bluuebunny/crossref_metadata_2025_split huggingface dataset:
P445 Network meta-analysis to evaluate the comparative efficacy of intravenous and subcutaneous infliximab and vedolizumab in the maintenance treatment of adult patients with Crohn’s Disease and Ulcerative Colitis
Authors: Peyrin-Biroulet L , Bossuyt P , Bettenworth D , Loftus Jr. E V , Anjie S , D’Haens G , Saruta M , Arkkila P , Kim D H , Choi D , Reinisch W 
Published: January 2023

Abstract

Background
Network meta-analysis (NMA) using randomised controlled trial (RCT) data can provide indirect evidence on comparative efficacy of various treatments.1 The NMA reported herein was conducted to evaluate infliximab (IFX) and vedolizumab (VDZ) comparative efficacy during maintenance treatment of moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), covering various dosing regimens and administration routes for each biologic.

Methods
Studies were identified by literature searches that included publications up to 1 November 2022. Parallel-group RCTs evaluating IFX or VDZ (intravenous [IV] or subcutaneous [SC]) for maintenance treatment of adult patients with moderate-to-severe CD or UC that reported clinical remission rates were included. Eligible studies treated patients for a minimum of 22 weeks, with follow-up of 30–60 weeks for maintenance. Clinical remission rates in tumour necrosis factor inhibitor (TNFi)-naïve patients from each study were analysed in a Bayesian NMA fixed-effect model.

Results
Overall, 13 RCTs were identified and included in the analysis (Table 1 for CD and Table 2 for UC). The difference in study design between IFX (treat-through) and VDZ (re-randomisation of induction responders only) was noted. A connected network of evidence could be generated using CD and UC studies (Figures 1A and 1B, respectively). In both CD and UC, IFX SC 120 mg had the highest odds ratio (95% confidence interval [CI]) vs. placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90–18.2]; UC: 5.45 [1.94–15.3]), albeit with the CIs overlapping with the CIs of the other tested regimens (Figures 2A and 2B). In both CD and UC, IFX SC 120 mg ranked highest for clinical remission among the biological agents, dosing regimens, and routes of administration tested.

Conclusion
In both CD and UC, IFX SC showed a favourable efficacy profile for achieving clinical remission during maintenance treatment of TNFi-naïve adult patients, when compared with the other IFX IV or VDZ IV/SC regimens tested.
References:
1 Rouse B et al., Intern Emerg Med 2017;12(1):103-111.
P449 Minimally invasive IPAA in UC: Preliminary results from a referral center
Authors: Fortuna L , Bottari A , Ficari F , Cricchio M , Cianchi F , Scaringi S 
Published: January 2023

Abstract

Background
Minimally invasive approaches in performing restaurative total proctocolectomy in Ulcerative Colitis(UC) have been increasingly adopted. In particular, the robotic approach could be used with more benefits in proctectomy with ileal pouch anal anastomosis (IPAA). In fact, the robotic device seems to potentially overcome all the limitations found in laparoscopic and conventional open surgery. The aim of our study was to compare and evaluate early and late functional postoperative outcomes and complications after IPAA, performed with open, laparoscopic and robotic techniques in UC patients.

Methods
At our institution, 397 UC patients who underwent restorative proctocolectomy with IPAA during the period 1986-2022, consecutively treated either with open surgery, laparoscopic or robotic techniques were enrolled. The incidence of early (&lt;30 days) and late (&gt;30 days) postoperative complications (intestinal occlusion, haematoma/wound infection, anastomotic dehiscence), hospital stay and an assessment about continence, autonomic nerve damage, incidence of pouchitis and cuffitis was evaluated.

Results
About the 397 patients, 344 underwent conventional open IPAA, 31 laparoscopically and 22 robotically. Comparable early and late postoperative surgical complications were recorded among the different techniques [early and late complications respectively 24/53 (45,2%) and 146/344(42,4%)] in minimally invasive and open groups. Minimally invasive surgery showed a better outcome regarding wound infections [0/53 (0%)], anastomotic dehiscence and reduced length of stay but open surgery demonstrated a better result on early and late intestinal occlusion [8/53 (15%)vs 22/344 (6,39%)] and anastomotic stenosis [5/53 (9,43%) vs 15/344 (4,36%)]. Lastly, the rate of cuffitis was higher in open surgery than in the minimally invasive group [(3/53 (5,66%) vs 46/344(13,37%)] and within these, robotic approach seems to show better results compared to laparoscopy.

