Introduction

For autoimmune atrophic gastritis (AAG) two pathogenetic models are proposed: a pure autoimmune disorder or gastric autoimmunity triggered by Helicobacter pylori (Hp) infection. In AAG, the diagnosis of Hp infection with conventional methods is challenging due to oxyntic mucosa atrophy, hypochlorhydria, and gradual Hp clearance. Formerly, Hp seropositivity in AAG with negative Hp histology was shown by Western blotting. A Hp multiplex serology assay allowing simultaneous detection of antibodies to several Hp proteins and virulence factors has not been used so far in sera of AAG pts to test for Hp exposure.

Aims & Methods

The aim was to assess seroreactivity against Hp proteins in AAG pts, Hp negative at histological evaluation of gastric biopsies and without history of Hp infection.
Single centre case-control study on 75 adults with histological AAG diagnosis, age 63 (18-88) yrs, F:M 2.4:1, parietal cell (PCA)-intrinsic factor autoantibodies (IFA) positivity in 81.3%-41.3%. AAG pts were compared with 2 control groups: 62 healthy stomach subjects (HS), age 65.5 (23-90) yrs, F:M 1.1:1, and 16 controls with Hp-positive antral non-atrophic gastritis (NAHp), age 59.5 (31-78) yrs, F:M 1.7:1. All 153 subjects had gastroscopy with biopsies, according to the updated Sydney system, for clinical suspicion of AAG (anaemia or dyspepsia) or AAG follow-up. Frozen sera (-20°C) were analysed by Hp multiplex serology assay. This assay is based on a glutathione-S-transferase (GST) capture immunosorbent assay combined with fluorescent bead technology measuring antibody responses to 13 Hp proteins (CagA, VacA, UreA, HP0875, NapA, HpaA, HyuA, HcpC, Cad, GroEl, HP0231, HP0305, HP1564). Median fluorescent intensity (MFI) values for each antigen were determined in a 1:1000 serum dilution. Seropositivity to individual antigens was defined as MFI above cut-off. Hp seropositivity was defined as being positive for >3 or more antigens.

Results

AAG pts showed a higher, but not significantly, Hp seropositivity than HS (n=16/21.3% vs n=6/9.7%, p=0.06), but a significantly lower seropositivity than NAHp (12/75%, p<0.0001). The number of participants positive to none of the Hp antigens was similar in AAG and HS (n=22/29.3% vs n=24/38.7%,p=0.25), and significantly higher than in NAHp (n=1/6.2%,p=0.05). The number of seroreactive antigens was significantly higher in AAG than in HS (mean±SEM 2.2±0.3 vs 1.4±0.2, p=0.04), and lower than in NAHp (5.4 ± 0.7, p<0.0001). Hp antigens seroreactive in >50% of the 16 Hp seropositive AAG pts included GroEL, NapA, CagA, HyuA, Catalase, HcpC, and HP1564; UreA and VacA were seropositive in 37.5%/16 seropositive AAG pts.
Severe corpus atrophy was significantly more frequent in the 22 AAG pts without any seroreactivity (0 Hp antigens) than in seropositives (p=0.019) suggesting more severe disease in pts never exposed to Hp. IFA positivity was nearly 2x in Hp seronegatives compared to seropositives (45.8% vs 25%, p=0.137) albeit not significant. An inverse relationship between anti-UreA and IFA titers was shown (Spearman’s rho -0.25 (95%CI -0.46 to -0.03), p=0.03), suggesting an opposite trend of Hp immunoreactivity and gastric autoimmunity.

Conclusion

By Hp multiplex serology, 30% of histologically Hp negative AAG pts had complete absence of seroreactivity, likely belonging to the pure AAG type. In contrast, 20% of AAG pts showed exposure to Hp, indicating that infection might have played a role in triggering gastric autoimmunity. The remaining 50% of AAG pts showed a weak seropositivity, probably belonging to a grey zone, not definitively categorizable by this approach.

