bluuebunny/crossref_metadata_2025_split huggingface dataset:
P662 Discontinuation of biologic therapy in Inflammatory Bowel Disease: longer term outcomes
Authors: Al-Talib I , Iqbal M , Slater J , Bates B , Jones J , Rattehalli D , King D , De Silva S 
Published: January 2024

Abstract

Background
The National Institute of Health and Care Excellence (NICE) in the UK recommends evaluation of all patients receiving biological therapy for IBD at 12 months, with a view to discontinuation of therapy for those with stable disease in remission. We recently evaluated the outcomes of discontinuation of biologics at our centre and the disease relapse rate at 12 months was 14.5%. Following this, longer-term outcomes were evaluated for patients who did not relapse at 12 months.

Methods
All patients on Biologics therapy who underwent biologics discontinuation were identified via our IBD registry. Retrospective data was collected between January 2015 and January 2022 and these included baseline demographics, disease type, type and duration of biological therapy, when therapy was discontinued and disease relapse initially at 12 months, and beyond. All patients had disease re-assessment prior to discontinuation. Disease relapse was defined as evidence of disease activity requiring steroid, biologic or surgical therapies. Patients with perianal Crohn’s disease were excluded.

Results
A total of 62 patients were included and divided in two groups. 37 (60%) patients had Crohn’s disease (CD) and 25 (40%) had Ulcerative Colitis (UC). Disease extent in the CD group included Ileal (32%), Colonic (53%) and Ileocolonic (15%). In the UC group disease extent included Proctitis (28%), Left sided (56%) and Extensive disease (32%).
At 12 months, 14.5% (9) patients had disease reactivation, 13.5% with CD and 16% with UC. The duration of treatment prior to discontinuation ranged between 9 to 74 months (Median 47.5).
Beyond 12 months of discontinuation, a total of 48 patients (CD 29 and 19 UC) had their data analysed, with 5 patients excluded due to being lost to follow up. 29% of these patients eventually had a relapse (CD 7, UC 7). The median follow up period was 53 months (range 21-84 months) in the CD group and 42 months (range 24-76 months) in the UC group. The rate of relapse post 12 months of de-escalation was 24% in the CD group and 36% in the UC group.

Conclusion
In this study, the rate of disease recurrence beyond 12 months of discontinuation of biological therapy was 29 % (median follow up in CD 53 months and UC 42 months) compared to 14.5% at 12 months. Despite careful selection of patients with up-to-date disease activity assessment prior to discontinuation, our data suggests that the overall disease recurrence rate was high at 40% (35% in CD and 48% in UC) and recurrence rates increase over time. We would therefore suggest that discontinuing treatment should only be considered after clear discussions with patients about the high risk of disease relapse and based on an individual basis.
P663 Efficacy of jak inhibitors in inflammatory bowel disease patients with extraintestinal manifestations– Retrospective study
Authors: Livne Margolin M , González Lama2 Y , Koutroubakis I , Drygiannakis I , Shitrit A , Goldenberg R , Farkas K , Molnar T , Ivány E , Amiot A , Carbonnel F , Girod P , Doherty G , Mateescu B , Ben-Horin1 S , Kopylov U 
Published: January 2024

Abstract

Background
JAK inhibitors have demonstrated efficacy in ulcerative colitis (UC), Crohn’s disease (CD), and inflammatory arthritis. However, limited data exist on their effectiveness in treating extraintestinal manifestations (EIM) in patients with inflammatory bowel disease (IBD) in real-world scenarios. This multicenter, retrospective study aims to assess the efficacy of JAK inhibitors (JAKI), specifically tofacitinib or upadacitinib, in IBD patients with EIM.

Methods
This was a retrospective multicenter cohort study. Inclusion criteria included IBD patients with active EIM documented before JAKI treatment initiation, with a follow-up up to 52 weeks. EIM Clinical response was defined as either improvement or remission of EIM complaints, as subjectively described by the patient or taken from the treating physician’s assessment.