Conclusion
UC patients undergoing IPAA could benefit from a minimally invasive surgical approach. Our experience confirms that robotics seems to be related to hopeful outcomes both in the short and long term period, even if more studies are needed to refine the promising results.
P451 Early infliximab trough levels in paediatric IBD patients predict sustained remission
Authors: Bevers N , Aliu A , Wong D , Derijks L , Winkens B , Vreugdenhil A , Pierik M , van Rheenen P 
Published: January 2023

Abstract

Background
Therapeutic drug monitoring (TDM) is an approach to improve treatment effectiveness of anti-TNF therapy in Inflammatory Bowel Disease (IBD), but timing and threshold trough levels (TL) are still subject of investigation, especially in paediatric populations.
The aims of our study were (1) to analyse induction – and post-induction infliximab TLs (respectively after 6 and 14 weeks) to predict sustained biochemical and clinical remission between 6 and 12 months in paediatric patients with IBD, and (2) to define paediatric threshold TLs at these timepoints.

Methods
We performed a retrospective study in 70 anti-TNF naïve paediatric IBD patients from two centres who were treated with an induction scheme of 5 mg/kg on 0, 2 and 6 weeks, and subsequently every approximately 8 weeks. We measured infliximab TLs at week 6 and 14 combined with (non)-invasive markers for disease activity. Patients were in sustained biochemical and clinical remission when they were asymptomatic and had normalised CRP and faecal calprotectin between 6 and 12 months after initiating therapy. Receiver operating characteristic (ROC) analysis was used to determine infliximab TL thresholds that best predicted sustained biochemical remission.

Results
Median infliximab TL at 6 and 14 weeks were higher for children in sustained remission versus children who were not (TL6 p=0.028 and TL14 p=0.028). Area under the ROC curve (AUROC) for infliximab TL6 and TL14 to predict sustained biochemical remission was 0.68 (95% Confidence Interval [CI] 0.53-0.83) and 0.67 (95%CI 0.53-0.82), respectively (Figure 1 and 2). The optimal infliximab thresholds were 13.2 mg/L and 6.9 mg/L for TL6 and TL14, respectively, yielding a sensitivity and specificity of 70% and 68% for TL6 and 57% and 76% for TL14.

Figure 1 ROC curve of infliximab trough level at 6 weeks for predicting sustained remission between 6 months to 12 months.

Figure 2 ROC curve of infliximab trough level at 14 weeks for predicting sustained remission between 6 months to 12 months.

Conclusion
In children with IBD treated with a regular infliximab induction scheme, infliximab TLs at week 6 and 14 both predicted sustained clinical and biochemical remission between 6 and 12 months after initiating therapy. TDM and early dose optimization may improve infliximab effectiveness and drug survival.
P453 The significance of the concentration of antibodies to infliximab on the frequency of loss of response when alternating the original drug infliximab and its biosimilar in patients with ulcerative colitis.
Authors: Zviaglova M , Knyazev O , Kagramanova A , Lischinskaya A , Podolskaya D , Nanaeva B 
Published: January 2023

Abstract

Background
Biosimilars are analogues of biopharmaceutical drugs, with a close, but not identical, parent molecule. Biosimilars offer greater access to affordable treatment for inflammatory bowel disease, while being comparable in efficacy and safety to brand-name products. However, switching from original genetically engineered biological drugs (GEBD) to biosimilars requires study and analysis.

Aim
To determine the concentration of antibodies to infliximab in patients with UC receiving infliximab by one trade name (TN) and when alternating infliximab and its biosimilars and to determine the frequency of loss of response during the year of observation.

Methods
In the Department of inflammatory bowel diseases of the A. S. Loginov Moscow Clinical Scientific Center of the Moscow Healthcare Department, were observed 38 patients with IBD, who regularly received the original drug infliximab (IFX) -group 1 (n=20), group 2 a group of patients (n=18) alternated the original drug infliximab and its biosimilar.The level of antibodies to IFX in the blood serum before the next scheduled administration of the drug 10 months after inclusion in the study by enzyme immunoassay using the Shikari Quantitative Determination of Infliximab (Q-INFLIXI) and Shikari Quantitative Determination of Antibodies to Infliximab (Q-ATI) kits (Matriks Biotek). The loss of response was assessed by clinical, laboratory and instrumental data. Comparative analysis was carried out by the method of four-field tables using non-parametric statistical tests.

