bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1012 Dose escalated Ustekinumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Barnett M , Mcnamara J , Wilson W , Pipicella J , Ghaly S , Gearry R , Begun J , Williams A , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Connor S J , Andrews J M 
Published: January 2024

Abstract

Background
Ustekinumab is a human monoclonal antibody targeting interleukin-12 and 23 with established efficacy in inflammatory bowel disease (IBD). Many people receiving ustekinumab do not achieve adequate or sustained response to standard dosing and require dose escalation (DE). We aimed to investigate the frequency and outcomes of escalated dosing regimens in an Australasian cohort.

Methods
Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in routine care across Australia and New Zealand. Data feeds continuously into a de-identified clinical quality registry (CQR). Data were interrogated in November 2023 comparing outcomes and healthcare utilisation prior to and at 12 months post ustekinumab DE. DE was defined as maintenance dosing &gt;90mg subcutaneously Q8 weekly and/or additional induction doses.

Results
A total of 790 people received ustekinumab, with 43.4% on DE therapy. Most of the cohort had Crohn’s disease (86.1%), followed by ulcerative colitis (11.3%) and IBD-unclassified (1.6%). The median age for the total cohort was 40 years (IQR 30-52) with an even gender distribution (50.3% female). The median age at diagnosis was 25 (IQR 18-38) with a median time to DE of 6 months (IQR 1-15). Age, age at diagnosis and disease duration did not significantly differ between DE and standard dose cohorts. Almost all people with IBD on DE ustekinumab continued on therapy beyond 12 months (84.5%).
Rates of faecal calprotectin remission (&lt;250ug/g), endoscopic remission and patient reported outcome (PRO2) remission were higher 12 months post DE (Table 1). Systemic steroid requirements fell significantly 12 months post DE. The number of endoscopies and radiological investigations fell at 12 months post DE, while the rates of hospital admissions did not significantly differ between the DE and standard cohorts. Clinical assessments (per person) reduced from 1.2 pre-DE to 0.9 post DE.

Conclusion
In a large real-world Australasian cohort of people receiving ustekinumab for IBD, close to half required DE. DE led to reduced systemic steroid use and improved endoscopic, PRO2 and FCP remission rates at 12 months. These data can be used to perform health economy analysis to determine the price points at which DE is cost effective, with additional data on quality of life and indirect healthcare costs being important to include for a robust holistic assessment of value in care.
P1023 Variability in Mesalazine Management for Ulcerative Proctitis Include Doses, Route of Administration and Use of Fecal Calprotectin: Insights from Clinical Practice Across Spain Beyond Clinical Guidelines
Authors: Bastida Paz G , Ceballos D , Ricart E , Marín-Jiménez I , Menchén L , Carpio D , Ginard D , Muñoz F , González-Lama Y 
Published: January 2024

Abstract

Background
Despite universal use of mesalazine in ulcerative colitis treatment, many aspects of clinical practice remain unclear or are not even addressed in clinical guidelines, leading to significant variations in mesalazine management among clinicians. We aimed to gather different approaches of mesalazine use in ulcerative proctitis (UP).

Methods
After discussion of a clinical case, a predefined questionnaire was anonymously answered throughout a series of meetings held at 10 different locations in Spain. Results were categorized according to experience levels and inflammatory bowel disease (IBD) focus.

Results
259 IBD treating gastroenterologists were engaged; 84% had &lt;10 years of experience and 25% had a specific focus on IBD.
Most participants (84%) manage UP based on clinical symptoms (i.e. fecal urgency). In case of a clinically moderate-severe UP, 81% would initiate treatment with high dose of combined mesalazine, while 11% proposed only suppositories. 60% of participants would assess response at 4 weeks. If clinical remission achieved, 85% would use fecal calprotectin (FC) to assess deep remission.
Upon initial failure of combined mesalazine treatment at standard dose, 59% attempt optimizing mesalazine doses, while 38% add beclomethasone dipropionate. Younger physicians without specific focus on IBD prefer modifying mesalazine doses (70.5% vs 37.1%), (P=0,006), whereas more experienced physicians with monographic dedication prefer adding beclomethasone dipropionate (60% vs 29.4%), (P=0,006).
For maintenance therapy (oral or topical mesalazine) the most important drivers in therapeutic decision-making were severity of the initial flare (40%) and patient preferences (36%). After a moderate-severe flare of UP, 80% would recommend maintenance therapy with high dose oral mesalazine and 3 suppositories/week.
For monitoring, less experienced physicians and those not working in IBD units more frequently relied only on clinical parameters (26.6% vs. 8.7%, p=0.01), using FC to a lesser extent (73% vs. 88%, p=0.1) compared to more experienced and IBD focused physicians. In the case of elevated FC in asymptomatic patients, 49% would prefer to scope, while 47% increase mesalazine dose directly.
The preferred high dose of mesalazine was 4g (55%) or 4-5g (44%). 73% would not reduce the dose upon achieving remission. Only 75% actively investigate therapeutic adherence.

