Introduction

Per the STRIDE II consensus, mucosal healing and normalization of quality of life are considered long-term treatment goals in ulcerative colitis (UC). Results from Phase 2/3 induction and maintenance trials (U‑ACHIEVE and U‑ACCOMPLISH) showed that patients with moderately to severely active UC treated with upadacitinib (UPA) had significant improvements in these outcomes individually. However, there is a need to understand better the extent to which patients treated with UPA can achieve both treatment goals jointly within one year of maintenance therapy.

Aims & Methods

In the U-ACHIEVE and U-ACCOMPLISH trials, patients with a clinical response after 8-week induction treatment with UPA 45 mg QD were re-randomized 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or placebo (PBO) QD. Long-term treatment goals were determined based on the percentage of patients who achieved the composite endpoint of endoscopic remission (ER), complete symptom resolution (CSR), and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at the end of induction week 8 and maintenance week 52. ER was defined as an endoscopic score of 0; CSR as stool frequency subscore ≤1, rectal bleeding subscore of 0, no bowel urgency, no abdominal pain; and IBDQ remission as IBDQ total score ≥170. The response rate between PBO and UPA was calculated using the Cochran-Mantel-Haenszel test, adjusting for baseline characteristics. The percentage of patients who maintained vs achieved ER+CSR+IBDQ remission during maintenance week 52 was also calculated.

Results

At induction week 8, a significantly greater percentage of patients treated with UPA 45 mg achieved ER+CSR+IBDQ remission vs PBO (6.4% vs 0.9%, respectively, p<0.001, Table). At maintenance week 52, the percentage of induction responders who achieved ER+CSR+IBDQ remission reached 18.3% with UPA 30 mg and 13.1% with UPA 15 mg vs 4.5% with PBO (p<0.001). Of the patients who achieved ER+CSR+IBDQ remission by week 0 of maintenance, 42.1% (8/19), 23.5% (4/17), and 22.2% (4/18) in the UPA 30 mg, UPA 15 mg, and PBO groups, respectively, sustained the composite endpoint at week 52. Among patients who did not achieve this composite endpoint by week 0 of maintenance, 16.2% (35/214), 12.3% (26/208), and 2.9% (6/205) in the UPA 30 mg, UPA 15 mg, and PBO groups, respectively, achieved it at week 52.

Conclusion

Results of this post hoc analysis indicate that the rigorous, long-term treatment goals of ER+CSR+IBDQ remission can be achieved with UPA in some patients with moderately to severely active UC by week 8 of induction. By maintenance week 52, nearly one in five patients treated with UPA 30 mg and approximately one in eight patients treated with UPA 15 mg achieved the stringent target. Sustained maintenance treatment with UPA results in an increasing proportion of patients achieving or maintaining these long-term goals of treatment after only one year.

Percentage of patients who achieved composite endpoint of endoscopic remission and complete symptom resolution and IBDQ remission at week 8 of induction and week 52 of maintenance
	Responder, n/N (%)	Adjusted rate diffa, % (95% CI)
Induction week 8
PBO	3/328 (0.9)	5.5 (3.3, 7.7)*
UPA 45 mg QD	42/660 (6.4)
Maintenance week 52b
PBO	10/223 (4.5)
UPA 15 mg QD	30/225 (13.1)	8.5 (3.4, 13.7)*
UPA 30 mg QD	43/233 (18.3)	13.7 (8.1, 19.3)*
*p ≤ 0.001 for UPA vs PBO. aAt week 8, the adjusted response rate between PBO and UPA 45 mg was calculated using the Cochran-Mantel-Haenszel (CMH) test adjusting for baseline corticosteroid use, Adapted Mayo score, and inadequate response to biologic (Bio-IR) status. At week 52, the rate difference between PBO and UPA 30 mg and 15 mg was calculated using CMH adjusted for Bio-IR status at induction baseline, and clinical remission status and corticosteroid use at week 0 of maintenance. Calculations were based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or non-responder imputation if there were no missing data due to COVID-19. bThe maintenance study population comprises patients who achieved clinical response after UPA 45 mg QD 8-week induction treatment in the Phase 2 and 3 programs and were enrolled in the 52-week maintenance treatment period. CI, confidence intervals; IBDQ, Inflammatory Bowel Disease Questionnaire (IBDQ), PBO, placebo; QD, once daily; UPA, upadacitinib.

