Introduction

Vedolizumab (VDZ) is approved for moderate-to-severe inflammatory bowel disease (IBD; ulcerative colitis [UC] & Crohn’s disease [CD]).^1,2 While the subcutaneous (SC) formulation of VDZ is effective as maintenance treatment (mTx) in patients (pts) responding to intravenous (IV) VDZ induction treatment (Tx),^1,3 real-world data on Tx patterns of pts switching mTx from VDZ IV to SC or initiating mTx VDZ SC after IV induction are limited.

Aims & Methods

This prospective, non-interventional, multicentre (NCT05384080) study (conducted under the umbrella VARIETY protocol) enrolled adults with UC or CD initiating/undergoing induction with VDZ IV or continuing VDZ IV mTx, with the option to switch to VDZ SC mTx. The primary endpoint was real-world Tx patterns with VDZ, including Tx persistence. Additional endpoints assessed pt characteristics, pt-reported outcomes, and safety (adverse events [AEs]). Data were descriptively analysed.

Results

Overall, 162 enrolled pts (August 2022–June 2023; UC, n=103; CD, n=59) were included in the interim analysis. At enrolment, 127 (78.4%) received VDZ mTx (UC, n=78; CD, n=49) and 35 (21.6%), VDZ induction (UC, n=25; CD, n=10). The mean (SD) age was 38.2 (12.3) yrs, and time since IBD diagnosis was 10.7 (11.1) yrs. Majority of pts were male (96 [59.3%]), currently employed (124 [76.5%]), had never smoked (109 [67.3%]), and reported previous biologic therapy (95 [58.6%]). Demographic and IBD Tx history data were consistent across cohorts. At baseline, in pts with UC, the mean (SD) partial Mayo score was 1.8 (2.7); in pts with CD, the mean (SD) Crohn’s Disease Activity Index (CDAI) score was 90.6 (70.1). During the 1-yr study period, 20.0% (n=7; UC, n=2; CD, n=5) of pts in the induction and 51.2% (n=65; UC, n=40; CD, n=25) in the mTx cohort switched to VDZ SC. At week (W) 52, Tx persistence was 40.0% (n=14; UC, n=11; CD, n=3) and 77.2% (n=98; UC, n=61; CD, n=37) in the induction and mTx cohorts, respectively, and highest overall in mTx pts who switched to VDZ SC (86.2%; n=56; Table). The most common reason for Tx discontinuation was investigator decision (64.7%; n=33). For VDZ IV and SC, the mean (SD) number of doses per pt was 10.5 (7.6) and 23.8 (15.0), respectively. The median time from VDZ Tx initiation to SC Tx was 383 days (induction: 98 days; mTx: 434 days). In the induction cohort, the mean (SD) Work Productivity & Activity Impairment (WPAI) scores improved from 32.7 (24.1) at baseline (n=21) to 21.5 (31.2) at W52 (n=11), and the Short IBD Questionnaire (SIBDQ) scores improved from 44.1 (10.0) at baseline (n=34) to 51.0 (12.9) at W52 (n=15). In the mTx cohort, WPAI and SIBDQ results remained consistent over time. Fifty-three AEs were reported, including 4 serious AEs (malignancy, IBD flare requiring hospitalization, abdominal abscess, and unconsciousness). One AE of special interest (hypersensitivity reaction) was considered VDZ-related.

Conclusion

In this Polish real-world study, high Tx persistence was reported, especially in pts who switched to VDZ SC. No new safety signals were noted. Overall, the results were consistent with those from other VARIETY cohorts,⁴ although lower persistence was observed during induction. The small size of the induction cohort was a limitation of this study.