References

1. Rugge M, et al. Autoimmune gastritis: histology phenotype and OLGA staging. s.l. : Aliment Pharmacol Ther., 2012. p. 1460-1466. Vol. 35.
2. D'Elios MM, et al. Helicobacter pylori and gastric autoimmunity. s.l. : Microbes Infect., 2004 . p. 1395-401. Vol. 6.
3. Bergman MP, et al. The story so far: Helicobacter pylori and gastric autoimmunity. s.l. : Int Rev Immunol., 2005. p. 63-91. Vol. 24.
4. Bergman MP, D'Elios MM. Cytotoxic T cells in H. pylori-related gastric autoimmunity and gastric lymphoma. s.l. : J Biomed Biotechnol., 2010. p. 104918. Vol. 2010.
5. Mini R, et al. Western blotting of total lysate of Helicobacter pylori in cases of atrophic body gastritis. s.l. : Clin Chem., 2006. p. 220-226. Vol. 52.
6. Annibale B, et al. CagA and VacA are immunoblot markers of past Helicobacter pylori infection in atrophic body gastritis. s.l. : Helicobacter., 2007. p. 23-30. Vol. 12.
7. Gao L, et al. Association between chronic atrophic gastritis and serum antibodies to 15 Helicobacter pylori proteins measured by multiplex serology. . s.l. : Cancer Res., 2009. p. 2973-2980. Vol. 69.
8. Michel A, et al. Helicobacter pylori multiplex serology. s.l. : Helicobacter, 2009. p. 525-535. Vol. 14.

Introduction

Helicobacter pylori (H. pylori) infection remains a major public health problem. Given the high resistance to antibiotics, different treatment strategies must be validated in each specific country. The recurrence rates of H. pylori infection and its predictors remain unclear.

Aims & Methods

To determine the independent factors predicting recurrence after successful eradication with a first-line treatment for H. pylori infection.
All patients were submitted to eradication treatment with five quadruple therapies (A-Concomitant with metronidazole 500mg tid, 14 days; B-Concomitant with metronidazole 500mg bid, 14 days; C-Quadruple with bismuth, 10 days; D-Sequential, 14 days; E-Hybrid, 14 days)) in a blind, randomized trial. Esomeprazole was the proton-pump inhibitor of choice. Efficacy rate at 1-2 months and recurrence rate at 12 months using ¹³C-urea breath test were evaluated. Sociodemographic data, personal/family history, health status and biochemical parameters were assessed using univariate and multivariate analyses.

Results

A total of 126 patients (42.9% males; mean age: 57.4±16.7 years) concluded the treatment protocol (A-25; B-21; C-27; D-24; E-29). Overall efficacy rate of quadruple therapy regimens was 98.4%(n=124): Group A-100%; Group B-100.0%; Group C-100.0%; Group D-100.0%; Group E-93.1% (p=0.147). Overall recurrence rate of quadruple therapy regimens was 4.1%(n=5/123): Group A-12.0%; Group B-9.5%; Group C-0.0%; Group D-0.0%; Group E-0.0% (p=0.009). After univariate/multivariate analysis, high LDL-cholesterol level (OR 1.032, p=0.042), non-bismuth concomitant H. pylori eradication regimen (OR 8.904, p=0.064) and alcoholism (OR 8.333, p=0.035) were independent risk factors for H. pylori reinfection.

Conclusion

In this South-European country, all quadruple therapy regimens with or without bismuth are very effective for H. pylori eradication. The 12-months recurrence rate of H. pylori infection after successful eradication is <5%. High LDL-cholesterol, non-bismuth concomitant H. pylori eradication regimen and alcoholism are independent predictors for H. pylori reinfection. A close surveillance on infectious state in high-risk patients is crucial to prevent long-term H. pylori-associated complications.

References

1. Zamani, M., Ebrahimtabar, F., Zamani, V., et al. (2018) Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 47(7), 868-876.
2. Malfertheiner, P., Megraud, F., O’Morain, C.A., et al. (2017) Management of Helicobacter pylori infection – the Maastricht V/Florence Consensus Report. Gut 66(1), 6-30.
3. Savoldi, A., Carrara, E., Graham, D.Y., et al. (2018) Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization Regions. Gastroenterology 155(5), 1372-1382.
4. Lopo, I., Libânio, D., Pita, I., et al. (2018) Helicobacter pylori antibiotic resistance in Portugal: Systematic review and metaanalysis. Helicobacter 23(4), e12493.
5. Hu, Y., Wan, J.H., Li, X.Y., et al. Systematic review with meta-analysis: the global recurrence rate of Helicobacter pylori. Aliment Pharmacol Ther. 2017;46(9):773-779.
6. Zhao, H., Yan, P., Zhang, N., et al. The recurrence rate of Helicobacter pylori in recent 10 years: A systematic review and meta-analysis. Helicobacter. 2021;26(6):e12852.

