bluuebunny/crossref_metadata_2025 huggingface dataset:
P624 Development and Validation of a Clinical Decision Support Tool to Predict Outcomes of ustekinumab Treatment in Patients with Crohn’s Disease
Authors: Yao L , Cao Y , Cao Q
Published: January 2024

Background

Ustekinumab (UST) has been demonstrated for the treatment of Crohn's disease (CD) with a high efficacy and safety profile. There is limited data concerning disease progression after UST treatment. This study aims to establish a clinical decision support tool (CDST) to identify Chinese patients with CD who are less likely to experience disease progression under UST treatment.

Methods

A multicentre, retrospective observational study was conducted among Chinese patients with CD initiating UST between 1 May 2020 and 20 October 2022. Disease progression (including CD-related surgery, hospitalization and complications) was evaluated at week 24 (±4w). Logistic regression analysis was performed to identify factors associated with disease progression. The CDST, established based on these factors, was both internally and externally validated. The performance of this tool was tested using receiver operating characteristic (ROC) area under the curve (AUC) analyses.

Results

A total of 519 patients were enrolled in this study. In the derivation analysis, four factors including prior biologics usage, prior immunosuppressant usage, baseline faecal calprotectin, and baseline haemoglobin were identified to correlate with progression. A good predictive ability of this model was confirmed by AUC as high as 0.76 for the internal validation cohort and 0.72 for the external validation cohort, respectively. The CDST stratified patients into low, intermediate, or high risk of progression with cut-off values of 6 and 16.

Conclusion

We developed and validated a scoring system to identify CD patients less likely to experience progression at week 24 with UST therapy. This CDST will facilitate therapy decision-making and precision medicine.
P627 Real-world clinical effectiveness and safety of vedolizumab and ustekinumab in biologic-naïve patients with Crohn’s disease by disease location: Results from the EVOLVE Expansion study
Authors: Scharl M , Christensen B , Bressler B , Brett N R , Gianchetti L , Kamble P , Adsul S , Farhat Z , Ferrante M
Published: January 2024

Background

Crohn’s disease (CD) location may affect disease course and treatment (Tx) decisions. This analysis compared real-world clinical effectiveness and safety of vedolizumab (VDZ) and ustekinumab (UST) in biologic-naïve patients (pts) by CD location.

Methods

Medical charts of biologic-naïve pts with CD aged ≥18 years initiating VDZ or UST in Australia, Belgium or Switzerland from 2016 to 2021 were analysed in a multicentre, observational, retrospective EVOLVE Expansion study (NCT05056441). Subgroup analysis evaluated outcomes with VDZ vs UST in pts with baseline ileal, ileocolonic and colonic CD (Montreal classification). Data were collected from Tx initiation to the first of chart abstraction initiation, Tx discontinuation, loss to follow-up or death. Inverse probability of Tx weighting (IPTW) was used to balance baseline characteristics between cohorts. Clinical outcomes (clinical response, clinical remission, mucosal healing), as assessed using published algorithms,1 and Tx persistence during 36 Tx months were analysed in time-to-event analyses (Kaplan-Meier method). Risks of safety (serious adverse events [SAEs], serious infections [SIs]) and healthcare resource utilisation (HCRU; CD exacerbations, CD-related hospitalisations, CD-related surgeries) outcomes with VDZ vs UST during 36 months were also compared.

Results

This analysis included 293 pts with ileal (VDZ:158, UST:135), 185 with ileocolonic (VDZ:91, UST:94) and 121 with colonic (VDZ:84, UST:37) CD. Baseline characteristics after IPTW were similar between VDZ and UST cohorts in all 3 subgroups. Cumulative rates during 36 Tx months were similar between VDZ and UST cohorts in ileal, ileocolonic and colonic CD subgroups for clinical response (p=0.67, p=0.94, p=0.22, respectively), clinical remission (p=0.51, p=0.20, p=0.52), mucosal healing (p=0.29, p=0.60, p=0.71) and Tx persistence (p=0.37, p=0.29, p=0.50) (Figure). There were no differences in the risks of SAEs, SIs, CD exacerbations and CD-related hospitalisations between cohorts across disease location; risk of CD-related surgeries was similar in pts with ileocolonic and colonic CD, and higher in VDZ vs UST cohort (p=0.02) in pts with ileal CD (Table). However, in ileal CD subgroup, CD-related surgeries during 36 months were reported only in 12/158 (7.6%) pts in VDZ and 3/135 (2.2%) pts in UST cohort.

Conclusion

During 36 Tx months, effectiveness, safety and HCRU outcomes were similar between VDZ and UST cohorts regardless of baseline disease location; risk of CD-related surgeries was higher with VDZ vs UST in pts with ileal CD and similar between cohorts in other subgroups. However, the absolute number of pts requiring CD-related surgeries was low.

Reference:

1. Bressler B, et al. J Crohns Colitis. 2021;15(10):1694-1706.
P632 Isolation of a novel metalloproteinases transcriptional signature with robust anti-TNF therapy predictive power in patients with Ulcerative Colitis
Authors: Arosa García L , Camba-Gómez M , Calviño-Suárez C , Bastón-Rey I , Ferreiro-Iglesias R , Porto M , Nieto L , Domínguez-Muñoz J E , Barreiro-de Acosta M , Conde-Aranda J
Published: January 2024

Background

Anti-TNF agents were the only biologic for Inflammatory Bowel Disease (IBD) patients. However, new drugs targeting α4β7 integrin, IL-12/IL-23, and janus kinases were added to the IBD therapeutic armamentarium. Anti-TNFs are first-line biological agents in our country, and for that reason, the discrimination of patients who will be refractory of those therapies before treatment is relevant to prevent IBD patients from the exposition to multiple therapeutic failures. Therefore, we wanted to isolate robust and reproducible transcriptional markers able to specifically predict the response to anti-TNF therapy, which will contribute to targeted prevention, improve individual outcomes and decrease therapy expenditures.

