bluuebunny/crossref_metadata_2025 huggingface dataset:
P439 Induction of endoscopic response, remission and ulcer-free endoscopy with upadacitinib is associated with improved quality of life in patients with Crohn’s disease
Authors: Panés J , Louis E , Bossuyt P , Joshi N , Lee W J , Lacerda A , Remple V , Xuan S , Loftus Jr. E V
Published: January 2023

Background

Patients with Crohn’s disease (CD) experience reduced quality of life (QoL), and disease-related impact on work productivity, contributing to a high disease burden. This study evaluated the association of achieving endoscopic outcomes at week 12 and associated QoL at week 52 in patients with CD treated with upadacitinib (UPA).

Methods

This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and one maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Meaningful improvement in QoL outcomes (Inflammatory Bowel Disease Questionnaire [IBDQ] remission ≥170, IBDQ response increase ≥16, Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F] response increase ≥9, Short Form 36 [SF-36] Physical Component Score [PCS] and Mental Component Score [MCS] change ≥5, and Work Productivity and Activity Impairment Questionnaire [WPAI] change ≥7%) was evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test.

Results

Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.2%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained a meaningful improvement in PROs by week 52 (IBDQ remission, 52.6% vs 30.3%; IBDQ response, 56.6% vs 36.8%; FACIT-F response, 46.7% vs 25.9%; SF-36 PCS 49.3% vs 30.8% and MCS 39.5% vs 25.9%; all P≤0.01, Table 1). Additionally, patients who achieved endoscopic response (vs those who did not) at the end of induction were more likely to attain meaningful improvement in WPAI overall work impairment by week 52 (47.1% vs 26.5%, P≤0.01, Table 1). Similar findings were observed in patients who achieved endoscopic remission (P≤0.01, Table 1) and ulcer-free endoscopy (P≤0.05, Table 1) vs those who did not at end of induction.

Conclusion

Achieving endoscopic outcomes at end of induction treatment was associated with meaningful improvement in quality of life and overall work productivity at 52 weeks for patients with CD receiving UPA. Endoscopic remission and ulcer-free endoscopy were associated with very similar long-term benefit.
P441 Long-term CD treatment failure and dose modification rates with vedolizumab and other biologics: Results from a large prospective observational study
Authors: Siegmund B , Siegel C A , Sebastian S , Zhou J , Jones S , Adsul S , Louis E
Published: January 2023

Background

Durable treatment effectiveness is an important consideration in the long-term management of patients with Crohn’s disease (CD) receiving biologic therapy. The aim of this analysis was to evaluate rates of failure and dose modification for biologic treatment over time in patients with CD using data from a large long-term observational study evaluating secondary outcomes in patients initiating treatment on vedolizumab (VDZ) and other biologics.

Methods

We analysed data from a multicentre, prospective, observational, post-authorisation safety study (PASS; NCT02674308, EUPAS6469) following VDZ or other biologic treatment cohorts under routine standard of care. Longitudinal data on treatment failure (including biologic discontinuation†, IBD non-surgical hospitalization, primary IBD surgery and corticosteroid initiation) up to 36 months and dose modification at any time during the study were analysed in biologic-naïve and biologic-experienced patients with CD in the treatment cohorts.

Results

The cohort comprised 1338 biologic-naïve patients (pts) (VDZ, n=312; other biologics, n=1026) and 1543 biologic-experienced pts (VDZ, n=829; other biologics, n=714). Baseline pt characteristics (Table 1) were broadly similar across different treatment cohorts, although there were some notable differences with respect to fistulising disease and age at CD diagnosis.

Treatment failure rates for biologic-naïve and biologic-experienced pts cumulatively over time at specific time points are shown in Table 2. The proportion of pts continuing biologic treatment with dose modification at any time during the study period for biologic-naïve pts was 13/312 (4.2%) in VDZ-treated pts vs 502/1026 (48.9%) in the group treated with other biologics and 34/829 (4.1%) vs 433/714 (60.6%), respectively for biologic-experienced pts.

Conclusion

This large observational study reported rates of treatment failure, hospitalization, and IBD-related surgeries during long-term follow-up of biologic-naïve and biologic-experienced pts with CD. Dose modification occurred less frequently in biologic-naïve and biologic-experienced pts treated with VDZ compared with pts receiving other biologic treatments during the study.
P442 Endoscopic resection of visible precancerous lesions in patients with colonic Inflammatory Bowel Disease
Authors: Busacca A , De Sire R , Capogreco A , Dal Buono A , Gabbiadini R , Loy L , Finati E , Spadaccini M , Maselli R , Hassan C , Repici A , Armuzzi A
Published: January 2023

Background

IBD patients have an increased risk of reporting a colorectal cancer. According to SCENIC, endoscopic resection (ER) should be preferred to biopsies for visible precancerous lesions in absence of stigmata of invasive cancer or submucosal fibrosis. However, the evidence is still lacking on specific outcomes of ER for the management of dysplastic lesions in IBD. Aim of this study was to evaluate the effectiveness and safety of ER of visible precancerous lesions in IBD patients.

