bluuebunny/crossref_metadata_2025 huggingface dataset:
P1053 Clostridioides difficile Infection in Admitted patients with Ulcerative Colitis: Analysis of 23 Years through Propensity Score Matching
Authors: Alañón P , Carrillo B , Benítez J M , Soto P , Marín Pedrosa S , Iglesias-Flores E , Gros B
Published: January 2025

Background

Clostridioides difficile infection (CDI) represents the leading cause of nosocomial diarrhea in the Western world. Patients with ulcerative colitis (UC) have a higher risk of developing this infection, which has been associated with an increased risk of flare-ups, need for surgery, and mortality. The aim of the present study was to evaluate the impact of this infection in patients hospitalized for a UC flare-up.

Methods

Retrospective case-control study including all patients hospitalized for a UC flare-up at Reina Sofía Hospital in Córdoba between January 2000 and January 2023. To avoid potential selection biases, Propensity Matching Score (PMS) adjusted for age, gender, duration, and extent of the disease, with a 1:2 ratio was used. Primary objective was to assess the need for treatment intensification (initiation or dose escalation of biologics/small molecules or immunosuppressant). Secondary endpoints included readmission rate, colectomy, mortality, and CDI risk factors identification.

Results

During the study period, 419 patients were hospitalized for a UC flare-up, of whom 251 (59.9%) were men, with a median age of 41 (IQR 28-55) years and disease duration of 0.89 (0-5.8) years. Baseline characteristics of patients at admission are shown in Table 1. Of all admissions, 46 (11%) had CDI. After PMS, CDI was associated with increased therapeutic intensification between 3-12 months after discharge (27.5% vs. 11.7%, p = 0.004) and a higher risk of readmission at 12 months (37.5% vs. 13.7%, p = 0.009) but not to risk of colectomy or mortality (Table 2). Infection recurrence was detected in 8 (16.7%) patients.

Classical risk factors for CDI were not found to increase the risk of CDI among UC patients, however antiTNF therapy was associated to CDI in both models: full cohort (OR 3.52, 95%CI 1.46-8.49) and PMS (OR 4.63, 95%CI 1.32-16.31).

Conclusion

CDI in UC was associated with a greater need for therapeutic intensification and a higher readmission rate at one year. There was no evidence of an increased risk of colectomy or mortality in these patients. Classical risk factors for CDI were not identified but patients on antiTNF were at higher risk of CDI.
P1054 Filgotinib effectiveness and safety as second or third-line therapy in patients with ulcerative colitis: data from a real-world study
Authors: Mocci MD FRCP G , Costa F , Ceccarelli L , Savarino E , Mucherino C , Marzo M , Scaldaferri F , Napolitano D , Pugliese D , Gravina A G , Pellegrino R , Spagnuolo R , Cuomo A , Maconi G , Bertani L , Bodini G , Orrù G , Piergallini S , Scarcelli A , Capone P , Cortellini F , Rodinò S , Vespere G , Gaiani F , Pagnini C , Graziani G , Allegretta L , Ferronato A , Ribaldone D G , Aragona G , Forti G , Di Fonzo M , Iacopini F , Pica R , Onidi M F , Usai Satta P , Elisei W , Picchio M , Papa A , Tursi A ,   De Barba Caterina D’Antonio Elvira Montesano Laura Luzza Francesco Donnarumma Laura Cataletti Giovanni Pasta Andrea Serio Mariaelena Sebkova Ladislava Sedda Silvia D’Onofrio Vittorio De Luca Leonardo Kayali Stefano Di Paolo Maria Carla Cazato Alessia Immacolata Scorza Stefano Perazzo Patrizia Cassieri Claudio
Published: January 2025

Background

Filgotinib (FILGO), a selective anti-JAK1, has obtained refundability from the Italian National Health System in February 2023 for its use in patients with Ulcerative Colitis (UC) refractory to other therapies, including anti-TNF-α, anti-integrins and ustekinumab. At present, no Italian data are available yet about its effectiveness and safety in Real World.