Results
Of the 20 patients with UC of the 1-st group, 3 (15.0%) had antibodies to IFX, on average, its concentration was 8.5 ± 2.2 ng/ml (normal values &lt;5 ng/ml). Of the 18 patients of the 2nd group 10 (55.5%) antibodies to IFX were detected, on average - 187.9 ± 38.2 ng/ml. (OR - 0.141; 95% CI 0.030-0.658; x2 - 6.923, p= 0.023).During the year of observation among patients of the 1st group receiving the original IFX, the loss of response occurred in 2 (10.0%) patients with UC. Of the patients of the 2nd group, the loss of response occurred in 8 (10.0%) (RR - 0.139; 95% CI 0.025 - 0.785; x2 - 5.797; p = 0.017).

Conclusion
The concentration of antibodies to infliximab is higher in patients with UC when alternating IFX and its biosimilars than in patients with UC who regularly receive IFX by one TN. The frequency of loss of response when alternating infliximab and its biosimilars is significantly higher in patients with UC who regularly receive the drug for one TN.
P460 Preoperative nutrition supplementation may prevent one-year endoscopic recurrence in Crohn’s disease patients
Authors: Inniss S , Simpson K , Fragkos K , Wood C , Smith A , Rahman F 
Published: January 2023

Abstract

Background
Despite improved postoperative management, endoscopic recurrence after surgery remains common in Crohn’s disease (CD) patients [1]. It is widely accepted that patients receiving preoperative nutrition supplementation are less likely to experience postoperative complications [2]. However, little is known about the long-term effects of preoperative nutrition supplementation on surgery. In this study we aimed to assess the long-term effects of preoperative nutrition supplementation on endoscopic recurrence.

Methods
Single centre retrospective data was collected between 2015 and 2021 on patients who had surgical resection with ileocolonic anastomosis. Follow up data was retrospectively collected at 12 months after surgery. Endoscopic recurrence was defined as a Rutgeerts score of 2 or more. Statistical analysis included demographics and inferential analyses. Missing data was attributed to the absence in clinic notes.

Results
This study included 50 CD patients [50.0% male, median age of 31.0 (18.0-68.0), 81.8% non-smokers] who had ileocolonic anastomosis. Most patients had ileocolonic CD (76.0%, 38/50) and either stricturing (46.0%, 23/50) or penetrating (26.0%, 13/50) disease behaviour. Almost half (49.0%, 24/49) of CD patients received preoperative nutrition supplementation prior to surgery, with 61.9% on oral nutrition supplementation. No statistical difference was found between the demographics of patients receiving nutrition supplementation and patients without nutrition supplementation, p&gt;0.05 (table 1). Endoscopic recurrence was observed in 43.5% (10/23) of patients at 12 months. 80.0% (8/10) of patients who experienced endoscopic recurrence did not receive preoperative nutrition supplementation (figure 1). Logistic regression indicated that patients receiving nutrition supplementation may be 84.4% less likely to experience endoscopic recurrence at 12 months compared to patients without nutrition supplementation (OR 0.16 (CI 0.023-1.056)(p=0.057)). The type of preoperative nutrition supplementation did not significantly impact endoscopic recurrence (p&gt;0.05).

Conclusion
Preoperative nutrition supplementation may reduce the risk of endoscopic recurrence one year after surgical resection. The use of preoperative nutrition is highly recommended for all CD patients undergoing surgery. More extensive research is needed to confirm study findings.
P462 Delayed Responders with Ustekinumab in Ulcerative Colitis Have Increased Inflammatory Burden but Similar Long-term Outcomes as Early Responders
Authors: Wong E , Dulai P , Marshall J , Jairath V , Reinisch W , Narula N 
Published: January 2023

Abstract

Background
Differences in one-year outcomes among early compared to delayed responders to vedolizumab have been demonstrated in ulcerative colitis. However, it is unclear whether differences exist with ustekinumab, and what factors differentiate delayed responders from non-responders.

Methods
This was a post-hoc analysis of patient-level data from the UNIFI clinical trial. Ustekinumab-treated patients with clinical response, defined as reduction in total Mayo score ≥30% and ≥3 points from baseline with reduction in rectal bleeding subscore (RBS)≥1 or RBS≤1, at week 8 were deemed early responders and their outcomes were compared with delayed responders (week 8 non-responders who subsequently responded at week 16). The primary outcome assessed was one-year clinical remission (CR), defined as total Mayo score ≤2 and no subscore &gt;1. Other one-year clinical, endoscopic, and histologic outcomes were also assessed. Outcomes were compared using t-tests and biomarkers compared using one-way repeated measures analysis of variance.

