bluuebunny/crossref_metadata_2025 huggingface dataset:
P419 Long-term outcome of ulcerative colitis in pediatric patients who achieved mucosal and histological healing: a real-life referral center experience
Authors: Scarallo L , Peruggia E , Fioretti L , Renzo S , Paci M , Naldini S , Barp J , Di Paola M , Lionetti P
Published: January 2022

Background

Ulcerative colitis tend to present with a more extensive phenotype and a more aggressive behavior in pediatric populations when compared to adult ones. Treatment targets are shifting from symptom alleviation to more objective outcomes, such as the healing of the mucosa and the complete resolution of microscopic inflammation. However, data regarding real-life attainment of such outcomes and their prognostic implications are lacking.

Methods

We performed a retrospective analysis on pediatric patients affected by UC who were followed up for at least, 12 month at a tertiary referral center. We included only patients who underwent endoscopic reassessment during clinical remission.

Results

Eighty-four patients were included. At diagnosis, patients were divided with regard to the extent of disease as assessed by the Paris classification as follows:, 45 (53.6%) showed pancolitis E4, 2 (2.4%) left colitis E3, 22 (26.2%) proctosigmoiditis E2, and, 15 (17.8%) proctitis E1. Globally, 14 (16.7%) patients presented with an acute severe colitis (ASC) attack at diagnosis. The median age at diagnosis was, 13 years and, 7 months (IQR=94 months). Patients were followed for a median time of, 18 months (IQR:, 22 months). The second endoscopy was performed after a median time of, 27 months (IQR=32). At the second endoscopic re-evaluation, 64 (76.2%) patients out of the total had regression of disease; whereas, 20 (23.8%) patients out of the total had progression of disease. Twenty (23.8%) patients had a Mayo score of, 1, whereas, 36 (42.8%) patients had a Mayo score of, 0. Complete histological healing was achieved by, 17 (20.2%) patients. When observing recurrence-free survival, patients who achieved partial and complete MH showed a significantly higher recurrence-free survival (p<0.001 and p<0.001, respectively). Lastly, when considering only patients who achieved at least partial MH, the subgroup with complete HH showed lower recurrence rates compared to those with persistent microscopic inflammation (p=0.049)

Conclusion

We reported the long-term outcomes of a selected group of pediatric patients with ulcerative colitis. Achievement of mucosal and histological healing appeared to protect against disease recurrence, with patients who resolved completely microscopic inflammation showing longer relapse-free survival rates.
P447 Positioning of ustekinumab affects its effectiveness, drug persistence and serum exposure in Crohn’s disease
Authors: Alsoud D , Sabino J , Ferrante M , Vermeire S , Verstockt B
Published: January 2022

Background

Ustekinumab (UST), an anti-IL12/23p40 monoclonal antibody, has been approved for treating Crohn’s disease (CD). As for all biologicals, efficacy is reduced in patients with previous anti-TNF exposure. We here sought to investigate whether UST outcomes and serum exposure are affected by UST positioning as first-, second-, or third-line biological treatment and type of previous biologicals (anti-TNF biologicals and vedolizumab [VDZ]).

Methods

Data on primary (non)-response, drug persistence and serum trough levels were collected from CD patients who started UST as a first-, second-, or third-line biological treatment from December 2015 through October 2020, allowing a follow-up of ≥12 months. Differences in rates of primary non-response (< 50% decrease in SES-CD and absence of any clinical improvement) after 6–12 months, and UST persistence were compared based on UST positioning and previous biologicals. Finally, we compared serum UST exposure profiles between groups.

Results

A total of 181 CD patients with active disease started UST as first- (n=41; 22.65%), second- (n=57, 31.5%) or third-line (n=83, 45.85%), respectively (Table 1). Of second-line UST starters, 52 (28.7%) patients were exposed to one anti-TNF biological and 5 (2.8%) to vedolizumab. Of third-line UST starters, 41 (22.65%) patients were exposed to both one anti-TNF and VDZ, while 42 (23.2%) were exposed to two anti-TNFs. Second-line UST starters with previous VDZ were excluded from further analysis due to small sample size (n=5). A gradual decrease in response rates (p=0.02; Figure 1) and drug persistence (p=0.03; Figure 2) was observed with increasing lines of biologicals given prior to start UST, with patients starting UST as third-line treatment after two anti-TNFs having the highest rates of primary non-response (43%) and the shortest drug persistence. This finding was paralleled by a progressive decrease in UST serum levels with increasing number of previous biologicals and number of previous anti-TNFs (Figure 3), in 71 patients of whom induction and maintenance UST serum levels were available.

Conclusion

Both short term response rates, as well as long term UST persistence rates, decreased with increasing lines of previous biological therapies. Patients exposed to two anti-TNFs had worse UST outcomes on short-term and long-term, and lower serum trough levels than patients who received only one or no anti-TNF biological before or prior VDZ exposure. These data help in positioning UST in CD and in framing the discussion with patients.
P457 Long-term cumulative safety of ustekinumab in bionaive patients with Crohn’s Disease and Ulcerative Colitis
Authors: Danese S , Hanauer S B , Jairath V , Mihaly E , Vicente Lidón R , Ott E , Gasink C , Miao Y , Ma T , Marano C , Sands B E
Published: January 2022

Background

Ustekinumab (UST) is an approved biologic for the treatment of adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]). Previously, an integrated analysis of safety data through up to 5 years (yrs) showed a favourable safety profile for UST that was generally similar to placebo (PBO) in patients (pts) with IBD, and to the well-established safety profile across other approved indications. Several treatment options exist for newly diagnosed pts with moderate to severe IBD; therefore, long-term safety data from bionaive pts are important to help inform treatment selection in this population. Here, we present an integrated analysis incorporating UST Phase 2/3 long-term safety data from IBD studies through up to 5 yrs in CD and 2 yrs in UC for bionaive pts.

