bluuebunny/crossref_metadata_2025 huggingface dataset:
P332 External validation of intestinal ultrasound scores to detect endoscopic activity in children and adults with Crohn's disease: A prospective cohort study
Authors: Aronskyy I , Spencer E , Kellar A , Pittman N , Dubinsky M , Dolinger M
Published: January 2023

Background

Intestinal ultrasound (IUS) scores were developed for adults and children with Crohn’s disease (CD) but have not been externally validated with endoscopy. This study aimed to externally validate all CD IUS scores with endoscopy.

Methods

Prospective cross-sectional study of children and adults with CD who underwent IUS and colonoscopy within 60 days. The International Bowel Ultrasound Segment Activity Score (IBUS-SAS), Simple Ultrasound Score for Crohn’s disease (SUS-CD), Simple Ultrasound Activity Score for Crohn’s disease (SUAS-CD), and Simple Pediatric Activity Ultrasound Score (SPAUSS) were compared to the Simple Endoscopic Score for Crohn’s disease (SES-CD). Primary outcomes were the area under the receiver operating curve (AUROC) for each IUS score for moderate (SES-CD ≥ 5) and any (SES-CD ≥ 3) CD activity. Secondary outcome was the correlation of IUS scores and SES-CD.

Results

82 CD patients (53 (65%) children, 29 (35%) adults, 41 (50%) female; 50 (61%) ileocolonic disease location) underwent IUS of 150 (74 (49%) terminal ileum) bowel segments with IUS scores and SES-CD. In both children and adults, all scores performed with high accuracy to detect SES-CD ≥ 5 and moderate accuracy to detect SES-CD ≥ 3. To detect SES-CD ≥ 5 in children, a SUAS-CD ≥ 4.5 had the highest AUROC [95% CI] =0.91 [0.85-0.97] (sensitivity=90%, specificity=81%), followed by an IBUS-SAS ≥ 37.8 (AUROC=0.89 [0.83-0.96]), SPAUSS ≥ 4 (AUROC=0.89 [0.81-0.96]), and SUS-CD ≥ 2 (AUROC=0.88 [0.80-0.95]). To detect SES-CD ≥ 5 in adults, an IBUS-SAS ≥ 34.2 had the highest AUROC=0.85 [0.71-98] (sensitivity=70%, specificity=87%) followed by a SAUS-CD ≥ 5.45 (AUROC =0.84 [0.71-0.98]), SUS-CD ≥ 1 (AUROC=0.81 [0.65-0.97]), and SPAUSS ≥ 5 (AUROC=0.78 [0.65-0.97]). To detect SES-CD ≥ 3, SPAUSS ≥ 4 (AUROC=0.78 [0.69-0.87], sensitivity=56%, specificity=92%) and SUS-CD ≥ 3 (AUROC =0.78 [0.68-0.86], sensitivity=56%, specificity=89%) had the highest accuracy in children followed by a SAUS-CD ≥ 4.5 (AUROC=0.74 [0.63-0.86]) and IBUS-SAS ≥ 34 (AUROC=0.73 [0.62-0.84]). In adults, SAUS-CD ≥ 2.68 and IBUS-SAS ≥ 11.2 (AUROC = 0.68 [0.50-0.85], sensitivity=63%, specificity=72%) had the highest accuracy to detect SES-CD ≥ 3 followed by a SUS-CD ≥ 2.5 (AUROC = 0.65 [0.50-0.81]), and SPAUSS ≥ 6 (AUROC = 0.61 [0.45-0.77]). IUS scores moderately correlated with SES-CD in children and adults, of which the IBUS-SAS had the highest (r=0.66 in children vs. r=0.57 in adults).

Conclusion

CD IUS scores are accurate for the detection of endoscopic activity in children and adults. IUS scores may be more accurate in children and correlate better with endoscopy but more studies are needed. This data supports the use of IUS as an accurate monitoring tool, reflective of endoscopic activity.
P340 Issues on implementing treat-to-target approach in Asia Pacific, Middle East and Africa: Reality, gaps, and way forward -APMA IBD Coalition
Authors: Akyüz F , An Y K , Aniwan S , Bui H H , Chan W P , Choi C H , Chopdat N , Connor S , Desai D , Flanagan E , Kobayashi T , Leong R W , Leow A , Leung W K , Limsrivilai J , Peddi K , Pribadi R R , Ran Z , Wei S C , Wu K , Ye B D ,   APMA IBD Group
Published: January 2023

Background

To understand the real-world issues and difficulties in implementing treat-to-target (T2T) approach in managing inflammatory bowel disease (IBD) patients in the Asia Pacific, Middle East and Africa (APMA) region.

Methods

A structured survey of 10 questions was sent to 19 IBD specialists from 14 economies/countries in the APMA region between June and August 2022, followed by three hybrid roundtable discussions to identify, elaborate and validate the gaps and challenges in T2T adoption in their healthcare setting. The survey used a series of questions exploring experts’ current practice and preference of treatment endpoints, diagnostic and monitoring tools, and major desirable improvement if resources are not constrained.

Results

The two major gaps expressed by of IBD specialists in the APMA region are to early diagnose and treat IBD patients (61.1%), and the lack of trained IBD nurses (50%) (Figure 1.The major gaps in the diagnosis and monitoring of IBD in routine clinical practice in APMA). While T2T approach is widely accepted among IBD specialists across the APMA region, blood tests (such as CRP, ESR) and faecal calprotectin (FC) test are two commonly used modalities by 77.8% and 72,2% IBD specialists, respectively However, the availability and cost of FC test is the second leading challenge (55.6%) faced by these specialists, with patient compliance being the most challenging (66.7%)(Figure 2.The biggest challenges in monitoring IBD patients in APMA). As to the most desired IBD monitoring tool, 88.9% considered the application of validated and reproducible intestinal ultrasound (Figure 3.Most desired IBD monitoring tool in APMA if resources are not a problem). The availability of trained IBD nurse (39%) and increasing awareness and training of general practitioner (33%) are the two most important factors that IBD specialists considered to improve care of IBD patients in the region (Figure 4.Major improvements required in diagnosis to improve IBD patient care in APMA).