Disclosure

J Panes received financial support for research from AbbVie and Pfizer; consultancy fees/honorarium from AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Robarts, Sanofi, Takeda, Theravance and Wasserman; reports payment for lectures including service on speaker bureau from Abbott, Ferring, Janssen, Pfizer and Takeda; and reports payment for development of educational presentations from Abbott, Janssen, Pfizer Roche and Takeda.
R Panaccione has received consulting fees, speaker fees, research/educational support from, and/or advisory board member for AbbVie, Abbott, Alimentiv (formerly Robarts), Amgen, Arena, AZ, BI, BMS, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Progenity, Protagonist, Roche, Satisfai, Sandoz, Schering-Plough, Shire, Sublimity, Theravance, Takeda, and UCB.
MC Dubinsky has received consultancy fees from AbbVie, Allergan, Amgen, BI, Celgene, Gilead, Janssen, Lilly, Pfizer, Prometheus, Roche, Takeda, and UCB; and is a shareholder of Trellus Health.
Y Ishiguro has received a research grant from Mitsubishi Tanabe Pharmaceutical; speaker/consultation fees from AbbVie, Janssen, Daiichi-Sankyo, Kissei Pharmaceutical and EA Pharma.
J Tran is currently a contractor at AbbVie and a funded PhD candidate at the University of Washington.
D Ilo, J Eccleston, Y Sanchez Gonzalez are full-time employees of AbbVie and may hold AbbVie stock and/or stock options.
B Feagan is a consultant, member of the speakers bureau, and/or member of the scientific advisory board for AbbVie, AbolerIS, AgomAB, Allianthera, Amgen, AMT, AnaptysBio, Arena, Atomwise, Avoro Capital Advisors, Axio, BI, BioJamp, Biora, Boxer, Celgene/BMS, Celsius, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge Bio, Hot Spot, Imhotex, Immunic, Index, JAKAcademy, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lilly, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Play to Know AG, Progenity, Protagonist, PTM, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, Ysopia, and Zealand; is a stock shareholder for Gossamer; is an employee of Western University; and is Senior Scientific Director of Alimentiv Inc.

Introduction

Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC), shares chronic and inflammatory characteristics with Non-Alcoholic Fatty Liver Disease (NAFLD). While their precise pathogenesis remains unclear, emerging evidence implicates dysbiosis and metabolic changes. This study aims to investigate the association between IBD and NAFLD, focusing on metabolic syndrome and its nutritional implications

Aims & Methods

Objective: To evaluate the nutritional status and body composition in IBD patients, comparing groups with and without NAFLD, and identifying the associated factors.
Methods: A cross-sectional study was conducted, assessing clinical data, metabolic syndrome presence, nutritional status, and biochemical markers. Patients were categorized into IBD+NAFLD and IBD-only groups based on hepatic ultrasound findings. Statistical analysis included descriptive statistics and logistic regression.

Results

127 patients were included, comprising 58 CD and 69 UC, with a mean age of 45.56 years. Most patients were female and did not engage in physical activity. Patients were mostly in clinical remission and endoscopic activity. 58 patients (45.67%) had hepatic steatosis on ultrasound, forming the IBD+NAFLD group. The IBD+NAFLD group had higher BMI, fat mass, and all circumference values, Table 1, as well as a higher prevalence of hypertension (p=0.0446) and dyslipidemia (p=0.0377). It is noteworthy that, although most of these patients were classified as overweight by BMI, considering anthropometric data, most IBD+NAFLD patients were classified as eutrophic. 86.21% of patients in the IBD+NAFLD group met the criteria for MAFLD. No difference was observed regarding medication in use. Regarding biochemical tests, the IBD+NAFLD group had higher values of hematocrit (p=0.0023), liver enzymes (AST, p=0.0141 and ALT, p<0.0001), fasting glucose (p=0.0107), glycated hemoglobin (p=0.0146), basal insulin (p=0.0003), and triglycerides (p=0.0001), with lower HDL cholesterol (p=0.0101)