Conclusion
Management of mesalazine in UP patients is highly heterogeneous, and clinical guidelines do not address all issues arising in clinical practice. Nevertheless, clinicians in our setting often use high oral and rectal mesalazine doses for both induction and maintenance and they commonly monitor patients using FC.
P1026 Clinical decision support tool for vedolizumab could not predict outcome in ulcerative colitis patients – a retrospective real-life single-centre cohort study
Authors: Molinari N , Maček P , Ocepek A 
Published: January 2024

Abstract

Background
Early intervention with biologics can slow the progression of ulcerative colitis (UC), thus improving long-term outcomes. As treatment options in UC expand, the positioning of advanced therapies is becoming more important. The ability to identify patients with UC who are more likely to respond well to a specific drug before initiation of treatment could help physicians navigate within the proposed treatment algorithm. Dulai et al. derived and validated a clinical decision support tool (CDST) for the prediction of response to vedolizumab (VDZ) in UC.

Methods
We performed a retrospective single-centre cohort study based on UR-CARE registry data. Data for 72 UC patients treated with VDZ from July 2016 until April 2023 were analysed. CDST for UC was calculated using four variables: absence of exposure to a tumour necrosis factor (TNF) alpha inhibitor, disease duration of ≥ 2 years, moderate baseline endoscopic activity and baseline albumin concentration. Patients were then stratified into three probability groups: group 0 with low (≤ 26 points), group 1 with intermediate (27 to ≤ 32 points) and group 2 with high (&gt; 32 points) probability of response. To test the association between CDST, clinical remission (CR) (defined as PRO2 £ 1 with rectal bleeding score 0), corticosteroid-free remission (CSFR) and endoscopic activity (defined as no change in endoscopic activity, endoscopic improvement (EI) (change of endoscopic Mayo of ≥1), or endoscopic remission (ER) (endoscopic Mayo ≤ 1)) chi2 test was used. The difference in faecal calprotectin (FC), depending on whether VDZ was continued or not, was tested by the Mann-Whitney U test.

Results
In our cohort, 59.7% of patients were male, the median age was 32.1 years, the median duration of disease until VDZ was 2.6 years, and 63.9% had pancolitis. 34.7% of patients had concomitant corticosteroid treatment at baseline, and 52.8% had been exposed to a TNF-alpha inhibitor. We found no statistically significant association between the CDST group and CR or CSFR at weeks 14 and 52 nor endoscopic activity at follow-up endoscopy. All patients in group 2 responded with lowering of FC 3-6 months after initiating VDZ and continued treatment. Also, patients in CDST group 1 who experienced lowering of FC continued VDZ therapy. In contrast, all patients in CDST group 0 and patients in group 1, who had persistently elevated FC, eventually failed VDZ regardless of optimisation. The difference in FC between those who discontinued VDZ and those who did not was statistically significant (p=0.004).

Conclusion
Our results did not confirm the predictive value of existing CDST for VDZ in UC patients. Novel prediction tools in UC are needed.
P1032 Ileoanal Pouch Salvage Rates with Endoluminal Vacuum Therapy for Early vs. Late Anastomotic Leaks
Authors: Alipouriani A , Lavryk O , Lipman J , Hull T , Steele S , Liska D , Holubar S 
Published: January 2024

Abstract

Background
Anastomotic leakage is a dreaded complication after ileal pouch-anal anastomosis (IPAA) that occurs in 5-10% of cases. Endoluminal vacuum (EndoVac) therapy has emerged as a minimally invasive option that promotes healing by applying negative pressure to the associated abscess cavity through the anastomotic defect but is typically applied only to early IPAA leaks. We hypothesized that EndoVac for early compared with late leaks would be associated with a higher pouch survival rate.