Conclusion

Considerable gaps in implementing T2T approach to managing IBD patients in the APMA region are identified via this survey by IBD specialists. Lack of training of general practitioners, IBD nurses and availability of affordable FC are common issues identified in this region, which would deserve implementation of new educational initiatives and resources reallocation.
P365 Psoriasis in Inflammatory Bowel Disease: Comparison of Extraintestinal Manifestations and Effect of Anti-TNF Therapies
Authors: Kilic D T , Yuksel I
Published: January 2023

Background

Psoriatic lesions may develop in inflammatory bowel disease (IBD) patients as an extraintestinal manifestation or an adverse effect of anti-TNF therapy. The aim of this study was to compare the clinical characteristics of IBD patients with psoriasis between extraintestinal manifestations and the effect of anti-TNF therapies.

Methods

In this cross-sectional study, data was identified between March 2019, and October 2022. Demographic and clinical data of patients with IBD were recorded at baseline and during follow-up. All patients were questioned for psoriasis, and the "onset of psoriasis" was recorded as before or after anti-TNF therapies.

Results

In our tertiary center, a total of 1125 IBD patients were identified through the database (543 with CD, 549 with UC, and 33 with IBD unclassified (IBDU)) and a 336 (29.9%) had an exposure to adalimumab, 322 (28.6%) to infliximab, and 27 (2.4%) to certolizumab. In our cohort, a total of 37 (3.3%) patients, suffered from psoriasis, in which 18 (48.6%) patients on anti-TNF therapy (7 adalimumab, 10 infliximab and 1 certolizumab) developed a drug-induced psoriasis, while 19 (51.4%) patients had psoriasis as an extraintestinal manifestation before the anti-TNF therapies. In patients with all psoriasis, 24 (%64.9) were female and 28 (75.7%) had CD. CD was statistically significantly more common in patients with psoriasis induced by anti-TNF therapy (17 (94.4%) vs. 11 (57.9%), p=0.019).

Anti-TNF therapy induced psoriasis had statistically significantly longer disease duration than psoriasis as an extraintestinal manifestation group (11.5 vs 6 median years, respectively p=0.005), while other baseline characteristics such as age, sex, smoking status, family history of IBD, disease location, behavior, perianal disease, and other extraintestinal involvements were similar. At baseline, serum hemoglobin (13 vs. 12 mg/dL; p=0.069), albumin (4.2 vs.4.3 g/dL; p=0.505), partial MAYO score (6 vs 7 median score; p=0.247) and CDAI (360 vs. 320 median score; p=0.339) were all comparable between the two groups, respectively. Whereas baseline CRP level in extraintestinal manifestation group was significantly higher than anti-TNF therapy induced group (66 vs. 2.8 mg/L; p=0.003).

Conclusion

In this study, we found that up to 3.3% of all IBD patients had psoriasis; half of these cases were anti-TNF therapy induced psoriasis, and the rates of psoriasis in CD patients and female patients were greater than those in UC and male patients. Anti-TNF therapy induced psoriasis had a statistically significantly longer disease duration and lower baseline CRP in comparison to psoriasis as an extraintestinal manifestation.
P372 Endoscopic ultrasonography in the differential diagnosis of Ulcerative colitis and Crohn's disease.
Authors: Belousova E ,   Author(s): Budzinskay A.2 Belousova E.1 Lomakina E.1 Levitskaya A.1 Institute(s): 1Moscow Regional Research and Clinical Institute (MONIKI) Department of Gastroenterology Moscow Russian Federation 2 Moscow Regional Research and Clinical Institute (MONIKI) Department of Endoscopy Moscow Russian Federation Budzinskay A. MD PhD Senior Researcher Belousova E. MD PhD Professor Lomakina E. MD Researcher Levitskaya A. phD candidate
Published: January 2023

Background

Background & Aim: Differential diagnosis between Crohn's disease (CD) and ulcerative colitis (UC) could be a challenge, since the endoscopic and clinical characteristics of both may resemble. Furthermore, radiological methods do not provide complete information.To assess the possibilities of endoscopic ultrasonography (EUS, endosonography) for the differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD) in doubtful or controversial cases.

Methods

Methods: We examined 50 IBD patients during the active phase: CD-28 patients (M: W=16:12,average age 27.3 ± 0.7 years), UC-22 patients (M: W=8:14, average age 32 .6 ±1.7 years). The control group included 15 patients without UC or CD. All patients underwent EUS colonoscopy for measurement of wall thickness, assessment vascularization degree and compression elastography was perform.

Results

Results.It was found that wallthickness in CD was 5.66 ± 0.36 mm, was 1.5 times more than in UC (3.96 mm ± 0.13 mm) and 2 times more than in controls(2, 62 ± 0.11mm). Frequency of all intestinallayers in CD was noted in 68% vs 9% in UC (p < 0.02). On the contrary, in UC, wall thickening due to the mucosa and submucosa was significantly more common than in CD (82% and 7.2%, respectively, p < 0.05). Vascularizationdegree of colon wall in UC in most cases was reduced, while in CD, on the contrary, it was increased. According to elastometry, type 1 staining according to Ueno E., corresponding to the soft-elastic structure of colon wall, was detected in UC in 78% of cases, in CD in 54%. Type 2 according to Ueno E. was verified in 22% in UC, in 45% in CD, which indicates the presence of fibrosis foci in colon wall, mainly in CD patients.

