bluuebunny/crossref_metadata_2025_split huggingface dataset:
P521 Effectiveness of ustekinumab as therapy for chronic antibiotic refractory pouchitis
Authors: Outtier A , Louis E , Dewit O , Schops G , Verstockt B , Sabino J , Vermeire S , Ferrante M 
Published: January 2023

Abstract

Background
Up to 10% of patients with ulcerative colitis 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 and maintenance therapy with ustekinumab (UST).

Methods
We performed a prospective, multicentre, open-label study of patients with CARP (mPDAI ≥5 with an endoscopic subscore ≥2) . Patients received a weight-range-based infusion of UST at baseline (~6mg/kg) and subcutaneous injections of 90mg UST every 8 weeks thereafter until week 48. Patients underwent a pouchoscopy at baseline, week 16 and week 48, with assessment of the modified pouchitis disease activity index (mPDAI). The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI &lt;5 and reduction by ≥2 points from baseline) at week 16. For this abstract we focus on the secondary endpoints at week 48 including the proportion of patients achieving steroid-free remission and response (reduction of mPDAI by ≥2 points from baseline) using a non-responder imputation. For patients still continuing UST at week 48, we evaluated the change in symptomatic and endoscopic mPDAI subscore, 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 enrolled 22 patients (59% male, median age 42.2 years, median time after surgery 8.2 years). Twelve (54.5%) patients had previously been treated with biologics for CARP (table 1). At week 16, steroid-free remission was achieved in 27.3% of patients. At week 48, steroid-free remission was achieved in 36.4% and response in 54.5% of patients. In the 14 patients continuing UST at week 48, a significant decrease in total mPDAI (4 (1.8-7.3) vs. 8 (8-10), p&lt;0.001), clinical subscore (1 (0-2.3) vs. 3 (2-4), p=0.001), and endoscopic subscore (3 (1.8-4.3) vs. 6 (4.8-6), p=0.001) was observed compared to baseline (figure 1). Faecal calprotectin (129 (80-344) vs. 229 (139-541) mg/kg, p=0.17) and CRP (2.5 (1.3-4.4) vs. 3.8 (1.6-9.3) mg/L, p=0.09) levels did however not decrease significantly (figure 2 and 3). 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, maintenance therapy with UST showed a clinical and endoscopic effect in half of the patients, but was not associated with changes in inflammatory biomarkers. These promising results warrant confirmation in a placebo-controlled study with UST for the treatment of CARP.
P534 Dual biologic or small molecules therapy in refractory paediatric inflammatory bowel disease (DOUBLE-PIBD): A multi-center study from the paediatric IBD Porto group of ESPGHAN
Authors: Cohen S , Olbjorn C , Kolho K L , Aloi M , Musto F , de-Carpi J M , Lozano-Ruf A , Yogev D , Matar M , Scarallo L , Bramuzzo M , de Ridder L , Kang B , Norden C , Wilson D C , Tzivinikos C , Turner D , Yerushalmy-Feler A 
Published: January 2023

Abstract

Background
Current data on dual biologic or small molecules therapy in children are limited. The aim of the study was to evaluate the effectiveness and safety of dual therapy in paediatric patients with IBD.

Methods
This was a retrospective multicenter study from 14 centers affiliated with the IBD interest and Porto groups of ESPGHAN. We included children with IBD who were treated with combination of biologic agents or biologic and small molecule, with at least 3 months of follow-up under this therapy. Demographic, clinical, laboratory, endoscopic and imaging data were collected. Adverse events were recorded. All analyses were done in the intention-to-treat population. Children that discontinued therapy were considered treatment failures and were imputed for non-response, while missing data was imputed according to the last observation carried forward method.