Methods

A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of FILGO.

Results

We enrolled 102 patients with a median follow-up of 24 weeks (M/F 54/48, median age 47). The clinical remission and clinical response rates at 8 weeks were 12% (13/102) and 29% (30/102), respectively, and 51% (20/39, p<0.01) and 82% (32/39, p<0.01) at 24-week follow-ups, respectively. Adverse events occurred in 6 (5.8%) patients and severe in 2 (1.9%).

Conclusion

Our realworld data confirm that FILGO is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.
P1068 Preventable hospitalisations for patients with IBD are relatively uncommon in a modern multidisciplinary IBD service, and due to non-adherence or non-engagement in a significant proportion
Authors: Massouridis B , Lucas S , Lewis D , Garg M
Published: January 2025

Background

Despite tighter treatment targets and an expanding array of therapeutics, hospitalisations for patients with inflammatory bowel disease (IBD) continue to occur, resulting in significant healthcare expense. This study aimed to identify factors associated with hospitalisation.

Methods

Patients seen at specialist IBD clinics at a tertiary health service and those hospitalised over a 13-month period from September 2022 to September 2023 were identified, and medical records interrogated for demographic and disease characteristics. Data including indication for admission, length of stay and cost was recorded.

Results

1082 patients with IBD (median age 48 [IQR 34-63] years, 495 [48.2%] female) were seen in specialist IBD outpatients clinics during the study time frame. Of these, 468 (43.3%) had Crohn’s disease (CD), 464 (42.9%) ulcerative colitis (UC), 13 (1.2%) IBD-unclassified, and 143 (13.2%) had other/uncertain diagnoses.

During the same period, 115 patients (48 [41.7%] female, median age 35 [IQR 27-51] years), with either new or pre-existing diagnosis of IBD, were admitted to hospital for a total of 138 admissions. 18 patients had multiple admissions (twice, n=14; thrice, n=3; four times, n=1). 64 (55.7%) had CD, and 48 (41.7%) UC. The main reasons for presentation for UC-related admissions included active disease (55.2%, n=32) and acute severe ulcerative colitis (36.2%, n=21). For Crohn’s-related admissions, main reasons for presentation were active disease without obstructive symptoms (53.9%, n=42) and small bowel obstruction (19.2%, n=15).

31 (27%) were unknown to the health service prior to their admission, and a further 23 (20%) patients (12 with CD and 11 UC) were newly diagnosed with IBD as the index hospitalisation. Of the remaining 61 patients who were known to the IBD service (5.6% of total), non-adherence and/or non-engagement was a contributing factor in 20 (32.8%) patients. Progressive, treatment refractory disease or loss of response to medications was noted in 43 (70.5%), with Clostridium difficile infection in 5 (8.2%) patients.

Across all admissions, median length of stay was 3 (IQR 2-6) days. 5 patients were readmitted within 30 days (UC, n=3; Crohn’s, n=2) and 13 patients were readmitted within 90 days (UC, n=6; Crohn’s, n=7). Cost of hospitalisation as per DRG codes was available from September 2022 to June 2023, with median cost being $13,308 AUD (IQR $9,464-$21,058 AUD).

Conclusion

The proportion of patients requiring hospitalisation in a 12-month period seen at a modern IBD service is small, and accounted for by non-adherence and/or non-engagement in a third. Measures to reduce non-adherence and non-engagement may result in further reduction in hospitalisation.
P1070 Comaparison of Effectiveness and Perisitence Anti-TNF drugs on Perianal Fistulizing Crohn’s Disease: A Single Tertiary IBD Referral Center Experience
Authors: Koç Ö , Acehan M F , Yılmaz V , Guvenir S T , Toruner M
Published: January 2025

Background

Perianal Crohn’s disease (CD) is a debilitating and often challenging manifestation of Crohn’s disease that involves the formation of fistulas, abscesses, and other inflammatory lesions around the anus and perineal area. It is associated with significant morbidity, including pain, recurrent infections, and impairment of daily activities. Treatment of perianal CD is complex, requiring a multidisciplinary approach to control disease activity, promote healing, and preserve anal function. Anti-TNF (tumor necrosis factor) biologic agents, such as infliximab and adalimumab, have become a mainstay in the management of perianal Crohn’s disease. However, there is still a debate which anti-TNF agents acts better than other in this subset of patients. Here in this study, we aimed to evaluate the compare the efficacy and persistence of two Anti-TNF agents in perianal Crohn’s disease.