Conclusion

Conclusion. The obtained EUS data can be as criteria for differential diagnosis between UC and CD in compound cases and clarify the presence and degree of fibrosis, for example, if strictures in CD.
P393 Effect of filgotinib on anaemia in patients with Ulcerative Colitis in SELECTION
Authors: Loveikyte R , de Haas A , Oortwijn A , Eskens B , Jamoul C , Muller K , van der Meulen-de Jong A
Published: January 2023

Background

Patients with ulcerative colitis (UC) often have anaemia owing to inflammation and/or blood loss.1 Filgotinib (FIL) is a once-daily, oral, Janus kinase (JAK) 1 preferential inhibitor approved for the treatment of UC, which may be associated with fewer haematological events than pan-JAK inhibitors. In the phase 2b/3 SELECTION trial (NCT02914522),2 FIL 200 mg (FIL200) was well tolerated and effective vs placebo (PBO) in patients with UC. This post hoc analysis of SELECTION data compared haematological events across the FIL and PBO treatment arms.

Methods

In SELECTION, adults with moderately to severely active UC were randomized 2:2:1 to receive FIL200, or FIL 100 mg, or PBO once daily for 11 weeks during induction. FIL responders (clinical remission or a Mayo Clinic Score response at week 10 [W10]) were rerandomized to continue their induction FIL dose or PBO in the 47-week Maintenance (MNT) Study. PBO responders continued PBO during MNT. This analysis evaluated the proportions of patients with haematological events (anaemia, leukopenia, lymphopenia, neutropenia and thrombocytopenia) at baseline (BL), W10 and W58. Haematological events were defined based on the relevant laboratory parameters being below the lower limit of normal. For anaemia at W10 and W58, patients were further stratified by rectal bleeding (RB) status (no: RB subscore=0; yes: RB subscore ≥1) at W10 and W58, respectively.

Results

At BL, ~50% of patients had anaemia in all treatment arms. Among these patients, the proportion without anaemia at W10 was similar across the FIL and PBO arms (25.0–30.7%; Table 1). Among patients without BL anaemia, the proportion with anaemia at W10 was also similar across all arms (12.1–17.3%). Among patients without RB at W10, the proportion of patients with a change in anaemia status from BL to W10 was also similar across arms. At W58, the proportion of patients with anaemia was similar across all arms, although ~40% of patients overall had missing data (Table 2). At BL, <5% of patients had leukopenia across all treatment arms (Tables 3 and 4). Lymphopenia, neutropenia and thrombocytopenia were also uncommon at BL (<10%, <4%, and <1% of patients, respectively). Among patients without these four haematological events at BL, <5%, <6%, 4% and ~1%, respectively, had them at W10.

Conclusion

Treatment with JAK1-preferential FIL up to W58, was not associated with anaemia, thought to occur via JAK2 inhibition, in patients overall and in those without RB at W10, compared with PBO. The small numbers of patients with haematological events excluding anaemia at BL limit rigorous inter-arm comparison.

1. Malesza IJ et al. Nutrients 2022;14:3478. 2. Feagan BG et al. Lancet 2021;397:2372–84.
P396 Ustekinumab Is A Promising Option For The Treatment Of Postoperative Recurrence Of Crohn’s Disease
Authors: Macaluso F S , Grova M , Mocciaro F , Di Mitri R , Privitera A C , Distefano M E , Vitello A , Camilleri S , Ferracane C , Pluchino D , Belluardo N , Giangreco E , Fries W , Viola A , Cappello M , Amato L , Bertolami C , Ventimiglia M , Renna S , Casà A , De Vivo S , Orlando A ,   Sicilian Network for Inflammatory Bowel Disease (SN-IBD)
Published: January 2023

Background

Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of Ustekinumab (UST) as therapeutic option for the POR of CD is currently unknown

Methods

All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR with Rutgeerts score ≥ i2 who were treated with UST after the baseline colonoscopy, and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at the end of follow-up and defined in case of occurrence of one of the following: mild clinical relapse (Harvey-Bradshaw Index 5-7), clinically relevant relapse (Harvey-Bradshaw Index > 7), UST discontinuation due to adverse events, need for new resection.

Results

Fifty-nine patients started UST for the management of POR. Five patients were excluded due to the absence of the baseline colonoscopy, 5 were excluded due to absent or mild POR (i.e. Rutgeerts score i0 or i1), and 5 patients were excluded due to short follow-up and the consequent absence of post-treatment colonoscopy. Finally, 44 patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed an intermediate severity of recurrence (Rutgeerts score i2) in 25.0% of patients, and a severe recurrence (Rutgeerts score i3 or i4) in 75.0% of patients. Only 5 patients (11.4%) were naïve to biologics, while most had previous failure to one (61.4%), two (15.9%), or three (11.4%) biologics. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. None of these 22 patients with endoscopic success fulfilled the criteria for clinical failure. Clinical failure at the end of follow-up was reported in 12 out of 44 patients (27.3%); none of these 12 patients had achieved endoscopic success at post-treatment colonoscopy. At univariate Cox regression analysis, the number of previous biologics (HR 2.59 per-unit increase, 95% CI 1.33-5.03; p=0.005), previous surgery (HR 3.45, 95% CI 1.37-8.84; p=0.008), and need for steroids at baseline (HR 3.13, 95% CI 1.03-10.87; p=0.044) were associated with clinical failure at the end of follow-up.