References

1. Sandborn WJ, et al. Gastroenterology. 2020;158:562–72.e12.
2. Loftus EV Jr, et al. Aliment Pharmacol Ther. 2020;52:1353–65.
3. Vermeire S, et al. J Crohns Colitis. 2022;16:27–38.
4. Novacek G, et al. J Crohns Colitis. 2024;18(suppl 1):i1506–7

Disclosure

Conflicts of interest: Agata Michalak received lectures fees and/or travel grants from AbbVie, Bayer, Biocodex and Takeda. Katarzyna Karłowicz received lecture fees, consultancy fees or travel educational grants from Bristol Myers Squibb, AbbVie, Polpharma, Takeda and Pfizer. Renata Talar-Wojnarowska received lecture fees and/or travel grants from AbbVie, Astellas, Ferring, Janssen and Takeda. Adam Fabisiak received fees and/or travel grants from Bristol Myers Squibb, Pro. Med. CS, Pfizer and Polpharma. Magdalena Achtenberg received lecture fees from Ferring. Piotr Eder received lecture fees and/or travel grants from Takeda, Ferring, Astellas, Pfizer and Janssen. Maria Kłopocka received payment for lectures from Janssen, Takeda, Ferring, Alfasigma and Pharmabest and travel/accommodation/meeting expenses from Ferring, Janssen, Takeda, Alfasigma and Pharmabest. Maciej Gonciarz received compensation and/or research/educational grants from Pfizer, Polfarma, Abbvie, BMS, Ewoppharma, Ferring, Astellas, Takeda, Jansen-Cilag, Celtrion, Johnson & Johnson, and Sanofi. Grażyna Rydzewska received speaker and consultant fees from AbbVie, AlfaSigma, AstraZeneca, Bayer, Biocodex, Bristol Myers Squibb, Ferring, Janssen, Lilly, Pro. Med. Pl., Recordati, Sanprobi, SOBI and Takeda and travel/accommodation meeting expenses from AbbVie, Ferring and Takeda. Eliza Majewska is a permanent employee of Takeda Pharma Sp. z o.o. Maria Kopertowska-Majchrzak, Tomasz Romańczyk, Halina Cichoż-Lach, Małgorzata Zwolińska-Wcisło, and Elżbieta Poniewierka declare no conflicts of interest.
Funding: The study was funded by Takeda Pharma Sp. z o.o.
Acknowledgements: Medical writing support was provided by Michelle Rebello, PhD, of Cactus Life Sciences (part of Cactus Communications) and funded by Takeda Pharma Sp. z o.o.

Introduction

Resolution of pain, fatigue and other symptoms are key treatment goals for many patients (pts) with Crohn’s disease (CD);^1,2 however, time to symptomatic improvement in pts treated with vedolizumab (VDZ) has not been formally evaluated.

Aims & Methods

VOICE (NCT06249555) is a prospective, observational study in pts with CD aged ≥18 years initiating VDZ or anti-IL-23 antagonist treatment (tx) per product labelling as part of standard of care, with the main objective to explore the time course of response to VDZ as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) domain Short Form (SF) scores. Inclusion criteria include baseline PROMIS Pain Interference (PI)-SF T-score ≥55 (0.5 SD above general population). We enrolled pts via Takeda pt support program in Canada, with additional pts enrolled at US and Canada sites. Planned sample size is 300 pts (VDZ, 200; anti-IL-23 antagonist [reference group not for formal comparison], 100); planned follow-up is 52 weeks (wks), with PROMIS PI data reported weekly for the first 14 wks. The primary endpoint is time to the first meaningful clinical improvement in PROMIS PI-SF T-score, defined as ≥2-point decrease in PROMIS PI-SF T-score from baseline. We also collect data on improvement in 7 PROMIS domains with clinical improvement defined as 5-point (0.5 SD)³ change in T-score from baseline, Short Inflammatory Bowel Disease Questionnaire (SIBDQ; including SIBDQ improvement [≥9 point increase from baseline] and SIBDQ remission [score of ≥60]) and safety. Here, we report the results from pts with ≥1 VDZ dose and ≥1 post-baseline PI assessment included in the interim analysis (IA; prespecified to occur after 50 pts from VDZ group completed or discontinued before the wk 14 assessment to provide an early evaluation of tx response and safety).

