to non-CeD individuals after 17 years with borderline significance (14.1% vs. 25.6%, p=0.059).

Conclusion

Population-representative individuals with screen-detected celiac disease exhibit a more favorable metabolic profile, but have lower hemoglobin and iron levels and a higher prevalence of pre-eclampsia at diagnosis. Gluten-free diet does not appear to cause adverse effects. Screen-detected patients may also have a reduced long-term mortality, although further research is needed.

Introduction

Anti-tissue transglutaminase IgA antibodies (tTG) are used in the follow-up of celiac disease (CD) to assess adherence to a gluten-free diet (GFD). Persistent positivity may indicate the need for histological reassessment. There is limited information about the rate of complete normalization of tTG and associated factors. Our objective was to evaluate the percentage, kinetics, and factors related to tTG normalization.

Aims & Methods

This was a retrospective observational study including patients with tTG testing at diagnosis and follow-up monitoring of these antibodies from 1991 to 2023 in a specialized unit dedicated to patients with CD. Inclusion criteria were: patients over 16 years of age at diagnosis, initially elevated tTG titres, and at least one serological follow-up after starting a GFD. Time to tTG normalization was estimated using the Kaplan-Meier method. Comparisons between groups were performed using the log-rank test. The association between demographic and clinicopathological characteristics at diagnosis and time to tTG normalization was assessed using Cox regression analysis.

Results

A total of 179 patients were included (75% female, mean age 40 ± 16 years). Duodenal atrophy was present in 81%, and 79% had symptoms. 83% strictly adhered to a GFD. Median follow-up was 3 years. The incidence rate of tTG normalization was 35% per patient-year. The cumulative tTG normalization rate was 38% (95% CI: 30-45) at 1 year, 61% (53-69) at 2 years, 70% (63-77) at 3 years, 80% (73-87) at 4 years, 81% (74-89) at 5 years, and 95% (88-100) at 10 years. The median time to tTG normalization was 24 months (95% CI: 20–28). Table 1 shows Kaplan–Meier estimates expressed as percentages of tTG normalization by adherece to GFD and baseline tTG. In the multivariable analysis, two factors were found to be significantly associated with the normalization of tTG: lower baseline tTG and good adherence to a GFD. Regarding baseline tTG level, patients with titres ≤ 286 U/ml (median) had 2.46 times higher likelihood of antibody normalization compared to those with higher titres (HR: 2.46; 95% CI: 1.69–3.56; p < 0.001). Regarding adherence to a GFD, patients who followed a strict GFD had 5.38 times higher likelihood of tTG normalization (HR: 5.38; 95% CI: 2.79–10.36; p < 0.001).

Table 1. Kaplan–Meier estimates expressed as percentages of normalization (with 95% CIs) after CD diagnosis, by adherece to GFD and baseline tGA titres.

Conclusion

1. The incidence rate of tTG normalization in CD patients after initiating a GFD was 35% per patient-year of follow-up.
2. In the long-term (10 years), 95% of CD patients achieved tTG normalization.
3. Lower tTG titres at diagnosis and good adherence to the GFD were predictive factors for tTG normalization.
4. Understanding the kinetics of tTG normalization according to various factors is essential before considering histological reassessment for suspected poor disease progression.

Introduction

Qualitative exit interviews provide key insights into patient experience and treatment expectations, which are particularly important in celiac disease (CeD) for which there are no current medications. Data relating to patients’ experiences are critical to understand what is considered a ‘meaningful change’ to patients when they participate in clinical trials. The objective of this study was to understand the clinical trial participants’ experience of CeD, their treatment expectations, and how they define meaningful changes in their symptoms as they exited from a phase 2 clinical trial.

Aims & Methods

Semi-structured telephone interviews of 60 minutes were conducted with eligible patients following a phase 2 double-blind, randomized, placebo-controlled trial in patients with moderate-to-severe CeD who maintained a gluten-free diet (GFD) for ≥ 12 months (NCT05353985).¹ Patients could provide more than one response to some questions. Interviews were blinded to treatment assignment and were audio recorded, transcribed and coded guided by an a priori coding dictionary and a qualitative analysis plan. Transcript analysis was facilitated by ATLAS.ti 9 software. This study was approved by the relevant Institutional Review Boards as part of the phase 2 trial.