Results
Eighty-six patients from eight centers were included, with 64% having UC (n=55). Women constituted 60% of the patients (n=51). Tofacitinib and upadacitinib were administered to 63% (n=54/86) and 36% (n=32/86) of patients, respectively. Eleven patients (13%) were biologically naïve, all treated with tofacitinib. Arthralgia was the predominant complaint, affecting 55% (n=30/54) of tofacitinib-treated and 44% (n=14/32) of upadacitinib-treated patients. Patient characteristics, including EIM distribution, are detailed in Table 1.
At 3 months, 86% (n=72/83) achieved EIM clinical response, with tofacitinib responders at 94% (n=49/52) compared to 74% (n=23/31) for upadacitinib (p=0.01). Seven percent (n=6) discontinued treatment due to lack of response. Peripheral arthralgia improved or achieved remission in 86% (n=32/38) of patients, while 68% (n=13/19) with axial arthropathy experienced clinical response.
At 6 months, EIM clinical response was achieved by 76% (n=44/75), with tofacitinib at 86% (n=44/51) and upadacitinib at 54% (n=13/24) (p=0.004). Twelve percent(n=10) discontinued treatment due to loss of response. Peripheral arthralgia responded in 86% (n=31/36), and axial arthropathy responded in 42% (n=8/19).
At 12 months, 65% (n=44/68) of patients improved or had remission, with tofacitinib responders at 73% (n=35/48) and upadacitinib responders at 45% (n=9/20) (p&lt;0.05). Eighty-eight percent (n=23/26) with peripheral arthralgia and 50% (n=5/10) with axial arthropathy achieved clinical response.

Conclusion
This study demonstrates the effectiveness of JAK inhibitors in treating EIM, with a high percentage of responders. Tofacitinib appears more effective than upadacitinib, possibly influenced by a higher proportion of biologically experienced patients and differences in IBD subtype distribution between the two groups, with upadacitinib mainly used in CD patients and tofacitinib in UC patients.
P668 Dashboard-guided anti-TNF induction as an effective proactive strategy in Inflammatory Bowel Disease's treatment
Authors: Céspedes Martínez E , Robles-Alonso V , Herrera-De Guise C , Mayorga L , Serra X , Pérez Z , Oller E , Larrosa M , García-García S , Casellas F , Borruel N 
Published: January 2024

Abstract

Background
Infliximab (IFX) and Adalimumab (ADA) are effective treatments for managing Inflammatory Bowel Disease (IBD) but treatment failure is common. Therapeutic drug monitoring (TDM) of trough serum drug concentrations (C Trough) has been used to optimize treatment induction, mitigate immunogenicity, and ensure appropriate drug exposure. HLA DQA1*05 genotype variants have been identified as predictors of immunogenicity. This study aimed to investigate the impact of dashboard-guided optimized induction dosing strategy on clinical and pharmacokinetics outcomes of anti-TNF, with the goal of analysing the HLA DQA1*05 effect.

Methods
We conducted a retrospective single-centre cohort analysis of IBD patients, Crohn’s disease (CD) and Ulcerative Colitis (UC), who initiated treatment with IFX or ADA between January 2020 and March 2023, using a pharmacokinetic dashboard-guided induction, protocolized with the Pharmacy Department. C Trough measurements were taken at week 2, 6 and 14, first drug intervention based on the model was in week 4. Targeted C Trough levels during induction were set at 10-15 mcg/mL for ADA and &gt; 17 mcg/mL for IFX. Primary objective was to assess clinical remission (CR). Secondary outcomes included treatment failure (TF) and endoscopic remission (ER). We performed a descriptive analysis and generated Kaplan Meier curves to assess drug survival

Results
We enrolled 147 patients, 92 having CD (74 treated with ADA and 18 with IFX) and 55 having UC (36 treated with ADA and 19 CU with IFX). HLA DQA1*05 genotype variant was present in 44,14% of patients. Combined treatment with thiopurine was used in 45,58% and 11,54% had been previously received biologic treatment. After 24 weeks, 91,83% (135/147) of patients achieved CR and 65,81% (77/117) at week 56. ER was observed in 59,84% (76/127) after a year. Anti-TNF drug survival probability was 85% after a year, meanwhile ADA drug survival in UC patients was 75%. A 77,7% of patients were prescribed an accelerated dose in the first year, which was associated with improved drug durability. Only a patient out of 147 developed antibodies to ADA. The HLA DQA1*05 variant was not a statistically significant predictor of adverse treatment or pharmacokinetic outcomes.