Results

Overall, 64 pts with ≥1 VDZ dose and ≥1 post-baseline PROMIS PI assessment (mean±SD age, 43.1±17.0 years, 35.9% male, 92.2% White) were included in the IA. Disease duration (mean±SD) was 6.4±12.1 years; 84.4% of pts were anti-TNF-naïve. Data collection is ongoing for 57 pts (49 with and 8 without completed wk 14 PROMIS PI questionnaire); 7 pts discontinued from the study. The median time to achieve the first ≥2_-point decrease in PROMIS PI-SF T-score (in n=56 pts) was 12 days (95% CI, 6-13). Baseline PROMIS domain scores indicated notable impairment; by wk 14, improvements in mean PROMIS scores from baseline were observed in all 7 measured domains, with ≥5-point improvements in 4/7 domains (Table). At wk 14, 37.5% (24/64) and 7.8% (5/64) pts achieved SIBDQ improvement and remission, respectively. One pt had serious adverse events of appendicitis and diverticulitis, and another pt had a fatal event; none of these were related to VDZ tx.

Table. Summary of PROMIS domain T-scores

Conclusion

The IA results through wk 14 show an early improvement across multiple symptom domains and quality of life in pts with CD starting VDZ tx. Time to first ≥2-point decrease in PROMIS PI-SF T-score was short, with a benefit observed after 12 days from VDZ initiation. Study recruitment and data collection are ongoing.

References

1. Keefer L, et al. Gastroenterology. 2022;162(5):1439-1451.
2. Kitchen H, et al. Crohns Colitis 360. 2020;2(2):otaa033
3. Cella D, et al. Value Health. 2019;22(5):537-544.
4. Shaw BE, et al. Cancer. 2018;124(4):841-849.

Disclosure

This study was sponsored by Alimentiv, Inc.
V. Jairath reports consulting/advisory board fees from AbbVie, Alimentiv, Anaptyis Bio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Tillotts and Fresenius Kabi.
M. Long reports consulting fees from AbbVie, Alimentiv, Bristol Myers Squibb, Intercept, Janssen, Lilly, Pfizer, Prometheus, Roivant, Syneos Health and Takeda; and research support from Lilly, Pfizer and Takeda.
M.D. Kappelman reports being a consultant to Eli Lilly and Takeda.
G. Radulescu and N. Li are employees of Alimentiv.
J.J. Wu, I. Romo Bautista, A. Insogna and C. Agboton are employees of Takeda and hold stock and/or share options in Takeda.
N. Narula has received advisory board/consulting honoraria from Abbvie, Amgen, Eli Lilly and Company, Ferring, Fresinius Kabi, Innomar Strategies, Iterative Health, Janssen, Novartis, Organon, Pfizer, Sandoz and Takeda.

Introduction

Crohn’s disease (CD) is a chronic condition characterized by a relapsing-remitting course, often requiring intestinal resection. Postoperative management primarily aims to maintain clinical remission. The advent of biologic therapies has undoubtedly improved disease prognosis following initial surgery. However, access to this therapeutic class remains limited in lower-middle income countries such as Tunisia, necessitating the use of alternative agents, notably azathioprine (AZA), which has been widely used for this indication, albeit with controversial results.

Aims & Methods

This study aimed to evaluate the effectiveness of AZA in maintaining remission after a first intestinal resection in patients with ileal or ileocolonic Crohn’s disease, and to identify factors associated with treatment failure.
​We conducted a retrospective, descriptive, and analytical study in the gastroenterology department of Sahloul University Hospital in Sousse (Tunisia) over a 4-year period (2020–2024). We included all patients with ileal or right ileocolonic CD who underwent intestinal resection and received AZA in the postoperative period.

Results

A total of 66 patients were included, with a mean age at diagnosis of 31.50 ± 12.24 years and a male-to-female ratio of 1.06. The median interval between diagnosis and surgery was 21.5 months. During follow-up, AZA failure occurred in 63.6% of patients (n=42), with a mean time from surgery to failure of 44.71 ± 37.74 months. In univariate analysis, ileocolonic disease location (p=0.042), the total number of flares (p=0.007), and the number of severe flares (p<0.001) prior to surgery were significantly associated with AZA failure. Failure rates were also significantly higher in patients who underwent emergency surgery (p=0.007). Inflammatory resection margins (p<0.001) and severe inflammatory activity (p=0.007) were also significantly associated with treatment failure. In multivariate analysis, three independent risk factors were identified: the number of severe flares before surgery (p=0.031), preoperative inflammatory syndrome (p=0.008), and histopathological evidence of disease at the resection margins (p=0.004).