Conclusion

The study highlights a significant association between nutritional status and NAFLD in IBD patients. Those categorized as eutrophic had a higher prevalence of hepatic steatosis, potentially linked to dietary factors.

References

Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and
natural history of non‐alcoholic fatty liver disease and non‐alcoholic
steatohepatitis in adults. Alimentary pharmacology & therapeutics.
2011;34(3):274-285./ Silva A.F; Schieferdecker M.H; Amarante M. B. Ingestão alimentar em pacientes
com doença inflamatória intestinal ABCD, arq. bras. cir. dig. 24 (3) • Set 2011/ Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA.
2015;313(22):2263-73

Introduction

Perianal fistulising Crohn’s disease (PFCD) affects up to 20% of patients with Crohn’s Disease (CD). PFCD can cause pain, purulent discharge and faecal incontinence, leading to significant morbidity and reduction in quality of life. The use of biologic therapy, antibiotics and surgical intervention remain the mainstay of management of perianal fistulas.

Aims & Methods

This study aims to review current practices in the management of PFCD across two large tertiary IBD centres. This retrospective cohort study assessed adult patients with PFCD between two tertiary Australian hospitals between 2006 to 2024. Patients with PFCD were identified using prescribing data. CD phenotype, therapy and fistula-related data were extracted. Biologic choice and therapeutic drug monitoring, antibiotic choice and duration, surgical intervention, and length of stay in hospital were monitored. Cross-sectional disease activity of perianal fistulizing disease was assessed at the time of data collection using clinical fistula symptom grade and radiological assessment were available. Clinical remission was defined as fistula symptom grade of 1 or less. Radiological remission was defined by healing fistula tracts or no active inflammation seen on MRI. The study was approved by the Central Adelaide Local Health Network Human Research Ethics Committee (HREC19145).

Results

Gender Male, n Female, n Age, y, median (IQR)	n = 57 30 27 40 (31-54)
Active Smoker, n (%)	14 (24.5)
Median length of clinical follow up, months, n (IQR)	46.5 (23.8-72.3)
Antibiotics Prescribed Metronidazole, n treated (%) Amoxicillin / Clavulanic acid, n treated (%) Others, n treated (%)	47 (68.1) 13 (27.7) 9 (4.2)
Duration of Antibiotics Metronidazole, median duration, days (IQR) Amoxicillin / Clavulanic acid, median duration, days (IQR) Others, median duration, days (IQR)	5 (5-7) 5 (5-10) 14 (7-14)
Biologic therapy Total patients on biologic therapy, n (%) Infliximab, n (%) Adalulimab, n (%) Ustekinumab, n (%)	56 (98.2) 43 (75.4) 11 (19.3) 2 (3.5)
Therapeutic Drug Monitoring (Infliximab) Infliximab level performed, n (%) Subtherapeutic (Infliximab level <10), n (%) Active disease and subtherapeutic (Infliximab level <10), n (%)	37 (86%) 30 (81.1%) 12 (40%)
Remission status Clinical Remission, n (%) - Defined as Fistula symptom grade of 1 or less Radiological Remission, n (%) - Defined as healing fistula tracts or no active inflammation seen on MRI	48 (84.2) 33 (57.8)
Subtherapeutic Therapeutic Drug Monitoring (All biologic agents) In Remission, n (%) Active Disease, n (%)	18 (56.2) 14 (43.8)