Conclusion

Ustekinumab could be a promising option for the treatment of POR of CD
P412 Time trend in clinicopathological features and prognosis of Ulcerative Colitis associated neoplasia: A nationwide cohort in Japan
Authors: Komatsu K , Shinagawa T , Noguchi T , Uchino M , Ikeuchi H , Okabayashi K , Tanaka S , Futami K , Itabashi M , Watanabe K , Nagahara H , Okita Y , Shimada Y , Mizuuchi Y , Okamoto K , Yamada K , Sato Y , Mizushima T , Kimura H , Takahashi K , Hida K , Kinugasa Y , Ishida F , Okuda J , Daito K , Yamamoto T , Yamamoto S , Koyama F , Hanai T , Komori K , Shida D , Arakaki J , Akagi Y , Yamaguchi S , Ueno H , Matsuda K , Ajioka Y , Sugihara K , Ishihara S ,   The Study Group for Inflammatory Bowel Disease Associated Intestinal Cancers by the Japanese Society for Cancer of the Colon and Rectum
Published: January 2023

Background

With an increase in the number of Ulcerative Colitis (UC) patients in Japan, UC associated neoplasia (UCAN) cases have been accumulated. Laparoscopic surgery for sporadic advanced colorectal cancer was approved in 2002 and biologic agents have been approved for UC from 2010 in Japan. However, few reports have ever examined the time trend using a large patient cohort. We aimed to clarify time trend in clinicopathological features and prognosis of UCAN with a nationwide cohort. This study was conducted as a sub-analysis of the nationwide retrospective study across 47 institutions from the Japanese Society for Cancer of the Colon and Rectum.

Methods

A total of 1,139 UCAN patients were identified in the nationwide cohort from 1983 to 2020. Clinicopathological features, 5-year cancer specific survival (CSS) and overall survival (OS) were compared among the following three groups by the period of UCAN diagnosis, before 2000, 2001-2010 and 2011-2020 (the results are shown in this order).

Results

The number of UCAN patients registered in the database were 59, 340 and 740 in each period. Age at UCAN diagnosis (47, 51, 54, median, p<0.01) and the disease duration from UC diagnosis to UCAN diagnosis (14.3, 16.0, 17.5 years, mean, p<0.01) increased through the study periods. The rate of a surveillance colonoscopy as a diagnostic procedure (36.2%, 58.6%, 72.8%, p<0.01) increased without a change in the ratios of early (pathological stage 0-I) neoplasia (60.7%, 59.5%, 62.2%, p=0.72). Laparoscopic surgery became a dominant surgical procedure in the recent cases (1.7%, 33.2%, 47.7%, p<0.01) without an increase in postoperative complication rate (39.7%, 29.2%, 29.8%, p=0.26). Improvement in 5-year CSS (77.2%, 87.5%, 90.7%, p<0.05) and OS (77.2%, 84.3%, 88.5%, p<0.05) was observed. Among pathological stage III patients, better curative resection rate (66.7%, 92.6%, 97.1%, p<0.01) and the more use of adjuvant chemotherapy in the last decade (50.0%, 58.5%, 76.6%, p<0.05) were observed.

Conclusion

Longer duration of UC before the diagnosis of UCAN was observed in recent cases, which might be due to the improvement of medical therapy, including biologic agents. Minimally invasive surgery prevailed without an increase in postoperative complications. Curative resection and adjuvant chemotherapy might play a role in improvement of 5-year CSS and OS.
P463 Crohn’s disease–associated anorectal cancer has a poor prognosis with high local recurrence: a subanalysis of the Nationwide Japanese Study
Authors: Ogino T , Mizushima T , Sekido Y , Fujii M , Eguchi H , Nezu R , Ikeuchi H , Uchino M , Futami K , Okamoto K , Ajioka Y , Sugihara K , Ishihara S ,   The Study Group for Inflammatory Bowel Disease Associated Intestinal Cancers by the Japanese Society for Cancer of the Colon and Rectum
Published: January 2023

Background

Cancer is the worst prognostic factor for patients with Crohn’s disease (CD). Previous studies of CD-associated colorectal cancer (CRC) have involved only small numbers of patients, and no large series have been reported. The aims of this study are to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC using a large nationwide database from the Japanese Society for Cancer of the Colon and Rectum.

Methods

A large nationwide database covering data from 1980 to 2020 was used to identify patients with CD-CRC (n=233) and sporadic CRC (n=129,783). The clinicopathological features, 5-year overall survival (OS), and 5-year recurrence free survival (RFS) for patients with CD-CRC were compared with these outcomes in sporadic CRC. The data were further analyzed based on tumor location in the colon (CC) or anus/rectum (RC). Propensity score (PS) matching was used to account for selection bias. A binomial logistic regression model was used to estimate the PS, using the nine effective covariates: age at cancer diagnosis, sex, CEA, surgical treatment, adjuvant chemotherapy, tumor depth, lymph node metastasis, distant metastasis, and residual tumor.

Results

Compared with sporadic cases, patients with CD-CRC were younger, more often had RC, multiple lesions, and mucinous adenocarcinoma. R0 resection was less common with CD-CRC (77.43%) vs sporadic CRC (90.99%; P<0.001). Five-year OS was worse with CD-CRC vs sporadic CRC (53.99% vs 71.17%, P<0.001). Evaluation by tumor location showed significantly worse 5-year OS and RFS with CD-RC compared with sporadic RC, whereas 5-year OS and RFS in CD-CC vs sporadic CC was comparable. A higher recurrence was found with CD-RC (39.57%) compared with sporadic RC (21.97%, P<0.001), but the recurrence rates did not differ between CD-CC and sporadic CC. The most frequent sites of recurrence in CD-RC were local. Following PS matching, 5-year RFS with CD-RC was significantly worse than with sporadic RC (52.41% vs 78.74%, P<0.001), but 5-year RFS did not differ between CD-CC and sporadic CC (81.07% vs 82.04%, P=0.900).