Conclusion

Our findings suggest that thiopurines remain a valuable therapeutic option in the management of Crohn’s disease, particularly in our setting, where access to alternative therapies is limited and associated with high costs.

Introduction

The use of biologics has become an increasingly common treatment option for inflammatory bowel disease (IBD). However, data on maternal and fetal exposure to ustekinumab (UST) and vedolizumab (VDZ) remain scarce.

Aims & Methods

This systematic review and meta-analysis aimed to assess the safety of UST and VDZ in pregnant women with IBD. We systematically searched PubMed, Embase, and Cochrane Library databases in March 2025. The inclusion criteria were randomized and non-randomized studies comparing UST and VDZ for the treatment of IBD in pregnant patients and evaluating at least one predefined outcome of interest. Primary outcomes were spontaneous abortion and preterm delivery. Secondary outcomes included live birth, low birth weight, serious infections, neonatal intensive care unit (NICU) admission, and malignancies. Statistical analysis was performed using RStudio, applying a random-effects model to calculate the pooled risk ratios (RRs) for binary outcomes.

Results

This systematic review included six studies. Median maternal age ranged from 30 to 33 years, with similar distributions between groups. The average disease duration ranged from 8 to 14 years. Crohn’s disease was more prevalent in the ustekinumab group, while ulcerative colitis was more common in the vedolizumab group. No statistically significant differences were observed in spontaneous abortion (RR 1.66; 95% CI 0.89–3.10), preterm delivery (RR 0.60; 95% CI 0.31–1.16), live birth (RR 0.97; 95% CI 0.90–1.05), low birth weight (RR 0.65; 95% CI 0.31–1.40), serious infections (RR 1.34; 95% CI 0.39–4.66), NICU admission (RR 1.02; 95% CI 0.56–1.85), or malignancies (RR 1.25; 95% CI 0.67–2.32) between UST and VDZ treatments.

Conclusion

No significant differences were observed across the outcomes analyzed when comparing ustekinumab and vedolizumab for the treatment of pregnant patients with IBD.

Introduction

The Pisa EoE Adaptation Questionnaire (PiEAQ) on adaptive behaviors at mealtime significantly improves the correlation between dysphagia scores and histological disease activity (HDA) in eosinophilic esophagitis (EoE) [Reference 1].

Aims & Methods

Whether longitudinal variations of PiEAQ scores (∆PiEAQ) can capture HDA trends following pharmacological treatment of EoE has not been investigated. Consecutive adults (>18 years) with histologically active EoE (i.e., ≥15 eos/high-power field) were prospectively enrolled. Clinical characteristics, HDA, a recall-modified dysphagia symptom questionnaire (mDSQ), esophageal hypervigilance and anxiety scale (EHAS), and PiEAQ (drinking water to push the bolus, lubricating food, chewing for long, and blending food) were recorded longitudinally at baseline (T0) and 12 weeks post-treatment using a 30-day recall period (T1). ROC curve analysis with DeLong test was used to calculate the diagnostic accuracy (AUC) of clinical scores for predicting HDA following treatment. Significance threshold was p<0.05.

Results

Thirty-seven histologically active EoE patients were included (Table 1). The mDSQ, PiEAQ, and EHAS score at baseline were 2.97 (IQR, 2-5), 2.00 (IQR, 1-3), and 21 (IQR, 14– 25), respectively. Following treatment with budesonide orodispersible tablets (72.2%), PPIs (19.6%), dupilumab (5.5%), or milk-free diet (2.7%), histological remission was achieved in 78.4% of patients, while 21.6% remained histologically active. Post-treatment (T1), mDSQ, PiEAQ, and EHAS scores decreased significantly only in patients who achieved histological remission (Table 2 and Figure1). ROC curve analysis showed that a post-treatment reduction of at least 2 adaptive behaviors compared to baseline (∆PiEAQ=-2) had AUC of 85.0%, with 100% specificity and 64% sensitivity for the identification of patients achieving histological remission following treatment. Similarly, a post-treatment reduction of at least 3 points in mDSQ scores compared to baseline (∆mDSQ=-3) had AUC of 81.1% with 100% specificity and 57.7% sensitivity. The non-inferiority analysis showed that the ∆PiEAQ had similar performance to ∆DSQ (DeLong p-value= 0.46). A combined score integrating both ∆PiEAQ and ∆DSQ scores increased the AUC of clinical scores for capturing variations of HDA post-treatment to 90%, with 100% specificity and 73.1% sensitivity for detecting patients achieving histological remission post-treatment (Figure 2).