Table 1. Baseline characteristics

57 patients (median age, 40 years (31-54); 52.6% male) with PFCD were included in the study and followed over a median duration of 46.5 months (23.8-72.3). There were a total of 157 individual surgical procedures over the period, 2.75 per patient, most of which (94.2%) were examination under anaesthesia. Antibiotic therapy was dispensed for either perianal sepsis or an actively draining fistula in 26 patients, 2.65 number of courses per patient. The most common antibiotic prescribed was Metronidazole (68.1%), followed by Amoxicillin / Clavulanic acid (27.7%). The median duration of antibiotic therapy was 5 days (5-7) for Metronidazole and 5 days (5-10) for Amoxicillin / Clavulanic acid. There were 56 (98.2%) patients on biologic therapy. The most common biologic agent was Infliximab (75.4%), followed by Adalimumab (19.3%) and Ustekinumab (3.5%). At the time of analysis, 48 patients (84.2%) were in clinical remission and 33 patients (57.8%) were in radiographical remission. In patients treated with infliximab, 37/43 (86%) had therapeutic drug monitoring performed. Amongst these, 30 (81.1%) had subtherapeutic levels (defined as Infliximab level < 10), with 12/30 (40%) of patients having active PFCD.

Conclusion

Across two tertiary IBD centres, management of PFCD is variable and not in keeping with current guidelines. Short courses of antibiotic therapy were used, and the majority of patients had subtherapeutic drug levels when tested. Optimising outcomes for patients with PFCD requires awareness of best practice and a multidisciplinary team approach.

Introduction

Intestinal ultrasound (IUS) has proven to be a valuable tool for accurately detecting intestinal damage and characterizing disease behavior in Crohn’s disease (CD). IUS scoring systems for CD activity have been developed, however all the studies had methodological flaws. Therefore, studies comparing and validating the existing IUS scores in CD patients are required.

Aims & Methods

In this study, we aimed to compare two main existing scores, Bowel Ultrasound Score (BUSS) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in patients with ileal CD using the simplified endoscopic activity score for CD (SES-CD).
An observational cross-sectional study was performed to evaluate the disease activity in adult CD patients with ileal involvement between November 2019 and February 2024. All patients had undergone ileocolonoscopy and IUS, the time interval between the two procedures was lower than 10 days. Receiver operating characteristic (ROC) curve analyses was performed for BUSS and IBUS-SAS to predict SES-CD ≤2 for CD.

Results

Total 56 adult patients with ileal CD were included in the study, 38 patients (67.9%) were male, the median age was 40.5 (IQR 26-46.75) years and the median duration of the disease was 8.4 (IQR, 4.93-10.29) years. In the endoscopically remission (SES-CD ≤2) group; the median BUSS was 2.63 (IQR 2.12-3.45) and the median IBUS-SAS was 14 (IQR, 11.3-18.4), while in the endoscopically active (SES-CD >2) group; the median BUSS was 5.67 (IQR, 3.47-7.76) and the median IBUS-SAS was 49.7 (IQR, 23.3-72.65). The median BUSS and median IBUS-SAS in the endoscopically remission group were significantly lower than those of the endoscopically active group (p< 0.001, for both). The cut-off value for BUSS to determine endoscopic remission (SES-CD ≤2) was 3.9 (AUC: 0.839, 95% CI: 0.737-0.941, sensitivity: 92%, specificity: 73%, p < 0.001), while the cut-off value for IBUS-SAS to establish endoscopic remission (SES-CD ≤2) was 24.4 (AUC: 0.871, 95% CI: 0.780-0.962, sensitivity: 100%, specificity: 73%, p < 0.001).
There was a very high positive correlation between BUSS and IBUS-SAS (r=0.914, p<0.001), a high positive correlation between BUSS and SES-CD (r=0.659, p<0.001), a moderate positive correlation between BUSS and CRP (r=0.577, p<0.001). There was a high positive correlation between IBUS-SAS and SES-CD as well as IBUS-SAS and CRP (r=0.728, p<0.001 and r=0.657, p<0.001 respectively).