Results
We included 642 ustekinumab-treated patients, including 321 (50%) early responders, 115 (17.9%) delayed responders, and 205 (32.1%) non-responders (Table 1). No differences were observed for one-year CR among early vs. delayed responders [132/321 (41.1%) vs. 40/115 (34.8%), p=0.233], nor for any other outcome assessed (Table 2). Similar findings were observed among delayed responders regardless of weight-based vs. fixed ustekinumab induction dose (Table 3). Compared to early responders, delayed responders had more severe endoscopic disease at baseline as measured by the MES [88/115 (76.5%) vs. 206/321 (64.2%), p=0.015] and were more likely to have abnormal CRP at baseline based on a threshold &gt; 3mg/L [83/115 (72.2%) vs. 183/321 (57%), p=0.004]. Compared to non-responders, delayed responders had a significant decline in CRP (F(4, 844), p&lt;0.0001) and fecal calprotectin (F(4, 818), p&lt;0.0001) through week 16 (Figure 1).

Conclusion
Compared with early ustekinumab responders, delayed responders had greater inflammatory burden at baseline. Early and delayed responders have similar one-year outcomes. Biomarker decline can be observed in delayed responders and help differentiate them from non-responders. The decision to prolong ustekinumab among initial non-responders should be informed with biomarkers and weighing the overall risk to benefit.
P466 Efficacy and safety outcomes in patients with moderate to severe ulcerative colitis stratified by ethnicity and race: a pooled analysis of data from GEMINI 1, VARSITY, and VISIBLE 1
Authors: Mukherjee R , Khan R M Q , Liu J J , Ananthakrishnan A N , Lichtenstein G R , Uddin S , Young L , Boules M , Adamson P , Reeves V 
Published: January 2023

Abstract

Background
Ulcerative colitis (UC) is an inflammatory bowel disease with an estimated prevalence of 181 cases per 100,000 adults in the USA. Hispanic or Latino individuals comprise 19% of the US population and 24% of individuals are races other than White; however, the efficacy and safety of advanced therapies for UC in these populations remains uncertain because of their underrepresentation in clinical trials. Underrepresentation has the potential to bias evidence towards therapies with understudied efficacy and safety in minority ethnic and racial groups. This post hoc analysis used pooled clinical trial data of advanced therapies in patients with UC stratified by ethnicity and race in order to identify differential efficacy and safety outcomes among the populations investigated.

Methods
GEMINI 1, VARSITY, and VISIBLE 1 were phase 3 or 3b clinical trials investigating vedolizumab (intravenous or subcutaneous) versus placebo or adalimumab in patients with moderately to severely active UC. Data from these trials were pooled to create three cohorts of patients who received adalimumab, vedolizumab, or placebo. The number and proportion of patients with each efficacy and safety outcome at week 52 were reported for each of the treatment cohorts, stratified by ethnicity and race. Ethnicity and race were self-reported in the three trials.

Results
Overall, 1,358 patients were included in the pooled treatment cohorts. Of the 465 patients with available ethnicity information, only 40 patients (8.6%) reported their ethnicity as Hispanic or Latino. Efficacy and safety outcomes were similar when stratified by ethnicity with some exceptions (Table 1). When stratified by race, efficacy and safety outcomes were similar among White and Asian patients (Table 2). In the vedolizumab cohort, 47.3% and 47.1% of White and Asian patients, respectively, had mucosal healing. Some differences were observed in the efficacy and safety outcomes of Black patients compared with White and Asian patients; however, the treatment cohorts included fewer than 10 Black patients.

Conclusion
In the GEMINI 1, VARSITY, and VISIBLE 1 trials, efficacy and safety outcomes were similar among racial and ethnic groups, with the exception of Black patients. However, this analysis was limited by the small sample size of patients of races other than White, as well as the limited availability of ethnicity information, which prevented robust comparisons of outcomes between patients of different ethnicities and races. Future clinical trials of advanced therapies should aim to recruit and report a diverse patient population with UC who are representative of the patients who will receive these treatments.
P471 A Transcriptome-dependent Prognostic Model of Response in Patients with Ulcerative Colitis
Authors: Johnson T , Reinisch W , Steere B , Milch C , Harris C , Morris N , D'Haens G , Huang K , Krishnan V 
Published: January 2023

Abstract

Background
Mirikizumab (miri), a p19-directed IL-23 antibody, showed efficacy in ulcerative colitis (UC)1. Miri modulates transcripts associated with disease activity and anti-TNF resistance in UC and increases expression of transcripts associated with healthy mucosa2. Here, we evaluate the transcription profile of patients with UC who respond to placebo (PBO, 20.6%) or miri 200mg treatment (59.7%) versus non-responders and build a model that can predict response in patients with UC.