Conclusion

The PiEAQ is the first questionnaire investigating adaptive behaviors as a standalone domain in EoE. We demonstrated that longitudinal variations in PiEAQ scores are sensitive to HDA variations over time and can monitor histological disease activity trends after treatment. This study confirms that, similar to dysphagia, adaptive behaviors contribute to disease burden in EoE and improve with treatment.

References

1. Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 30. doi: 10.14309/ajg.0000000000003272. Epub ahead of print. PMID: 39787341.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

Dutch society has witnessed significant societal and demographic changes over the decades. With 28% of the Dutch population having a migration background in 2023, understanding diversity within the gastroenterology workforce is imperative. This study examines the evolution of sex, ethnic, and socio-economic diversity among Dutch gastroenterologists from 2005-2023.

Aims & Methods

This repeated cross-sectional study utilized pseudonymized data from the BIG-register, paired with demographic variables from Statistics Netherlands (CBS), covering the years 2005, 2010, 2015, 2020, and 2023. The total population sample in each year consisted of all individuals registered as gastroenterologists for at least one day in a respective year. Variables such as sex, migration background, year of birth, and parental socio-economic status indicators were analyzed to assess trends and identify factors associated with being a
gastroenterologist. Descriptive and logistic regression analyses were employed to explore these trends and compare generational differences.

Results

The study revealed a narrowing sex gap with an increase in female gastroenterologists (28% to 43% from 2005-2023), particularly among the younger cohort (60% female). However, ethnic diversity has not kept pace, with a decline in the representation of gastroenterologists from migration backgrounds among younger professionals (27% to 18% for gastroenterologists < 1979 and ≥ 1980, respectively). Socio-economic analysis indicated that approximately 75% of gastroenterologists have parents from top-20% assets category.

Conclusion

The gastroenterology field in the Netherlands shows significant advancements in gender diversity, but lags in ethnic and socio-economic diversity. The increasing trend of gastroenterologists from medical families highlights the need for policy adjustments, to ensure access to candidates from more diverse socio-economic backgrounds. Policies should focus much more on promoting comprehensive diversity to enhance healthcare outcomes and reflect the demographic changes within society.

References

1. Stanford FC. The Importance of Diversity and Inclusion in the Healthcare Workforce.
J Natl Med Assoc. 2020;112(3):247-9.
2. Gomez LE, Bernet P. Diversity improves performance and outcomes. J Natl Med
Assoc. 2019;111(4):383-92.
3. Juch A. 100 jaar Maag-Darm-Leverarts in Nederland 1913-20132013. 336 p.
4. Brach C, Fraser I. Reducing disparities through culturally competent health care: an
analysis of the business case. Qual Manag Health Care. 2002;10(4):15-28.
5. Moberly T. Men outnumber women three to one in some specialties. Bmj.
2018;363:k4098.
6. Subramaniam M, Azad N, Wasan SK, Long MT. Equal Opportunity: Women
Representation on Editorial Boards and Authorship of Editorials in Gastroenterology and
Hepatology Journals. Am J Gastroenterol. 2021;116(3):613-6.
7. Dossa F, Baxter NN. The place of women in gastrointestinal medicine and surgery:
the need for progress. Lancet Gastroenterol Hepatol. 2023;8(11):965-6.
8. Kesavarapu K, Schwartz J, Ikonomi E, Ahmad A. What's holding women back? A
review of gender inequality in gastroenterology in the USA. Lancet Gastroenterol Hepatol.
2019;4(12):898-900.
9. Esposito I, Simsek C, Nowak A, Tiniakos D, Equality UEG, Diversity G. United
European Gastroenterology Equality and Diversity Plan. United European Gastroenterol J.
2023;11(5):484-7.

Disclosure

OKB, ABB, PK and LM have no conflict of interests, CJJM is consultant for Douglas (New Zealand) and HLW (The Netherlands). All outside submitted work.