Disclosure

None of the authors have anything to declare with regard to personal or financial interests in carrying out this work.

Clinical Case Summary

Materials and methods: 24-year-old man with an episode of nausea, anorexia and loss of 4-5 kg in a week, which resolved spontaneously without drugs. During the episode had hyperchromic urine, yellowing of skin and eyes.After 1 month small increase of serum transaminases x 1.5. Regular bowel function. No clinical signs. US regular. Anti-HbsAg and HCV-Ab negative. After another month he had highly increase of serum transaminases with AST x 27 and ALT x50 GGT x3, Total bilirubin 2.85. Negative ANA, AMA, LKM, IgA anti TTG, anti EBV, anti CMV, alpha1 anti trypsian slight increase. He performed a new serum analysis with increase of anti-TTG IgA. He subsequently performed genetics for celiac disease and confirmed homozygous DQ2.Performs EGDS for suspected celiac disease which documents nodularity in bulb and DII scalloping. Histological examination shows Marsh 3B.After 150 g gluten daily intake had IgA anti TTG x 4. A diagnosis of celiac disease is made and he started GFD with serum transaminases x 2After 2 months with good adherence to GFD has AST x20 and ALT x 50. He denies alcohol abuse.Negative hemochromatosis mutations. Stable weight, Regular bowel function. We perform liver biopsy. The histological examination documents Histological Activity index acc. Knodell modified by Ishak: 7 Grading.
Results: Diagnosis is moderately active chronic autoimmune hepatitis.Therapy is started with prednisone 40 mg daily. With AST x10 and ALT x 20After 15 days of therapy AST x 5 and ALT x9, therefore values halving and normal bilirubin. Currently under follow-up in our Hospital
Conclusions: Although the history is still unknown and the histological exam is compatible but not certain, the good response to steroid therapy is a positive factor that proves the correctness of the diagnosis. This diagnostic difficulty leads us to always evaluate the autoimmune cause in a young patient without risk factors with a small increase in transaminases.

References

University of Salerno

Introduction

Non-coeliac gluten/wheat sensitivity (NCGWS) is characterized by gastrointestinal and extra-intestinal symptoms triggered by gluten/wheat ingestion in patients without coeliac disease (CD) or wheat allergy. There are controversies on the mechanism leading to this phenomenon, including media influence and the presence of a nocebo effect. Moreover, after the COVID-19 pandemic, a decrease in the rates of NCGWS diagnosis has been noted. The only treatment available for the management of NCGWS is a gluten/wheat-free diet (GFD), yet long-term outcomes are poorly understood. This study aimed to evaluate post-pandemic trends in NCGWS and the long-term GFD adherence in patients with NCGWS. The secondary goals are the assessment of the perceived efficacy of GFD and the need of further medical support.

Aims & Methods

We retrieved data from gluten-free products vendors up to September 2024 (top 6 retailer in the UK) and gluten free products customers up to July 2021, using a questionnaire. Subsequently, patients with self-reported NCGWS referred to a tertiary center clinic from 2006 to 2018 completed a questionnaire regarding their dietary habits and further need of medical advice for symptoms related to their diagnosis. The Biagi score was used to assess their adherence to a GFD. We compared the dietary adherence scores to age and sex matched controls cohort of patients with CD to validate the results.