Results
Sixty-two children [35 Crohn’s disease (CD), 27 ulcerative colitis (UC)], with a median age of 15.5 (IQR 13.1-16.8) years and disease duration of 3.8 (IQR 2.5-6.1) years were included. All children failed previous biologics and 47 (76%) failed at least two biologic agents. The dual therapy included anti-TNF agent and vedolizumab in 30 children (48%), anti-TNF and ustekinumab in 21 children (34%), vedolizumab and ustekinumab in 8 children (13%), and tofacitinib and other biologics in 3 children (5%). Clinical remission was observed in 21 (35%), 30 (50%) and 38 (63%) children at 3, 6 and 12 months, respectively. Of 27 children who were treated with corticosteroids at baseline, 20 (74.1%) were weaned within 3 months after the initiation of dual therapy. At 12 months of follow up, normalization of C-reactive protein and decrease in fecal calprotectin to &lt; 250 mcg/g were achieved in 75% and 64%, respectively. Endoscopic and transmural healing were observed in 2/23 (9%) and 5/16 (31%) children, respectively. Male sex and diagnosis of UC were associated with higher likelihood of clinical remission (p=0.017 and p=0.020, respectively). Adverse events were reported in 29 (47%) children. While most adverse event were mild, 8 were regarded as serious and 6 (10%) led to discontinuation of dual therapy. The serious adverse events included infusion reaction to infliximab, fatigue and headache following vedolizumab infusion, severe skin eruptions (3 patients), cellulitis and skin abscess, elevated liver enzymes and deep vein thrombosis.

Conclusion
Dual biologic or small molecules therapy may be effective in children with otherwise refractory IBD. The risk of serious adverse events should be considered before recommending dual therapy.
P537 Prevalence of post-COVID-19 vaccination IBD flare-ups: a single-center prospective study.
Authors: Roblin X , Williet N , Faure J , Bastide L , Barrau M , Paul S 
Published: January 2023

Abstract

Background
Case reports of IBD flares after COVID-19 vaccination have been reported. These cases appear to be rare. In a recent study analyzing adverse event rates and impact on clinical activity of IBD after COVID-19 vaccination, the authors reported a rate of IBD reactivation in 2% of cases defined as reactivation of symptoms associated with a change in therapy (Prevent COVID Study) (Weaver et al. IBD 2022).

Methods
Any patient with IBD, followed as an outpatient in our department and having accepted to be vaccinated against COVID-19, was proposed this study. All the patients included in the study had to contact the department if, within one month of receiving the COVID-19 vaccine, they presented a clinical picture suggestive of an IBD relapse. The patients were reviewed in emergency and an assessment of IBD activity was made: clinical activity score, CRP and/or calprotectin dosage, short endoscopy in case of UC, colonoscopy or MRI in case of CD. The link between vaccine and relapse was defined by the absence of clinical activity for at least 3 months before vaccination and relapse of the disease at the latest within 30 days after vaccination without therapeutic modification in between.

Results
231 patients (mean age: 44.6 years, sex ratio M/F=1.1, 43.3% MC) were eligible. 176 patients had at least three doses of vaccine, all with mRNA, and 55 with no more than two doses. 97 patients (42%) were infected at least once with COVID 19, confirmed by PCR after at least one dose of vaccine, all without resorting to hospitalization, resuscitation or death. 29 patients (12.5%) developed IBD after vaccination (43.6% MC, sex ratio=1, 80% of cases after 3 doses of vaccine) after a median time of 8.5 days (5-17 days). Patient characteristics, treatment received, number of vaccinations, or Covid infection were comparable between groups with and without reactivation after COVID-19 vaccine (P=NS). The risk of relapse after vaccination was 29 per 646 vaccine doses (4.4%). Table 1 reports pre-exacerbation treatments and proposed treatment changes as well as medium-term response. For IBD flares, no severe forms, hospitalization or surgery were observed. Fifteen patients were optimized on their treatment and 18 were switched to another treatment. All were put into clinical remission of their disease. In univariate analysis, no clinical parameter (type of IBD, age, sex, smoking), the number of previous vaccinations, a previous infection with covid 19 or the type of treatment was associated with a significant risk of relapse after vaccination.