Conclusion

In this study, we found that the most accurate cut-off value for BUSS was 3.9 and the most accurate cut-off value for IBUS-SAS was 24.4 in CD patients with endoscopic remission (SES-CD ≤2) group. Also, we have confirmed that both BUSS and IBUS-SAS significantly correlate with endoscopic activity in a real-world cohort.

Introduction

Proctitis, a form of ulcerative colitis, is often highly symptomatic and challenging to manage. Data regarding the outcomes of biologic and small molecule therapy (advanced treatment) for patients with UC proctitis are limited, largely because these patients are usually excluded from randomized controlled trials.

Aims & Methods

Our aim was to evaluate the persistence of advanced treatment in patients with UC proctitis. From the Czech national prospective registry of biologic and innovative therapy of inflammatory bowel disease (CREdIT) which contains 9033 patients with IBD, we identified 200 treatment courses of advanced therapy among 167 patients with UC proctitis and ≥3 months follow-up. In this preliminary analysis, we employed mixed-effects Cox regression models to attempt to identify an association between treatment type and time to treatment discontinuation. An individual, medical centre, and time period were added as random effects into the models. To ensure a balance between the groups inverse probability of treatment weighting (IPTW) was used when comparing persistence between anti-tumor necrosis factor inhibitors (anti-TNF) and vedolizumab. We further analysed corticosteroid-free persistence after 6 months of treatment for those observations where this data were available. Missing data of co-variables were imputed using multiple imputation.

Results

Among 200 treatment courses, 78 were with infliximab (39%), 39 with adalimumab (20%), 59 with vedolizumab (30%), 13 with tofacitinib (7%), three each with filgotinib, golimumab, and ustekinumab, and two with upadacitinib. Most of the treatment courses were given as 1^st line (1^st 129, 65%; 2^nd 46, 23%; >2^nd 25, 13%). Concomitant corticosteroids at the start of advanced treatment course were reported in 119 (60%) of cases. Comparison of different treatment types revealed that persistence on vedolizumab was longer than on infliximab in the final adjusted model (Hazard Ratio [HR] 2.33, 95% CI 1.17 - 4.67, p-value=0.017). Moreover, vedolizumab was also more persistent compared with anti-TNF drugs as a group in the IPTW analysis (HR 8.03, 95% CI 2.60 - 24.84, p-value=0.001). Corticosteroid-free persistence at 6 months was found in 31/50 (62%) courses of vedolizumab and 56/97 (58%) courses of anti-TNF treatment. Although vedolizumab did not show greater corticosteroid-free persistence at 6 months than infliximab (HR 1.50, 95% CI 0.56-3.96, p-value=0.417), IPTW analysis revealed that vedolizumab was significantly more corticosteroid-free persistent compared to anti-TNF drugs as a group (HR 9.55, 95% CI 2.90-31.42, p-value=0.001).

Conclusion

Based on data from real clinical practice, the persistence of advanced treatment in UC proctitis seems to be low. Treatment with vedolizumab appears to be more persistent than anti-TNF therapy. However, efficacy data must also be analysed before vedolizumab can be considered preferable.

Disclosure

OH: Lectures/congress fees/consultancy: MSD, Abbvie, Takeda, Nutricia, Sandoz, Eli Lilly
ML: Lectures/congress fee/consultacy: Johnson&Johnson, Celltrion, Abbvie, Takeda, Biogen, Phizer
PD: Lecture fee/consultancy: AbbVie, Pfizer, Takeda, Janssen, Eli-Lilly, Sobi, Celltrion
TV: Lecture fee/consultancy: AbbVie, Takeda
ZS: Lecture fee/consultancy: Takeda
LN: Lecture fee/consultancy: Pfizer, Takeda, Janssen (Johnson and Johnson),Ferring
MB: Lecture fee/consultancy: AbbVie, Pfizer, Takeda, Janssen Cilag, Eli-Lilly, Ferring,
Celltrion, Alfasigma, SOBI, PRO.MED.CS
DD: Lecture fee/consultancy: AbbVie, Pfizer, Takeda, Janssen, Eli-Lilly, Ferring