bluuebunny/crossref_metadata_2025_split huggingface dataset:
P806 Development of a clinical model to predict secondary non-response of anti-TNFα treatment on Crohn's disease
Authors: Xiang L , Xiaomei S , Yan L , Wei T , Hong G 
Published: January 2024

Abstract

Background
Secondary non-response to anti-tumor necrosis factor-α (including Infliximab and Adalimumab) in patients with Crohn’s disease (CD) is common. Prediction of secondary non-response is essential for treatment decision for individual patients.

Methods
The clinical model was constructed in a training cohort. Clinical features, serological parameters, genetic biomarkers etc. were obtained as predictors after anti- TNFα therapy. Univariate analysis was performed to eliminate irrelevant predictors with secondary non-response. A logistic regression model was developed using genetic biomarkers and predictors with P &lt; 0.1 in the univariate analysis. Finally, the model was validated with reference to its calibration and clinical decision curve.

Results
In a univariate analysis, infliximab antibodies,white blood cell(WBC), albumin(Alb), previous use of immunosuppressant, switching to other drugs, immunological preparation were found associated with secondary non-response to IFX. Logistic regression analysis with stepwise backward selection P &lt; 0.01 and a clinical model was developed based on the above predictors.

Conclusion
The study presents a model to predict secondary non-response to anti-TNFα in CD. This model can be used to help clinicians adjust the therapeutic strategy for CD patients.
P810 Fecal microbiota transplantation in Ulcerative rectocolitis
Authors: Ferreira F , Sousa M , Melado M , Pacheco M , Trindade L , Lorentz F , Carmo L , Clara A 
Published: January 2024

Abstract

Background
The objective of this work was to carry out a systematic review of the literature to evaluate interventional trials that compare fecal microbiofa transplantation (FMT) with a control group and evaluate the incidence of remission of ulcerative colitis as an outcome.

Methods
The search was conducted using the database from PubMed, from February 2021 to April 2023. In all, 303 articles were found. After reading the titles, 43 articles were selected for the abstract reading. After all the analysis with inclusion and exclusion criteria, 7 articles were fully analyzed in the present study. Of the 7 selected studies, 71% (5/7) performed clinical trials.

Results
In all the studies, a total of 352 patients were submitted to the FMT, with a average of 63 participants per study. The age of the participants vary from 18 to 75 years old, with all the studies having an average age in the third or fourth decade. All articles included patients with clinical disease activity, and 85.7% used the Mayo severity index. Regarding the stool administered, in 71.4% of the studies the participants received frozen stool and the preparation was carried out with saline solution. The infusion was performed with colonoscopy on 85% (6/7) of the studies, however there was no standardized approach to the transplant protocol or preparation of the patients before the FMT. The association between the FMT and the clinical remission has been positive in 85% (6/7) of the studies. 4 of the 5 articles that evaluated the clinical response pointed to an improvement of the patients submitted to the transplant over the placebo group. The endoscopic remission were analyzed in all the 7 studies showing positive results in 43% (3/7) of them. The laboratory were performed in just 1 of the studies and they reported substantial improvement of the evaluated parameters of the FMT group. There was no significant difference between the risk of developing adverse effects between the FMT and the placebo groups.

Conclusion
The FMT has been shown to be effective on the induction of clinical remission of Ulcerative Colitis, however, clinical studies with greater scientific impact are needed to implement this new therapeutic modality.
P834 Choosing wisely: Ustekinumab in Elderly Crohn’s Patients – A Comparative Study
Authors: Dar Antaki L , Shani U , Dotan A , Ukashi O , Ben-Horin S , Kopylov U , Levartovsky A 
Published: January 2024

Abstract

Background
The burden of Inflammatory Bowel Disease (IBD) in elderly patients derives from background comorbidities and the elevated risk associated with immunosuppressive treatments. In the present study, we aimed to assess the efficacy and safety of ustekinumab (UST) in elderly patients with Crohn's disease (CD).