Conclusion
Optimizing anti-TNF induction with a Dashboard-guide dosing strategy proves to be a valuable approach to enhance clinical remission and durability rates in IBD patients. The role of HLADQA1*05 variant in immunogenicity appears to be mitigated by the model.
P669 Efficacy of Ustekinumab-based integrated medicine therapy in patients with symptomatic stricturing Crohn's disease: a multicentre, prospective, observational cohort study
Authors: Liu J , Hu W , Li S , Xu D , Wu Q , Chen Y 
Published: January 2024

Abstract

Background
Strictures are the most common structural complication of Crohn's disease (CD). Surgery and endoscopic balloon dilation are the main treatments; however, there is no data about the efficacy of ustekinumab (UST) in patients with symptomatic stricturing CD.

Methods
In this multicentric study, we prospectively included adult CD patients treated with their first UST therapy for symptomatic strictures (confirmed on endoscopy or imaging). The primary endpoint was success at week 52, defined as UST continuation without prohibited treatment (corticosteroids, other biologics), endoscopic dilation, or bowel resection. The long-term endpoint was discontinuation of treatment for failure, bowel damage progression and time to surgery in the whole cohort. The effectiveness was determined by the relief of stenosis while the baseline factors independently associated with success were identified using a logistic regression model.

Results
Overall, 28 patients were included and analyzed for baseline [median age-34 (range 24-46) years; males-64.3%; median disease duration-10 (range 2–216) months; active smokers-10.7%]. The ileum was the most common site of stricture (67.9%), 21.4% of patients had colonic strictures, and 17.9% had multiple strictures. 35.7% of patients were steroid-dependent. Before enrollment, 10.7% of patients had got bowel surgery, 25.0% got perianal surgery, and 3.6% got endoscopic dilation treatment. 14.3% had received treatment of other biologics.
The rate of success at 52 weeks was 71.4% while 8 patients quit due to stricture surgery, changed to anti-TNFs, or resumed exclusive enteral nutrition. In terms of stenosis remission, the SES-CD of strictures and DBE-CD decreased from 6.71±0.18 and 3.85±0.15 to 3.14±0.14 and 3.04±0.24, respectively. The Crohn’s disease obstructive score (CDOS) significantly decreased from 4.85±0.61 to 1.14±0.39 (p=0.025).
In the assessment of disease activity, UST down-regulated the IBUS-SAS of ultrasound from 71.71±5.23 to 54.73±5.41 (p=0.036). HBI (p=0.14) had a downtrend during the follow-up period, and the concentrations of CRP (p=0.04) and FCP (p=0.025) also decreased respectively.
The predictive factors of remission in patients who received ustekinumab were bowel wall thickness &lt; 5 mm (p=0.031). No significant risk of surgery or failure has been observed yet (p=0.25).

Conclusion
Ustekinumab seems to be effective in controlling the progress of intestinal strictures in CD patients. Nevertheless, further cohort size expansion and data analysis are indispensable.
P694 Age is a strong of predictive risk factor for anti-TNF therapy related adverse events in IBD patients
Authors: Majumder S , Bhaduri A , Sharma N , Mohammed Nabil Quraishi N Q , Cooney R , Ghosh S , Iacucci M , Shivaji U N 
Published: January 2024

Abstract

Background
Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. We aimed to record AEs and understand factors that could predict risk of AEs.

Methods
All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary hospital between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Adverse events (AEs) were recorded as per relevant systems involved e.g.- haematological, cardiac etc., including infections and malignancies as separate categories. All analysis (normalization, hypothesis testing, and visual reports were performed using R software package Version: R 4.2.1.

Results
A total of 844 IBD patients (Male =408) were included with an age range of 18-75yrs. Majority were Caucasian in ethnicity (514) and more patients with CD [605(71%)] were exposed to anti-TNF than UC. The age profiling analysis was performed across ethnic groups (Asian, Caucasian and Others). Age associated AE was reported across all the groups (data not shown). It must be mentioned that though not significant, Caucasian patients were more susceptible towards AE as compared to Asian.