Methods

This was a single center, retrospective cohort analysis of patients with Crohn’s disease either received adalimumab or infliximab as a first line biologic treatment. A total of 396 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 446 Crohn’s disease patients, 128 patients had perianal Crohn’s disease. Gender, smoking, extraintestinal manifestations presence and family history were not different between patients with and without perianal disease. However, in perianal disease group there was more concomitant immunomodulator use than in patients with no perianal involvement (61.5% vs 49.4%, p<0.05). Anti-TNF drug persistence was significantly higher in patients without perianal involvement when compared to patients with with perianal involvement (Figure 1). There was no significant difference in drug persistence rates in perianal Crohn’s disease between infliximab and adalimumab treatment (Figure 2). The concomitant use of immunomodulator drugs did not make any impact.

Conclusion

In Crohn’s disease patients, anti-TNF medication persistence rates was observed to be significantly lower in those with perianal involvement. However, which anti-TNF agent was chosen as first line biologic did not change medication persistence rates. Concomitant thiopurine use did not make any impact on the results.
P1073 Clinical characteristics and outcomes of patients with Inflammatory Bowel Disease under long term (>10years) anti-TNFa treatment
Authors: Orfanoudaki E , Foteinogiannopoulou K , Theodoraki E , Drygiannakis I , Panayiotou S , Papatzelou I , Koutroubakis I
Published: January 2025

Background

There is limited information in the literature regarding long term effectiveness and safety of anti-TNFa agents in patients with Inflammatory Bowel Disease (IBD). We aimed to study the effectiveness and safety of anti-TNFa agents in IBD patients receiving this treatment beyond 10 years .

Methods

Consecutive IBD patients under anti-TNFa treatment >10 years were prospectively studied. Demographic and clinical characteristics as well as treatment details and outcomes were recorded based on an updated IBD registry. Outcomes included need for treatment optimization [dose escalation or immunosuppressant (IMM) addition], disease related hospitalizations and surgeries, serious infections and malignancies. Drug survival of anti-TNF treatment >10 years was assessed (at 13 and 15 years).

Results

Out of 395 patients being initiated with any anti-TNFa in our department, 56 with at least 10 years of anti-TNFa use [males 32(57%), mean age (±SD) 53.3(±13) years, mean disease duration (±SD) 22.8 (±1.15) years were included. Patients were 82%(46/56) with CD, mean duration of anti-TNFa use (±SD) 162 (±32.93) months, 39 (70%) under infliximab, 17 under adalimumab, while anti-TNFa represented the first biologic in 88% of them. More than half of the patients [54%(30/56)] were under combination treatment with IMM (24 azathioprine, 6 methotrexate) and 45% (25/56) needed dose escalation. During follow up 75% (42/56) remained on the index anti-TNFa, precisely 84% (31/37) at 13 and 55% (16/29) at 15 years after drug initiation respectively (figure 1). Main causes of discontinuation were loss of response (8/14), patient preference 1, malignancy 2, osteonecrosis 1, death of other cause 1 and deep remission 1. During follow up, a total of 30 disease related hospitalizations in 18 patients, 12 serious infections, 6 malignancies (non Hodgkin lymphoma of the liver, prostate carcinoma, thyroid gland carcinoma, hepatocellular carcinoma and two cases of non melanoma skin cancer) and 4 disease related operations were recorded.