Methods

Data from 4 Phase 2/3 UST IBD studies were pooled. In Phase 3, pts received a single IV PBO or UST (130mg or ~6mg/kg) induction dose followed by SC maintenance doses of PBO or UST (90mg q8w or q12w). Patients identified as bionaive (never treated with a biologic) were included in the analysis of data through up to 5 yrs in CD and up to 2 yrs in UC. Concomitant immunomodulators and corticosteroids were permitted. All pts who received ≥1 UST dose were included. Safety outcomes are presented as event rates per 100 patient yrs (PY) of follow-up and 95% confidence interval (CIs). Bionaive UST data from the SEAVUE study (N=191) adjusted for exposure with events per 100 PY, will be shown for comparison.

Results

Through up to 5 yrs, 425 bionaive IBD pts received PBO (376 PYs) and 771 pts received UST (1511 PYs). Mean duration of follow-up (weeks) for PBO and UST was similar through 1 yr, and >2-fold longer for UST though 5 yrs. Rates per 100 PY for adverse events (AEs), serious AEs, infections, serious infections, major adverse cardiac events (MACE), and malignancies were similar between PBO and UST through up to 1 yr in bionaive IBD pts (Table 1). Rates per 100 PY for AEs, serious AEs, infections, serious infections, and MACE were similar and/or numerically lower for UST vs PBO through up to 5 yrs (Table 2). Overall, malignancies were infrequently reported through up to 5 yrs. Malignancy rates in bionaive UST pts were not significantly different than PBO through 1 yr (PBO: 0.44; UST: 0.34) or through 5 yrs (PBO: 0.27; UST: 0.46). A total of 2 deaths were reported in bionaive pts treated with UST through up to 5 yrs (0.13/100 PY); both assessed as unrelated (Table 3).

Conclusion

The safety profile of UST in the long-term IBD pooled safety dataset was favourable among bionaive pts and consistent with the well-established safety profile across approved indications.
P496 Efficacy and safety of ustekinumab for chronic antibiotic refractory pouchitis: A Belgian open-label multicentre pilot study
Authors: Outtier A , Louis E , Dewit O , Schops G , Verstockt B , Sabino J , Vermeire S , Ferrante M
Published: January 2022

Background

Up to 10% of ulcerative colitis patients who undergo a proctocolectomy with ileal pouch-anal anastomosis, will develop chronic antibiotic refractory pouchitis (CARP). As there is a large unmet need in the management of these patients, we evaluated the efficacy and safety of induction therapy with ustekinumab (UST) for this indication.

Methods

We performed a prospective, Belgian, multicentre, open-label study of patients with CARP. Patients received a weight-range-based infusion of UST at baseline (6mg/kg) and one subcutaneous injection of 90mg UST at week 8. The first 4 weeks, ciprofloxacin 500mg BID was added as bridging therapy, but need of antibiotics thereafter was regarded as treatment failure. Patients underwent pouchoscopy at baseline and week 16, with assessment of the modified pouchitis disease activity index (mPDAI). The primary endpoint was the proportion of patients achieving clinically relevant steroid-free remission (mPDAI <5 and reduction by ≥2 points from baseline) at week 16. Secondary endpoints at week 16 were the proportion of patients achieving response (reduction of mPDAI by ≥2 points from baseline), change in symptomatic and endoscopic mPDAI subscore, and change in C-reactive protein (CRP) and faecal calprotectin levels compared to baseline. Descriptive statistics and paired nonparametric tests (Wilcoxon signed-rank) of changes from baseline were performed.

Results

We report the first 18 patients (56% male, median age 41.5 years, median time after surgery 11.2 years) who reached the primary endpoint assessment. Eleven (61.1%) patients had previously been treated with biologics (anti-TNF, n=8; vedolizumab, n=6; tofacitinib, n=1) for CARP (table 1). At week 16, clinically relevant steroid-free remission was reached in 27.8% and response in 50.0% of patients. A significant decrease in total mPDAI (8.0 (7.0–8.3) vs. 6.5 (3.8–9.0), p=0.04) and clinical subscore (3.0 (2.0–4.0) vs. 2.0 (1.0–3.3), p=0.04) but not endoscopic subscore (5.0 (4.0–6.0) vs. 4.0 (3.0–6.0), p=0.1) was observed at week 16 (figure 1). Faecal calprotectin (288.0 (154.8–634.8) vs. 145 (88.3–749.3) mg/kg, p=0.47) and CRP (4.8 (1.9–7.2) vs. 3.9 (1.9–8.9) mg/L, p=0.63) levels did however not decrease significantly (figure 2). Three serious adverse events (hospitalization for subobstruction, worsening pouchitis and choledocholithiasis) were recorded, but were not considered related to UST.