Methods
This study was designed as a retrospective-cohort study including patients ≥ 60 years old (elderly) and patients &lt; 60 years (non-elderly) who commenced UST for CD at a large, tertiary medical center. Outcomes were assessed by clinical response evaluation through parameters such as physician global assessment (PGA) and the Harvey-Bradshaw index (HBI), alongside assessment of clinical biomarkers, hospitalization rates, treatment persistence, and the necessity for surgical interventions. A secondary analysis was conducted of elderly patients treated with UST compared to elderly patients treated with vedolizumab (VDZ).

Results
In total, the primary analysis included 99 patients treated with UST (34 elderly patients and 65 non-elderly patients). Duration of follow-up was a median of 12 months (IQR 0). Elderly patients had predominantly an isolated ileal disease (68%) compared to an ileo-colonic disease (36%) in non-elderly patients (p = 0.017). The median age of onset was 68 years (IQR 64-75), and 34 years (IQR 28-42), respectively. Furthermore, elderly individuals were more likely to receive corticosteroids as their initial treatment (44% vs. 14%, &lt;0.001). No differences were demonstrated in disease duration, EIM, phenotype, or previous biological therapy. Following six months of therapy, elderly patients were more likely to achieve complete clinical remission (31% vs. 12%, p = 0.035) as assessed by PGA. The elderly group experienced higher hospitalization rates during the 6-month (21% vs 4.6%, p = 0.029) and the 12-month follow-up period (15% vs. 3.1%, p = 0.045), while surgery rates were comparable between non-elderly and elderly groups (table 1). Concerning elderly UST vs elderly VDZ patients (n=69), no significant differences were observed in clinical response and remission rates between the groups after 6 and 12 months of follow up. In addition, no significant differences were shown in regard to safety (hospitalizations, surgery or therapy cessation rates).

Conclusion
UST is an effective treatment option in elderly CD patients. However, this population had higher hospitalization rates compared to non-elderly patients, greatly owing to age and comorbidities.
P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic review
Authors: Forss A , Flis P , Sotoodeh A , Kapraali M , Rosenborg S 
Published: January 2024

Abstract

Background
Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN.

Methods
We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database.

Results
Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN.

Conclusion
In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.
P845 Vedolizumab induces endoscopic healing uniformly irrespective of disease location: post-hoc analysis of the LOVE-CD trial
Authors: Hens B , Oldenburg L , Molnár T , Baert F , Clasquin E , Vermeire S , Löwenberg M , D'Haens G 
Published: January 2024

Abstract

Background
Vedolizumab (VDZ) is a gut-selective anti–α4β7-integrin monoclonal antibody approved for the treatment of Crohn's disease (CD). We performed a post-hoc analysis of the LOVE-CD trial to evaluate the effect of disease location on endoscopic healing.

Methods
LOVE-CD is a prospective multicentre study of VDZ therapy in adult patients with moderate-severe CD (Crohn's Disease Activity Index (CDAI) &gt;220 and presence of ulcers at endoscopy). Patients received VDZ 300 mg infusions at weeks 0-2-6 followed by 8 weekly infusions up to week 52. An additional infusion at week 10 was given to patients without clinical response (CDAI decrease &lt;70 points). Corticosteroids had to be withdrawn by week 26. Ileocolonoscopies were performed at weeks 0, 26, and 52, recorded, and centrally scored by 2 independent readers using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The primary endpoint for this analysis was the proportion of patients, stratified by disease location (according to Montreal classification), with ulcer-free endoscopy (absence of any ulceration; SES-CD ulcer score 0) at week 52. Key secondary endpoints at week 52 were the proportion of patients, stratified by disease location, with endoscopic remission (SES-CD &lt;4 for L2/L3 CD or &lt;2 for L1 CD, and no subscores &gt;1), with combined steroid-free clinical and endoscopic remission (CDAI&lt;150 and endoscopic remission), the segmental healing rates, and ulcer healing rates stratified by disease duration.