Conclusion

Poor prognosis with CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.
P479 Reliability and responsiveness of histologic disease activity indices in Crohn’s Disease
Authors: Solitano V , Schaeffer D F , Hogan M , Pai R K , Zou G , Pai R K , Vande Casteele N , Parker C E , Remillard J , Christensen B , Panaccione R , Sands B E , D’Haens G , Feagan B G , Ma C , Jairath V
Published: January 2023

Background

The operating properties of histologic indices are poorly characterized in Crohn’s disease (CD) and no validated index exists. We assessed the reliability and responsiveness of histologic indices/items, developed an exploratory index, and compared different methods of scoring.

Methods

Using baseline and week 12 histologic image sets from the EXTEND placebo-controlled trial, blinded central readers scored 4 histologic indices (the Global Histologic Activity Score [GHAS], Geboes Score [GS], Robarts Histopathology Index [RHI], and Nancy Index [NHI]) and 3 additional novel items identified by an expert panel (mucin depletion, basal plasmacytosis, and pyloric gland metaplasia in the ileum). Reliability and responsiveness were evaluated for a global score (4 colonic segments + ileum), colonic score (4 colonic segments) and ileal score (ileum only) using the intraclass correlation coefficient (ICC) and area under the receiver operating curve (AUC), respectively. Change was defined using treatment assignment and improvement in histologic disease activity as measured on a 100-mm visual analogue scale (VAS) in responsiveness testing. Exploratory indices were developed using backward stepwise linear regression analysis. Candidate independent variables were items with an ICC ≥0.4 and AUC ≥0.56. The VAS served as the dependent variable.

Results

Paired histologic images were analysed from 55 subjects. Inter-rater reliability was substantial to almost perfect (ICC=0.73-0.85) and responsiveness was small to large (treatment assignment AUC=0.50-0.65; VAS AUC=0.71-0.94). The GHAS, GS, RHI, and NHI reached the minimum threshold for reliability (ICC ≥0.4) and responsiveness (AUC ≥0.56) regardless of whether the global and colonic scores were calculated using the worst affected segment, average of the included segments, or sum of the included segments (Table 1-3). Five items were tested as candidate predictors. Three exploratory indices were developed, each consisting of 3 items: a global index (neutrophils in the lamina propria, neutrophils in the epithelium, and erosion/ulceration), colonic index (chronic inflammatory infiltrate, neutrophils in the lamina propria, and erosion/ulceration) and ileal index (chronic inflammatory infiltrate, neutrophils in the epithelium, and erosion/ulceration). The novel indices highly correlated with the GHAS, GS, RHI, and NHI, with correlation coefficients ≥0.80 (Table 4).

Conclusion

The 4 existing indices were similarly reliable and responsive in measuring CD histologic activity, regardless of the method for calculating global and colonic scores and could be used in clinical trials. Attempts at novel index development did not offer benefit over current histologic indices.
P491 Efficacy and safety of upadacitinib for the treatment of fistulas and fissures in patients with Crohn’s disease
Authors: Colombel J F , Irving P , Rieder F , Panaccione R , Schwartz D , Hayashi R , Zhu X , Lacerda A P , Dubcenco E , Marced E , Hecht P , Feng T , Berg S , Reinisch W
Published: January 2023

Background

Intestinal and perianal fistulas and fissures are associated with significant morbidity and decreased quality of life in patients with Crohn’s disease (CD). We evaluated rates of fistula and fissure improvements with upadacitinib (UPA), an oral selective Janus kinase inhibitor, in patients with CD who had fistulas or fissures at baseline in phase 3 induction and maintenance trials.

Methods

In the U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) phase 3 induction trials, patients with moderate-to-severe CD were randomized to UPA 45 mg once daily (QD) or placebo (PBO) for 12 weeks. Patients who achieved clinical response after 12 weeks of induction were eligible for U-ENDURE (NCT03345823) and rerandomized to UPA 30 mg QD, UPA 15 mg QD, or PBO for an additional 52 weeks of maintenance treatment. Fistula activity was assessed by presence of external openings and draining upon gentle compression. Presence of perianal fissures was also assessed. The proportion of patients with external closure of fistula openings, complete resolution of draining, and ≥ 50% reduction in draining was recorded at weeks 12 and 52. Endpoints were analyzed using non-responder imputation.

Results

Of 1021 enrolled patients, 143 patients had fistulas (124 [86.7%] perianal; 19 [13.3%] enterocutaneous) and 54 patients had perianal fissures at baseline. The proportion of patients who achieved external closure of fistula openings was higher with UPA vs PBO at week 12 (Fig 1A) and at week 52 (Fig 2A). The proportion of patients who achieved complete resolution of draining and ≥ 50% reduction in draining was higher with UPA vs PBO at week 12 (Fig 1B and 1C) and at week 52 (Fig 2B and 2C). A higher proportion of patients achieved complete resolution of fissures with UPA vs PBO at week 12 (Fig 1D) and at week 52 (Fig 2D). At weeks 12 and 52, a higher proportion of patients with fistulas treated with UPA vs PBO achieved clinical remission and endoscopic response (Fig 1E and 2E). Rates of adverse events (AEs), serious AEs, or AEs leading to study drug discontinuation were similar in UPA groups compared with PBO during the induction and maintenance periods. Rates of abscess formation were 1.8% with UPA 45 mg and 6.8% with PBO at week 12, and 3.0% with UPA 30 mg, 6.4% with UPA 15 mg, and 2.5% with PBO at week 52.

