Introduction

Proton pump inhibitors (PPIs) are among the most commonly prescribed drug classes in most western countries. Their clinical effect is mediated by inhibition of acid secretion from stomach parietal cells, and relieve gastro-esophageal reflux disease, peptic ulcers, and dyspepsia (1). Despite the perceived safety of PPIs, increasing evidence links PPI treatment to bacterial enteritis, and clostridium difficile enterocolitis (2). Alteration of gut microbiota seems to be the common denominator of these adverse outcomes (3), which may trigger inflammation in IBD (4). Several studies link proton pump inhibitor (PPI) use and adverse outcomes in patients with inflammatory bowel disease (IBD) (5-7). On the other hand, PPI prescription may also mark the onset of symptoms from IBD flare-ups, and in that case indicate confounding by indication – a protopathic bias. Thus, it remains unresolved whether PPI use have an adverse impact on the clinical course of IBD, or whether an association between PPI use and deterioration of IBD is the result of a protopathic bias. An analysis of the interaction between time since PPI prescription and the adverse outcomes would aid to the clarification of that (8).

Aims & Methods

We aimed study the association between PPI use and hospitalizations/surgery in IBD patients.
We identified all Danish residents diagnosed with IBD in 2000–2018 in a nationwide healthcare register (18). The data were analyzed as separate PPI treatment episodes allowing an individual to enter with more than one PPI episode. We used propensity score weighted Cox regression to estimate the hazard ratio (HR) for hospitalization and surgery for PPI-users compared with non-users adjusted for age, sex, IBD duration, calendar year of diagnosis, disease category (Crohn’s disease / Ulcerative colitis), Charlson Comorbidity Index score, previous IBD-related hospitalizations, previous IBD-related surgery, maintenance therapy (5-aminosalicyclic, thiopurines or anti-tumor necrosis factor-a agents [infliximab/adalimumab], and prescription of NSAIDs).

Results

We identified 40,767 patients with IBD (69.2% with ulcerative colitis, 30.8% with Crohn’s disease). Before first IBD diagnosis, 34.0% had filed at least one PPI prescription. Five years after IBD diagnosis, 39.9% had had at least one PPI prescription. The weighted HR for hospitalizations was 1.71 (95% CI: 1.62–1.81) during the first year after PPI prescription, and 1.33 (95 % CI: 1.18–1.50) thereafter. The weighted HR for IBD-related surgery was 1.39 (95% CI: 1.18–1.50) the first year and 1.40 (95% CI: 1.20–1.64) thereafter.

Conclusion

We identified a 40–70% higher rate of hospitalization and surgery the first year after PPI prescription in IBD patients, and a 10–30% higher rate for the remaining follow-up.

References

References

1. Moayyedi PM, et al. ACG and CAG Clinical Guideline: Management of Dyspepsia. ACG. 2017;112(7):988-1013.
2. Deshpande A, et al. Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(3):225-33.
3. Imhann F, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65(5):740-8.
4. Prosberg M, et al. The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis. Scand J Gastroenterol. 2016;51(12):1407-15.
5. Lu TX, et al. The influence of proton pump inhibitor therapy on the outcome of infliximab therapy in inflammatory bowel disease: a patient-level meta-analysis of randomised controlled studies. Gut. 2020.
6. Shah R, et al. Gastric Acid Suppression Is Associated with an Increased Risk of Adverse Outcomes in Inflammatory Bowel Disease. Digestion. 2017;95(3):188-93.
7. Juillerat P, et al. Drugs that inhibit gastric acid secretion may alter the course of inflammatory bowel disease. Aliment Pharmacol Ther. 2012;36(3):239-47.
8. Tamim H, et al. Application of lag-time into exposure definitions to control for protopathic bias. Pharmacoepidemiol Drug Saf. 2007;16(3):250-8.
9. Schmidt M, et al. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449-90.

Introduction

Despite being a frequent step in clinical practice, there is little real world evidence supporting the benefit of optimizing mesalamine in ulcerative colitis (UC) patients who have a mild to moderate flare. The aim of this study was to assess the role of optimizing 5-ASA in patients in clinical remission (CR) who suffer clinical relapse.

Aims & Methods

Patients in CR who developed a mild to moderate flare treated with 5-ASA optimization from 2015 to 2023 were included. Patients under immunosuppression were excluded, as well as flares treated with oral or topical corticosteroids (CS). The primary outcome was corticosteroid-free clinical remission (CFCR) at six months. Secondary outcomes were need for CS at six months and deep remission (DR) defined as fecal calprotectin <250 ug/g or Mayo endoscopic score of 0.