Methods

We analysed publicly available microarray and RNAseq datasets of colon biopsies (GSE12251, GSE16879 and GSE73661) and whole blood cells from different cohorts of patients with Ulcerative Colitis (UC) (GSE191328). R package was used to perform the differential expression analyses and calculation of receiver operating characteristic (ROC). Cytoscape software and Morpheus (broadinstitute.org) was used to perform network data integration and visualization. Also, we used our local cohort of UC patients to further validate our results by RT-qPCR (n=21).

Results

We isolated a transcriptional signature composed of eight metalloproteases (MMPs) with high association with disease activity. Most of the transcripts of that signature were significantly upregulated in colon biopsies of non-responder patients to anti-TNFs before treatment in three different microarray datasets, but not in vedolizumab-treated patients. ROC curves of the different MMPs showed variability in the correlation to anti-TNF response among the different datasets analysed. Only three out of eight MMPs were still showing robust predictive power with an area under the curve around of 80% when all dataset were combined. Interestingly, PBMCs isolated from our local cohort of IBD patients presented increased expression of those MMPs in refractory patients to anti-TNF therapy, confirming that these three MMPs have the highest predictive power both in colon tissue and in peripheral mononuclear cells.

Conclusion

Overall, our study revealed a novel and robust MMP-transcriptional signature associated with anti-TNF but not vedolizumab therapy response. Nevertheless, our results should be corroborated in independent cohorts of patients with UC to test their efficacy and sensitivity in the clinical setting. Our data definitively contribute to the change from a reactive approach to predictive, preventive and personalised medicine.
P633 First-in-Human Pharmacokinetic and Safety Study of an Anti-TL1A Antibody, TEV-48574, in Healthy Volunteers and Asthma Patients
Authors: Balyan R , Ghibellini G , Sunzel E M , Dreymann J , Radivojevic A , Dotan O , Angeles T , Li S , Papp A , Rasamoelisolo M , Rabinovich-Guilatt L
Published: January 2024

Background

TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). TEV-48574 is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD); and has been shown to reduce fibrosis, inflammation, and mortality in animal models of IBD and asthma.1 The main objectives of this phase 1 study were to characterize the pharmacokinetics (PK) and safety of TEV-48574 in healthy subjects and mild asthmatic patients.

Methods

In the single ascending dose part of the study (SAD), healthy subjects were randomized 6:2 to active and placebo treatment; specifically participants were either administered TEV-48574 single dose (1, 4, 12, 36, 90, 200, 400, or 1000 mg) or placebo by subcutaneous route (SC). In the multiple ascending dose part of the study (MAD) patients with asthma were randomized 9:3 to active and placebo treatment in three cohorts. Cohort 1 received TEV-48574 200 mg Q2W or placebo (days 1, 15, and 29). Cohort 2 received a loading TEV-48574 dose of 800 mg on day 1 followed by 2 maintenance doses of 600 mg on days 15 and 29 (800/600 mg Q2W) or placebo. Cohort 3 received a loading TEV-48574 dose of 2300 mg on day 1 followed by 2 maintenance doses of 1600 mg on days 15 and 29 or placebo. Safety, tolerability, PK, and anti-drug antibody (ADA) levels were assessed at predetermined times. Measurement of total and free TL1A using ligand binding assays will be reported elsewhere.

Results

TEV-48574 was absorbed slowly with peak concentrations appearing at 72- 96 hours following SAD and MAD administration. It was eliminated gradually in a monophasic manner and the rate of elimination appeared similar across dose levels (Figure 1). Exposures as defined by maximum concentration (Cmax) and area under the curve (AUC) of TEV-48574 increased in a dose-proportional manner with no accumulation. Mean t½ estimates ranged from 6.5 to 9.6 days (Table 1).

Administration of TEV-48574 was generally well tolerated at doses up to 2300 mg. ADA-positive responses were observed at doses of 200 mg or lower in 23 of 48 TEV-48574-treated subjects in the SAD portion of the study and in 3 of 27 TEV-48574-treated patients in the MAD portion of the study and were not associated with safety signals.

Conclusion

TEV-48574 was well tolerated at all tested doses in healthy subjects and participants with asthma, with dose proportional increases in exposure and minimal accumulation after multiple dosing every two weeks. The data support further development of TEV-48574 in patients with IBD.

1. Clarke A. et al. mAbs.2018;10:664-677.
P635 Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in Acute Severe Ulcerative Colitis: a randomized controlled trial
Authors: Mundhra S , Madan D , Golla R , Sahu P , K Vuyyuru S , Kante B , Kumar P , Matthew D , Prasad S , Vaishnav M , Verma M , Virmani S , Bajaj A , Markandey M , Kumar Ranjan M , Arora U , Kumar Singh M , K Makharia G , Kedia S , Ahuja V
Published: January 2024

Background

30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties can further improve steroid response in ASUC, which was evaluated in present study.