Conclusion
· Patient age above 50yrs has a strong predictive risk factor for AEs related to anti-TNF therapy for IBD.
· In our cohort, more than half of patients &gt;50yrs reported at least one AE in UC, and the age was lower in CD.
· Although Caucasians were more vulnerable to AEs, this was not statistically significant.
· Clinicians should consider and discuss this risk before selecting patients for anti-TNF therapy.
· With multiple biologic choices currently available, another class could be considered where possible, for the &gt;50yr patient cohort.
P702 Long term outcomes following de-escalation of dose-intensified ustekinumab in patients with Crohn’s disease
Authors: Demase K , Smith R L , Luber R , Taylor K M , Ward M G , Sparrow M P , Little R D 
Published: January 2024

Abstract

Background
Data on outcomes following de-escalation of dose-intensified ustekinumab (UST) in Crohn’s disease (CD) have not been reported. This retrospective cohort study aimed to evaluate the failure rates 6, 12, and 24 months after de-escalation from dose-intensified UST to standard dose UST and identify predictors of failure.

Methods
Single centre, retrospective study of consecutive CD patients undergoing de-escalation of dose-intensified UST (90mg 4-weekly) to standard dosing (90mg 8-weekly). De-escalation and post de-escalation decisions were informed by protocolised 6-monthly assessment using Harvey-Bradshaw Index, C-reactive protein (CRP), faecal calprotectin (FCP), drug level and intestinal ultrasound. Failure was defined by re-escalation of UST, corticosteroids, switch out of class, or IBD-related hospitalisation or surgery. Success was defined by continued standard UST dosing. Categorical variables were compared using Fisher-exact and continuous variables using Mann-Whitney U tests between groups.

Results
14 patients underwent de-escalation from April 2020 to March 2023. The median age was 41 years, disease duration 15 years, and duration on dose-intensified UST 34 months. 43% received IV reinduction at time of escalation, 86% had previous exposure to advanced therapies, of which 43% were dose-intensified. 36% were on an immunomodulator (IMM) at de-escalation. In the 6 months prior to de-escalation, the median CRP was 3.5mg/L, FCP 96mg/g, and 91% were in sonographic remission. 5/14 (36%) failed de-escalation at 6 months and 9/14 (64%) failed by 12 months. Of those with 24 months follow up, 9/12 (75%) failed de-escalation. Median time to failure was 8 months (IQR 4.5-13). All patients who failed underwent re-escalation and 2 required surgery. UST drug levels reduced from 3.6 to 1.9mg/mL 6 months post de-escalation. Re-escalation successfully recaptured response in 7/9 (78%). A greater proportion of patients with successful de-escalation at 12 months received concomitant IMM compared to those that failed (80% vs. 11%, respectively; p = 0.02). There were no other significant differences in clinical or disease characteristics between those with failure vs. success at 6, 12, or 24 months, although numbers were small (Table 1).

Conclusion
One-third of patients failed de-escalation of dose-intensified UST at 6 months, two-thirds failed at 12 months and three-quarters by 24 months. Patients considered for a trial of de-escalation need close, objective monitoring as most failure occurs early, and re-escalation is successful in the majority. Concomitant IMM may reduce failure rates and should be considered. Further studies are required to confirm these findings and identify additional predictors of de-escalation failure.
P705 Assessment of age on the efficacy and safety among patients in the etrasimod ELEVATE ulcerative colitis clinical programme
Authors: Lichtenstein G R , Allegretti J R , Loftus Jr E V , Irving P M , Banerjee R , Charabaty A , Kuehbacher T , Bananis E , Woolcott J C , Dalam A B , Lazin K , Keating M , McDonnell A , Danese S 
Published: January 2024

Abstract

Background
Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Previous work has shown age can impact treatment safety and efficacy in patients with inflammatory bowel disease.1 This post hoc analysis investigated the impact of age on the safety and efficacy of etrasimod in patients with UC in the phase 3 ELEVATE UC clinical programme.

Methods
Data pooled from the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials were analysed in patients receiving etrasimod 2 mg QD and placebo. ELEVATE UC 52 had a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. ELEVATE UC 12 was a 12-week induction trial. Proportions and incidence rates (IRs) per 100 patient-years from pooled data of treatment-emergent adverse events (TEAEs) and events of interest were stratified by age (&lt;40 years, 40–59 years, ≥60 years) and analysed in patients who received ≥1 dose of etrasimod or placebo. Efficacy analyses were evaluated in patients with baseline Modified Mayo score (MMS) 5–9 for the primary efficacy endpoint (clinical remission) and select secondary endpoints at Week 12 (both trials) and Week 52 (ELEVATE UC 52) stratified by age.