Conclusion

In this open-label pilot study in patients with CARP, induction therapy with UST showed a clinical effect in half of the patients, but was not associated with endoscopic improvement or changes in inflammatory biomarkers. Placebo-controlled studies are needed for further positioning UST in the treatment algorithm of CARP.
P503 Early TNF-antagonist maintenance therapy results in better outcomes than immunomodulators in paediatric Crohn’s disease: A multi-centre prospective cohort study
Authors: Schneider R , Jacobson K , Huynh H , Mack D , Deslandres C , deBruyn J , El-Matary W , Otley A , Lawrence S , Wine E , Sherlock M , Critch J , Jantchou P , Rashid M , Carroll M , Bax K , Seidman E , Benchimol E , Ricciuto A , Wu A , Pullenayegum E , Walters T , Nguyen G , Griffiths A , Church P
Published: January 2022

Background

Early initiation of TNF-antagonist (aTNF) therapy for Crohn’s disease (CD) is associated with greater clinical and endoscopic improvement but trialing an immunomodulator (IM) first remains common in paediatrics. This study aimed to determine if early aTNF is superior to IM maintenance therapy in paediatric luminal CD.

Methods

Children 2–17 years old with newly diagnosed CD were enrolled prospectively at one of 12 sites of the Canadian Children IBD Network. Patients with luminal inflammatory disease receiving IM or aTNF-based first maintenance therapy, following induction with steroids, exclusive enteral nutrition (EEN), or aTNF, were included. Those with perianal disease as the sole indication for aTNF were excluded. The primary outcome was sustained steroid-free clinical remission, defined by the short Pediatric CD Activity Index, at 6, 12, and 18 months, while continuing initial maintenance. A secondary outcome was combined sustained steroid-free clinical and endoscopic remission by 18 months, defined as the absence of ulcers at follow-up colonoscopy when ulcers were present at baseline. Multivariable logistic regression modeled the propensity of receiving aTNF maintenance therapy and 1:1 Greedy matching, without replacement, was used to match each of the participants who received aTNF with a participant who received an IM. The primary outcome was analyzed in the whole cohort, and in the subgroup receiving steroids or EEN as induction, using a Chi-square test, as well as in the matched group with a McNemar’s test, generalized estimating equation (GEE), and with a mixed model to account for clustering by centre. Sensitivity analyses with inverse probability treatment weights using GEE were performed.

Results

Among children with CD enrolled in the inception cohort study between 01/2014 and 12/2018, 464 met inclusion criteria and received IM (n=284) or aTNF (n=180 of whom 88 received steroids or EEN induction) as first maintenance therapy (Table 1). 162 patients were included in the matched cohort. In every analysis, more of the aTNF group achieved sustained 18-month steroid-free clinical remission, despite more severe baseline disease (Figure 1). The result remained significant in sensitivity analyses (Table 2). In patients with ulcers at baseline, 57.1% of the aTNF group versus 4.6% of the IM group achieved sustained steroid-free clinical remission and endoscopic remission by 18 months (p<0.001).

Conclusion

In this paediatric cohort, aTNF was superior to IM as first maintenance therapy. These results may help advocate for better access and funding for early aTNF therapy in paediatric CD.
P511 Efficacy of Crohn’s Disease exclusion diet in different clinical scenarios in paediatrics; at onset of the disease and after loss of response to biological therapy
Authors: Jijón M C , Pujol-Muncunill G , Lozano Ruf A , Vila Miravet V , Alvarez Carnero L , García Arenas D , Egea Castillo N , Martín de Carpi J
Published: January 2022

Background

Crohn’s disease (CD) exclusion diet (CDED) associated with partial enteral nutrition (PEN) has showed to induce remission in different clinical scenarios of the disease. Our aim is to evaluate its efficacy at onset and after loss of response to biological treatment in paediatric CD.

Methods

Retrospective observational cohort study of children with CD treated with CDED+PEN. Demographic (gender, age at diagnosis and at CDED initiation), clinical (Paediatric Crohn’s Disease Activity Index (PCDAI) and weight Z score), and analytical (faecal calprotectin (FC), haemoglobin, albumin, C reactive protein (CRP), iron, ferritin, and erythrocyte sedimentation rate (ESR)) variables were analysed at 0, 6, 12, and 24 weeks of treatment. Primary outcome was clinical remission, defined as PCDAI <10 points.

Results

Fifteen patients were included (8 male); group A (n 9; mean age 15.8 years, [IQR:12.6–18.1]) received CDED+PEN at onset, while group B (n 6; mean age 12 years [IQR:10.7–15]) received it after loss of response to biologics. All patients in group A and 2 in B received azathioprine. In group B, 3 patients were on Adalimumab and 3 on Ustekinumab. Adherence at week 6 was 100% in both groups. Group A had a mean PCDAI of 15 [IQR: 11.25–17.5] at baseline and 100% of the patients achieved clinical remission by week 6 and maintained it through week 12; 87% (7/8) maintained clinical remission by week 24. One patient required step-up to Adalimumab due to sustained FC elevation. In group A PCDAI significantly improved at week 6 (p0.09), 12 (p0.002) and 24 (p0.006). FC and albumin also improved at week 6 (p0.02; p0.03), 12 (p0.016; p0.03) and 24 (p0.019; p0.016). ESR improved at weeks 12 (p0.021) and 24 (p0.027). Haemoglobin and iron only improved at week 24 (p0.048; p0.003). The weight Z score, CRP, and ferritin did not improve significantly in group A. In group B mean PCDAI at baseline was 20 [IQR: 3.75–39.38]; 100% achieved clinical remission at week 6 and maintained it at week 12. By week 24, 60% (3/5) maintained clinical remission (1 patient required steroids due to a relapse (moderate activity assessed by colonoscopy) and 1 patient presented with clinical relapse. PCDAI and FC decreased over time but did not reach statistical significance. The rest of variables did not show significant improvement in group B.