Methods
We retrospectively reviewed the medical records of consecutive patients who developed a pouch anastomotic leak after IPAA and were treated with EndoVac therapy at our institution between 2005-2023. Patients were stratified into early (30 days) and late (&gt;30 days) leaks. Anastomotic healing was defined as complete closure of the leak site, as evidenced by resolution of symptoms, normal endoscopic and radiographic evaluation, and no further drainage from the presacral space or abdominal wall. Pouch failure was defined as a permanent ileostomy or pouch excision. Figures represent frequency (proportion) or median (range). The probability of pouch survival over time was estimated using the Kaplan-Meier method.

Results
A total of 13 pouch patients underwent EndoVac therapy for leaks by six surgeons (median age, 34 years; 62% male; median body mass index 25.8 kg/m2. Diagnoses: ulcerative colitis (n=11), and familial adenomatous polyposis (n=2). The median time to leak diagnosis was 32 (12- 340) days; of these 6 (46%) were early and 7 (54%) were late. All (100%) patients were diverted at the time of EndoVac therapy, 10 (77%) patients were still diverted, and 3 (23%) were rediverted. Patients underwent a median of 5 EndoVac changes (2-22) over a median duration of 34.5 (21-125) days. After EndoVac therapy, complete/near-complete defect healing occurred in 9 (69%), 1 whom required suturing of a small residual defect. Of those with incomplete healing (n=4), 3 (23%) underwent pouch excision and 1 (7.7%) a redo pouch. Comparing early and late leaks, defect healing (66.7% vs 71.4%, p=0.72) and pouch survival (83.3% vs 71.4%, p=0.65) were similar. The overall pouch salvage rate was 77% (10/13).

Conclusion
EndoVac therapy is effective for postoperative pouch leaks and achieves a high rate of pouch salvage in both early and late leaks.

Figure 1. CONSORT-style flowchart of IPAA leaks treated with EndoVac therapy.
P1041 Coconut water modulates dietary potassium and gut microbiome to induce remission in ulcerative colitis: randomized controlled trial
Authors: Kedia S , Virmani S , Bajaj A , Markandey M , Singh N , Madan D , Kaushal K , Sahu P , Vuyyuru S , Kante B , Kumar P , Thomas D , Mundhra S , Singh M , Verma M , Sharma R , Das P , Dash N , Monga N , Awasthi A , Makharia G , Ahuja V 
Published: January 2024

Abstract

Background
High potassium intake is associated with decreased risk of inflammatory bowel disease(IBD), urinary potassium has been correlated with disease activity in ulcerative colitis(UC), and gut microbiome modulation improves outcomes in UC. We evaluated coconut water as potassium rich diet and gut microbiome modulator in patients with mild-moderate UC.

Methods
This single-center double-blind placebo-controlled trial randomized patients with mild-moderate (simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC (ulcerative colitis endoscopic index of severity-UCEIS&gt;1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water (200-250mg potassium/100ml) was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤ 2) and secondary outcome measures were clinical response (SCCAI decline ≥ 3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks.

Results
Of 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2 ± 11.2years; males-54.1%; disease duration-48 (IQR:24–90) months; pancolitis - 26.1%; SCCAI-5 (IQR:4 – 6); UCEIS-4 (IQR:3 – 5)]. There was significant increase in dietary potassium and decline in sodium/potassium ratio at 8 weeks in CW. Clinical response [57.1% vs 28.3%, p=0.01, OR-3.4 (95%CI:1.4 – 7.9)], remission [53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin (FCP)&lt;150μg/g [53.6% vs 14.3%, p=0.01, OR-6.9(95%CI:1.6 – 28.9)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8 weeks in CW. Adverse events were comparable and no patient developed hyperkalemia.