Conclusion

Among patients with CD complicated with fistulas and/or fissures at baseline, UPA treatment led to higher rates of external closure of fistula openings, resolution of draining, and healing of fissures, along with clinical remission and improvements in luminal disease compared with PBO. No new safety concerns were identified.
P531 A model-based tool for guiding infliximab induction dosing to maximise long-term deep remission in children with inflammatory bowel diseases
Authors: Kantasiripitak W , Wicha S G , Thomas D , Hoffman I , Ferrante M , Vermeire S , van Hoeve K , Dreesen E
Published: January 2023

Background

Adequate infliximab (IFX) concentrations during induction treatment are predictive for deep remission (corticosteroid-free clinical and endoscopic remission) at six months in children with Crohn’s disease (CD) and ulcerative colitis (UC).1 Under standard IFX induction dosing, children often have low IFX trough concentrations.2 Model-informed precision dosing (MIPD) is advocated as a promising IFX dosing strategy. We aimed to develop and validate an MIPD framework for guiding paediatric IFX induction treatment.

Methods

Data from 31 children (4-18 years, 15-76 kg, 20:11 CD:UC) receiving standard IFX induction dosing (5 mg/kg at week [w]0, w2, and w6) were repurposed.1 Eight paediatric population pharmacokinetic models were evaluated (six 2-compartment models and two 1-compartment models). Modelling and simulation were used to identify exposure targets, an optimal sampling strategy, and to develop a multi-model prediction algorithm for implementation into an MIPD software tool.3 A role for IFX clearance monitoring was evaluated.

Results

A total of 251 IFX concentrations were available (6-10 samples per patient). One patient had undetectable IFX concentrations at w6 and w12 but had no measurable antibodies to IFX (ATI). At six months after start of the IFX treatment, 58% (18/31) of patients achieved deep remission.

The measured IFX concentration at w12 was the best predictor and classifier for deep remission. A 7.5 mg/L IFX concentration target at w12 was associated with a 64% probability of deep remission at six months (Figure 1). With standard dosing, less than 80% of simulated children <40 kg attained this target (Figure 2). Immunomodulator combo-therapy only subtly improved probability of target attainment. Presence of ATI lowered the target attainment considerably.

The w12 target was most accurately and precisely achieved by implementing MIPD at w6 using the w6 IFX concentration. The multi-model algorithm outperformed single models when optimising the w6 dose based on combined w2 and w4 concentrations. MIPD using only the w2 concentration resulted in biased and imprecise predictions. The predictive performance of the MIPD multi-model algorithm was robust to misspecification of ATI status.

IFX clearances at w6 and w12 were predictive for deep remission (P=0.02) (Figure 3).

An IFX module was added to the TDMx software tool to facilitate MIPD and clearance monitoring (https://tdmx.shinyapps.io/Infliximab_paediatric/).

Conclusion

A freely available, interactive, multi-model MIPD software tool is provided to facilitate IFX induction dosing and improve deep remission rates in children with CD and UC.

1van Hoeve et al. J Pediatr 2022.

2van Rheenen et al. J Crohns Colitis 2020.

3Kantasiripitak et al. CPT:PSP 2022.
P570 Safety and Effectiveness of Tofacitinib in Ulcerative Colitis: Real-world Data from TOFA-UC, a SN-IBD Study
Authors: Macaluso F S , D'Antonio E , Fries W , Viola A , Ksissa O , Cappello M , Muscarella S , Belluardo N , Giangreco E , Mocciaro F , Di Mitri R , Ferracane C , Vitello A , Grova M , Renna S , Casà A , Ventimiglia M , Orlando A ,   Sicilian Network for Inflammatory Bowel Disease (SN-IBD)
Published: January 2023

Background

Real-world evidence is necessary to determine the safety and effectiveness of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC) in clinical practice.

Methods

TOFA-UC is a multicenter observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) on a prospectively maintained database. All consecutive patients with UC starting TOFA from its introduction in Sicily (June 2021) to June 2022 (12 months) were enrolled. The primary outcome was the assessment of safety, in terms of rate of adverse events (AEs). Secondary outcomes included the rates of clinical response, steroid-free clinical remission (based on partial Mayo score) and C-Reactive Protein (CRP) normalization after 8 weeks and at the end of follow-up, the rate of loss of response, and treatment persistence.

Results

111 patients were included (mean follow-up: 31.5 ± 15.2 weeks). Only 8 patients (7.2%) were naïve to biologics, while most had previous failures to one (27.0%), two (26.1%), three (32.4%), or four (7.2%) biologics. Nineteen adverse events were reported (17.1%; incidence rate: 28.6 per 100 patient-year), including 11 cases of hypercholesterolemia, 3 infections (no cases of herpes zoster reactivation), nausea in two patients, paresthesia in one case, one colorectal cancer and one pulmonary embolism. At week 8, the rates of clinical response, steroid free clinical remission, and CRP normalization were 74.8%, 45.0%, and 56.9%, respectively, and 68.5%, 51.4%, and 65.2%, respectively, at the end of follow-up. Eighteen patients experienced a loss of response after successful induction (21.7%; incidence rate: 33.2 per 100 patient-year). The dose was increased to 10 mg bid in 15 patients, and 7 of them recaptured the response. A total of 26 patients (23.4%) discontinued TOFA over time, of whom 3 due to AEs. At multiple model regression analysis, being former smoker (hazard ratio=4.03; 95% CI=1.36-10.25; p=0.015) was the only variable associated with higher risk of treatment discontinuation. No significant differences in all outcomes of effectiveness were detected when the subgroup of patients naïve to biologics or with only one previous line of biologic therapy was compared with those with at least two previous lines of biologics.