Conclusion

Treatment with CDED+PEN was well tolerated and patients had excellent adherence. Our cohort showed better results at disease onset than after loss of response to biologics. However, CDED+PEN is a new promising rescue strategy to treat CD after failure to previous biologics in a safe manner, and without needing to change the therapeutic target.
P527 Telemedicine in IBD patients: results of a national survey of the Italian IBD patients’ association (AMICI Onlus)
Authors: Costantino A , Caprioli F , Vecchi M , Stocco D , Aloi M , Armuzzi A , Ficari F , Manguso F , Mocci G , Orlando A , Pironi L , Radice S , Rizzello F , Tongiorgi A , Leone S , Bossa F
Published: January 2022

Background

Telemedicine is one of the major changes that clinicians have encountered over the past decade; in particular during the COVID-19 pandemic, televisits were rapidly implemented to guarantee patients’ assistance, with the intention of Health Care Providers (HCPs) to continue to use them beyond the pandemic.

The aim of our national survey was to evaluate the current usage of telemedicine for IBD patients from their perspective, investigating patients’ impressions about telemedicine and factors affecting them through a Machine Learning (ML) analysis.

Methods

In March 2021, the Italian IBD patients’ association (AMICI Onlus) distributed to their members - through its mailing list and on social media platforms - an anonymous online questionnaire investigating the use of telemedicine.

Socio-demographic and IBD characteristics were collected; the usage, patients’ satisfaction and trust of telemedicine were assessed through Likert scales.

ML tools - Decision Trees (DT) and Random Forest (RF) - were applied to identify the determinants of patient’s perceptions about telemedicine; the produced RF ranking displays two indicators: %IncMSE and IncNodePurity.

Results

Nine hundred and seventy-eight IBD patients (women 58.9%) from every Italian region completed the questionnaire.

Among the respondents, 87 (8.9%) personally had a telemedicine experience; 153 reported that their Centre performed a telemedicine service during the COVID-19 pandemic (24.2% televisits, 39.2% e-mails, 24.8% phone-calls, 3.9 % dedicated website, 7.9% others).

Overall, 707 (72.3%) would trust a telemedicine service, 760 (77.7%) would like to have it also with another HCP (e.g., nutritionist, psychologist) and 778/961 (81%) would like to use telemedicine in the future (17 did not answer to this specific question); 792 (81%) stated they thought useful to have the possibility to use telemedicine and 847 (86.6%) would like their Centre to offer them this facility.

Considering this last question as the output at the DT, the variable which have been found to influence the most this patients’ willingness is patient’s perception of the usefulness of telemedicine in treating their disease, since it represented the root of the tree explaining the results. The RF rankings confirmed that this variable influenced the most patients’ perception with the highest levels of %IncMSE and IncNodePurity(Figure 1).

Conclusion

The practice of telemedicine in the management of IBD patients has not been very relevant throughout Italy so far (less than 10%), but more than four every five respondents would like to use telemedicine.

Machine learning analysis shows that the perceived usefulness of telemedicine service is the key point for patients who would like it was a part of usual clinical practice.
P529 Evolution of COVID19 serology in a real-life population of IMID patients. Results of the BELCOMID study: BELgian Cohort study of COVID-19 in Immune Mediated Inflammatory Diseases (IMID)
Authors: Geldof J , Sabino J , Ferrante M , Lambert J , Lapeere H , Hillary T , Van Laethem A , De Vlam K , Verschueren P , Lobaton T , Vermeire S
Published: January 2022

Background

Immunomodulators (IMM) and Targeted Immune-Modulating Therapies (TIMT) such as anti-TNF, anti-interleukins and Janus Kinase inhibitors, for treatment of Immune Mediated Inflammatory diseases (IMID) could theoretically interfere with the cytokine storm and humoral immune response against COVID19 infection and vaccination. We investigate seroprevalence and evolution of SARS-CoV2 antibodies in relation to previous vaccination and/or exposure to COVID19 and ongoing IMID-treatment in a Belgian, real-life population of IMID patients.

Methods

A cross-disciplinary, prospective, observational cohort study was set up at two university hospitals. All patients with IMIDs of the gut (Crohn’s disease, ulcerative colitis), joints (rheumatoid, psoriatic or spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa, atopic dermatitis) visiting the respective clinics were asked to participate. Patients had to fill out an electronic survey (REDCap®, based on WHO-ISARIC) and blood samples were drawn for serology testing (anti-Spike(S) and anti-viral Nucleocapsid(N) protein antibody IgG, Abbott). Results at baseline, prior to the national vaccination program and at 6 months follow-up are presented. R version 4.0.2 was used for statistical analyses.

Results

At baseline 2165 IMID patients consented to take part. In 3.2% SARS-CoV2 anti-N seroconversion was confirmed. Of the anti-N seroconverted patients 72.9% reported a positive PCR test prior to inclusion.

At 6-months follow-up, data of 1853 IMID patients was collected. Of these, 81.7% were fully and 14.4% partially vaccinated. Seroconversion for anti-N antibodies was confirmed in 2.5% of all participants and seroconversion for anti-S antibodies in 90.8%. In 5.1% (61/1483) of fully vaccinated IMID patients no seroconversion in anti-N nor anti-S antibodies was found.

Chi Square analyses show, at 6-months follow-up, no significant association between anti-S seroconversion rate and treatment with systemic steroids (RiskRatio 1.22, 95%CI 0.38–3.9, P=0.99), TIMT (RiskRatio 0.57, 95% CI 0.3–1.1, P=0.12), IMM (RiskRatio 1.65, 95% CI 0.85–3.19, P=0.19) or combination treatment IMM/TIMT (RiskRatio 1.60, 95% CI 0.75–3.4, P=0.32).