Methods

In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + SOC + EEN vs. SOC + EEN (Jan2021 – Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was steroid failure (need for rescue medical therapy or colectomy) and proportion of patients with adverse events.

Results

Sixty-one patients (albumin-30, SOC-31) (mean age-31.6 ± 10.4 years, male- 57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm (10/30 (33.33 %) vs 13/31 (41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate (10 % vs 9.68 %, P=1), response to salvage medical therapy (88.89 % vs 76.92 %, P=0.62) and median duration of hospitalization (10.5 (7-16) vs 10 (7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04 % vs 17.86 %), although it did not reach statistical significance.

Conclusion

There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.
P636 Comparison of the real-world efficacy of filgotinib with tofacitinib in patients with refractory ulcerative colitis: A single-center retrospective study
Authors: Yagi S , Fukui H , Yokoyama K , Kaku K , Takagi Y , Ikenouchi M , Sato T , Kawai M , Kamikozuru K , Yokoyama Y , Tomita T , Shinzaki S
Published: January 2024

Background

Several Janus kinase inhibitors have recently been launched for the treatment of ulcerative colitis (UC). However, there are few reports comparing the efficacy and safety of each drug in patients with refractory UC, especially with filgotinib (FIL), which was recently launched and can be concomitantly used with thiopurines. We herein aimed to compare the real-world efficacy and safety of tofacitinib (TOF) and FIL in induction therapy for patients with refractory UC.

Methods

Patients with refractory UC, who received either TOF 20mg/day or FIL 200mg/day from May 2018 to October 2023 in Hyogo Medical University Hospital were included in this study. Primary outcomes were clinical response rates at 2, 4, and 8 weeks after administration of TOF or FIL. Clinical response was defined as a decrease of partial Mayo Score (pMS) of ≥2 from baseline and rectal bleeding subscore is ≤1 or a decrease of ≥1 from baseline. Secondary outcomes were cumulative incidences of adverse events during the observation period.

Results

Of the 230 refractory patients with UC, 197 received TOF and 33 received FIL treatment. The median age was 37 [IQR 27–49] and 49 [33–54] years, and the median disease duration was 3 [1–10] and 5 [2–10] years, respectively. Median durations of observation were 118 [52–188] weeks in the TOF group and 41 [29–60] weeks in the FIL group, median baseline pMS were 6 [5–7] and 5 [5–6], and serum CRP levels were 3.8 [1.3–12.3] and 1.8 [0.3–3.3] mg/L, respectively. Thirty-eight (19.3%) patients in the TOF group and 3 (9.0%) patients in the FIL group received systemic steroids, and 8 (24.2%) in the FIL group received thiopurine at baseline. The clinical response rates at 2, 4 and 8 weeks were 58.4%, 59.4% and 62.9% in the TOF group, and 42.4%, 57.6% and 48.9% in the FIL group, respectively, and the rate tended to be higher in the TOF group than in the FIL group at 2 weeks (p = 0.092). Of the patients who did not respond at 4 weeks, the TOF group had a significantly higher clinical response rate (31.3%) than the FIL group (0%) at 8 weeks (p = 0.032). Among 124 patients with prior anti-TNF-α antibody failure, 59.6% (65/109) of patients in the TOF group and 46.7% (7/15) in the FIL group achieved comparable clinical responses at 8 weeks (p = 0.407). Fifteen of 197 (7.6%) patients in the TOF group and 2 of 33 (6.1%) in the FIL group did not continue treatment until 8 weeks due to adverse events, but there were no significant differences between the groups.

Conclusion

Even in patients without a response for up to 4 weeks, TOF treatment may provide a higher clinical response than FIL treatment at 8 weeks.
P641 Faecal calprotectin determines non-response to corticosteroids in patients with immune checkpoint inhibitor colitis
Authors: Crothers-Stomps L , Kuo H , Teh W X , White L , Mohsen W , Kakkadasam Ramaswany P , Mason R , Dzienis M , Patrick D
Published: January 2024

Background

Immune checkpoint inhibitor (ICI) therapy has improved survival outcomes in patients with advanced malignancy. ICI colitis (ICI-C) is one of the most common adverse events which often leads to cessation of an otherwise effective therapy.1,2 Corticosteroid therapy remains first-line treatment in patients with ICI-C. The aim of this study was to assess predictors of non-response to corticosteroid therapy to help guide early escalation to biologic therapy.

Methods

Multicentre retrospective analysis of adults hospitalized with ICI-C between July 2018 to March 2023. ICI-C was defined by patients who had current or prior immunotherapy who presented with diarrhoea with negative infective faeces PCR testing and admission diagnosis of ICI-C by their treating Physician. Baseline demographic, clinical, biochemical, and endoscopic data were collected. Grading of clinical severity on presentation and response to immunosuppression was defined by CTCAE diarrhoea grading with response defined as improvement to grade 1 or less.

Results

82 patients were analysed. 31 (38%) female, median age was 65.5 years (IQR 59-72)], 27 (33%) failed corticosteroid therapy and required biologic therapy. 34 (42%) had a faecal calprotectin on admission. On univariable analysis faecal calprotectin emerged as the sole predictor of corticosteroid non-response. ROC analysis identified an optimal faecal calprotectin cut-off of 620 mcg/g to identify corticosteroid non-responders [Sensitivity 75% (57.6-92.7), Specificity 77.8% (52.4-93.6), Accuracy 76.5%, PLR 3.37 (1.36-8.38), NLR 0.32 (0.13-0.78), AUROC 0.76 (0.616-0.911), OR 10.5 (2.24-49.3), PPV 75 (47.6-92.7), NPV 77.8 ( 52.4-93.6)].12/16 (75%) of patients with a faecal calprotectin ≥ 620 required biologic therapy.