Results

From 908 UC patients screened, 116 flares met the inclusion criteria. The average disease duration was 9.1±7.0 years. The majority were under oral therapy (91%), 6% topical therapy and the remainder combined therapy. Most flares were mild (81.9%). Optimization of 5-ASA recaptured CR in 72.4% and 37.1% of those were in DR at six months. Around 15% required CS at six months. The absence of a flare in the previous year (OR 13.5; p<0.01) and lower PRO-2 score (OR 2.07; p=0.020) were identified as predictive factors for CFCR at six months, as well as both DR and need for CS at six months. Non-extensive UC (E1/E2) was also a predictive factor for DR and need for CS at six months (p<0.05). The type or formulation of 5-ASA (granules vs tablet), pre-flare or optimized 5-ASA dose were not associated with primary or secondary outcomes.

Conclusion

Optimizing 5-ASA therapy recaptured CR in a significant number of patients. Those with extensive UC, previous flares and with higher symptom burden should be closely monitored.

Disclosure

The authors declare that there are no conflicts of interest related to this study.

Introduction

Gastric outlet obstruction (GOO) is a debilitating condition commonly caused by malignant or benign diseases, impairing gastric emptying and nutritional status. While surgical gastrojejunostomy (SGJ) has traditionally been the standard palliative approach, endoscopic ultrasound-guided gastrojejunostomy (EUSGJ) has recently emerged as a minimally invasive alternative. This systematic review and meta-analysis aimed to compare the efficacy and safety of EUSGJ versus SGJ for the management of GOO.

Aims & Methods

A systematic search of PubMed, Embase, Medline, and Cochrane Library was conducted to identify studies directly comparing EUSGJ and SGJ in adult patients with GOO. Nine retrospective studies comprising 1,086 patients (654 EUSGJ; 432 SGJ) were included. Primary outcomes included technical and clinical success, length of hospital stay (LOS), operative time, and overall complication rates. Secondary outcomes included infection, ileus, hemorrhage, perforation, and re-intervention. Meta-analyses were performed using fixed or random effects models depending on data heterogeneity.

Results

EUSGJ was significantly superior to SGJ in terms of technical success (OR = 0.16; 95% CI: 0.05–0.45; p = 0.0006), shorter operative time (MD = –96.89 minutes; 95% CI: –146.16 to –47.61; p < 0.00001), reduced postoperative LOS (MD = –4.79 days; 95% CI: –6.52 to –3.06; p < 0.0001), lower overall complication rates (OR = 0.24; 95% CI: 0.17–0.33; p < 0.00001), reduced postoperative ileus (OR = 0.07; 95% CI: 0.02–0.17; p < 0.00001), and fewer infections (OR = 0.17; 95% CI: 0.08–0.37; p < 0.00001). No statistically significant differences were found regarding clinical success, re-intervention, hemorrhage, or perforation.

Conclusion

EUSGJ demonstrates superior procedural outcomes and safety profiles compared to SGJ in the management of GOO and represents a valuable tool in expert hands. However, further prospective studies and randomized trials are necessary to validate these findings, assess long-term outcomes, and define its role within individualized patient care and clinical guidelines.

Disclosure

No conflict of interest

Introduction

Filgotinib, a selective JAK1 inhibitor, has emerged as a promising therapy for moderate-to-severe ulcerative colitis (UC). However, real-world data, especially in multi-refractory patients, remain scarce. The Filguito registry, conducted across 11 Andalusian centers, provides a comprehensive assessment of filgotinib’s effectiveness and safety over 12 months in routine clinical practice.

Aims & Methods

This ambispective, multicenter study included 77 UC patients treated with filgotinib. Clinical and biochemical parameters were collected at baseline, weeks 8 and 16, and months 6 and 12. Clinical remission (CR) was defined as a partial Mayo score <3; combined clinical-biochemical remission (CBR) as partial Mayo <3 plus fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as partial Mayo <3 without corticosteroids since week 8. Effectiveness outcomes were stratified by prior exposure to advanced therapies.