Conclusion
The risk of IBD relapse in patients in durable clinical remission is possible after COVID-19 mRNA vaccination but remains low (4%). No risk factors were isolated in this work.
P538 Suboptimal disease control is common in patients with Crohn’s perianal fistulas with capacity to optimise medical and surgical treatment in real-world experience: A cross-sectional analysis of baseline disease characteristics in the FINESS study
Authors: De Gregorio M , D’Souza B , Connell W , Kamm M A , Woods R , Connor S J , Thompson A J , Ding N S 
Published: January 2023

Abstract

Background
Crohn’s perianal fistula treatment is often challenging, requiring combined medical and surgical treatment with heterogeneity in real-world practice. We herein evaluate disease activity and management history of patients with Crohn’s perianal fistulas, identifying those with active disease amenable for treatment optimisation.

Methods
We present the results of a cross-sectional study of disease characteristics among patients with Crohn’s perianal fistulas at a single specialist Inflammatory Bowel Disease service. Patients with Crohn’s perianal fistulas seen in clinic from February 2021 to June 2022 (new and review appointments) were sequentially enrolled. Patients were excluded based on rectovaginal or rectovesical fistulas, proctectomy, pregnancy or breastfeeding. Baseline disease activity was defined as active (stage A/B: sepsis, actively draining), optimised with a chronic seton in situ (stage C), or remission (stage D: no discharge from fistula tract external opening). Radiologic disease activity was assessed with magnetic resonance imaging using the Van Assche Index (VAI), VAI-inflammatory sub-score (VAIinfl; derived from T2-hyperintesnity, collections &gt;3mm diameter, and rectal wall involvement), and Magnetic Resonance Novel Index for Fistula Imaging in Crohn’s Disease (MAGNIFI-CD) score.

Results
Sixty patients were included with a median age of 39 years (IQR 17.7), 52% male, median clinic attendance of 6 years (IQR 7.9), median Crohn’s and perianal disease duration of 13 (IQR 16.8) and 8 (IQR 13.5) years, respectively. Majority were on anti-tumour necrosis factor-α therapy (28% infliximab, 40% adalimumab) and an immunomodulator (55% thiopurine, 5% methotrexate). Forty-two percent had undergone perianal surgical intervention within the preceding 12 months, see Table 1. Forty-eight percent (n=29), 7% (n=4), and 45% (n=27) had stage A/B, C, and D disease activity, respectively. Radiologic disease activity scoring indices were lower between stage D and A/B (VAI 4 vs 12; VAIinfl 0 vs 8; MAGNIFI-CD 2 vs 6, respectively), see Table 2. Of those with stage A/B disease activity, 31% were not on a biologic (63% new diagnosis, 25% prior remission, 13% comorbidities precluding), 52% were infliximab naïve (71% new diagnosis, 14% prior remission, 14% contraindications), 85% who were on a biologic had potential for initial or further dose escalation, and 31% did not undergo perianal surgical intervention in the preceding 12 months.

Conclusion
In a single specialist centre, almost half the patients with Crohn’s perianal fistulas have clinically active disease, with capacity to optimise medical and/or surgical treatment in the majority. Prospective assessment of a model of care directed towards optimising treatment in these patients is needed.
P544 Low TNF production and low TREM1 expression as negative predictors for remission under adalimumab therapy in Crohn′s Disease patients
Authors: Jessen B , Tóth M , Freise I , Staudacher J , Haag L M , Kredel L , Schumann M , Weidinger C , Sonnenberg E , Siegmund B 
Published: January 2023

Abstract

Background
Approximately one third of IBD patients show a primary non-response to anti-TNF therapy. An individualized treatment approach requires clinical predictors. Our previous study showed that LPS-stimulated TNF production can be used to predict response to infliximab in Crohn′s Disease patients. The expression of the myeloid receptor TREM1 is also known as a potential predictive marker for anti-TNF therapy response. The aim of this study is to compare these two predictors for response to adalimumab.