Conclusion

Faecal calprotectin is a predictor of non-response to corticosteroid therapy in patients with immune checkpoint inhibitor colitis. This study identified a faecal calprotectin threshold of 620mcg/g as the optimal cut-off to identify corticosteroid non-response and need for second-line immunosuppression. These findings may help to reduce the need for endoscopic assessment and guide early escalation to biologic therapy.

REFERENCES:

1. Fujii T, Colen RR, Bilen MA, et al. Incidence of immune-related adverse events and its association with treatment outcomes: The MD Anderson Cancer Center experience. Invest New Drugs. 2018;36(4):638-646. doi:10.1007/s10637-017-0534-0

2. Wang Y, Abu-Sbeih H, Mao E, et al. Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis. Inflamm Bowel Dis. 2018;24(8):1695-1705. doi:10.1093/ibd/izy104.
P644 Body composition does not predict clinical course in patients with acute severe ulcerative colitis
Authors: Tassone D , Xu E , Winata S H L , Hale P , Basnayake C , Schulberg J , Flanagan E , Wright E , Kamm M A , Lust M , Niewiadomski O , Tambakis G , Clark N , Hartley I , De Gregorio M , Sutherland T , Thompson A J , Connell W R , Ding N S
Published: January 2024

Background

Acute Severe Ulcerative Colitis (ASUC) is a life-threatening complication of UC. Previous research has shown that body composition parameters, including sarcopaenia, are associated with outcomes in IBD. However, the relationship between body composition and the clinical outcomes of patients hospitalised with ASUC has not yet been clearly defined. We sought to further evaluate the prognostic role of body composition and further explore predictors of clinical outcome in ASUC.

Methods

We performed a cohort study of hospitalised ASUC patients. Body composition was assessed using fat and muscle segmentation, at the level of the L3 vertebral body, in patients who underwent abdominal computed tomography (CT) during hospitalisation. We defined sarcopenia according to skeletal muscle index (SMI) < 38 cm2/m2 in females and < 42 cm2/m2 in males. Clinical endpoints included length of hospitalisation, need for rescue medical therapy or colectomy. Between group comparisons were performed and logistic regression was used for risk factor analysis.

Results

We studied 116 patients with ASUC, 51 of whom underwent abdominal CT imaging during their hospitalisation. Median age was 32 years and 64% of patients were female. Sixty-two patients (53.5%) required rescue medical therapy. Rescue medical therapy was successful in 48 patients (77.4%) and 14 patients (22.6%) required an inpatient colectomy. Patients who underwent CT imaging during admission required increased rescue medical therapy (66.7% vs 43.1%, p=0.02) and were hospitalised for longer (11 vs 6 days, p<0.001). Compared to non-sarcopaenic patients, sarcopaenic patients did not require increased rescue medical therapy (60.7 % vs 79 %, p= 0.22) nor longer median hospitalisation (10.5 vs 11.4 days, p=0.69). We observed a trend towards increased rescue therapy failure in patients with sarcopaenia (52.9% vs 33.3%, p=0.31). Higher Mayo score at presentation was associated with increased need for rescue medical therapy (OR 2.18, 95%CI: 1.43-3.33, p<0.001) and an increasing C-reactive protein (CRP) to albumin ratio predicted prolonged length of stay (OR 1.44, 95%CI: 1.18-1.77, p=<0.001).

Conclusion

Sarcopaenia did not predict ASUC outcomes in this cohort. Higher Mayo score and increased CRP to albumin ratio at admission predicted prolonged hospitalisation and need for rescue medical therapy.
P664 Anti-TNF exposure is associated with an increased risk of urgent and one-year colectomy in Acute Severe Ulcerative Colitis
Authors: Bourgonje A R , Posner H , Mehandru S , Colombel J F , Kayal M
Published: January 2024

Background

Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is significantly associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains clinically challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC.

Methods

A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Patients with well-documented data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. Multivariable logistic regression analyses were performed to identify clinical, biochemical, and endoscopic parameters associated with colectomy risk in patients with ASUC.

Results

Out of the 158 patients included, 34 (21.5%) underwent colectomy during hospital admission, and 41 (25.9%) within one year after admission. On multivariable analysis, adjusting for age, sex, body mass index (BMI), and disease duration, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P=0.005) and the use of biologics (any type) at admission (OR 3.31, 95%CI: 1.14-9.63, P=0.028) were associated with an increased risk of 1-year colectomy. Conversely, the use of mesalamines at admission was associated with a decreased risk of 1-year colectomy (OR 0.31, 95%CI: [0.13-0.72], P=0.006). Furthermore, recent UC-related hospitalization (within one year of admission) (OR 2.72, 95%CI: 1.15-6.43, P=0.022) and increased number of bowel movements after 3 days of treatment (OR 1.18, 95%CI: 1.04-1.34, P=0.011) were associated with higher risk of 1-year colectomy. Biomarkers measured at admission including hemoglobin and albumin were associated with a decreased risk, while CRP was associated with an increased risk of urgent and 1-year colectomy. Patients with deep ulcerations observed at endoscopy tended to have an increased risk of urgent colectomy, although this was not statistically significant (univariable OR 3.36, P=0.081). Finally, treatment of ASUC with anti-TNF was strongly associated with a decreased risk of urgent (OR 0.30, 95%CI: 0.13-0.73, P=0.007) and 1-year colectomy (OR 0.31, 95%CI: 0.14-0.73, P=0.007).