Results

The study population had a mean age of 39.5 years and a mean disease duration of 13.5 years. Most patients (62%) presented with extensive colitis, and the majority had a history of multiple failed advanced therapies (mean 2.1). At baseline, disease activity was high, with a mean partial Mayo score of 5.6 and mean fecal calprotectin of 2,325.5 μg/g. Only a minority were corticosteroid-dependent at initiation.
Filgotinib induced rapid and sustained reductions in disease activity, with the partial Mayo score decreasing from 5.6 at baseline to 1.2 at 12 months (p<0.001). Fecal calprotectin levels fell by 76% (2,325.5 to 548.2 μg/g, p=0.006), and CRP declined significantly by year-end (12.4 to 3.1 mg/L, p=0.022). Clinical remission rates rose sharply to 56.9% by week 8, stabilizing at 53% by 12 months. Composite and steroid-free remission peaked at 32.8% and 45.8%, respectively, during follow-up (Table 1).
Differential Response by Prior Treatment Exposure
Patients with ≥2 prior advanced therapy failures showed markedly lower effectiveness:

• 12-month clinical remission: 32% vs. 58% in those with 1 prior failure (p=0.029).
• Steroid-free remission: 28% vs. 64% (p=0.014).
• Composite remission: <25% across subgroups, with no significant intergroup differences.

By the end of follow-up, 29.8% of patients had discontinued filgotinib, mainly due to lack of primary or secondary response. Only two patients stopped treatment because of adverse events (fever), and one due to pregnancy. No serious adverse events were reported, confirming a favorable safety profile in this real-world cohort.

Table 1: Effectiveness Outcomes

Timepoint	Baseline (n=77)	8 Weeks (n=70)	16 Weeks (n=49)	6 Months (n=46)	12 Months (n=29)	p¹
Partial Mayo Index (mean)	5.6	2.6 (<0.001)²	1.9 (<0.001)²	1.8 (<0.001)²	1.2 (<0.001)²	<0.001
CRP (mg/L, mean)	12.4	6.9 (0.567)²	7.2 (0.567)²	4.8 (0.079)²	3.1 (0.022)²	0.019
Calprotectin (μg/g, mean)	2325.5	1941.0 (0.628)²	1083.2 (0.036)²	813.7 (0.218)²	548.2 (0.005)²	0.006
Clinical Remission (%)	6.5%	56.9% (<0.001)³	54.1% (<0.001)³	54.1% (<0.001)³	53.1% (<0.001)³	-
Clinical-Biochemical Remission (%)	1.3%	25.0% (<0.001)³	16.4% (0.004)³	32.8% (<0.001)³	22.4% (0.009)³	-
Steroid-Free Remission (%)	-	45.8%	37.7% (0.333)³	42.6% (0.014)³	38.8% (0.002)³	-
Treatment Discontinuation	-	11/77 (14.2%)	14/77 (18.1%)	20/77 (25.9%)	23/77 (29.8%)	-

¹ Friedman test for related samples (two-way ANOVA by ranks).
² Pairwise comparisons using the Friedman test.
³ McNemar test for related samples.

Conclusion

In this real-world, multicenter Andalusian cohort of patients with refractory UC, filgotinib demonstrated sustained clinical and biochemical effectiveness over one year, with a favorable safety profile. Although response rates were lower in patients with multiple prior advanced therapy failures, clinically meaningful improvements were observed even in this challenging population. These results support filgotinib as an effective and safe therapeutic option for UC in routine clinical practice

Introduction

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disorder of the bile ducts, associated with significant morbidity and an increased risk of malignancy. Preclinical studies in mice deficient in the multidrug resistance protein 2 (Mdr2−/−) have demonstrated that the integrin αvβ6 plays a critical role in biliary fibrosis by activating latent transforming growth factor (TGF)-β1, the main profibrotic cytokine in the liver. Moreover, several studies have shown that autoantibodies against integrin αvβ6 exhibit good diagnostic accuracy in ulcerative colitis (UC). The aim of this meta-analysis is to evaluate the diagnostic performance of anti-integrin αvβ6 autoantibodies in PSC.

Aims & Methods

A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (PubMed, Scopus, ScienceDirect, and the Cochrane Library) were systematically searched up to February 2025. Eligible studies included those involving patients with PSC as well as non-PSC control groups, in which the overall sensitivity and specificity of serum anti-integrin αvβ6 autoantibodies for the diagnosis of PSC were reported. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using a random-effects model. Subgroup analyses were conducted based on the presence or absence of concomitant UC. Meta-analyses were performed using RevMan version 5.4.