Results

The marked data analysis showed a persistent rise in the sales of gluten free products, from £200B in 2014 vs £600B in 2024. Moreover, NCGWS patients account for 9.7% of the total number of buyers and for 26% of the spent for GF products.
In our cohort, out of 186 patients with NCGWS, 111 answered the questionnaire (response rate 59.7%, female 82.0%, average age 54 ± 13 years). Of these 111, 58 are not currently following a GFD. Out of the 53/111 patients following a GFD, only 27/53 (50,9%) are adhering strictly (Biagi score 3-4), 2/53 had a Biagi score of 2 (3,8%) indicating poor adherence to a gluten free diet, and 24/53 (45,2%) voluntarily ate gluten (Biagi 1-0). Only two patients report that gluten/wheat is not causing them any symptoms if eaten. The average time patients remained on a gluten free diet was 141±58 months. Compared to patients with CD those with NCGWS on a GFD showed a significantly lower adherence to a GFD (Biagi score of 0-1 NCGS: 73.9% vs CD: 8.1%, p<0.05; Biagi score 3-4, NCGWS: 24.3% vs CD: 90.1%, p<0.05). After being discharged, 40 patients (36.0%) sought medical advice again, but no significant correlation was found between the adherence to a GFD and need for further medical intervention.

Conclusion

Self-reported NCGWS is still consistently present among general population. Unlike CD, the vast majority of patients with self-reported NCGWS do not continue a GFD or significantly reduce their level of adherence. Still, NCGWS patients account for a vast part of the expenses in the gluten-free market. However, over a third of NCGWS sought further medical advice to manage their symptoms. These findings underline the need of a better understanding of this condition and the challenges in the management of these patients.

References

1. Ciacci C, Valitutti F. Where are the non-celiac gluten-sensitive patients gone? The COVID-19 effect. Dig Liver Dis. 2023 May;55(5):690-691. doi: 10.1016/j.dld.2023.02.004. Epub 2023 Mar 3. PMID: 36872202; PMCID: PMC9983782.
2. Barbaro MR, Cremon C, Wrona D, Fuschi D, Marasco G, Stanghellini V, et al. Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders. Nutrients. 2020 Dec 4;12(12):3735.
3. de Graaf MCG, Lawton CL, Croden F, Smolinska A, Winkens B, Hesselink MAM, et al. The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study. Lancet Gastroenterol Hepatol. 2024 Feb;9(2):110–23.

Introduction

Inappropriate proton pump inhibitor (PPI) use is a growing concern, with estimates of up to 70% of long-term use lacking a valid indication (1,2).

Aims & Methods

This study investigates the feasibility of PPI deprescribing in a primary care setting and evaluates its impact on gastrointestinal symptoms and blood values. General practitioners (GPs) recruited long-term, chronic PPI users without strict indication. Demographics, PPI duration/dosage, medical history, and GP-estimated success probability were registered at baseline (Visit 0). Patients on healing-dose PPIs at baseline were down-titrated to maintenance dose for 1 month before deprescription at Visit 1. At Visit 1, all patients were instructed to deprescribe their PPI within one month. After this period, patients returned for Visit 2, where the PPI was stopped completely if feasible. One month later, during Visit 3, patients entered a one-year follow-up period. Patients returned after 6 and 12 months for Visit 4 and 5, respectively, with online questionnaires at 3 and 9 months. Gastrointestinal symptoms (nausea, fullness, bloating, upper abdominal pain, lower abdominal pain, heartburn) were assessed using the PAGI-SYM questionnaire. Successful deprescription was defined as ≤3 PPI doses/month. Optional blood samples at baseline and end of study measured gastrin, magnesium, calcium, iron, and vitamin B12 levels. Results are shown as median(IQR).

Results

Sixty GPs included a total of 640 patients (62(50-70) years, 60% female, BMI 27(25-31) kg/m²). Down-titration from healing to maintenance dose (n=128) before PPI deprescription was successful in 92% of the patients.
One month after deprescribing, 76% of patients (n=444/582) had successfully interrupted their PPI intake. Of these, 78% maintained success, resulting in a sustained success rate of 61% (n=264/432). Success rates did not differ by initial PPI indication (dyspepsia, low-grade GERD, NERD, non-gastric indications), demographics or initial PPI dose. However, GP-estimated success probability at baseline was associated with successful deprescribing at 6 months (p=0.0075, OR = 2.6, 95%CI: 1.3–5.2).
Patients who successfully reduced PPI intake reported a transient increase in heartburn (p<0.0001) after deprescribing (visit1), returning to baseline during follow-up. Interestingly, bloating and postprandial fullness decreased significantly during follow-up (visits 2-4) compared to baseline (both p<0.0001).
A significant difference in delta magnesium (+0.01 vs -0.03 mmol/l, p=0.004) and gastrin levels (-57 vs. -19 pg/mL, p=0.002 ) was observed between successfully (n=105) and unsuccessfully (n=41) deprescribed patients.