Conclusion

TOFA is safe and effective in patients with UC, including those with multiple previous failures to biological therapies.
P579 Real-world comparison of effectiveness between tofacitinib and ustekinumab in patients with ulcerative colitis exposed to at least one anti-TNF agent: results from the TORUS study
Authors: Buisson A , Serrero M , Altwegg R , Guilmoteau T , Bouguen G , Nachury M , Amiot A , Vuitton L , Treton X , Caillo L , Pereira B , Fumery M
Published: January 2023

Background

We aimed to compare the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent.

Methods

In this multicenter study, we retrospectively included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, having who started tofacitinib or ustekinumab between January 2019 and June 2022.

The primary endpoint was steroid-free clinical remission (pMS ≤ 2) (CFREM) at week 16 (W16).

Secondary endpoints were endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and histological remission (CFREM + MES ≤ 1 + Nancy index ≤ 1).

Comparisons were performed using propensity score analyses adjusted on potential confounders.

Results

Overall, 289 patients were included (tofacitinib = 124 patients, ustekinumab = 165 patients). The groups were comparable (tofacitinib vs vedolizumab) for male gender (50.8% vs 43.3%), mean age (40.7 vs 42.9 years), median UC duration (8.6 vs 9.3 years), concomitant use of 5-ASA (13.7% vs 9.7%), steroids (25.0% vs 29.7%), immunosuppressants (7.3% vs 5.5%), and ≥ 2 prior biologics (85.5% vs 82.4%). Tofacitinib group had more pancolitis (55.6% vs 42.4%, p = 0.026) and UC with pMS > 6 (64.5% vs 50.3%, p = 0.016). In our study, 42.1 % of the patients treated with tofacitinib continued using a dose of 10 mgx2/day until W16 while 47.3% of the patients on ustekinumab required dose escalation to 90 mg/4 weeks before W16.

After propensity score analysis, the rate of CFREM at W16 was 37.8% and 35.6% in the tofacitinib and ustekinumab arms, respectively arm (p=0.75). CFREM at W16 was achieved in 43.3% vs 57.1% (p = 0.48) after failure of one biologic, 20.7% vs 37.9% (p=0.16) two biologics and 46.7% vs 23.2% (p=0.047) or ≥ 3 biologics, in tofacitinib and vedolizumab arms, respectively. After primary failure to at least one biologic, the rate of CFREM at W16 was 46.3% on tofacitinib vs 25.9% on ustekinumab (p = 0.13). CFREM at W16 was similar with tofacitinib and ustekinumab in case of more severe UC such as pMS ≥ 6 (40.6% vs 41.5%) and CRP > 30 (27.2% vs 33.0%).

No predictor of tofacitinib effectiveness has been identified. Factors associated with no CFREM at W16 on ustekinumab were male gender (p=0.035), ≥ 3 prior biologics (p=0.013), prior use of tofacitinib (p=0.03), primary failure to at least one biologic (p=0.013).

Endoscopic remission was achieved in 17.0% vs 11.7% (p =0.47) and histological remission in 4.4% vs 7.8% (p=0.32) of the patients treated with tofacitinib and ustekinumab, respectively.

Conclusion

Tofacitinib and ustekinumab have similar effectiveness in UC after anti-TNF failure.

However, the efficacy of ustekinumab could be more impacted by prior therapeutic failures.
P589 Effectiveness of partial enteral nutrition to treat adults with Crohn's Disease who lost response to biological therapy
Authors: Nardone O M , Calabrese G , Alfonsi L , Rispo A , La Mantia A , Fierro G , Ferrante M , Testa A , Guarino A D , D'Alessandro E , Pasanisi F , Castiglione F
Published: January 2023

Background

Partial enteral nutrition (PEN) is a consolidated treatment in children with active Crohn’s disease (CD). However, the benefit of PEN is not well-established for adults with CD. Based on the assumption that diet could aid in treating active disease, we aimed to assess the effectiveness of PEN in combination with biological therapy on transmural response/remission and selected clinical outcomes in adults with CD who lost response to biologics

Methods

We performed a single-centre retrospective observational study by including patients who received PEN due to loss of response to biologics. The primary endpoint was the rate of transmural response/remission at 6 months. We defined transmural remission as a bowel wall thickness ≤3 mm, while transmural response as a decrease in BWT≥25%. Secondary endpoints included clinical remission, defined as Harvey Bradshaw Index<5, and selected clinical outcomes such as surgery, hospitalisations, and change of therapy, including switch and dose/interval escalation at 6 months. Patients were considered adherent when they completed PEN for 6-8 weeks as required for induction of remission, whereas not adherent when they stopped it or if they did not tolerate.

Results

A total of 42 patients,25 males (59,5%) with mean age of 36,1 ±15,6 yo and a mean duration of disease of 138,0 ±113,1 months were enrolled [Table 1].

Overall, 14 patients completed PEN at 8 weeks, with a rate of adherence of 33,3%. Whilst 16(38.1%) patients stopped the treatment for intolerance and maintained only biological therapy and 12(28.6%) underwent surgery before 6 months follow-up.At 6 months, patients treated with PEN in combination with biologic had a transmural response of 64,9% compared to 25% treated only with biologics (p=0.03). In both groups, no patients achieved transmural remission. Nevertheless, clinical remission was obtained in 9 (64,3%) patients treated with PEN + biologic compared to 4 (25%) with biologic (p=0.03). Overall,3 patients (18.7%) underwent surgery, all of them were intolerant to PEN. Patients who interrupted PEN and maintained biologics had a higher rate 56,2% of dose escalation/interval and 68,7% changed therapy at six months compared to 7,1% and 14,2% respectively treated with PEN+biologic (p<0.05) [Table 2].At multivariate analysis multiple treatment failures were associated with adherence to PEN (OR=1,583; CI=1,06-2,36; p<0.05).