Conclusion

More than half of the patients under long-term anti-TNFa treatment (>10 years) continue to receive the agent for an additional 5 years. Rates of serious infections and malignancies are no negligible and close monitoring is needed in these patients.
P1076 Improvement of Work Productivity and Activity Impairment (WPAI) in patients with moderate to severe UC using Biologics therapy; the MOSAIK cohort study
Authors: Seong G , Park Y , Lee K M , Jung S A , Park Y S
Published: January 2025

Background

The patients with ulcerative colitis (UC) can have low quality of life and their work productivity can be also impaired. The aim of this study is to investigate the work productivity and activity impairment (WPAI) of moderate to severe UC patients with biologics treatment, using the MOSAIK cohort (ClinicalTrials.gov: NCT02229344).

Methods

In this cohort, we enrolled patients with moderate to severe UC diagnosed for the first time and collected their WPAI questionnaires annually from the time of diagnosis. WPAI questionnaires scored overall work impairment and social activity impairment from 0 to 10. We compared the scores between the patients treated with biologics and without biologics.

Results

In a total 346 patients, 69 (19.9%) patients started biologics during 5 years of observation period. 43 (12.43%) patients started biologics within 1 year from diagnosis. At baseline, mean score of overall work impairment (10 points scale) in biologics group was higher than that of non-biologics group (4.8 and 3.8, respectively). During the treatment, both groups showed numerical improvement of work productivity and social activity. At 1 year, the difference in scores of work productivity impairment between the two groups decreased to 2.6 and 1.8, respectively. Finally at 5 year, the scores of work productivity impairment were similar in the biologics and non-biologics group (1.5 and 1.4, respectively).

Conclusion

In moderate to severe UC, the patients receiving biologics due to their high disease activity can experience impaired work productivity. However, work productivity and social activity can be improved in biologics group as much as in the non-biologics group. Therefore, it is important to start biologics timely to control the disease activity and eventually restore the patients’ daily work and life.

References

1.A new opportunity for innovative inflammatory bowel disease research: the moderate-to-severe ulcerative colitis in Korea (MOSAIK) cohort study. Intest Res. 2019;17(1):1-5. Published online January 25, 2019
P1077 Early detection of non-response to non-anti-TNF treatment in Inflammatory Bowel Disease patients using neutrophil-to-lymphocyte ratio as a biomarker
Authors: Rellou S , Kordalis L , Spyrantis A , Lamprou S , Efstathiou S , Pagoni A , Manou D , Sdonas T , Tasovasili A
Published: January 2025

Background

The neutrophil-to-lymphocyte ratio (NLR) has been proposed as a potential marker of subclinical inflammation. Previous studies suggest NLR may predict therapeutic response to anti-tumor necrosis factor (anti-TNF) drugs1,2. However, there is a lack of published data investigating the role of NLR as a predictor for non-anti-TNF treatments.

Methods

In this retrospective analysis, medical records of 55 patients followed in the inflammatory bowel disease (IBD) outpatient department from January 1, 2020, to July 1, 2024, were reviewed. All patients initiated non-anti-TNF biologic treatment during this period. NLR was measured at week 4 of treatment, and non-response (NR) was assessed at week 16. Patients were divided into two groups: Group A (n = 11)/non-responders and Group B (n = 44)/responders. Statistical analysis of NLR measurements was performed using R. Logistic regression was conducted to evaluate the relationship between NR and ln(NLR).

Results

The study included 55 IBD patients (27 with ulcerative colitis [UC] and 28 with Crohn’s disease [CD]), with a mean age of 49.81 years. The cohort comprised 23 females and 32 males. Treatment distribution was as follows: ustekinumab (n = 26), vedolizumab (n = 22), upadacitinib (n = 6) and tofacitinib (n = 1).The non-parametric Wilcoxon test revealed statistically significant differences in median NLR between Group A and Group B (P = 0.01464 < 0.05). Logistic regression demonstrated a significant relationship between NR and ln(NLR) (P = 0.024844 < 0.05). The ROC curve analysis yielded an area under the curve (AUC) of 0.7407, with a threshold achieving a sensitivity of 0.9091 and a specificity of 0.5227.