Methods
In this prospective observational study 24 adults with Crohn′s Disease starting adalimumab treatment were included. Disease activity was assessed clinically (Harvey-Bradshaw-Index (HBI)), through lab results (leukocytes, C-reactive protein, calprotectin) and per ultrasound (Limberg-Score) at the time point of adalimumab induction, after 6 and 12 weeks. TNF-production of LPS-stimulated peripheral blood mononuclear cells was measured via ELISA at the baseline. The expression of TREM1 and its soluble isoform TREM1sv was quantified from whole blood RNA via qPCR. Primary endpoints were clinical response after week 6 and 12. Response was defined as a decrease in HBI ≥2, remission as HBI &lt;5. Cut-off values for low- and high-producers were defined via receiver operating characteristic (ROC). Results were tested for significance with chi²-Test.

Results
Of 24 recruited patients 18 have currently reached week 12. 5 patients have not reached remission within 6 weeks, 4 have not reached remission within 12 weeks. TNF production and TREM1 expression differed among patients at baseline. After definition of a cut-off value 6 low-TNF-producers, 8 low-TREM1-producers and 7 low-TREM1sv-producers could be identified. Three out of 6 low-TNF-producers were in non-remission after 6 weeks compared to 2 out of 12 high-TNF-producers (p=0.1366). Five out of 8 low-TREM1-producers were in non-remission after 6 weeks compared to 0 out of 9 high-TREM1-producers (p=0.0048, 1 missing value). Four out of 7 low-TREM1sv-producers were in non-remission after 6 weeks compared to 1 out of 10 high-TREM1sv-producers (p=0.0488, 1 missing value).

Figure 1) Remission after 6 weeks of adalimumab treatment - low vs. high TNF

Figure 2) Remission after 6 weeks of adalimumab treatment - low vs. high TREM1

Figure 3) Remission after 6 weeks of adalimumab treatment - low vs. high TREM1sv

Conclusion
Low TREM1 and TREM1sv expression seem to be stronger predictors for non-remission after 6 weeks of adalimumab treatment compared to TNF-production. These results are to be validated with increased patient numbers.
P547 Rate of Colectomy Increases within Twelve Months of Sequential Therapy for Ulcerative Colitis
Authors: Barnes E , Zhang X , Long M , Herfarth H , Kappelman M 
Published: January 2023

Abstract

Background
Even the best medical treatments for ulcerative colitis (UC) are often ineffective, with up to 15% of patients requiring a colectomy within the first 10 years of diagnosis. In the current era, patients have access to an increasing number of medical therapies that may prevent and/or delay surgery. To evaluate the relative effectiveness of sequential therapies for UC, we evaluated the 12-month colectomy rate among patients switching to a second, third, or fourth-line biologic or small molecule therapy for UC.

Methods
We conducted a retrospective cohort study, using a new-user design, evaluating patients with commercial insurance in the MarketScan database between 2000 and 2019. The index date for the study was defined as the date of the first claim for a second, third, or fourth biologic or small molecule therapy. The primary outcome was defined as colectomy-free survival at 12 months after the index date. Significance of 12-month colectomy rates over time was evaluated using the Cochran-Armitage test of trend and a Generalized Estimating Equation (GEE) model adjusting for age (18-35, 36-55, &gt;55), sex and index year (year 2007-2014 and 2015-2019).