Methods

In this retrospective study, we included consecutive IBD patients referred to an Endoscopy Unit (2016-2022) to undergo a ER, including endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and hybrid EMR-ESD (hESD), of visible precancerous lesions. The primary outcome was the assessment of rates of en bloc resection, R0 resection and adverse events (AEs). The secondary outcome was the rate of post-ER surgery and surgery for refractory IBD. En bloc resection was defined as excision of the targeted lesion in a single specimen. R0 resection was defined as resection with lateral and deep margins free of dysplasia/neoplasia on histopathology. Among AEs, we considered bleeding and perforation.

Results

A total of 67 visible lesions (64.18% non-polypoid, 53.73% left-side colon, median size 25 mm±20 mm, 65.67% neoplastic pit-pattern) in 67 patients with colonic IBD (56.72% male, median age 58 yrs±15 yrs, 68.66% ulcerative colitis, median disease duration 160 months±98 months, 58.21% active disease) were included. ESD, hESD, and EMR was performed in 20.9%, 6%, and 73.1% of cases. The final histopathological diagnoses after ER were inflammatory polyp in 32.84%, SSL in 8.96%, LGD in 40.30%, HGD in 13.42%, adenocarcinoma in 2.99%, and squamous cell carcinoma in 1.49% of cases. Excluding inflammatory polyps, en bloc resection was achieved in 14/14(100%), 3/4(75%), and 15/27(55%) lesions in case of ESD, hESD, and EMR (ESD+hESD vs EMR p<0.05). R0 resection was achieved in 12/14(86%), 3/4(75%), and 15/27(55%) lesions in case of ESD, hESD, and EMR (ESD+hESD vs EMR p=0.05). AEs occurred in 21% (2 bleedings and 1 perforation), 0%, and 3% (1 perforation) of patients treated by ESD, hESD and EMR (ESD+hESD vs EMR p=N.S.). Post-ER surgery rate was 21%, 25%, and 3% for patients treated by ESD, hESD, and EMR. Surgery for refractory IBD rate was 7%, 0%, and 18% for patients treated by ESD, hESD, and EMR.

Conclusion

Our findings showed that ER (including ESD, hESD, and EMR) of visible precancerous lesions performed in a tertiary center might be considered feasible, safe and effective in IBD patients, despite the presence of submucosal fibrosis. These data should be confirmed in a wider IBD population referring from different specialized Endoscopy Units.
P452 Fecal Microbiota Transplantation Leads to Lower IBD Related Complications in Hospitalized Inflammatory Bowel Disease Patients with Clostridioides difficile Infection: A retrospective cohort study
Authors: Le P H , Chiu C H , Chiu C T , Kuo C J , Yeh P J , Chen C C , Pan Y B
Published: January 2023

Background

Clostridioides difficile (C. difficile) infection (CDI) increases the risks of hospitalization, colectomy, and mortality in inflammatory bowel disease (IBD). There has been no study comprehensively evaluating the risk factors, clinical characteristics, and outcomes of CDI in IBD.

Methods

In this retrospective cohort study, we enrolled hospitalized IBD patients with toxin A/B results for C. difficile in a medical center between April 2007 and April 2021. They were divided into CDI group and control groups. The risk factors, clinical presentations and outcomes were analyzed.

Results

A total of 144 IBD inpatients (45 CDI group and 99 control group) were enrolled for analysis. The median follow-up duration was 15.5 months. The incidence of CDI in IBD inpatients was 31%. The risk factors of CDI included longer IBD duration, biological failure, and biological user. More patients presented as abdominal pain in CDI group (77.8% vs 55.6%, P=0.011). After antibiotics treatment and fecal microbiota transplantation, 83.3% patients had negative result, and 61.9% had improved clinical symptoms. Regarding clinical outcomes, CDI led to more hospitalizations (median 2 times (range 0-12 times) vs median 1 time (range 0-19 times), P=0.008), lower steroid free remission rate (46.7% vs 67.7%, P=0.017) and higher Mayo score (median 5 points (range 2-12 points) vs median 3 points (range 0-12 points)). Compared to antibiotics treatment, the patients receiving fecal microbiota transplantation (FMT) had less times of hospitalization and less IBD related complications during follow-up.

Conclusion

CDI led to more hospitalizations, lower steroid free remission rate and higher Mayo score in IBD inpatients. FMT should be considered in refractory or recurrent CDI in IBD to improve the clinical outcomes.
P465 Health-related quality of life from the Inflammatory Bowel Disease Questionnaire in patients with ulcerative colitis treated with etrasimod in the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials
Authors: Armuzzi A , Rubin D T , Schreiber S , Panés J , Fellmann M , Bartolome L , Goetsch M , Bhattacharjee A , Wu J , Chaparro M , Dubinsky M C
Published: January 2023

Background

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5) in development for the treatment of moderately to severely active ulcerative colitis (UC). ELEVATE UC 52 and ELEVATE UC 12 were two phase 3 studies that demonstrated efficacy and safety of etrasimod in patients with UC in which several patient-reported outcomes were collected. Health-related quality of life (HRQoL) was assessed in a post hoc analysis of the ELEVATE programme with the validated Inflammatory Bowel Disease Questionnaire (IBDQ).1

Methods

In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). Patients in the full analysis set with modified Mayo Scores 5-9 with a completed 32-item IBDQ questionnaire at baseline, week 12 (both trials) and week 52 (ELEVATE UC 52 only) were included in this analysis. Least squares mean (LSM) change from baseline for IBDQ total score and IBDQ domain scores were compared between etrasimod and PBO arms in both trials at each time point (data as observed), along with the proportion of patients who achieved IBDQ remission (IBDQ total score ≥170; nonresponder imputation).