Results
There were 787 patients enrolled in the ELEVATE UC programme, of whom 420 (53.4%) were aged &lt;40 years, 276 (35.1%) were aged 40–59 years and 91 (11.6%) were aged ≥60 years. The proportions and IRs of TEAEs and events of interest were mostly similar between age groups and treatment arms (Table). IRs of arthralgia, fatigue, hypertension and pyrexia were higher in older age groups, regardless of treatment arm. Serious AEs and AEs leading to treatment discontinuation were low and consistent across all age subgroups. Serious infections and infection events of interest were balanced across age groups and treatment arms. Regardless of age subgroup, significantly more patients treated with etrasimod 2 mg QD vs placebo achieved the primary and select secondary efficacy endpoints at Week 12 and Week 52 (Figure).

Conclusion
The safety profile of etrasimod 2 mg QD in the UC population was consistent across age groups, and with no new risks other than the estimated risks associated with increasing age.2 Patients receiving etrasimod in the ELEVATE UC programme showed significant clinical benefit as assessed by clinical remission, symptomatic remission and endoscopic improvement compared with placebo, regardless of age.
References
1. Lichtenstein GR et al. Inflamm Bowel Dis 2023; 29: 27–41.
2. Luo J et al. JMIR Med Inform 2016; 4: e30.
P713 The introduction of an intestinal ultrasound service significantly reduces diagnostic endoscopy usage in an Inflammatory Bowel Disease service – The SCOPELESS Study
Authors: Feng G , Little R , Ardalan Z , Friedman A , Smith R , Taylor K , Sparrow M 
Published: January 2024

Abstract

Background
Endoscopic assessment is the gold standard for monitoring of inflammatory bowel disease (IBD) activity. Intestinal ultrasound (IUS) is increasingly utilised as a non-invasive, alternative disease monitoring strategy. Our study aim was to quantify and compare endoscopy usage for evaluation of IBD disease activity before and after the introduction of an IUS service.

Methods
A retrospective single-centre study was performed. Total numbers of lower GI endoscopies (ileocolonoscopy or flexible sigmoidoscopy) performed for luminal Crohn’s disease (CD) or ulcerative colitis (UC) disease evaluation were collected across two 5-year time periods: the pre-IUS era (2010-2014) and the IUS era (2015-2019). Endoscopies for dysplasia surveillance were excluded. The primary endpoint was a comparison of the cumulative number of endoscopies for IBD disease activity evaluation annually relative to the annual number of patients seen in clinic in the pre-IUS and IUS eras. Secondary endpoints included evaluating the number of endoscopies by individual year within each time period, endoscopies according to diagnosis (CD vs. UC), and the number of IUS performed within the IUS era. Categorical variables were compared using a Chi-squared test. A p value &lt;0.05 was considered statistically significant.

Results
The number of endoscopies performed for IBD disease evaluation decreased from 576 in the pre-IUS era to 474 in the IUS era despite an increase in cumulative annual patient reviews (1985 vs. 3337 patient reviews, respectively). The annual number of endoscopies for disease evaluation per patient in the pre-IUS and IUS eras is illustrated in Figure 1. The proportion of cumulative annual endoscopies relative to patients reviewed across the 5-years reduced from 29 per 100 patients in the pre-IUS era to 14 per 100 patients in the IUS era (OR 2.47, 95% CI 2.15-2.84; p &lt; 0.001). There was a reduction in total endoscopies for CD evaluation from 325 to 264 and UC evaluation from 251 to 210. The proportion of endoscopies performed for CD vs. UC was unchanged between the two eras (56.4% vs. 55.7%; p = 0.81). In the IUS era, a total of 3319 IUS were performed (2673 CD, 646 UC). This included 1467 IUS for assessment of suspected activity (44 per 100 patients/year) and 1852 IUS for objective confirmation of clinical remission (55 per 100 patients/year).

Conclusion
In the 5 years following introduction of an IUS service, the number of endoscopies performed for evaluation of IBD activity per patient was halved. IUS was performed for both assessment of disease activity and objective confirmation of clinical remission. The potential workflow and cost savings of reduced endoscopies for IBD disease activity evaluation are significant.