Methods
In the phase 2 AMAC trial (NCT02589665), patients were randomized 1:1:1:1 to receive intravenous PBO (N=63), 50mg miri (N=63), or 200mg miri (n=62) with possible exposure-based dose increases or fixed 600mg miri (n=61) at Week (W)0, 4 and 8. Colonic biopsies were collected at baseline, W12, and W52. An Affymetrix HTA2.0 microarray measured gene expression. Limma comparing values at baseline and W12 determined differentially expressed genes (DEGs). DEGs maintaining their W12 expression level through W52 among responders in either the PBO and miri 200mg arms were designated as similarly expressed genes (DEGSEGs).
XGBoost models3 were trained to predict clinical response (decrease in 9-point Mayo subscore [rectal bleeding, stool frequency, endoscopy] of ≥2 points and ≥35% from baseline [BL] with either a decrease of RB subscore of ≥1 or an RB subscore of 0 or 1) using baseline levels of DEGSEGs and TNF biomarkers. Leave-one-out cross validation of the models using AMAC data and validation experiments by training on the PROTECT data4 then predicting in AMAC were used to evaluate our models.

Results
Miri 200mg responders were associated with 84 DEGSEGs, PBO responders were associated with 26 DEGSEGs, and 21 DEGSEGs were common to both. When using the PROTECT data as the training data and AMAC data as the validation cohort (Figure A), we were able to achieve high ROC-AUC and PR-AUCs using the top 36 (FC &gt; 1.5) miri DEGSEGs (PR-AUC=0.78), TNF biomarkers (PR-AUC=0.91), or combined (PR-AUC=0.93) gene sets as the features (Figure B-E) and found that the response prediction was significantly higher in AMAC responders vs. non-responders (Figure F).

Conclusion
Baseline transcript features were predictive of clinical response in patients with UC treated with miri 200mg and our model distinguished responders from non-responders. Future studies may further validate this model.
References:
1 Sandborn WJ, et al. Gastroenterology. 2020;158(3):537-549.e10
2 Steere B, et al. J Crohns Colitis. 2020;S103-S104
3 Chen T, et al. Proceedings of the 22nd ACM SIGKDD International Conference. 2016;7285-794
4 Hyams JS, et al. Lancet Gastroenterol Hepatol. 2017;2(12):855-868
P478 Platelet-related indicators for predicting vedolizumab response in patients with Ulcerative Colitis
Authors: Jiao J , Liu W , Wang B , Cao H 
Published: January 2023

Abstract

Background
Ulcerative Colitis (UC) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasis, there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions. However, whether PLT are related to the efficacy of biologic agents is unknown. This study aimed to investigate whether platelet ratio before and after induction therapy can be predictive biomarkers for the therapeutic outcomes of vedolizumab therapy in UC.

Methods
Patients with moderate-to-severe UC receiving vedolizumab in our hospital between November 2020 and November 2022 were retrospectively evaluated. Patients with concomitant corticosteroid treatment≥20 mg, immunomodulators, or other conditions that could modify the platelet count were excluded. The primary endpoint was clinical response at the end of the induction period (at 14 weeks). We analyzed the association between platelet count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), fecal calprotectin, and the clinical efficacy of vedolizumab. The above indicators between the response and nonresponse groups were compared via a univariate analysis. The independent risk factors of nonresponse were identified via a multivariate analysis.

Results
Seventy-one patients with moderate-to-severe active UC started treatment with vedolizumab and 20 patients (28.2%) experienced loss of response (LOR) after induction therapy. The platelet count, albumin, CRP, NLR, PLR, MLR, and Particul Mayo score between the LOR and response groups significantly differed. The Platelet ratio before and after induction therapy cut-off value of 1.077 was predictive of LOR, using receiver operating characteristic analysis (sensitivity:78.0%, specificity:81.8%). A univariate analysis revealed a significant relationship between LOR and the platelet ratio (P＜0.05). Multivariate analysis indicated the platelet ratio as an independent prognostic factor for LOR (OR=11.219, 95% CI:3.316-37.959, P＜0.05).

Conclusion
Platelet ratio before and after induction therapy is a useful prognostic marker in patients with moderate-to-severe active UC treated with vedolizumab, and may contribute to appropriate use of vedolizumab LOR. A large sample from multiple centers is needed to validate the association between platelet-related measures and the rate of vedolizumab response.