Results

At baseline, a total of 237 and 191 etrasimod-treated patients and 112 and 96 PBO-treated patients completed the IBDQ for ELEVATE UC 52 and ELEVATE UC 12, respectively. LSM change from baseline in IBDQ total scores for etrasimod vs PBO were 42.8 vs 27.4 (difference [95% CI] 15.4 [6.5, 24.4]; P<0.001) and 55.8 vs 38.1 (difference [95% CI] 17.7 [6.6, 28.6]; P=0.002) at week 12 and week 52, respectively, in ELEVATE UC 52, and 47.5 vs 30.2 (difference [95% CI] 17.3 [8.5, 26.2]; P<0.001) at week 12 in ELEVATE UC 12 (Figure 1A). A greater proportion of etrasimod-treated patients achieved IBDQ remission at week 12 in both trials and week 52 in ELEVATE UC 52 (Figure 1B). Etrasimod-treated patients demonstrated significant improvements from baseline vs PBO in all 4 IBDQ domains in both trials (Figure 2). Across all IBDQ domains, improvements were seen at 12 weeks and the LSM change from baseline was greatest among etrasimod-treated patients at all time points.

Conclusion

Patients treated with etrasimod demonstrated greater improvement from baseline in total and all 4 domain scores of the IBDQ at the end of the 12-week induction phase and 52-week maintenance phase in comparison with PBO. These findings demonstrate the benefits of etrasimod on disease-specific HRQoL and support the clinical findings from the ELEVATE programme.

Reference:

1. Chen XL, et al. Health Qual Life Outcomes. 2017;15:1-13.
P469 Effect of mirikizumab on clinical and endoscopic outcomes based on prior advanced therapy failure in patients with moderately to severely active ulcerative colitis
Authors: Navabi S , D’Haens G , Samaan K H , Li X , Arora V , Redondo I , Danese S
Published: January 2023

Background

In Phase 3 induction (LUCENT-1) and maintenance (LUCENT-2) studies, mirikizumab (miri), was well-tolerated and efficacious in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response, loss of response or intolerance to conventional or advanced therapy. This analysis evaluated clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy based on number and types of prior targeted immune modulator (TIMs) failures, where TIMs include biologics (anti-TNFs, vedolizumab (VDZ)) and tofacitinib.

Methods

Patients were randomized at induction baseline to receive 3 intravenous doses of 300mg miri or PBO every 4 weeks (Q4W). Responders to miri induction at Week 12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W40 (52 weeks of continuous therapy). Endpoints evaluated were clinical remission, clinical response, symptomatic remission, and endoscopic remission at Week 12 of LUCENT-1, and clinical remission, corticosteroid (CS)-free remission, endoscopic remission, and histologic-endoscopic mucosal remission (HEMR) at Week 40 of LUCENT-2. Efficacy in the subgroup of patients who failed 0, 1, ≥2 prior TIMs, anti-TNFs, VDZ, or both anti-TNF and either VDZ or tofacitinib (anti-TNF+1) were assessed. There were not enough patients with prior tofacitinib failure alone for statistical significance analysis.

Results

At LUCENT-1 baseline, 58.8%, 21.1%, and 20.2% of patients failed 0, 1, and ≥ 2 prior TIMs, respectively. 36.3% failed anti-TNFs, 18.8% failed vedolizumab (VDZ), and 15.2% failed an anti-TNF +1 other TIM. At Week 12 of LUCENT-1 and Week 40 of LUCENT-2, a greater proportion of miri-treated patients achieved efficacy endpoints compared with placebo for all subgroups (Table 1). The treatment differences [95% CI] were significant for all subgroup analyses except for some subgroups from two endpoints: clinical remission at Week 12 of induction and HEMR at week 40 of maintenance (Figure 1). Three subgroups in the Week 12 clinical remission analysis did not achieve significant treatment differences: 1 prior TIM failure (6.5% [-2.9%, 15.8%]), ≥2 prior TIM failures (7.6% [-0.3%, 15.5%]), and anti-TNF failure (6.4% [-0.6%, 13.4%]). For the HEMR endpoint all subgroups achieved significant treatment differences except for the 1 prior TIM failure subgroup (15.3% [-1%, 31.6%]).

Conclusion

Regardless of the number and types of failed prior advanced therapies, mirikizumab is efficacious for both induction and maintenance therapy in patients with moderately to severely active UC.
P470 Evolution of asymptomatic unresected lesions in patients operated for multifocal Crohn’s disease.
Authors: Abdalla S , Lelievre O , Carbonnel F , Penna C , Benoist S , Brouquet A
Published: January 2023

Background

Surgery for Crohn’s disease (CD) aims to treat symptomatic lesions. In multifocal CD, when surgery is required for a specific symptomatic location, should asymptomatic lesions be resected during the same procedure?

Methods

In this retrospective cohort study, all consecutive patients undergoing bowel resection from 2012 to 2021 for multifocal CD and for which CD lesions were not resected (anoperineal disease excluded) were included. Primary endpoint was recurrence on the unresected CD lesions requiring medical treatment intensification or surgery. Univariate analysis of the risk factors for recurrence on the unresected lesions was carried out.