Results

Four studies, comprising a total of 1,228 participants, met the predefined eligibility criteria. All studies defined the positivity threshold as the mean value in control groups plus three standard deviations (SD). The pooled sensitivity and specificity for the diagnosis of PSC were 0.679 (95% CI: 0.670–0.689) and 0.940 (95% CI: 0.939–0.941), respectively, with high heterogeneity (I² = 99%).
In the subgroup analysis, the sensitivity and specificity of the test for diagnosing PSC in the absence of concomitant UC were 0.075 (95% CI: 0.071–0.080) and 0.940 (95% CI: 0.939–0.941), respectively. In contrast, in the subgroup of patients with both PSC and UC, sensitivity reached 0.960 (95% CI: 0.959–0.961), while specificity was 0.720 (95% CI: 0.713–0.727).
Sensitivity analyses performed to explore the observed heterogeneity revealed that exclusion of one study (Bloeman, 2024) significantly improved diagnostic performance across all subgroups, with a pooled sensitivity of 0.831 (95% CI: 0.8236–0.8384) and specificity of 0.946 (95% CI: 0.9451–0.9468).

Conclusion

Serum anti-integrin αvβ6 autoantibodies demonstrate diagnostic value in PSC, with consistently high specificity across all patient groups and notably high sensitivity in those with concomitant ulcerative colitis. The high specificity supports a strong negative predictive value. Given the supporting preclinical evidence, integrin αvβ6 warrants further investigation not only as a diagnostic biomarker but also as a potential therapeutic target.

Disclosure

​No conflict of ​Interest

Introduction

Symptoms such as fatigue and bowel urgency (BU) significantly impact patients' daily functioning and well-being. Despite their relevance, they are often underreported or not adequately assessed in clinical practice. The NAVETA telemedicine project monitors patients with chronic diseases, including Crohn's disease (CD), systematically collecting electronic Patient-Reported Outcome Measures (ePROMs) to evaluate the health-related quality of life (HRQoL) of patients treated with biologics or JAK inhibitors (JAKi).

Aims & Methods

An observational, retrospective study was conducted, including adult patients with CD who participated in the NAVETA project (January 2021 - September 2024) from three hospitals in the Balearic Islands. Sociodemographic and clinical characteristics, as well as PROMs (using Manitoba Inflammatory Bowel Disease Index (MIBDI), Inflammatory Bowel Disease Questionnaire (IBDQ-32), IBD-Control questionnaire, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, and Work Role Functioning Questionnaire (WRFQ)) were collected at baseline and over 48 months. BU was approximately explored using item "How often have you been worried about not finding a restroom nearby in the last two weeks?" from IBDQ-32. General Pearson correlations were calculated using available data matched by time on treatment.

Results

A total of 118 CD patients receiving biologics or JAKi were included. Most patients were male (53.0%) with a mean age of 43.5 ± 13.0. Around half were on their first treatment line (53.4%). Fatigue correlated with quality of life, meaning greater fatigue linked to worse perception of overall well-being. It also showed correlation with disease activity, perceived disease control and work functioning, suggesting that higher inflammation and lower sense of control worsen fatigue, ultimately affecting daily life. On the other hand, BU had correlation with quality of life, highlighting its impact on well-being. There was also a correlation with disease activity, indicating that greater inflammation is associated with greater concern about finding a bathroom.
Table 1. Pearson correlations between the different PROM questionnaires used to assess HRQoL.

	FACIT-Fatigue	IBD Control	IBDQ-32	IBDQ-32_item*	MIBDI	WRFQ
FACIT-Fatigue	1	0.46	0.29	0.48	0.57	0.44
IBD Control	0.46	1	0.22	0.39	0.43	0.39
IBDQ-32	0.29	0.22	1	0.32	0.27	0.24
IBDQ-32_item*	0.48	0.39	0.32	1	0.45	0.43
MIBDI	0.57	0.43	0.27	0.45	1	0.46
WRFQ	0.44	0.39	0.24	0.43	0.46	1

All correlations are significant (p<0.05).
*Approximation of BU: How often have you been worried for fear of not finding a restroom nearby for the last two weeks?.

Conclusion

These results highlight that symptoms such as fatigue and BU are significantly associated with HRQoL in CD patients, underscoring the importance of routine, systematic evaluation and management of these symptoms to improve clinical outcomes and patient well-being.

Disclosure

Marisa Iborra declares payments or honoraria for consulting fees and/or lectures, presentations, speaker bureaus, writings or educational events and/or support attending meetings from: Abbvie, Pfizer, Takeda, Johnson and Johnson, Eli Lilly. Silvia Díaz-Cerezo, Itxaso Aguirregabiria, Sebastián Moyano, and Hugo Gabilondo are employees and minor shareholders of Eli Lilly and Company.