Results
186 patients were included in this intention to treat (ITT) analysis: 42 (22.6%) with L1, 52 (28.0%) with L2, and 92 (49.5%) with L3 disease. Baseline characteristics are shown in table 1. At week 52, the primary endpoint (absence of all ulcerations) was attained in 15/42 patients with L1 (35.7%), 20/52 with L2 (38.5%) and 25/92 with L3 CD (27.2%) (ITT, NRI (p=0.327)). Endoscopic remission was observed in 12/42 patients with L1 (28.6%), 20/52 with L2 (38.5%), and 29/92 with L3 disease (31.5%) (ITT, NRI (p=0.558)). The combined endpoint of clinical-endoscopic remission was reached in 9/42 L1 (21.4%), 16/52 L2 (30.8%), and 23/92 L3 patients (25.0%) (ITT, NRI (p=0.571)). Resolution of ileal ulcers was achieved in 15/40 L1 patients (37.5%) and 37/90 L3 patients (41.1%) (ITT, NRI (p=0.698)), resolution of colonic ulcers in 21/52 L2 (40.4%) and 45/90 L3 patients (50.0%) (ITT, NRI (p=0.268). Patients with early CD (disease duration &lt;2 years) had higher ulcer healing rates than patients with late CD (47.5% versus 24.8%) (ITT, NRI (p=0.002)).

Conclusion
This post-hoc analysis of LOVE-CD shows that disease location does not affect endoscopic healing rates with VDZ in CD. However, early CD is associated with significantly higher endoscopic remission rates compared to late CD.
P847 Effectiveness of tofacitinib in ulcerative proctitis compared to left sided colitis and pancolitis
Authors: Singh A , Mahajan R , Midha V , Kaur K , Singh D , Bansal N , Sood A 
Published: January 2024

Abstract

Background
Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC).

Methods
This was a prospective observational cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure.

Results
Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 55%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. (Figure 1) Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary non-response at week 48. The median fecal calprotectin values at week 8 were 119.5 (53.75-611.25), 134 (63-456) and 208 (48.25-876) in patients with UP, LSC and PC, respectively. Similarly at week 48, the median fecal calprotectin values were the lowest in patients with UP (57[36-99]) as compared to patients with LSC (113[41-572]) and PC (150[89-1562]). The endoscopic remission rates at week 48 were similar in all the three groups (31%, 21% and 18% in groups UP, LSC and PC, respectively (UP vs LSC, p=0.25; UP vs PC, p=0.18; LSC vs PC, p=0.68). The probability of sustained clinical response was highest in patients with UP (cumulative probability of maintaining response 0.88) followed by groups LSC (cumulative probability of maintaining response 0.74) and PC (cumulative probability of maintaining response 0.60). The between group difference, was significant (Log Rank, p=0.03). (Figure 2) Patients with UP had the lowest incidence of adverse effects.

Conclusion
The effectiveness of tofacitinib in inducing and maintaining remission is greater in patients with UP compared to LSC and PC.
P849 Bayesian network meta-analysis of the efficacy of advanced therapies for patients with moderately to severely active ulcerative colitis naïve to advanced therapy
Authors: Jairath V , Leahy T P , Potluri R , Wosik K , Gruben D , Cappelleri J C , Bartolome L 
Published: January 2024

Abstract

Background
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In the absence of head-to-head randomised controlled trials (RCTs), network meta-analyses (NMA) offer insight into the comparative effectiveness of treatment options. NMA were conducted to examine the relative efficacy of etrasimod vs other advanced therapies (AT) with licensed dosing (European Medicines Agency) for the treatment of UC in patients naïve to biologic agents and/or Janus kinase inhibitors.

Methods
A systematic literature review (SLR) was performed on 15 November 2022, and covered all available records without time limit, using NICE DSU and PRISMA guidelines. NMA were conducted under a Bayesian framework, and a multinomial fixed-effect approach was used to model outcomes, clinical response and clinical remission, in the induction phase and among induction phase responders in the maintenance phase, in patients naïve to AT. Reported outcomes from trials with a treat-through design, such as ELEVATE UC 52, were recalculated to mimic those of a responder re-randomisation design; only responders in the induction phase were analysed in the maintenance phase. Data are presented as median relative risk (RR) of the treatment vs its comparator, along with corresponding 95% credible intervals (CrI). Prespecified sensitivity analyses were performed.