Appearance of COVID19 symptoms followed the epidemiological curve in Belgium (Fig1).

Conclusion

In this real-life IMID cohort, the number of COVID19 cases confirmed by PCR prior to vaccination was low. Seroconversion rate for anti-N antibodies was lower at 6-months follow-up, suggesting decrease in antibody titre over time. Full COVID19 vaccination led to a high anti-S antibody seroconversion rate. Nonetheless, 5.1% of fully vaccinated patients showed no antibody seroconversion. So far, no significant association between anti-S antibody seroconversion and IMID treatment was noted.
P538 Implementation of Kono-S anastomosis as a new standard of surgical care
Authors: Adamou A , Müller G , Iesalnieks I
Published: January 2022

Background

The Kono-S ileocolic anastomosis is thought to reduce the risk of clinical and surgical recurrence in Crohn’s disease patients. The Kono-S anastomosis was established as a new standard of care at our institution in 2018, however, it was not performed in all patients. The present study describes the learning curve and reasons for hesitation to use the new technique.

Methods

Consecutive patients undergoing bowel resection with formation of ileocolic anastomosis since starting to use Kono-S technique were included in the present retrospective analysis. Intraabdominal septic complications (IASC) were peritonitis, anastomotic leak, intraabdominal fistula and abscess.

Results

Since starting to use Kono-S anastomosis, 90 patients underwent ileocolic resection (45M, 45F). However, during this period, conventional side-to-side ileocolic anastomosis was still performed in 26 patients (29%). Kono-S anastomosis was performed in 46% of cases during the first 6 months, in 76% during the next 6 months and in 82% of cases after the first year since implementation (p=0.005). There was no difference in postoperative IASC rate between patients with or without Kono-S anastomosis (2% vs. 4%, p=0.5). Also, postoperative overall complication rate, incidence of postoperative small bowel obstruction and length of postoperative hospital stay did not differ between groups. There were no anastomotic leaks. By the multivariate analysis, the presence of intraabdominal abscess or fistula (Hazard ratio 0.25, p=0.037) was the main reason to perform the conventional hand S/S anastomosis instead of new technique.

Conclusion

Some hesitation to use Kono-S anastomosis could be observed after the implementation of the new standard of care, especially during the first six months and in patients presenting with more complex intraabdominal findings. However, the learning curve has no impact on postoperative morbidity.
P547 Early modification of inflammatory burden through treatment with vedolizumab or adalimumab is predictive of long-term treatment success in patients with Ulcerative Colitis from the VARSITY Study
Authors: Schreiber S , Galinsky K , Aubrecht J , Juarez J , Agboton C , Loftus E V , Danese S
Published: January 2022

Background

Use of inflammatory biomarkers is common practice in ulcerative colitis (UC) management1. This study examined the utility of faecal calprotectin (FCP), C-reactive protein (CRP), and albumin biomarkers and their combination, for predicting outcomes of clinical remission and disease control (composite of clinical, endoscopic and histologic disease activity measures2) in patients (pts) with UC under therapy with vedolizumab (VDZ) or adalimumab (ADA) in the VARSITY study.

Methods

VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-control trial evaluating VDZ (anti-α 4β 7 integrin) vs ADA (anti-tumour necrosis factor-α) treatment in pts aged 18–85 years with moderate-to-severe UC (NCT02497469; EudraCT:2015-000939-33). Pts received either VDZ IV infusions (300 mg) on Day 1 and at Weeks (WKs) 2, 6, 14, 22, 30, 38, and 46 or ADA SC injections (40 mg), total dose 160 mg at WK1, 80 mg at WK2, and 40 mg every 2 weeks thereafter until WK50. In this post hoc analysis of data from 769 pts, the probability of clinical remission (total Mayo score ≤2, no subscore >1) and disease control (pt-reported outcome-2 [PRO2, Mayo subscores of stool frequency and rectal bleeding]; Mayo endoscopic subscore ≤1 [endoscopic improvement], and Robarts Histopathology Index score <5, [absence of histologic active disease]) were assessed at WK52 based on baseline and WK14 levels of dichotomized FCP (high-risk: ≥100 µg/g), CRP (high-risk: ≥5mg/L), and albumin (high-risk: <45 g/L) including the composite of high-risk CRP and FCP termed ‘inflammatory burden’ (IB).

Results

In comparison with biomarkers measured at baseline, FCP at WK14 was the most predictive of WK52 clinical remission after VDZ or ADA treatment3; WK14 FCP was also predictive of disease control using a combined endpoint of PRO2, endoscopy and histologic remission/response. VDZ-treated pts with low-risk FCP (<100 µg/g) at WK14 had a 76% chance of achieving WK52 clinical remission vs 35% for pts with high-risk FCP (70% vs 33% for ADA-treated pts with low and high-risk FCP, respectively). VDZ-treated pts with IB (high-risk levels of FCP and CRP) at WK14 had a 16% chance of clinical remission at WK52 vs a 57% probability for this endpoint in pts without IB at WK14; the risk difference for this composite biomarker was 42% (Table).

Conclusion

The addition of CRP to FCP as a composite biomarker of IB at WK14 after treatment initiation can be a useful negative predictor of pts who are likely to achieve significant long-term benefits, including remission and disease control, with VDZ or ADA treatment.