Results

Among 318 patients operated for CD, 28 (9%) were included. Median CD evolution duration was 9.5 years. Twenty-five patients (89%) had at least one medical treatment line and 7 (25%) had previous bowel resection for CD. Indication for surgery was complicated CD (stricture, internal fistula) in 24 patients (86%) and CD refractory to medical treatment in 4 patients (14%). Surgery consisted in small bowel resection in 3 patients (11%), ileocolic resection in 13 (46%) and colectomy in 12 (43%). The unresected lesions were located in the small bowel in 7 patients (25%), colon and/or rectum in 12 (43%) and both in the small bowel and colon in 9 patients (32%). At 6 months, clinical improvement was obtained in 18 patients (64%). After un median follow-up of 58.5 months, 13 patients (46%) required treatment step-up, among which 6 (31%) required surgery targeting symptomatic unresected CD lesions refractory to medical treatment. Median progression-free duration was 43.5 months. Risk factors for recurrence on the unresected lesions were associated anoperineal CD (n=8/10, 80% vs n=5/18, 27.8%, p=0.016) and number of preoperative treatment lines≥3 (n=7/8, 87.5% vs n=6/20, 30%, p=0.011).

Conclusion

In complicated or refractory multifocal CD, surgery targeting most severe lesions allows clinical improvement in 65% of patients at 6 months. Although nearly half of the patients require medical treatment adaptations for the unresected lesions, only 21% require surgery for these lesions. This strategy combining targeted surgery and medical treatment could be more widely suggested in multifocal CD.
P472 Cyclosporine versus infliximab in patients with Acute Severe Ulcerative Colitis: A single-centre retrospective study
Authors: Karpavičiūtė V , Kiudelis G , Kupčinskas J , Kupčinskas L
Published: January 2023

Background

In steroid refractory acute severe ulcerative colitis (ASUC), cyclosporine or infliximab are potential rescue treatments to avoid colectomy. Our objective is to assess the short-term and long-term efficacy and safety of cyclosporine versus infliximab as rescue agents.

Methods

We performed a retrospective analysis of 121 patients admitted with ASUC to a single gastroenterology centre during 2010-2020. ASUC was defined by the Truelove & Witts criteria. Primary outcome was short-term colectomy-free rate, secondary outcomes were severe adverse events, re-hospitalization or need of treatment with steroids within 2 years due to flare ups and colectomy rate at 2-year follow-up.

Results

119 patients initially received intravenous corticosteroids, while 2 patients underwent emergency colectomy on the first day. Sixty-four (53%) were females, median age of all patients was 33 (IQR 27-49) years. 66 (55%) patients responded to intravenous corticosteroids (IVS), while 53 (45%) failed to respond to steroid therapy: 45 (37%) patients received second-line rescue therapy (29 with cyclosporine, 16 with infliximab). Evaluating the short-term efficacy of treatment there was no significant difference between cyclosporine and infliximab: during admission colectomy was performed in 10.3% vs. 12.5% of patients, respectively (p=0.826). In terms of long-term outcomes, the colectomy rate was higher in the infliximab group at 2-year follow-up, although the difference did not reach statistical significance (10.3% vs. 31.2%, p=0.079). The need for oral steroids during follow-up was comparable in both groups (38,5% vs. 50%, p=0.481). Comparing patients who did not undergo colectomy, patients in the infliximab group were more often re-hospitalized due to the need for IVS at 2-year follow-up (7.7% vs. 50%, p=0.002). No severe side effects due to infliximab and cyclosporine were observed.

Conclusion

In the treatment of steroid refractory ASUC infliximab and cyclosporine were equally effective in short-term period and there was no difference in safety, however cyclosporine treated patients trended to have better long-term outcomes, with significantly rarer re-hospitalization. Additional analysis is needed for other factors that may have contributed to differences in long-term outcomes between the cyclosporine and infliximab groups.
P475 Infections and malignancies during anti-TNF therapy in IBD patients affect all age groups – results from a 13-yr real-world retrospective study
Authors: Majumder S , Melanie L , Joanne D , Naveen S , Quraishi M N , Cooney R , Ghosh S , Iacucci M , N Shivaji U
Published: January 2023

Background

Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. We aimed to report on AEs with a focus on risk of infections and malignancies in this large cohort.

Methods

All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary referral centre between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. The data were analysed and statistical analysis carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0.

Results

Total of 844 patients (M=408, 48%; median age 37years) were included, of which 61% were Caucasian. Majority had CD (608;72%) with mean age at diagnosis of 27y (SD 15y) and a median disease duration of 12years. About 50% of patients were on monotherapy and adalimumab was most frequently used (52%).There were 392 cumulative AEs recorded in this cohort with 78 infections (20% of all AEs). Among these, majority were bacterial infections, followed by Clostridium difficile. Tuberculosis(TB) was diagnosed in 5 patients. Infections were distributed evenly across all age groups with no significant difference between monotherapy or combination therapy. Majority of infections responded to anti-microbials and patients were able to resume anti-TNFs without major complications. One death recorded due to viral hepatitis. Detailed breakdown is given in Table 1. Malignancies were recorded in 16 (2%) patients and 6 were on combination therapy. Skin cancers were most common and there were no lymphomas noted. The details of malignancy are given in Table 1.