Conclusion

PPI deprescription is highly feasible in primary care, with a sustained success rate of 61% after 6 months. While heartburn may transiently increase, bloating and postprandial fullness improved. In patients who successfully reduced PPI intake. Magnesium levels increased while gastrin levels decreased.

References

1. Boghossian TA et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017 Mar 16;3(3).
2. Heidelbaugh JJ, Kim AH, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219–32.

Disclosure

All authors have declared no conflict of interest.

Introduction

Helicobacter pylori (H. pylori) is the most widespread infection globally and the main cause of chronic gastritis, peptic ulcer disease, and gastric cancer. Its eradication is primarily managed in primary care. Assessing real-world clinical management practices of H. pylori infection and their adherence to clinical guidelines is essential to inform and optimize treatment strategies.

Aims & Methods

To assess the current H. pylori management strategies followed in Primary Care, we conducted an epidemiological cohort study using data from BIFAP, a Spanish healthcare database containing real-world data on the clinical practice of Primary Care physicians.
Patients aged ≥18 years with a recorded H. pylori infection between January 1, 2003, and June 30, 2023, and a prescription for infection treatment were selected. Two algorithms were developed: one to identify potential cases of H. pylori infection, based on ICD-9/10, and SNOMED CT codes, supplemented by clue words; and another to detect prescribed treatment patterns, constructed from guideline-based recommendations compiled from Spanish and European Consensus Conferences between 1997 and 2022, encompassing 19 possible combinations. A validation process was conducted to confirm the accuracy of infection records through manual review of a random sample of electronic health records. Treatment prescriptions were validated based on active ingredients recorded. We analysed the treatment prevalence stratified by clinical and demographic factors. Continuous and categorical variables were summarized using medians and proportions, respectively. First-line treatments were compared with those of the European Registry on H. pylori Management (Hp-EuReg) to contrast Primary and Specialised (that is, gastroenterologists) Care, respectively.

Results

A total of 211,972 subjects were identified with a H. pylori infection record and, at least, one of the possible treatment patterns. The median age at infection diagnosis was 55 years (IQR, 44-66), with women representing 65%. The most frequent first-line treatments included: proton pump inhibitor (PPI) plus a single-capsule containing bismuth, tetracycline and metronidazole (Pylera®) (PPI+ScBQT) with 36% of cases; PPI, clarithromycin, amoxicillin (PPI+C+A) with 30%; and the combination PPI, clarithromycin, amoxicillin, metronidazole (PPI+C+A+M), with 26%. The most commonly used first-line combination among individuals aged 18-64 years was PPI+ScBQT, as well as in those with a recorded diagnosis of obesity, chronic kidney disease, and in current smokers. However, among individuals aged ≥65 years, as well as in those with a recorded diagnosis of peptic ulcer, the most frequent first-line treatment was PPI+C+A. Comparison between Specialised and Primary Care showed that, since 2013, the use of PPI+C+A by Gastroenterologists has decreased from 40% to less than 1% by 2023, with a similar trend observed in Primary Care, although it remains prescribed in over 10% of cases in 2023. The use of non-bismuth quadruple therapy (PPI+C+A+M) significantly increased since 2015, with a higher proportion in Specialised (40%) compared to Primary Care (30%). ScBQT is currently the most widely prescribed regimen, accounting for approximately 60% of prescriptions in both settings.

Conclusion

H. pylori eradication treatments in Primary Care are heterogeneous, with single-capsule bismuth quadruple therapy being the most prescribed. The use of first-line treatment guidelines has generally aligned with Spanish and European recommendations, although their adoption in Primary Care has been slower than in Specialised Care.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

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