Results
We identified 3,325 patients with UC that made at least 1 switch in biologic or small molecule therapy during the study period. Among these, 50% were female and the median age was 41 years (interquartile range 31-52 years, Table 1). The most frequent initial biologic switches were from an anti-tumor necrosis factor alpha (TNF) to an anti-TNF (1895 patients [57%]) and anti-TNF to vedolizumab (980 patients [30%]) were the most common sequences of therapies (Table 2). Overall, 392 (12%) patients underwent colectomy within 12 months of the first switch while 116 of 695 (17%) patients underwent colectomy within 12 months of the second switch. Among 161 patients that underwent 3 switches, 30 (19%) underwent colectomy within 12 months of the third switch (p&lt;0.001, Table 3). The rate of UC-related hospitalizations in the 12 months after switch also increased significantly with each subsequent switch (11% vs. 15% vs. 19% for first, second and third switches respectively, p&lt;0.001). The colectomy rate per switch in therapy appeared stable when stratifying by index date and age at index date (Figure 1).

Conclusion
Despite increases in the number of available mechanisms for the treatment of UC, a substantial proportion of patients will still require colectomy for UC. The absolute risk of colectomy within 12 months and other negative outcomes increase with each subsequent treatment. These data can help inform complex decisions regarding the timing of surgery relative to initiation of subsequent therapy in patients with medically-refractory disease.
P552 Anti-TNF Treatment and Risk of Atrial Fibrillation in Inflammatory Bowel Disease Patients
Authors: Cohen Y , Fischman M , Waterman M , Dolnikov K , Azzam Z S , Ghersin I 
Published: January 2023

Abstract

Background
Inflammation is thought to play a role in the development of atrial fibrillation (AF). Previous studies suggested that inflammatory bowel disease (IBD) is associated with increased risk of AF. These studies also found IBD patients receiving biologic agents were at higher risk of AF than patients not receiving them.
We sought to determine the association between anti-TNF treatment and the risk of AF in IBD patients

Methods
In this observational cohort, we included all adult IBD patients who were registered in Rambam Medical Center, diagnosed with IBD from November 1983 to October 2021. We excluded patients who were diagnosed with AF and/or stroke prior to IBD diagnosis. Disease severity was based upon IBD treatment. Mild disease was defined as no treatment, 5-ASA, or topical steroids, while moderate-to-severe disease was defined as any immunomodulator, biologic or systemic steroid therapy.
Primary outcome was AF diagnosis.
We used Cox proportional hazard model to compare AF in patients receiving anti-TNF treatment to those with mild disease. We further adjusted the hazard ratio of AF development based on known AF risk factors, including age, male gender, cardiovascular disease, chronic kidney disease, pervious venous thromboembolism, hyperlipidemia, diabetes, and thyroid disease.

Results
Our initial cohort included 5,326 patients. After exclusion, 4,886 patients were included.
Median follow-up time was 8.49 years
2,720 patients were considered as having mild IBD, while 787 patients received anti-TNF medications.
During follow-up period, cumulative incidence of AF was 1.50% (n=41) and 0.89% (n=7), respectively (p=0.21).
Unadjusted hazard ratio of AF occurrence in anti-TNF patients was 0.6 (95% CI; 0.27-1.3, p=0.211). After adjustment, hazard ratio of AF occurence was 1.33 (95% CI; 0.53-3.3, p=0.545).

Conclusion
Anti-TNF treatment was not associated with increased risk of AF among IBD patients. This provides reassurance regarding the cardiovascular safety of anti-TNFs in a real-world IBD cohort.
P553 Active tuberculosis and opportunistic infections: Pooled safety analysis of ustekinumab through up to 5 years across all approved indications
Authors: Ghosh S , Long M , Ott E , Gasink C , Baker T , Godwin B , Miao Y , Loftus E 
Published: January 2023

Abstract

Background
Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment.

Methods
Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or &gt;16 weeks after the last UST dose for UST pts who switched to PBO.

Results
Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table 1); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a Hungarian CD pt 10 months after receiving last UST dose) and UST (n=1) pts (Table 1). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1).

Conclusion
Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 yrs with 13807 PYs of follow-up and not higher in UST pts vs PBO pts, suggesting no increased risk of OI with long-term UST treatment.