References

1. Turner D, et al. Gastroenterology 2021;160(5):1570-38.

2. Danese S, et al. J Crohn’s Colitis 2021;15(Suppl1):S305–S305.

3. Dulai PS, et al. Gastroenterology 2021;160(6):S-46–7.
P548 External validation and consistency in time of patient segmentation based on disease acceptance and perceived control in Inflammatory Bowel Disease
Authors: Van Erp L W , Thomas P W A , Groenen M J M , Bloem S , Russel M G V M , Römkens T E H , Wahab P J
Published: January 2022

Background

The patient segmentation model based on disease acceptance and perceived control may guide personalized inflammatory bowel disease (IBD) care. A first single-centre evaluation of the model showed its validity and found that disease acceptance and perceived control are important determinants of health-related quality (HRQoL) in IBD patients. We aimed to investigate the external validity of the segmentation model and its performance in course of time.

Methods

This is a longitudinal study of adult IBD patients guided at three secondary care centres with questionnaires on HRQoL (10-item Short IBDQ, range 10–70) and disease acceptance and control (3-items each, 7-point Likert scale). Two cohorts were created: 1) external validation cohort excluding participants of initial validation study and 2) follow-up cohort of patients with questionnaires after one year. Segments were formed based on mean acceptance and control (cut-off high score>5).

Results

The external validation cohort included 921 patients that were divided in four segments (Figure 1). The acceptance and control scale were unidimensional (85% and 83% of variability explained by the first factor) and internally consistent (Crohnbach’s alpha 0.92 and 0.90). The segments differed significantly in gender, disease duration, IBD medication and clinical disease activity (p<0.05). In multiple regression analysis, high acceptance and high control were significantly associated with a higher HRQoL compared with low acceptance and low control (Beta (95%CI) segment I=11.8 (10.5–13.2), segment II=9.4 (7.8–11.0) and segment III=3.8 (1.6–6.1), p<0.01). The follow-up cohort included 783 patients: 58% remained in the same segment while 42% differed in segment over time (Figure 2). HRQoL differed significantly between patients with positive, negative or no change in segment (p<0.001)(Figure 3). The change in HRQoL over time correlated positively with changes in segment (Spearman rho 0.38, p<0.001) (Figure 4).

Conclusion

This study demonstrated the patient segmentation model based on disease acceptance and perceived control is externally valid and shows consistency over time. The independent association between the different segments and HRQoL was confirmed. In many patients disease acceptance and perceived control remained low after one year. Future research and interventions should aim at improving disease acceptance and perceived control of IBD patients.
P555 Ustekinumab tissue and serum levels in patients with Crohn’s disease are closely correlated though not consistently associated with objective response after induction
Authors: Proietti E , Bayoumy A , Pauwels R , van der Woude J , Doukas M , Oudijk L , Peppelenbosch M , Grohmann U , Crombag R , de Vries A , Fuhler G
Published: January 2022

Background

Ustekinumab (UST), which targets p40 of IL23/IL12, is an effective treatment for Crohn’s disease (CD). Therapeutic drug monitoring (TDM) may optimize UST posology. The aim of this study was to investigate UST and IL23 serum and tissue concentrations in relation to mucosal inflammation and treatment response.

Methods

A prospective cohort study was performed in adult CD patients who initiated UST at Erasmus MC, the Netherlands, between December 2016 and November 2018. Endoscopies were performed at baseline and week 16. UST and IL23 serum and tissue concentrations were measured at week 16. Clinical and biochemical response were defined as decline of ≥3 points in Harvey Bradshaw Index and reduction of ≥50% in fecal calprotectin levels. Endoscopic response was defined as a ≥50% decline in simple endoscopic score or a decline of ≥1 points in Rutgeerts’ score. Histological remission was defined as GHAS score ≤4.

Results

All 56 included patients were previously treated with anti-TNFα-inhibitors prior to UST. Upon treatment with UST, 17 (30%) showed clinical response, 16/53 (30%) biochemical response, and 20/56 (36%) endoscopic response. UST, but not IL23, concentration in biopsies was correlated to levels in corresponding sera (p < 0.0001). No correlation was found between UST serum and tissue levels with clinical or endoscopic response, or histological remission. However, patients achieving biochemical response showed significantly higher UST serum levels as compared to those without biochemical response (3.12 µg/ml vs 1.41 µg/ml, p = 0.01). Furthermore, tissue IL23/UST ratio correlated with histologic mucosal inflammation (p = 0.01).

Conclusion

This is the first study to demonstrate a correlation between serum and tissue UST levels. We showed that the tissue IL23/UST ratio correlated with mucosal inflammation. UST tissue concentrations did not correlate with treatment response, while UST serum concentrations were associated with biochemical response at week 16. The role of UST levels for TDM in IBD warrants further research.
P576 Real-world effectiveness and safety of risankizumab in patients with moderate-to-severe multi-refractory Crohn’s disease: a Belgian multi-centric cohort study
Authors: Alsoud D , Franchimont D , D’Heygere F , Bossuyt P , Vijverman A , Van Hootegem P , Sabino J , Cremer A , Vermeire S , Ferrante M
Published: January 2022

Background

In recent phase 3 trials, risankizumab (RZB), a humanised monoclonal IgG1 antibody targeting the interleukin 23 p19 subunit, proved to be superior to placebo in inducing and maintaining clinical remission and endoscopic response in patients with moderate-to-severe Crohn’s disease. In this study, we aimed to evaluate the effectiveness and safety of RZB in a real-world cohort of multi-refractory CD patients.