Conclusion

NLR shows promise as a non-invasive, accessible, and cost-effective biomarker for the early detection of non-response to non-anti-TNF biologic therapy in IBD patients.

References

1.Langley BO, Guedry SE, Goldenberg JZ, Hanes DA, Beardsley JA, Ryan JJ. Inflammatory Bowel Disease and Neutrophil-Lymphocyte Ratio: A Systematic Scoping Review. J Clin Med. 2021;10(18):4219. Published 2021 Sep 17. doi:10.3390/jcm10184219

2.Qian G, Hongxia D, Jin LI. Nan Fang Yi Ke Da Xue Xue Bao. 2020;40(4):453-458. doi:10.12122/j.issn.1673-4254.2020.04.01
P1084 Safety of tofacitinib and upadacitinib compared to other advanced therapies in ulcerative colitis: a large real-world comparison
Authors: Fiorino G , Allocca M , D’Amico F , Rusconi F , Hernandez G , Zilli A , Parigi T , Furfaro F , Cosintino R , Faggiani R , Jairath V , Peyrin-Biroulet L , Danese S
Published: January 2025

Background

Whether adverse events of special interest[1] related to JAK inhibitors (JAKi) are a concern compared to other drugs used in ulcerative colitis (UC) needs investigation.

We aimed to assess and compare the frequency of adverse events of special interest by JAKi within the class, and with other advanced therapies, on a large real-world population of UC patients.

Methods

This was a non-interventional, retrospective study conducted with data obtained from TriNetX from patients with diagnosis of adult UC, exposed to advanced therapies (range 1-1095 days). The final cohort included 866 patients over 444,424 UC patients available in the database who matched the query criteria.

Adverse events (any), herpes zoster, cardiovascular events, thromboembolic events, cancer (any), non-melanoma skin cancer were investigated. We compared each JAKi with TNF, IL-23 antagonists, and vedolizumab, and within the class by survival analyses and log-rank test. Propensity score matching and adjustment for confounders, such as age, sex, first or second line advanced therapy, smoking habit and other known baseline risk factors, was done. Statistical significance was set as a p value < 0.05.

Results

Only tofacitinib and upadacitinib were included, as data on filgotinib were not available. Tofacitinib was associated with statistically significant lower rates of thromboembolic events than anti-TNFs (HR 0.61, 95% CI 0.38-098, p=0.04), and lower rates of cancer than vedolizumab (HR 0.63, 95% CI 0.41-0.96, p=0.03), but higher rates of herpes zoster than anti-IL23 (p=0.001). Upadacitinib showed lower rates of thromboembolic events (p=0.001), but higher rates of herpes zoster reactivation than IL-23 (p=0.001). Similar safety profile was found between tofacitinib and upadacitinib when they were directly compared.

Conclusion

Anti-JAK show a similar safety profile than all the other drug classes used in UC. Herpes zoster infection/reactivation remains the only adverse event of note for both JAKi.

References

1.European Medicine Agency. EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. 2022 [cited 2024 Jun 12]; Available from: https://www.ema.europa.eu/en/news/ema-recommends-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic-inflammatory-disorders.
P1085 Early and sustained improvement in patient-reported outcomes and biomarker concentrations with tulisokibart induction in patients with moderately to severely active ulcerative colitis: A post-hoc analysis from ARTEMIS-UC
Authors: Peyrin-Biroulet L , Yen M , Zhou W , Dong B , Danese S , Feagan B G , Sands B E
Published: January 2025

Background

In the phase 2, double-blind, placebo-controlled, multicenter ARTEMIS-UC trial, 12 weeks of induction treatment with the anti-tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody tulisokibart led to significant rates of clinical remission, endoscopic improvement and mucosal healing, and improvement in patient-reported outcome (PRO) measures and disease surrogate biomarkers in patients with moderately to severely active ulcerative colitis (UC).1 This post-hoc analysis from ARTEMIS-UC examined the time course of improvement from baseline in patient-reported symptoms (PRO-2 score [combined Mayo stool frequency and rectal bleeding subscores]) and biomarkers (fecal calprotectin and high-sensitivity C-reactive protein [hs-CRP]) with tulisokibart.