Conclusion

In this large cohort, infections were one of the commonest AEs recorded during exposure to anti-TNF therapy.Bacterial infections were most frequent across all age groups requiring pause of anti-TNF in most cases and withdrawal in very few. Opportunistic infections were few and reported TB cases was as low as 0.5% of total cohort. Skin cancer was the most common malignancy and no lymphomas were reported in this cohort. Clinicians need to be aware of these risks in younger patients as anti-TNFs result in infections and malignancies across all age groups and not particularly limited to the elderly.
P477 Patient satisfaction and cost saving analysis of telemedicine in patients with inflammatory bowel disease.
Authors: Bossa F , Carparelli S , Guerra M , Cocomazzi F , Martino G , Annese M , Nardella M , Bellucci N , Gagliardi R , Terracciano F , Pacilli L , Perri F
Published: January 2023

Background

Crohn’s disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Telemedicine (TM) is particularly useful in patients with chronic diseases who need frequent monitoring to achieve therapeutic outcomes and improve their quality of life. We examined the differences in patient satisfaction comparing telemedicine versus traditional in-person visits. We also examined the potential cost savings benefits of utilizing telemedicine.

Methods

All consecutive patients with IBD in clinical remission evaluated by Partial Mayo Score (PMS) for UC and Harvey Bradshaw Index (HBI) for CD were considered eligible (PMS<2 or HBI<5). Patients were randomized into two arms: telemedicine or in-person visits after a questionnaire investigating the Information and communication technology (ICT) skills . All patients were asked to respond to an 11-items survey investigating their trust in telemedicine at first in-person visit. Enrolled patients performed after 3 months a telehealth or an in-person visit. All patients answered a standard questionnaire to evaluate the indirect costs of managing their disease. Patients randomized into telemedicine arm answered a specific 28-item survey investigating their degree of satisfaction.

Results

We enrolled 30 patients with IBD randomized to telemedicine (n. 22; 11 CD; 13 female; mean age 45 years) or in-person visits (n. 8; 5 CD; 3 female; mean age 52 years). All patients randomized in TM (100 %) showed interest in this new clinical practice and were satisfied of the received information about telemedicine management. No patients thought that telemedicine would have no positive effects on their health status. Regarding demographic data, 6 out of 22 patients randomized to TM (27.2%) lived in a different province than our hospital’s and16 patients (72.7%) had high school diploma or degree. All TM patients (100%) were satisfied of the televisit and considered clear the information received during conversation with physician. From a technical point of view, only one patient had problems of connection and three patients needed the support of a caregiver. Eighteen patients (81.8 %) thought that the efficacy of the televisit was equivalent to the in-person visit. Nineteen patients (86.3 %) were convinced that televisit is a tool to be promoted for future clinical practice. Patients randomized to telemedicine had an average saving of 125 €. Data shown are illustrated in the figure 1.

Conclusion

In patients with IBD in remission, telemedicine is feasible and effective in the majority of patients. In addition, TM has allowed a significant cost savings without reducing the quality of the health assistance.
P481 Visceral fat to skeletal muscle area ratio predicts for Ustekinumab loss of response.
Authors: Tan Z , Chin A , Welman C J , Thin L W Y
Published: January 2023

Background

Loss of response (LOR) to anti-TNFα therapy in inflammatory bowel disease (IBD) is common and biologic therapies such as anti-IL12/23 agents have shown greater durability in efficacy. Anti-TNFα LOR is increased in higher body mass index (BMI) patients however the evidence for the association between body composition or BMI and Ustekinumab’s (Ust) therapeutic response is limited, with the latter not impacting clinical efficacy in the ‘IM-MUNITI’ post-hoc analyses. This study’s primary aim was to evaluate the impact of body composition on time to LOR to Ustekinumab in Crohn’s disease (CD) patients.

Methods

99 adult CD patients aged ≥16 yrs. from two tertiary IBD centres were studied retrospectively. Included patients had received Ust ≥12 weeks, abdominal imaging (CT or MRI) within 6 months of Ust induction, and documented follow up until 30th April 2022. A single experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat (VFA), skeletal muscle (SMA), and subcutaneous fat at the mid L3 vertebral level. Each compartment was corrected for height2 to derive visceral fat (VFI), skeletal muscle (SMI) and subcutaneous fat (SFI) indices. VFA:SMA ratio was also calculated. Clinico-demographic details including therapeutic and surgical history were recorded. Kaplan Meir survival analyses, univariate and multivariate cox regression analyses were performed to evaluate factors predictive of Ust LOR.

Results

99 patients met the inclusion criteria with mean age (±SE) 46.6yrs (±1.6) and 49 (49.5%) male. 63 (63.6%) patients were bio-experienced. Univariate Cox regression analyses of age, sex, BMI, peak C-reactive protein (CRP) and nadir Albumin level within 3 months of the CT/MRI scan, disease duration, prior biologic failure and concurrent immunomodulator used within 6 months of Ust induction showed that none of these were predictive of Ust LOR (P>0.05). There was a numerical trend for the middle VFI tertile (40.01-79.99cm2/m2) to having a lower risk for LOR compared to the lowest and highest VFI tertile (Fig. 1a), (HR=0.37, 95%CI= 0.13, 1.11, P=0.08), as well as a higher SMI for having a lower risk of LOR (Fig. 1b), (HR= 0.6, 95%CI= 0.24,1.31, P= 0.18), but these were not statistically significant. A higher VFA: SMA ratio however, was a significant predictor of LOR (HR=2.98, 95%CI 1.2,7.3, P= 0.02) (Fig. 1c), which persisted when it was adjusted on multivariate analysis for age, sex, albumin, CRP, BMI, disease duration, prior biologic failure and concurrent immunomodulator use (HR= 10.6, 95%CI 2.8-39.8, P=<0.0001).