Conclusion

In patients with ASUC, anti-TNF treatment is associated with a reduced risk of both urgent and 1-year colectomy. Conversely a history of anti-TNF exposure is linked to a higher risk of both urgent and 1-year colectomy. This data emphasizes the need for alternative therapies.
P672 Occurrence of malignancy among infliximab biosimilar and bio-originator initiators in Canada: a comparative population-based analysis
Authors: Birck M G , Lukusa L , Singh H , Narula N , Targownik L E , Leung Y , Afif W , Bernatsky S
Published: January 2024

Background

Infliximab (INF) downregulates the immune system. Given the immune system's role in deleting pre-cancerous cells, malignancy is a potential concern. Still, relatively few real-world data analyses have compared biosimilar versus bio-originator INF in terms of malignancy incidence. We aimed to compare malignancy occurrence among initiators of infliximab biosimilar (INF-B) and originator (INF-O).

Methods

We used data from the National Prescription Drug Utilization Information System (NPDUIS), containing pan-Canadian (except Quebec) claims-level data on prescription dispensations paid from public drug programs linked to comprehensive day surgery and inpatient care (Discharge Abstract Database, DAD) and hospital-based and community-based ambulatory care (National Ambulatory Care Reporting System, NACRS). We studied adults (≥18 years) initiating INF between January 2015 and December 2019 with no history of malignancy, HIV or organ transplant (1-year pre-baseline). Follow-up began 365 days after treatment initiation (lag period) and continued until the first cancer diagnostic code (ICD-10 C00-C97), treatment discontinuation + 365 days, or end of study period. We compared INF-B and INF-O using Cox regression models, adjusting for potential confounders/ effect modifiers: sex, age at treatment initiation, prior use of other biologics or prednisone, province (Ontario versus others), and calendar year.

Results

New users of INF-B (2,019) and INF-O (5,183) were about half female (52%), with a median age (interquartile range) of 45 years (28-62). Overall, the malignancy incidence rate was 10.2 (95% confidence interval, CI, 8.7-11.8) events per 1,000 person-years. Comparing INF-B to INF-O, the adjusted hazard ratio for malignancy was 0.97 (95% CI 0.63-1.48).

Conclusion

In this real-world dataset, we were unable to identify clear differences in malignancy comparing INF-B and INF-O. Limitations include the inability to control for residual confounders (e.g., disease severity), potential outcome misclassification, and selection bias.
P682 A Retrospective Comparison of Different Treatment Modalities in Patients with Chronic Pouchitis
Authors: Uchitel Y , Cohen N A , Hirsch A , Tulchinsky H , Zemel M , Maharshak N
Published: January 2024

Background

Chronic pouchitis affects ~30% of patients post total colectomy with ileal pouch anal anastomosis (IPAA) surgery. Treatment with anti-TNF, anti-integrin α4β7, anti-IL-12/23, or Crohn's disease exclusion diet (CDED), have shown promise in different studies. We aimed to compare the efficacy of these treatments in a real-world context and to detect factors that can aid in treatment choices.

Methods

A retrospective cohort study encompassing demographic, clinic, endoscopic, histologic and lab values of adult ulcerative colitis (UC) patients post-IPAA surgery with chronic pouchitis, treated with biologics or CDED at the Tel Aviv Medical Center. Data were collected at baseline, 12, 26, and 52 weeks of treatment. Primary outcomes were assessed using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI response was defined as a reduction from baseline of ≥2 points, while mPDAI remission was defined as mPDAI response in addition to mPDAI score ≤4.

Results

Therapeutic interventions among 51 patients included CDED (n=10), vedolizumab (n=21), ustekinumab (n=7) and adalimumab (n=13) [Table 1].

At 12 and 26 weeks, overall mPDAI response rates were 52% and 48%, respectively, with no significant difference between groups. At 52 weeks, mPDAI response rates were significantly higher for ustekinumab and vedolizumab (60% and 55%, respectively) compared with adalimumab and CDED (27.3% and 0%, respectively), p=0.043. Fecal calprotectin reduction at week-26 was greatest for ustekinumab (93%), followed by vedolizumab (73%), adalimumab (55%), and CDED (-13%), p=0.003.

Treatment persistence over 150 weeks was significantly higher for ustekinumab (100%) compared with adalimumab (46%), vedolizumab (33%), and CDED (20%), p<0.001 [Figure 1]. The predominant cause for treatment discontinuation was secondary loss of response (50%), followed by primary non-response and surgical complications (14.7% each), poor compliance (11.8%), side-effects (5.9%), and development of antibodies (2.9%).

Patients without prior biologic or immunomodulator treatment for pouchitis had significantly higher mPDAI response rates at 12 weeks (90%, p=0.016 and 73.3%, p=0.03, respectively). Patients with surgical pouch complications showed a trend towards lower mPDAI-defined response rates at 12 weeks (25% vs. 64.7%; p = 0.064).

