bluuebunny/crossref_metadata_2025_split huggingface dataset:
P385 Tailoring induction treatment for children with Crohn’s disease
Authors: Cuomo M , Carobbio A , Aloi M , Alvisi P , Banzato C , Bosa L , Bramuzzo M , Campanozzi A , Catassi G , D’Antiga L , Di Paola M , Felici E , Fioretti M T , Gatti S , Graziano F , Lega S , Lionetti P , Marseglia A , Martinelli M , Musto F , Sansotta N , Scarallo L , Zuin G , Norsa L 
Published: January 2022

Abstract

Background
Multiple clinical studies in children with Crohn’s disease (CD) have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission and even to promote mucosal healing.
However, EEN as inductive treatment may be not tolerated or inefficient and we are well aware of the paramount importance of a well conducted induction treatment for paediatric CD with the goal of an individualized induction treatment to improve the prognosis and the quality of life of inflammatory bowel disease (IBD) children.

Methods
A retrospective multicentre study including newly diagnosed children with CD treated with EEN as induction therapy was designed. The primary aim of the study was to study predictive factors of non- adherence to treatment. The secondary endpoint were predictive factors of clinical non-remission at the end of induction treatment. Those data together were analysed with the ultimate goal of trying to define an individualized induction treatment for children with CD.

Results
376 CD children from, 14 IBD paediatric referral centres were enrolled in the study. The rate of EEN adherence was, 89 %. Colonic involvement and FC &gt;, 600 μg/g at diagnosis were found associated with a reduced EEN adherence in univariate and multivariate analysis. The remission rate of those who completed induction treatment was, 67%. A multivariate analysis showed that factor determining lower remission rate were age &gt;, 15 years and PCDAI &gt;, 50. With those results we were able to create a decisional algorithm which is provided in figure 1.

Conclusion
EEN administered for, 8 weeks is effective for inducing clinical remission. The rate of adherence is high but there is a group of patients (colonic involvement + hight FC) which are at risk of non-adherence and thus may be candidate for alternative dietary induction regimens. Moreover, older patients with moderate to severe active disease (PCDAI&gt;40), are at higher risk of failing clinical remission achievement after EEN and may benefit from an early anti-TNF alpha treatment. Personalized treatment strategies should be proposed weighing the benefits and risks based on each patient’s disease location, phenotype and disease activity with the overall aim of obtaining rapid control of inflammation to reduce long-term bowel damage.
P389 Indicators for inadequate response to advanced therapy in patients with Ulcerative Colitis: results from a medical chart review in the United Kingdom
Authors: Lindsay J , Picker N , Kromer D , Smyth M , Patel H 
Published: January 2022

Abstract

Background
Patients with Ulcerative Colitis (UC) who commence advanced therapy may experience inadequate response or require therapy modification to achieve remission. Therapeutic modification increases health care costs and is associated with adverse events. This study aimed to examine the rates of inadequate response, therapeutic modification and subsequent remission among UC patients starting advanced therapy in the UK.

Methods
Using a retrospective chart review, patients with UC treated with an advanced therapy (adalimumab, infliximab, golimumab, vedolizumab, and tofacitinib) between, 01/2017 and, 09/2019 were selected from, 8 clinics across the UK. Patients with ≥12 months of data before and after starting an advanced therapy (Index Date) were included. Inadequate response was defined as at least one of the following events: index therapy discontinuation or switch due to lack of response, therapy escalation, augmentation with an additional conventional therapy, corticosteroid (CS) dependency (use for ≥12 weeks), new CS initiation, UC-related hospitalisation, surgery, or emergency department visit. Remission was assessed using components of the Mayo score. Kaplan-Meier analysis was used to examine remission rates over, 24 months. Subgroups included patients with prior exposure to biologics, and patients with vs. without remission at, 12 months. Factors associated with time to remission were assessed in a multivariate Cox regression model.

Results
Among, 238 patients included (female:, 46.6%; median age, 42 years; median follow-up:, 28.8 months), 178 (74.8%) patients were biologic-naïve, and, 60 (25.2%) were biologic-experienced. At, 12 months, 105 (44.3%) patients had ≥1 indicator for an inadequate response (Figure, 1); the median time to first event was, 18 months. Among those who discontinued (N=72), 69.4% switched to another advanced therapy. Inadequate response was more frequent in biologic-naïve vs. experienced patients (50.3% vs., 26.7%; p&lt;0.01) and among those without vs. with remission (56.3% vs., 34.4%; p&lt;0.01). At, 12 months, 61 patients (46.1%) had not achieved remission (median time to remission:, 7.6 months; Figure, 2). At, 12 months, one third (33.0%) of patients in remission required therapy modification (augmentation, dose escalation, and use of CS). In an adjusted model, chances of remission were halved in biologic-experienced patients vs. naive patients (hazard ratio:, 0.49; p&lt;0.05).

Conclusion
More than two-fifths of UC patients had an inadequate response, and nearly half did not achieve remission within one year after therapy start. Even among patients in remission, one third required additional therapy modifications. More effective therapies are needed to achieve better outcomes for patients with UC.
P407 A Phase IB/IIA study of remestemcel-L, an allogeneic bone marrow derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: An interim analysis
Authors: Lightner A , Dadgar N , Fulmer C , Ream J , Nachand D , Steele S 
Published: January 2022

Abstract

Background
Direct injection of mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease. However, no studies have looked at the direct injection of MSCs for luminal ulcerative colitis (UC).

Methods
Following screening and informed consent, patients with medically refractory UC were randomized in a, 2:1 fashion to receive remestemcel-L, an ex vivo expanded allogeneic bone marrow derived MSC product, at a dose of, 150 or, 300 million MSCs versus placebo delivered via direct injection using a, 23 G sclerotherapy needle at the time of colonoscopy. Patients were included if they had medically refractory UC defined as an established diagnosis for at least, 6 months prior to study enrollment and had lost response to at least one monoclonal antibody in the past. Patients were evaluated with validated clinical and endoscopic scoring systems at, 2 weeks, 6 weeks, and, 3 months post MSC delivery. Patients randomized to control crossed over at, 3 months to receive MSC treatment and followed the same schedule for post MSC evaluation.

Results
A total of six patients were enrolled and treated;, 4 were randomized to treatment and, 2 to placebo. All had been on prior anti-TNF or anti integrin-therapy. There were no adverse and serious adverse events related to investigational product.
In the treatment group (n=4), the Mayo score and Mayo endoscopic severity score decreased in all patients by two weeks after MSC delivery. By six weeks post MSC treatment, all treated patients had achieved clinical and endoscopic remission as defined by the Mayo score and Mayo endoscopic severity score. Patient reported number of daily bowel movements decreased as did urgency and presence of blood in the stool. With regard to patient reported outcomes, at three months, based on the inflammatory bowel disease patient reported treatment impact (IBD-PRTI), all patients were extremely satisfied or satisfied with their MSC treatment. Treated response was described as excellent or good in all patients.
In the control group (n=2), the Mayo score did not decrease. Patient reported number of daily bowel movements increased as did the number reporting blood in their stool; urgency remained unchanged. With regard to patient reported outcomes, at three months, based on the IBD-PRTI, one patient was neutral, and one patient was dissatisfied. Treated response was described as poor or unchanged in control patients.

Conclusion
MSCs offer a safe alternative therapeutic for the treatment of medically refractory UC. Early data suggests improved clinical and endoscopic scores by as early as two weeks following MSC delivery.
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

Abstract

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&lt;0.001 and p&lt;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

Abstract

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 (&lt; 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

Abstract

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 &gt;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

Abstract

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 &lt;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

Abstract

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&lt;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.