Conclusion
Coconut water increased dietary potassium, modulated the gut microbiome and was more effective than placebo for induction of remission in mild-moderate UC.
P1042 Serum N-glycan Biomarkers Predict Patient Response to Biologics for Crohn’s Disease
Authors: Elgood Hunt G , Spencer D , Senard T , Gardner R , Satsangi J , Adams A , Noble A , D’Haens G , Joustra V , Li Yim A , de Jonge W J 
Published: January 2024

Abstract

Background
Several therapeutic antibodies are approved to treat Crohn’s Disease (CD), for example, Vedolizumab (anti-α4β7), Ustekinumab (targets IL-12 and IL-23), Adalimumab and Infliximab (anti-TNF). Glycosylation alterations have been associated with CD, but have not been thoroughly investigated as potential predictors of disease remission¹. A comparison of serum N-glycan profiles between responders and non-responders prior to each therapy was used to detect potential biomarkers to response. The N-glycan composition after treatment was used to distinguish the different mechanisms of the biologics. In addition, a comparison of glycomic profiles across the different therapies could highlight the distinct biological pathways involved in response.

Methods
Serum samples, before (t1) and after (t2) treatment, were taken from 166 patients, containing the four sub-cohorts of patients under different biologics with CD. Treatment response, observed in 100 patients, was assessed by a combination of clinical and endoscopic outcomes. Firstly, the Serum N-glycans were detected by hydrophilic interaction liquid chromatography to produce a 62-peak chromatogram. Followed by quantifying the relative area of 62 glycan peaks via HappyTools². Logistic regression was used to determine which glycan peaks at t1 are predictive of response (p-value &lt;0.05) and which are markers of response (p-value&lt;0.05). 5 fold cross-validation tested on a variety of classifiers was used to derive the optimal predictor of response. The glycomic profiles across the four biologics, at both t1 and t2, were compared through the Kruskal test. The significant peaks (p-value &lt; 0.05) were then combined to generate a multiclass model to predict response in each therapeutic.

Results
The N-glycan classification models for all four sub-cohorts under different biologics, Ustekinumab (0.78 AUC), Adalimumab (0.82 AUC), Infliximab (0.75 AUC), Vedolizumab (0.75 AUC), performed moderately well at predicting therapy response prior to treatment(figure 1A). In turn, patients could be identified as responders after treatment by N-glycan based classification models, Ustekinumab (0.70 AUC), Adalimumab (0.86 AUC), Infliximab (0.85 AUC), Vedolizumab (0.84 AUC). Prior to treatment, patients who responded were strongly distinguished by the therapy type (0.96 AUC) through a combination of 13 significant glycan peaks (figure 1B).

Conclusion
This study has demonstrated multiple N-glycans are potential predictors of biological response, with the possibility to guide clinicians in the most appropriate form of treatment. These results require the integration of mass spectrometry and validation by larger cohorts.
P1048 Mirikizumab administration experience from Ulcerative Colitis patients: Survey data from the LUCENT clinical program
Authors: Clemow D , Radawski C , Milata J , Alaka K , Hunter Gibble T , Schaum A , Ezennia O , Martinez N , Szaloki T , Ito Y , Rodriguez D , Kirk K 
Published: January 2024

Abstract

Background
Mirikizumab (MIRI) is an anti-IL-p19 antibody approved for moderately-to-severely active ulcerative colitis (UC). The recommended dose regimen has 2 parts: MIRI administration begins with intravenous (IV) infusion every 4 weeks (Q4W; 3 total) and is followed by maintenance dosing of subcutaneous (SC) injections (2 injections per dose) Q4W. Self-injection of SC MIRI is allowed after patient training. This study investigated patient satisfaction with and acceptability of MIRI IV infusions and SC injections during the LUCENT program.

Methods
This was a cross-sectional, 30-min, web-based survey. Patients were eligible if they were enrolled in LUCENT-3, a phase 3, open-label, long-term extension study of MIRI. Patients entered LUCENT-3 from the AMAC phase 2 study, or the LUCENT-1 and LUCENT-2 phase 3 studies. The survey covered patient satisfaction with and acceptability of IV infusions during the AMAC, LUCENT-1, or LUCENT-2 (extended or reinduction) studies and SC injections during the AMAC, LUCENT-2, or LUCENT-3 studies (Figure 1). Survey questions had responses based on 5-point Likert scales (Table 1). The survey was completed during LUCENT-3; MIRI SC injection experience at the time of survey varied from &gt;2 yrs to ≥3 yrs. Subgroup analyses (primary: age and sex) were made using Fisher's exact tests.