Conclusion

Ustekinumab and vedolizumab demonstrate higher likelihood of maintaining long-term clinical and endoscopic response, along with greater reduction in fecal calprotectin compared with adalimumab and CDED. Biologic and immunomodulator therapy-naïve patients achieved higher induction response rates.
P685 Effectiveness of a second-line anti-TNFɑ agent compared to a different mechanism of action after first anti-TNFɑ failure in ulcerative colitis: CambiaCU Study
Authors: López-Vico M , Hernández-Martínez Á , Soto-Escribano P , Rojas-Feria M , Cornejo-Jiménez A , Caballero-Mateos A M , Trapero-Martínez A M , Sánchez-Capilla A D , Cabello-Tapia M J , Martín-Rodríguez M D M
Published: January 2024

Background

Ulcerative colitis (UC) is a chronic and relapsing disease for which the number of biological therapies available are increasing over the years. Data comparing the effectiveness of a second anti-TNFɑ (aTNF) and the switch to a different mechanism of action (MoA) such as Ustekinumab (UST), Vedolizumab (VDZ), Filgotinib or Tofacibinib (JAK) is lacking.

Methods

We performed a multicenter and retrospective study (6 Andalusian sites) in which patients diagnosed of UC who had failed a first biological therapy with an aTNF and started a second-line biological therapy with another aTNF or a different MoA (UST, VDZ, JAK) were included. Clinical response and remission were assessed at weeks 16 and 52. The aim of our study was to evaluate the effectiveness of a second-line biological therapy with aTNF compared to a different MoA after a first aTNF failure.

Results

185 UC patients were included. There were no differences in the demographic data except for disease duration (9 years with MoA vs 13 years in aTNF, p=0.02). As first aTNF, infliximab (IFX) was the most common in both groups (49% MoA group, 56% second aTNF), followed by adalimumab (ADA) (48% MoA group, 33% second aTNF). In the second aTNF group, immunomodulators were significatively more used (60% vs 38%, p=0.003). There were no differences in the concomitant use of steroids. 80 patients received a different MoA (37 VDZ, 24 UST, 7 JAK) and 105 a second aTNF (34 IFX, 60 ADA, 11 golimumab). At week 16, 52% of patients were in clinical response (70% with another MoA vs 54% with second aTNF, p=0.07; IFX 65%, ADA 53%, VDZ 68%, UST 71%, JAK 74%, p=0.07), being 15.6% more likely to achieve response with another MoA. Clinical remission at week 16 was obtained by 36% (39% with another MoA vs 33% with second aTNF, p=0.6; IFX 47%, ADA 30%, VDZ 35%, UST 46%, JAK 37%, p=0.1). At week 52, 48% achieved clinical response (51% with another MoA vs 45% with second aTNF, p=0.8; IFX 50%, ADA 42%, VDZ 49%, UST 54%, JAK 53%, p=0.5) and 39% were in clinical remission (40% with another MoA vs 38% with second aTNF, p=0.53; IFX 50%, ADA 32%, VDZ 35%, UST 38%, JAK 53%; p=0.06) (figure 1). When the effectiveness is analyzed by first aTNF used, independently of the aTNF, subsequent use of a different MoA achieves better results although not significant compared to a second aTNF. Partial Mayo and calprotectin showed a significant decrease at weeks 16 and 52 in both groups. Hemoglobin and albumin levels remained similar during follow-up in both groups.

Conclusion

Second-line biological therapy is effective regardless of biological therapy used in UC, but switching to a different MoA tend to achieve better results in terms of clinical response and remission compared to a second aTNF.
P686 Comparison between therapeutic sequences starting with IV induction-biologic versus SC-induction biologic in bionaïve-patients with ulcerative colitis: results from the APPETISER study
Authors: Buisson A , M'Baye D , Pereira B
Published: January 2024

Background

Recent data suggest that infliximab and vedolizumab would be more effective than subcutaneous anti -TNF as 1st line-biologic, leading therapeutic sequencing challenging.

We compared the effectiveness of a strategy starting with a first-line bologic with IV induction (IFX or VDZ = IV group) compared to a biologic with SC induction (adalimumab or golimumab = SC group) to induce and maintain steroid-free clinical remission during the first 24 months.

Methods

From a database of IBD referral center, all consecutive UC patients ≥ 18 years-old who started a first line of biologic (IFX, VDZ, ADAor GLM) for active UC with follow-up > 6 months were included. Prior colectomy or severe acute colitis were excluded.

The primary endpoint was remission defined according to PRO2 (PRO2-remission) as the absence of bleeding, normalization of transit (Mayo stool frequency subscore = 0) and no steroid. PRO2-remission was defined as a binary criterion each month (the statistical unit being the month and not the patient).

The secondary endpoints concerned the analysis by patient and were CFREM (partial Mayo score ≤ 2 without steroid) and endoscopic remission (CFREM + score Endoscopic Mayo ≤ 1) at week 12 .

All comparisons were adjusted using propensity scores on potential confounders. Analysis by month was performed using mixed models to account for repeated data.

Results

Overall, 130 patients were included including 60 patients in the IV group (IFX= 50 and VDZ= 10) and 70 in the SC group (ADA= 48 and GLM= 22). The populations had similar characteristics at baseline apart from concomitant immunosuppressant more frequent in IV group (55.9% vs 21.7%). 2nd line treatment was started in 26.7% of patients in IV group (ADA in 48.8%, VDZ 25.5% and ustekinumab 18.8%) and 87.1% of patients in SC group (IFX in 54.1%, VDZ 31.1%).