Conclusion

The ratio of VFA:SMA, but not BMI, is a superior predictor of losing response to Ustekinumab.
P486 Improving enhanced recovery after surgery (ERAS): the effect of a patient-centred mobile application on patient participation in colorectal surgery
Authors: Van Der Storm S L , Jansen M , Marsman H A , Molly G P , Consten E C , Groot L M , Boer F C , Corver M , Oosterling S J , Tuynman J B , Bemelman W A , Buskens C J , Schijven M P
Published: January 2023

Background

Perioperative care in colorectal surgery is systematically established in the Enhanced Recovery After Surgery (ERAS) protocol. The ERAS protocol improved perioperative colorectal care in a multidisciplinary and multimodal manner, simulating early and safe hospital discharge. In general, compliance with the ERAS protocol is adequate; however, there is still room for improvement in compliance by actively involving patients in their recovery. The main objective of this study was to investigate whether compliance with selected items in the ERAS protocol could be improved by actively involving patients in the ERAS colorectal care pathway using a patient-centred mobile application.

Methods

This multicentre, randomised controlled trial was conducted in accordance with the CONSORT statement. Patients aged 18 years or older who underwent elective colorectal surgery and had a smartphone were included. Patients in the intervention group used a mobile application combined with an activity tracker to be guided and simulated through the ERAS pathway. Patients in the control group received standard care and wore an activity tracker to monitor their daily activities. The primary outcome was overall compliance with the selected active elements of the ERAS protocol. Secondary outcomes included length of hospital stay, number of complications, reintervention, and readmission rates, and patient-reported outcome measures (PROMs) such as quality of life, and patient satisfaction with received care.

Results

Between October 2019 and September 2022, 170 participants were enrolled and randomised to either the intervention (n=84) or control (n=86) groups. Thirty participants (17.6%) were lost to follow-up and 140 participants were included in the primary outcome analysis. Compliance with the selected active ERAS elements was 76.8% and 63.7% in the intervention and control groups, respectively (p<0.001). Complications or patient reported outcomes did not differ between the groups.

Conclusion

A patient-centred mobile application improved compliance with the active elements of the ERAS protocol. The implementation of this mobile application is recommended for patients undergoing elective colorectal surgery.
P489 Surgery for enterocutaneous fistula: the strongest predictor of postoperative mortality in Crohn’s disease patients
Authors: Iesalnieks I , Adamou A , Bercher M
Published: January 2023

Background

To access the risk of bowel resection in Crohn’s disease patients with enterocutaneous fistulae.

Methods

Consecutive patients undergoing intestinal resections for Crohn’ disease between 1992 and 2021 were included in the present prospective observational study. Exclusion criteria were: a) abdominoperineal resections for perianal disease, b) surgery for colorectal cancer complicating Crohn’s disease, c) abdominal surgery without intestinal resection (e.g. stoma formation or closure, mere adhesiolysis etc. Enterocutaneous fistulae occurring after previous bowel resection were named “postresection fistulae”, all other – “non-postresection fistulae”.

Results

750 patients were included. At all, 70 patients (9%) underwent intestinal resections due to enterocutaneous fistulae. The frequency of surgery for enterocutaneous fistula decreased significantly during the last decade of the study (1992-2000: 13% of surgeries, 2001-2010: 12% of surgeries, 2011-2021: 6% of surgeries; p=0.05). The postoperative intraabdominal septic complication rate was 15% (n=111), six patients (0.8%) died. The mortality rate was 7% (5 of 79%) in patients with enterocutaneous fistulae. All latter death occurred only in patients with postresection fistulae. By multivariate analysis, surgery for enterocutaneous fistula (Hazard ratio 27.4, 95% CI: 2.9 – 255.6; p=0.004), age of 50 years and older (Hazard ratio 13.2; 95% CI: 2.0 – 87.7; p=0.008) and presence of intraabdominal abscess (Hazard ratio 11.8; 95% CI: 1.2 – 116.5; p=0.035) were associated with an increased risk of postoperative death. Age over 50 years was associated with an increased risk of death in patients with enterocutaneous fistulae (mortality rate 20% vs. 3.6%, Hazard ratio 16.61; 95% CI: 1.28 – 216.07; p=0.032).

Conclusion

Surgery for enteroctunaeous fistulae still poses significant risks, specially, when they occurred after bowel resection and in older patients.
P494 Impact of early optimization of ustekinumab on mid-term targets in severe Crohn’s disease: THE MUST study
Authors: Abdelmoula A , Chateau T , Hupe M , Boschetti G , Roblin X , Nancey S , Mathieu N
Published: January 2023

Background

As a substantial proportion of patients with Crohn’s disease (CD) experiences a refractory disease course, immediate drug intensification may be an option to optimize the effectiveness of current biotherapies. Aim : to compare the one-year efficacy of immediate dose escalation of ustekinumab 90 mg to 4-weekly with that of 8-weekly dosing after intravenous (iv) induction in severe active CD patients.