Results

Overall, 29 English-speaking patients from 15 clinical sites in the USA were interviewed. Three patients exited the trial early. Most participants were female (23/29, 79.3%), the mean age was 50.6 years, and the mean duration of disease before study enrollment was 6.9 years. These characteristics were similar to the full clinical trial population in which most patients were female (115/153, 75.2%), the mean age was 46 years, and the average time to CeD diagnosis was 9 years. The most commonly reported symptoms were abdominal pain (27/29, 93.1%), bloating (26/29, 89.7%), and diarrhea (24/29, 82.8%). The most bothersome symptom reported was diarrhea (12/29, 41.4%).
Participants most often stated that they were hoping for an improvement in their CeD (25/29, 86.2%) providing descriptions that included the desire to be able to eat without the worry of potential gluten contamination.
Participants were asked if a ‘symptom-free day’ (SFD) (defined as a day with no diarrhea, abdominal pain, bloating, or nausea) would be meaningful. All participants agreed that the concept of SFD is important, with the majority stating that an increase of 1–2 SFDs per week would be meaningful (20/28, 71.4%).
Participants were also asked what improvements on the PGIS (Patient Global Impression of Severity) and PGIC (Patient Global Impression of Change) scales would be meaningful to them (participants could provide multiple responses). The majority (31 responses) reported that a 2-point decrease in severity would represent a meaningful improvement, followed by 21 responses for a 1-point decrease in PGIS. Regarding PGIC, most patients (15/25, 60.0%) stated that ‘much improved’ would indicate a meaningful change, followed by ‘a little improved’ (6/25, 24.0%).

Conclusion

Despite adhering to a GFD, patients experienced frequent and bothersome symptoms, particularly abdominal pain, bloating, and diarrhea, prior to enrolling in the study. This study identified potential thresholds for meaningful improvement in weekly SFDs and PGIS and PGIC scales. These data are important to inform the design and interpretation of future CeD clinical trials.

References

1. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/study/NCT05353985 (Accessed April 1, 2025).

Disclosure

SG, MA, and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. NH and SM are employees of RTI Health Solutions which received funding from Takeda for participation in this study.

Introduction

Disease-specific knowledge plays a central role in chronic disease management. In patients with inflammatory bowel disease (IBD), limited knowledge is linked to poorer perceived health and increased discomfort (1).

Aims & Methods

This study assessed disease-specific knowledge among adult patients with IBD at a tertiary center and defined existing knowledge gaps. Factors associated with higher or lower levels of knowledge were explored.
The retrospective cohort study included 392 IBD patients who completed a comprehensive questionnaire between March 2020 and April 2021 (2). Questionnaire responses were analyzed alongside clinical records to quantify disease-specific knowledge. A scoring system was developed to quantify disease-specific knowledge (0–8 points), based on correct diagnosis, Montreal classification, complications, and current therapies. Scores were categorized as low (0–5) or high (6–8) knowledge levels. Associations between knowledge levels and disease-related, sociodemographic, and psychosocial factors were analyzed using logistic regression analysis.

Results

While most patients correctly identified their diagnosis (kappa: 0.863, CI: 0.816–0.905, p < 0.001) and advanced treatment (e.g. infliximab: kappa: 0.959, CI: 0.925–0.983, p < 0.001), knowledge gaps were observed regarding disease location (e.g. isolated proctitis in ulcerative colitis: kappa: 0.101, CI: –0.051–0.341, p = 0.128), complications, comorbidities, and certain other medications. In the univariate analysis a higher knowledge level was found in patients with Crohn’s disease, younger age at diagnosis, in patients with no disease activity, and treatment with biologics, in those receiving disability pension and in patients with a high Perceived Stress Questionnaire (PSQ) score for worries (table). A younger age at diagnosis (p = 0.028) and having Crohn’s disease (p < 0.001) were independently associated with higher knowledge levels whereas active disease was associated with lower disease-specific knowledge.
Table:
Univariate logistic regression analysis for items significantly associated with higher knowledge levels

Conclusion

Significant disease-specific knowledge gaps were identified, particularly concerning disease location, complications, and comorbidities. Targeted patient education should focus on addressing these specific deficits in susceptible groups.

References

1. Tormey LK, Reich J, Chen YS, Singh A, Lipkin-Moore Z, Yu A, et al. Limited Health Literacy Is Associated With Worse Patient-Reported Outcomes in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2019;25:204–12.
2. Koletzko L, Klucker E, Le Thi TG, Breiteneicher S, Rubio-Acero R, Neuhaus L, et al. Following Pediatric and Adult IBD Patients through the COVID-19 Pandemic: Changes in Psychosocial Burden and Perception of Infection Risk and Harm over Time. J Clin Med. 2021;10:4124.