After adjustment, the rate of CFREM at week 12 was significantly higher in the IV arm (70.8%) than in the SC arm (33.0%) (p < 0.001). The rate of endoscopic remission at W12 was 22.1% and 10.0% in the IV and SC arms, respectively (p =0.18).

In this study, 3350 months were analyzed (1180 in the IV arm and 1175 in the SC arm). The percentage of months spent in PRO2-CFREM in the first 24 months (primary endpoint) was greater in the IV arm than in the SC arm (74.2% vs 46.6%; p<0.001). The percentage of months spent in CFREM was higher in the IV arm in the first 6 months (60.4% vs 18.9%), but also between M7 and M12 (73.1% vs 38.6%), M13 and M18 (79.9% vs 57.0%) or M19 and M24 (83.3% vs 64.6%) (p < 0.001 for all comparisons).

Conclusion

A therapeutic sequence starting with IV induction biologic (IFX or VDZ) was more effective than starting with a SC induction anti-TNF (ADA and GLM ) to induce and maintain remission at short and long-term in UC.
P687 Ozanimod as a once-daily oral therapy for Japanese patients with ulcerative colitis: results from the induction period of a Phase 2/3 study (J-True North)
Authors: Matsuoka K , Nakase H , Fujii T , Hisamatsu T , Suzuki Y , Watanabe M , Uchikawa Y , Goto S , Fujimoto G , Zhang C , Hibi T
Published: January 2024

Background

Ozanimod is an oral, small molecule sphingosine 1-phosphate (S1P) receptor modulator that selectively targets the S1P1 and S1P5 receptor subtypes. Ozanimod is approved in multiple countries outside Japan for the treatment of moderately to severely active ulcerative colitis (UC) and/or relapsing forms of multiple sclerosis. We herein report the efficacy and safety results during the induction period of J-True North, a multi-centre, randomised, double-blind, placebo-controlled clinical Phase 2/3 study consisting of a 12-week induction period, followed by a 40-week maintenance period and an open-label extension period in Japanese patients with moderately to severely active UC.

Methods

Japanese male and female UC patients aged 18 to 75 years with moderately to severely active UC (defined as Mayo score of 6 to 12, with endoscopic subscore ≥2, rectal bleeding score (RBS) ≥1, and stool frequency score ≥1) were randomised in a 1:1:1 ratio to receive either 0.46 mg or 0.92 mg ozanimod, or placebo capsules orally once daily. All patients had received prior treatment with aminosalicylates or corticosteroids. The primary endpoint was clinical response at Week 12 (defined as a reduction from baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from baseline in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 point), and key secondary endpoints were clinical remission, clinical response, endoscopic improvement, mucosal healing and safety at Week 12 and 52.

Results

Patients were randomised to the ozanimod 0.46 mg group (n=68), 0.92 mg group (n=65), and the placebo group (n=65). At baseline, 36.4% of patients were female, mean age was 42.6 y and mean complete Mayo score was 8.4. The clinical response rate at Week 12 was 52.9%, 61.5%, and 32.3% in the ozanimod 0.46 mg, 0.92 mg, and placebo groups, respectively, demonstrating a statistically significant improvement of ozanimod vs placebo (Figure 1). Similarly, higher improvement rates were observed in all key secondary clinical and endoscopic endpoints in the ozanimod groups compared with the placebo group at Week 12. Frequent adverse events (AEs) observed in the induction period were nasopharyngitis, headache, et.al. (Table 1). AEs observed in the study were similar to those in the global phase 3 True North study with 0.92 mg ozanimod, and there were no new safety signals with ozanimod in the J-True North study.

Conclusion

Ozanimod as a once-daily oral therapy was effective as induction therapy for Japanese patients with moderately to severely active UC, and the safety profile was consistent with the results of previous studies.

Figure 1

Table 1
P689 Adaptive steroid tapering impedes corticosteroid-free remissions compared to forced tapering in UC clinical trials
Authors: Narula N , Hamam H , Wong E C , Marshall J K , Jairath V , Hanauer S B , Reinisch W , Dulai P S
Published: January 2024

Background

Protocols for managing steroids in clinical trials of ulcerative colitis (UC) vary. Most trials mandate steroid tapering at the beginning of maintenance phase. Adaptive steroid tapering allows for some discretion on whether to taper steroids for a patient. It remains unclear what impact steroid tapering protocols have on trial outcomes.

Methods

This post-hoc analysis from many clinical trials of advanced therapies in UC (VARSITY, ACT 1/2, PURSUIT, GEMINI1, OCTAVE and ULTRA2) was carried out under protocols with Vivli (00007656) and YODA (20224882). Responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for re-randomization designs and treatment exposure. Univariate analyses were conducted to identify baseline variables that had an association with the primary outcome of interest, one-year corticosteroid-free clinical remission (CR). All covariates with a significant univariate association (p < 0.05) were considered for inclusion in the multivariate model. Logistic regression was used to assess the impact of steroid-weaning regimen on the outcome of interest. Secondary outcome of interest was one-year CR.