Conclusion

For patients who lost response to biological therapy, the combination with PEN was associated with transmural response and clinical remission. Multiple failures to biologics were associated with adherence to PEN. Hence, the use of PEN dietary should be considered in difficult-to-treat patients
P612 Lack of seroconversion following COVID-19 vaccination, but not treatment, is an independent risk factor for breakthrough SARS-CoV-2 infection in patients with inflammatory bowel disease: data from ESCAPE - an IG-IBD Study
Authors: Macaluso F S , Principi M , Facciotti F , Contaldo A , Todeschini A , Bezzio C , Saibeni S , Castiglione F , Nardone O M , Spagnuolo R , Fantini M C , Riguccio G , Conforti F S , Caprioli F A , Viganò C , Felice C , Fiorino G , Correale C , Bodini G , Milla M , Scardino G , Vernero M , Desideri F , Bossa F , Guerra M , Ventimiglia M , Mannino M , Rizzo G , Orlando A ,   Italian Group for the study of Inflammatory Bowel Disease (IG-IBD)
Published: January 2023

Background

As patients with immune conditions were excluded from COVID-19 vaccine clinical trials, it is important to accumulate real-world data in this setting, particularly to identify those who would benefit from repeated doses.

Methods

Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE) is a prospective, multicentre, observational study assessing effectiveness and safety of COVID-19 vaccines in patients with IBD (ClinicalTrials.gov ID: NCT04769258). Here we present data on the rate of breakthrough SARS-CoV-2 infections in the timeframe between 14 days after the second dose and the third dose of COVID-19 vaccine (or a maximum of 9 months from the second dose). The risk factors for SARS-CoV-2 infection, including lack of seroconversion (cut-off for IgG anti-SARS-CoV-2: OD 0.28) and IgG anti-SARS-CoV-2 levels after 8 weeks from the second dose, and treatment for IBD, were assessed.

Results

Out of the 1076 patients with IBD enrolled in the ESCAPE study, data on breakthrough SARS-CoV-2 infection were available in 953 cases. Most of the patients received homologous, double-dose mRNA-based vaccines (BNT162b2 or mRNA-1273: 99.2%). Seroconversion was reported in 92.7% of cases (median OD 1.60 [IQR 0.8-3.6]), while SARS-CoV-2 infection was documented in 95 patients (10.0%), of whom 9 died. At multivariable regression analyses, age (OR 0.97, 95% CI 0.96-0.99; p<0.001) being former smoker (OR 2.23, 95% CI 1.26-3.88; p=0.005), and lack of seroconversion (OR 0.42, 95% CI 0.20-0.99; p=0.034) were independent predictors of SARS-CoV-2 infection. Conversely, none of the treatments for IBD was associated with breakthrough SARS-CoV-2 infection. Notably, all 9 patients who died had reported seroconversion after the second dose.

Conclusion

IBD patients without seroconversion after COVID-19 vaccines are at increased risk for SARS-CoV-2 infection, while medications for IBD had no impac
P667 USTEkinumAb Double intravenous loading induction therapY at week 0,4 in patients with Crohn’s Disease– results from STEADY study
Authors: Chin A , Jeffrey A , Teh W L , Menon S , So K , Venugopal K , Picardo S
Published: January 2023

Background

Ustekinumab (UST) is a safe and effective therapy for moderate to severe Crohn’s disease (CD). Standard induction therapy involves a single weight-based intravenous dose followed by a subcutaneous dose at week eight. Accelerated or dose intensified induction regimens have been associated with better clinical outcomes for various biologic therapies, however, these have not been investigated in patients commencing UST. UST re-induction has been shown to be effective in recovering response in patients who have previously lost clinical response. We aim to compare clinical outcomes in a group of CD patients who received standard intravenous induction (SII) of UST compared to double intravenous induction (DII).

Methods

A retrospective observational cohort study of all patients that commenced UST, aged ≥ 18 from a single tertiary inflammatory bowel disease (IBD) centre. Patients received either standard IV dosing or double IV dosing (IV dose at week 0 and 4) based on the discretion of the treating physician. Data was collected from a prospectively maintained database between the period October 2015 to October 2022. The primary outcome was clinical remission, defined as Harvey Bradshaw Index (HBI) <5 with scores collected at baseline and at week 52. Patients that discontinued therapy due to a lack or loss of response or progressed to require surgery were considered treatment failures. Two sample t-test was used for comparisons between groups for continuous variable and chi-square for categorical variables.

Results

47 patients were included of which 38 received SII and 9 had DII. There were no significant differences in baseline HBI or previous biologic exposures between groups (Table 1). All 9 patients that received DII were in clinical remission at week 52 compared to 29 out of the 38 that received SII, however, this was not clinically significant (Figure 1; 100% vs 76%, p=0.10). Of the 9 patients, not in clinical remission in the SII group, 5 were due to treatment failures (3 required surgery, 2 switched medical therapy) with the other 4 remaining on UST till week 52 (1 had a clinical response and 3 had no clinical response). There were no safety concerns (serious infections or malignancy) reported in the DII group.

Conclusion

● All Crohn’s patients that commenced double intravenous induction were in clinical remission at week 52.

● A higher proportion of patients that received DII vs SII were in clinical remission at week 52, however this was not statistically significant. Further larger studies and studies with longer duration of follow-up are required to determine a clinical difference.

● Double intravenous induction of UST is a safe and effective option for Crohn’s disease.