Results
The survey was completed by 93 patients from 11 countries (mean age, 42.9 yrs; 54.8% male; 69.9% White). Most patients were satisfied or very satisfied with IV infusions (82.8%) and SC injections (91.4%). More than 89% of patients retrospectively reported that their satisfaction with either administration method remained the same or improved over time. Most patients indicated receiving 2 SC injections (96.8%) and receiving SC injections Q4W (97.8%) were somewhat or completely acceptable. Patients (95.1%) agreed that the self-injection device was easy to use. 97.8% were satisfied or very satisfied with the administration of MIRI overall, 96.8% agreed or strongly agreed that they would recommend MIRI to someone with UC, and 90.3% agreed or strongly agreed that improvements in their UC outweighed any dissatisfaction with the administration method. Acceptability of MIRI administration differed by age (p=0.0369). More patients aged ≥40 yrs than &lt;40 yrs found the MIRI administration completely acceptable (98.2% vs. 89.2%). Overall satisfaction with the IV infusions differed by sex (p=0.0159). More females than males were satisfied or very satisfied with the IV infusions (92.9% vs.74.5%).

Conclusion
Most UC patients were satisfied with and acceptable of receiving MIRI by IV infusions and SC injections and found the dosing of 2 SC injections Q4W acceptable.
P1055 Intravenous to subcutaneous infliximab switch may reduce the risk of immunogenicity related treatment failure and can be used to facilitate immunomodulator withdrawal
Authors: Campbell I , Brownson E , Bailey E , Nowell E , Laird S , Seenan J P , MacDonald J 
Published: January 2024

Abstract

Background
Infliximab (IFX) is an effective treatment option for many patients with inflammatory bowel disease. Immunogenicity mediated treatment failure (IMTF) is a common clinical problem usually tackled by addition of an immunomodulator (IMM) and/or IFX dose escalation.
Switching stable patients on IV IFX maintenance therapy to SC IFX has been shown to be safe and effective.1 It is hypothesised that SC IFX may reduce the risk of IMTF but there is little data to support this. We aimed to explore whether switching selected patients at risk of IMTF from IV to SC IFX was safe and effective and assess whether this strategy can facilitate treatment de-escalation and IMM withdrawal.

Methods
The local IBD database was used to identify potentially suitable patients at higher risk of IMTF. This included those on escalated doses of IV IFX, those who had developed low level anti-drug antibodies (ADA), and those on combination therapy in whom it was felt desirable to withdraw IMM. Those who agreed to switch were commenced on SC IFX 120mg fortnightly and followed up clinically and with IFX drug levels (DLs) and ADA at week 8, 24 and 52.

Results
29 eligible patients underwent IV to SC IFX switch. Two patients were excluded: one returned to IV IFX and the other stopped IFX completely within 8 weeks of switch.
Outcomes for 27 patients were evaluated: 10 with UC, 14 CD, 3 IBD-unclassified. Median age was 38 (IQR 31-49). Median duration of IV IFX was 34 months (IQR 24-54 months). 17 patients were on accelerated IV IFX dosing.
All 27 patients remained on SC IFX at one year. Two required a course of steroids for disease flare. Of the 19 patients who had faecal calprotectin (FCP) data available, the mean FCP prior to switch was 66.1 (30-317) and post initiation of SC IFX was 189.6 (30 – 1800), but this did not reach statistical significance (p=0.172).
12/27 patients were on IV IFX plus IMM therapy. 9/12 successfully stopped IMM after switch to SC IFX.
Mean DL prior to switch was 7.13 (2.7-12.5) and post switch was 12.07 (1.6-14.5). In those who were on accelerated IV IFX dosing, 15/17 saw an increase in DLs post switch. In the 8 patients who had ADAs prior to switch, all saw a reduction, with 6 having no detectable ADAs post switch.

Conclusion
Switching from IV to SC IFX in this cohort was safe and effective. Most patients maintained steroid free remission at one year. All those who stopped IMM were successfully maintained on monotherapy at 1 year. 15/17 people treated with escalated IV dosing were successfully switched to standard SC IFX dosing with improvement in mean IFX DLs and without loss of clinical effect.