Results

There was a total of 861 patients from the seven included trials who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid weaning regimens were less likely to achieve one year corticosteroid-free CR (odds ratio (OR) 0.66 (95% CI 0.48-0.92), p=0.015). Patients with higher partial Mayo scores were also less likely to achieve one year corticosteroid-free CR (OR 0.88 (95% 0.8-0.97), p=0.012). Other variables found significant on univariate analysis were no longer significant once considered within the multivariate model (smoking, race, albumin, endoscopic Mayo score). For the secondary outcome of one year CR, patients using adaptive steroid weaning regimens had increased odds for achieving one year CR as compared to those using fixed regimens (OR 1.9 (95% 1.43-2.52), p<0.001). Several other variables were also found to have an association with one year CR within the multivariate model (Table 1).

Conclusion

Among patients with UC on corticosteroids at the time of study enrolment, adaptive steroid weaning regimens were less likely to achieve one-year corticosteroid-free CR but more likely to achieve one-year CR. This may help explain the findings within the VARSITY study, where patients treated with vedolizumab had increased odds for one-year CR but were less likely to achieve one-year corticosteroid-free CR. Consideration should be given to implementing mandatory steroid weaning protocols in future clinical trials of UC.
P693 Care needs and reasons for (not) seeking care among fatigued patients with Inflammatory Bowel Disease: A qualitative study
Authors: Bredero Q , ter Avest M M , Fleer J , Dijkstra G , Schroevers M J
Published: January 2024

Background

Fatigue is one of the most prevalent and burdensome symptoms experienced by patients with inflammatory bowel disease (IBD), even when the disease is in remission. Many patients report dissatisfaction towards fatigue-related care and uptake of available interventions is often low. This study aims to explore reasons why IBD patients do or do not engage in professional fatigue-related care and their needs regarding type of care and how to offer care.

Methods

We conducted a qualitative study, taking a phenomenological methodological approach. Sixteen adult IBD patients with disease in remission and severe fatigue (i.e., Checklist Individual Strength – subjective fatigue ≥ 35) were recruited from an academic hospital. We performed semi-structured interviews. Data were analysed using template analyses.

Results

We identified six themes regarding reasons why to (not) seek care for fatigue: 1) cognitions about fatigue and coping (e.g., a need to deal with fatigue alone), 2) perceptions of fatigue-related care and previous care experiences (e.g., perceiving that nothing can be done about fatigue), 3) knowledge and behaviour of the healthcare provider (e.g., fatigue complaints are not taken seriously), 4) somatic factors (e.g., physical symptoms of IBD), 5) social factors (e.g., feeling misunderstood by others) and 6) practical factors (e.g., time and money). Furthermore, we identified needs regarding how to offer care, i.e., proactive screening and active offer of care by healthcare providers, a holistic and person-centred approach and practical needs taken into account. Finally, regarding what care to offer, patients suggested a broad range of options, including information provision on fatigue management, eliminating physical causes of fatigue, discussing medication options, lifestyle support, psychological support, peer support and practical support.

Conclusion

IBD patients’ perceptions, coping and knowledge, as well as healthcare professionals’ behaviours play a major role in seeking fatigue-related care. Findings emphasize the importance of discussing IBD-related fatigue actively and taking a holistic and patient-centred approach to treat fatigue, targeting a broad range of physical- and psychological factors. These findings yield a better understanding of factors that hinder and facilitate care seeking in fatigued IBD patients and hereby provide ways to optimize the uptake of care.
P703 Comparison of infliximab and adalimumab therapies Persistence in patients with Ulcerative Colitis: Results from a Single Tertiary Turkish IBD Center Cohort
Authors: Eroglu Z , Yilmaz V , Guvenir T , Er R E , Toruner M
Published: January 2024

Background

In the last 25 years, the introduction of biological therapies has been a significant milestone in the management of inflammatory bowel diseases. Despite the recent emergence of new biological therapies and small molecules, Anti-TNF agents still play a crucial role in treatment. In a number of countries, anti-TNF agents are still reimbursed as a first line treatment following either a failure or intolerance to conventional therapies such as thiopurines and aminosalycilates. Many studies have been conducted previously to compare the efficacy of these drugs, but a clear conclusion could not be reached. In this study, we aimed to compare the persistence of infliximab (IFX) to adalimumab (ADA) in the treatment of ulcerative colitis at a tertiary IBD center in Turkey.

Methods

This was a retrospective cohort analysis of patients with ulcerative colitis either received adalimumab or infliximab as a first line biologic treatment. A total of 234 patients were included to this analysis. Demographic information such as gender, age, montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes.

Results

Out of the 234 patients included in the study, 116 had used infliximab, and 118 had used adalimumab as a first-line treatment. Age and gender of the patients in both groups did not differ from each other statistically. 88% of the patients treated with adalimumab and 84% of the patients treated with infliximab were thiopurine experienced. Montreal classification did not differ between two groups (in IFX group, 73% of the patients had Montreal E3 involvement where as in ADA group, 66% of the patients had Montreal E3 involvement, p>0.05). Primary non-response rates were not different between IFX and ADA group, 13.6% vs 13.4% respectively. In addition, clinical response rates after first year were 60% and 53% respectively. Drug persistency rates of adalimumab and infliximab in moderate to severe ulcerative colitis patients were not statistically different from each other (Figure 1).

Conclusion

Neither clinical efficacy rates nor drug persistency rates of adalimumab and infliximab in ulcerative colitis treatment were not different from each other. Factors such as age, gender, location of involvement, concomitant therapies, and smoking did not alter the outcome.