Methods

Adult CD patients from six Belgian IBD centres who initiated RZB prior to May 2021 as part of a medical need program were prospectively followed. Patients with an ostomy were excluded for the main analyses. The primary endpoint was steroid-free clinical remission at week 24 (average daily liquid stool frequency [SF] ≤2.8 and average abdominal pain [AP] score ≤1, both not worse than baseline). Secondary endpoints included clinical response, endoscopic remission, endoscopic response, biological remission, biological response, need for CD-related hospitalisation or surgery, and serious adverse events (definitions in Figure 1). Given that a follow-up endoscopy has not yet been performed in some patients, results are shown for both “all patients” (with non-responder imputation) and “as observed”.

Results

A total of 27 patients started RZB of whom 19 patients were eligible for this study with a minimal follow-up of 24 weeks (Table 1). Eight patients were excluded as they had an ostomy at time of RZB initiation. Eighteen patients (95%) had been exposed to more than 3 biologicals and 13 (68%) previously underwent a CD-related intestinal resection. By week 24, 7/19 (37%) and 7/19 (37%) patients achieved steroid-free clinical remission and endoscopic response, respectively (Figure 1). In the “as observed” analyses, these rates were 7/18 (39%) and 7/9 (78%), respectively (Figure 2). Five patients used concomitant steroids at baseline and were all able to stop it after a median of 10 weeks. Eventually, three patients had to be hospitalized for bowel resection (2 with placement of an ostomy) after a median of 24 weeks, two of them required earlier an emergent hospitalization due to flares of abdominal pain and bloody diarrhea. None of the patients experienced serious infections or intolerance. Based on physician global assessment, three out of eight patients with an ostomy did achieve clinical remission, and two other achieved clinical response. Endoscopic follow-up data were available in six patients, and three of them experienced endoscopic response.

Conclusion

In this real-world, multi-refractory cohort, clinical remission and endoscopic response were both observed by week 24 in more than one third of CD patients initiating RZB. RZB was well tolerated with no safety issues.
P588 T cell response to SARS-CoV-2 mRNA vaccines by an interferon-gamma release immunoassay in patients with Inflammatory Bowel disease receiving anti-TNF and thiopurine treatment
Authors: Mayorga Ayala L F , Herrera-deGuise C , Esperalba J , Martinez-Gomez X , Céspedes Martinez E , Robles Alonso V , Jimenez A , Perez Martinez Z , Oller E , Ibarz A , Fernandez-Naval C , Martinez-Gallo M , Lopez Messeguer M , Casellas F , Borruel N
Published: January 2022

Background

Treatment with anti-TNF agents and thiopurines has been associated with an impaired immune response to some vaccines. SARS-CoV-2 vaccination is very effective in healthy individuals, but studies in inflammatory bowel disease (IBD) populations are scarce, especially regarding T cell response. We aimed to evaluate the T cell and antibody response in a cohort of IBD patients on anti-TNF and thiopurine treatment who received two doses of the SARS-CoV2 mRNA vaccine.

Methods

An observational, prospective study was carried out at our IBD clinic. We included Crohn’s disease (CD) and Ulcerative colitis (UC) patients receiving anti-TNF as monotherapy or anti-TNF + thiopurine (combo) or thiopurines only for at least six months at inclusion. Blood samples were drawn for interferon-gamma release assay (IGRA) and antibody determination six (+/- 2) weeks after the second vaccine dose. The specific T cell response to SARS-CoV-2 was determined by IGRA using Qiagen® QuantiFERON® SARS-CoV-2 RUO tubes with a patented Spike protein combination. Interferon-gamma was measured by CLIA using the LIAISON® QuantiFERON-®TB Gold Plus assay. As there is no validated cut-off point, we used those obtained in a cohort of 20 healthy health professionals published by our group (doi.org/10.1016/j.medcli.2021.09.013). Antibodies to the Spike (S) SARS-CoV-2 protein were analyzed by CLIA. Adverse events (AEs) and clinical activity were recorded.

Results

We recruited 148 IBD patients, 57 treated with anti-TNF monotherapy, 53 with combo, and 38 with thiopurine only. Seventy percent had CD, and 60% were male. Using the cut-off value of the cohort mentioned above, the T-cell response was positive in 92% of anti-TNF monotherapy, 83% in combo, and 87% of the thiopurine group (p=ns). The anti-S antibodies were positive in 100% of our cohort. There were no changes in disease activity rates after the second vaccination, nor were severe AEs detected.

Conclusion

SARS-CoV-2 mRNA vaccination was very effective in IBD patients receiving anti-TNF (combo or monotherapy) or thiopurine treatment as measured by both T cell and antibody response. IGRA-specific tests may constitute a valuable tool in assessing cellular immunity in immunocompromised patients.
P623 The effectiveness and tolerability of Crohn’s disease exclusion diet in adult Crohn’s disease patients: a retrospective study
Authors: Mahajna H , Abu-Salah R , Tzur M , Kedar N , Ben-Horin S , Kopylov U , Engel T
Published: January 2022

Background

Crohn’s disease exclusive enteral nutrition (EEN), a dietary therapy which consists exclusively of liquid formula, was shown to be effective in the induction of remission in the pediatric population but limited by poor tolerability to avoiding oral food. Crohn’s disease exclusion diet (CDED) is based on excluding certain food components that are thought to negatively affect the gut immunity, the gut barrier, and the microbiome. In children and young adults, CDED combined with partial enteral nutrition (PEN) were highly effective in inducing clinical response and remission. Despite the promising data regarding the tolerability and effectiveness of CDED in prospective trials, real world data, especially those conducted on adult patients’ population, still lacks.

Methods

This is a retrospective study of adult CD patients treated with CDED at a tertiary medical center (Sheba medical center, Israel). All included patients had active CD (Harvey Bradshaw index >4). The study endpoint was a composite outcome of clinical response (HBI decline of at least 3 points) or remission (HBI decline to below 5 points) at 6 week and at 12–18 weeks.