Methods

The MUST (meta-optimization of Ustekinumab) study is a real-life multicenter observational French retrospective cohort study including patients with severe active CD. All patients from three academic IBD centers who received induction therapy with IV ustekinumab followed with subcutaneous (sc) UST 90 mg, either 4-weekly (MUST group) or 8-weekly (STD group) were included from Jan 2019 to Dec 2020. The choice of treatment regimen was left at the physician’s discretion. Severe active CD was defined by HBI > 16 and stool frequency (SF) ≥ 4 and abdominal pain (AP) ≥ 2 over one week and at least one objective evidence of inflammation (CRP ≥ 5 mg/L and/or FCal ≥ 250 μg/g and/or radiologic and/or endoscopic signs of disease activity). The primary endpoint was PRO-2 based clinical remission defined by SF≤2-8 and AP ≤1, and either FCal <250 μg/g and/or CRP <5 mg/L at week 52. Key secondary endpoints were PRO-2 remission, endoscopic improvement and steroid-free clinical remission at week 52.

Results

203 adult patients were included, either in the MUST group (n = 59) or in the STD group (n = 144). Baseline patient demographics and disease characteristics were similar between groups. Median disease duration was 9 years (IQR: 5 – 14 yrs), 66% were females. Disease location according to the Montreal classification was L1 and L3 in 36% and 44 % of patients. All had previously been exposed to more than one biotherapy, 27% experienced perianal CD, and 35% had undergone previous CD-related surgery. At week 52, the adjusted difference between the two groups for the primary endpoint was 15.8% (95% confidence interval (CI) 0.21 – 0.94; p = 0.029) with significantly higher clinical remission in the MUST group. The adjusted difference for PRO-2 remission was 3.7% (CI 0.45 - 1.66; p = 0.64). All patients, except one in the STD group, were weaned off steroids at week 52. Endoscopic improvement was similar in both groups (61.9% vs. 61.5%, p=0.98). Adverse events were not significantly different in both arms (42.4% vs 34.7%, p=0.338).

Conclusion

In the treat-to-target era, our real-life study shows that immediate escalation of ustekinumab therapy to 4-weekly dosing could achieve higher clinical remission at one year than 8-weekly dosing in severe CD. These findings should be confirmed in a dedicated prospective randomized trial.
P497 Is early bowel resection better than medical therapy for ileocolonic Crohn’s disease? A systematic review and meta-analysis
Authors: Husnoo N , Gana T , Hague A G , Khan Z , Morgan J L , Wyld L , Brown S R
Published: January 2023

Background

At least one third of patients with Crohn's disease (CD) have isolated ileocaecal disease. For a long time, surgery in this context has been seen as the "last resort" measure that is adopted when medical options have been exhausted. There is emerging evidence supporting early bowel resection (EBR) for ileocaecal CD as an alternative to conventional escalation of medical therapy (MT). We present a systematic review and meta-analysis of studies comparing the outcomes of EBR with those of MT in ileocolonic CD, with a focus on ileocaecal disease.

Methods

The MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials databases were searched for studies reporting the outcomes of EBR versus MT for ileocolonic CD. The Cochrane tools for assessment of risk of bias were used to assess the methodological quality of studies. The primary outcomes were recurrence rate and time to recurrence. Data on factors influencing duration of treatment effect, morbidity (including stoma rates), mortality and quality of life were extracted where available.

Results

Nine records (from 8 studies, with a total of 1867 patients) were included in the analysis. Six studies were observational and two were randomised controlled trials. Three observational studies were at serious risk, and one RCT was at high risk of bias. There was a reduced need for drug therapy in the EBR arm. The rate of intestinal resection at 5 years was 7.8% in the EBR arm and 25.4% in the MT group with a pooled OR of 0.32 (95% CI 0.19, 0.54; p<0.0001). The EBR group had a longer resection-free survival (HR 0.56, 95% CI 0.38, 0.83; p=0.004). The time to repeat resection following the initial surgery was longer also in the EBR group (HR 0.65, 95% CI 0.47, 0.91; p=0.01). The need for surgery at 5 years remained in favour of EBR in a subgroup analysis of patients with ileocaecal disease (HR 0.18; 95% CI 0.04, 0.88; p=0.03). Morbidity and quality of life scores were similar across the two groups.

Conclusion

EBR is associated with a more stable remission compared to initial MT for Crohn’s disease. Despite the paucity of relevant studies within the literature, and the studies being of variable methodological quality, there is enough evidence to support EBR as an alternative to escalation of medical therapy in selected patients with limited ileocaecal disease. EBR should be discussed with patients at an early stage to allow them to make an informed treatment choice.
P499 Exclusive enteral nutrition induces transmural healing in adults with active Crohn’s disease
Authors: Chu M , Day A , Mathias R , Direen T , Broad L , Lynch K , Bryant R
Published: January 2023

Background

Exclusive enteral nutrition (EEN) is a nutrition-based therapy for active Crohn’s Disease (CD). Transmural healing is a novel therapeutic paradigm in CD, holding benefit beyond endoscopic mucosal healing. There are limited data exploring EEN and transmural healing in CD. We aimed to examine the effect of EEN on inducing transmural response and healing as assessed by intestinal ultrasonography (IUS).