Results
Of 81 studies identified from the SLR, 21 and 11 RCTs were included in the induction and maintenance networks, respectively. For induction and maintenance phases, all therapies demonstrated benefit over placebo, consistent with phase 3 clinical trial data. In the NMA for clinical remission in the induction phase, etrasimod 2 mg had a statistically significant benefit over adalimumab 80/40 mg and 160/80 mg (RR [95% CrI] for treatment vs etrasimod 0.49 [0.29–0.78] and 0.67 [0.50–0.92], respectively), filgotinib 100 mg (0.55 [0.37–0.84]) and placebo; conversely, upadacitinib 45 mg had statistically significant benefit vs etrasimod (1.47 [1.07–2.03]; Table). There were no statistically significant differences for etrasimod vs other comparators. Similar results were observed for clinical response. In the maintenance phase, there were no statistically significant differences between etrasimod 2 mg and other treatments for clinical remission and clinical response (Table).

Conclusion
With respect to clinical remission and clinical response during induction and maintenance phases, etrasimod efficacy was similar to most comparators as a first-line AT. Differences in trial design and risk-benefit profiles of AT should be considered when interpreting NMA results.
P864 The Effect of Ustekinumab on Mucosal Inflammation in Paediatric Crohn’s Disease: The REALITI Real-World Evidence Effectiveness Study
Authors: Adler J , Steiner S , Saeed S , Colletti R , Strauss R , Godwin B , Sheahan A , Zhang R , Kim L , Xiao Y , Volger S 
Published: January 2024

Abstract

Background
Crohn's disease (CD) research using real world evidence (RWE) has been hampered by lack of validated endoscopic outcome measures. The recently validated Simplified Endoscopic Mucosal Assessment of CD (SEMA-CD) provides a reliable way to evaluate mucosal inflammation in paediatric CD patients (pts), making it suitable for use in clinical practice and relevant to real world data. REALITI is a RWE study of the effectiveness and safety of ustekinumab (UST) in paediatric pts.

Methods
REALITI used data from pts with CD in the ImproveCareNow (ICN) registry. Colonoscopy reports (reports) from 2010-2020 identified by chart review were redacted and uploaded to the registry. Central endoscopy readers underwent SEMA-CD training and were randomly assigned to score reports. No reader reviewed reports from their own institution. Three readers independently scored reports blinded to each other’s scores and to clinical information. Demographic and clinical data, prospectively recorded in ICN, were summarized and compared between pts with and without endoscopy. Clinical remission was defined as Short Paediatric CD Activity Index (sPCDAI) ≤10 and endoscopic remission as SEMA-CD ≤1.

Results
Analyses of mucosal inflammation by SEMA-CD in 114 pts age 2 to &lt;18 yr with moderate-severe CD (sPCDAI ≥30) and body weight ≥40 kg at UST initiation (baseline) and after 52 weeks (wk) of treatment are reported. Overall, 77/114 pt had ≥1 report during the study and 20 had a report at Wk 52. Baseline median age of all pts was 16 yr (interquartile range [IQR] 15-16). Pts with endoscopic assessments (N=77) vs pts without (N=37) were more often female (56% vs 41%) and had more ileocolonic disease activity (73% vs 54%), perianal disease (39% vs 35%), and stricturing phenotype (B2; 10% vs 5%), respectively. No pts had B2/B3 phenotype. At baseline, median sPCDAI for all pts was 40 (IQR 35-50; N=114) and median SEMA-CD was 8.5 (IQR 5-13; N=38). At Wk 52, 4/20 pts (20% [95% CI, 8.1%, 41.6%]) were in endoscopic remission. Despite small sample sizes, there appears to be lower clinical remission rates at Wk 52 in pts with baseline endoscopic assessments (17/77; 22.1% [95% CI, 14.3%, 32.5%]) vs without (10/37; 27.0% [95% CI, 15.4%, 43,0%).

Conclusion
Use of SEMA-CD to assess mucosal inflammation in paediatric pts with moderate-severe CD treated with UST demonstrated rates of endoscopic remission similar to clinical remission at Wk 52. Endoscopy was performed more often in sicker pts, with a greater proportion of pts who did not undergo endoscopy achieving clinical remission. Future routine SEMA-CD assessment of mucosal inflammation in clinical practice may improve analyses in observational and retrospective studies.