Results

Overall, 40 patients who met the inclusion criteria were treated by CDED between year 2020 and 2021. 67.5% were females; mean age 29.5±13.3; mean disease duration 3.4±4.7 years; mean CRP 20.1±26.1mg/dl; mean calprotectin 599.4±510.5 mcg/g at study onset;

At CDED initiation, 17 (42.5%) were bio-naive; 14 (35%) were under maintenance therapy with a biologic; for 15 (37.5%) patients, CDED was the first treatment for CD; eleven (27.5%) patients started CDED concomitantly with another treatment (7 with corticosteroids and 4 with biologics). Most (85%) of patients combined the CDED with partial enteral nutrition.

Forty patients and 20 patients underwent a follow-up assessment at week 6 and 12–18, respectively. The mean HBI at the beginning of the study was 8.0±3.9 and declined to 4.5±3.0 and 3.7±2.9 at weeks 6 and 12–18, respectively. Twenty-six (65%) patients and 16 (40%) patients achieved the study composite endpoint by week 6 and 12–18, respectively. Four (10%) patients required corticosteroid treatment during the CDED treatment. Patients who achieved the study endpoint at week 6 had shorter durations of the disease (2.3±3.8 vs 5.6±5.4 years, P=0.03) compared to patients who didn’t. No other significant differences were noted in disease characteristics and disease activity parameters between responders and non-responders.

Conclusion

In a real-world setting, treatment with CDED (either exclusive or combined with an additional treatment) appears to be effective in treating adult CD patients but adherence to the diet remains a challenge. Further and longer-term real-world studies are warranted.
P656 The impact of periodontitis on IBD disease activity
Authors: Madsen G R , Bertl K , Stavropoulos A , Burisch J
Published: January 2022

Background

Inflammatory bowel disease (IBD) and periodontitis are chronic, progressive, inflammatory diseases with similarities in their respective pathogenesis, which involve a complex interplay between a dysbiotic microbiota and a dysregulated immune-inflammatory response. Periodontitis has been associated with an adverse impact on other inflammatory diseases and the general health. Whether presence of periodontitis is associated with IBD disease activity is uncertain.

Methods

A questionnaire-based survey was conducted in Denmark. A total of 1,093 patients with IBD, i.e., 527 patients with Crohn’s disease (CD) and 566 patients with Ulcerative colitis (UC), answered the questionnaire. The survey included questions on social demographics, oral health, as well as IBD-related characteristics. Oral health was assessed by the number of teeth, the state of teeth and gums, and the Periodontal Screening Score (PESS) which is a validated instrument to screen for severe periodontitis. Disease activity in patients with UC and CD was assessed by the Simple Clinical Colitis Index (SCCAI) and the Harvey & Bradshaw’s Activity Index (HBI), respectively. Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI). Univariate and multivariate statistical analyses were performed to assess each variable.

Results

Patients with CD reported significantly fewer remaining teeth (p=0.004) and poorer state of teeth and gums (p=0.001) in comparison to patients with UC. Irrespective of IBD disease subtype, patients with a reduced number of teeth scored significantly higher on the IBD disability index (p=0.001) and reported an increased disease activity in the last 12 months (p=0.001). Patients with self-reported severe periodontitis scored significantly higher on the IBD disability index (p=0.041) and reported an increased disease activity in the last 12 months (p=0.001). For patients with UC, self-reported severe periodontitis was associated with a higher SCCAI score (p=0.031). Likewise, patients with CD who had a reduced number of teeth scored significantly higher on the HBI (p=0.017).

Conclusion

Periodontitis was significantly associated with increased IBD disease activity as well as increased IBD disease related disability. CD patients had significantly poorer oral health compared with UC patients. Our results highlight a need for an increased focus on oral health in patients with IBD.
P688 Sex difference in inflammatory bowel disease patients regarding depression: a nationwide population based study in Korea
Authors: Moon J M , Han K , Shin S Y , Choi C H , Kim J S
Published: January 2022

Background

Inflammatory bowel disease (IBD) patients are often exposed to the risks of developing psychological symptoms such as anxiety or depression. We aimed to investigate sex difference regarding incidence of depression among Korean IBD patients.

Methods

A cohort involving a total of 133,216 subjects were established using Korean HIRA (health insurance review & assessment service) database from January 2009 to December 2017. Newly diagnosed IBD patients were 47,416, according to the International Classification of Diseases, 10th revision (ICD-10). From the newly diagnosed IBD population, we defined incidence of depression using the ICD-10 code.

Results

Among the IBD population, 27,172 (57.3%) were male and they were slightly younger than female (39.09 and 39.81, p<001). During the follow-up period, a total of 5,355 were newly diagnosed as depression. The incidence of depression were more evident in the female both in ulcerative colitis (incidence ratio, IR, per 1000 of 23.55 and 32.81, to male and female, respectively) and crohn’s disease (IR per 1000 of 16.24 and 30.76, respectively) This trend was consistent even with variables adjusted to age, diabetes, hypertension and medication use (biologics, steroids, 5-ASA, immunomodulators and antibiotics) Female IBD patients were at an increased risk of developing depression compared to male with a hazard ratio of 1.40 (1.33–1.48, p<0.001). Further subgroup analyses were performed according to age, co-morbidities and biologics use, revealing similar results.

Conclusion

Risk of depression was elevated in Korean female IBD patients compared to males. Gastroenterologists managing IBD patients on clinics should be well aware of gender-specific issues regarding depression.