Methods

This was a prospective, multi-centre, open-label cohort study. Adults ≥18 years with active CD were enrolled between March to September 2022. Eligible, consenting participants were nutritionally assessed by a specialised IBD dietitian and prescribed 6 weeks of EEN therapy. A 1.5kcal/ml polymeric, low lactose, fibre-free formula was used and EEN prescriptions were personalised to 25-30kcal/kg IBW and 1.2-1.5g protein/kg IBW/day. Patients were allowed concurrent tapering corticosteroid therapy and biological therapy. Participants completed clinical, biochemical and nutritional assessments at weeks 0, 3 and 6 and IUS at weeks 0 and 6. This included Harvey Bradshaw Index (HBI), C-Reactive protein, faecal calprotectin (FCP), body mass index (BMI). IUS assessment was conducted at baseline and at week 6 and images were centrally read by a blinded, IUS-trained gastroenterologist. Transmural response was defined by ≥25% bowel wall thickness (BWT) reduction from baseline. Transmural healing was defined as BWT≤3mm, Doppler signal score≤1, normal bowel wall stratification, and absence of inflammatory fat.

Results

Fourteen patients, 9 were female (64.3%) and mean age of 44.4 years, were consecutively enrolled and completed 6-weeks of EEN therapy. Ten patients (71.4%) had ileal disease (L1), 4/10 had ileocolonic (L3) and predominant phenotype was inflammatory (B1, 7/14) and stricturing (B2, 6/14) disease. Mean disease activity was HBI 5.1±4.0.Two patients had perianal disease (14.3%). Nine patients (64.3%) reported 100% adherence and 4 patients (28.6%) reported 75-99% adherence to the exclusive diet by predefined adherence categories. At week 6, 11/14 (78.6%) of patients achieved clinical remission with 12/14 (85.7%) showing clinical response. Reductions in CRP and FCP were not statistically significant. Numerical reduction in BWT was observed 5.6±1.4mm vs 4.8±2.1mm (95% CI -1.94, 0.265, p = 0.124). Transmural response was achieved in 8/14 (57.1%) and transmural healing was reached in 2 (14.3%) patients. Most common side effect was constipation (42.9%).

Conclusion

EEN was identified to induce early transmural response and healing in patients with active CD. Further studies are required to evaluate the capacity for EEN to induce transmural healing and the role of IUS as an early assessment tool in monitoring therapeutic response in CD.
P501 Safety of peri-operative biologics in patients with IBD undergoing resective bowel surgery: experiences of a single center cohort
Authors: Ochsenkuehn T , Tillack-Schreiber C , Bader F , Maximilian S , Szokodi D , Tomelden J , Waggershauser C , Braun I , Schnitzler F
Published: January 2023

Background

Despite good safety data, the risk of peri-operative treatment with biologics in IBD is still discussed controversially. Recently, the prospective PUCCINI trial demonstrated that direct exposure to TNF-blockers within 12 wks. of abdominal surgery was not associated with more infectious complications. However, in daily clinical practice experiences on biological treatment peri-operatively are limited. In our current retrospective trial, we addressed the safety of different biologicals in a peri-operative setting.

Methods

Eligible pat. in this single center study were recruited from our IBD center between 2012 and 2022. Direct exposure to biologics was defined as exposure to biologics within 12 wks. before resective bowel surgery performed at our surgical department. To evaluate safety, the post-operative outcome focused on minor complications, defined as infectious complications, wound healing complications and major complications, defined as insufficiency of the anastomosis and abscess formation at surgery site post-operatively.

Results

A total of 447 IBD pat. (334 CD, 113 UC, 51.9% female) were included and followed for a median of 45 mo. [range 0-113]. Median age was 44 yrs. [19-89], median age at diagnosis was 24 yrs. [5-84] and median age at surgery was 41 yrs. [16/85]. Median disease duration until surgery was 11 yrs. [0-47]. 74.3% of pat. had moderate to severe disease activity at date of surgery. A total of 73.9% of pat. (326/447) had medical treatment at date of surgery, 61.5% of pat. (275/447) were treated with biologics within 3 mo. before surgery and 42.3% (189/447) had biologic treatment within 4 wks. before surgery. Overall, 36.9% of pat. (164/447) received infliximab, 13.0 % (58/447) adalimumab, 1.1% (6/447) golimumab, 5.8% (26/447) vedolizumab, and 6.5% (29/447) ustekinumab, peri-operatively. Most surgeries were planned electively (97.1%, 434/447) and performed laparoscopically (67.8%, 303/447). Minor and major post-operative complications occurred in 20.8% (93/447) of patients. Serious complications were observed in 9 pat., six had acute bleeding, one developed peritonitis and two died post-operatively (one with and one without biologics). Using logistic regression models, no significant differences regarding complications and safety were observed between pat. with versus without biologic treatment. Interestingly, CD pat. with direct exposure to biologics within 4 wks. were more likely to undergo minimal-invasive surgery (68.6%, 107/156) than pat. with biologics within 3 mo. before surgery (48.28%, 28/58, p=0.02).

Conclusion

This retrospective single center study of 447 IBD patients could demonstrate that biologic treatment before surgery, even within 4 wks, is not associated with a higher risk of complications.