Methods

Adults with moderately to severely active UC were randomized 1:1 to receive i.v. placebo or tulisokibart (1000 mg on Day 1 and 500 mg at Weeks 2, 6, and 10). The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in this post-hoc analysis. Participants recorded stool frequency and rectal bleeding scores daily using an e-diary. Fecal calprotectin was assessed at baseline and Weeks 6 and 12, and hs-CRP was assessed at baseline and Weeks 2, 6, 10, and 12. Symptomatic response was defined as a reduction from baseline in PRO-2 score ≥ 1 point. A mixed model repeated measures approach was used to compare tulikisobart to placebo for the difference in PRO-2 score for the first 14 days of treatment and the fold change from baseline in fecal calprotectin and hs-CRP at each timepoint.

Results

Among 135 randomized participants in Cohort 1, 60/67 (89.6%) receiving placebo and 68/68 (100%) receiving tulisokibart completed the 12-week induction period. The numerical difference in improvement of PRO-2 started as early as Day 2 and achieved significant improvement with tulisokibart compared to placebo at Day 9, with a sustained improvement persisting from the latter part of Week 2 through Week 12 (Figure 1, Table 1). Significant improvements with tulikisobart compared to placebo in fecal calprotectin and hs-CRP were observed by Weeks 6 and 2 (the first time point when these biomarkers were measured), respectively, which were maintained through Week 12 (Table 1).

Conclusion

In patients with moderately to severely active UC, induction with tulisokibart led to early and sustained improvement in patient-reported outcomes. Induction with tulisokibart also led to early and persistent improvement in biomarkers.

References

1. Sands BE, et al. N Engl J Med 2024;391:1119-29.
P1086 Achieving early symptom resolution and endoscopic outcomes is associated with improved long-term outcomes in ulcerative colitis: A post-hoc analysis of INSPIRE and COMMAND studies
Authors: Tinoco da Silva Torres J , Danese S , Tanida S , Dulai P S , Xuan S , Kalabic J , Morisset P , Vladea R , Sharma D , Panes J
Published: January 2025

Background

Early disease control, which includes symptom remission with mucosal healing (endoscopic and histological remission) is emerging as a potential therapeutic goal in ulcerative colitis, which may be achieved by effective therapeutic intervention.1 This post-hoc analysis examined the impact of achieving individual symptom resolution, endoscopic improvement (EI) or endoscopic remission (ER) post 12 Weeks (Wk) of risankizumab (RZB; a specific inhibitor of interleukin-23) induction treatment on achieving long-term clinical, endoscopic, and quality of life (QoL) outcomes at maintenance Wk 52.

Methods

This analysis included patients (pts) who achieved a clinical response after 12 wks of intravenous RZB in Phase 2b and Phase 3 INSPIRE induction studies and received subcutaneous RZB 180 or 360 mg in COMMAND maintenance study. The frequency and proportions of pts achieving maintenance Wk 52 outcomes (clinical remission [CR], EI, ER, or meaningful change in QoL) between pts who achieved the absence of symptoms (abdominal pain, bowel urgency [BU], tenesmus, fecal incontinence [FI], sleep interruption [SI], nocturnal bowel movements [NBM]), achieved fatigue normalization, or achieved EI/ER at end of induction vs those who did not was determined. Adjusted predictive analyses assessed the relationship between achieving outcomes at induction Wk 12 and maintenance Wk 52, reported as logistic regression-derived odds ratios (ORs) and 95% confidence intervals.

Results

In total, 179 and 186 pts received RZB 180 and 360 mg during maintenance, respectively. After adjusting for pt characteristics, pts who achieved absence of symptoms at Wk 12 had significantly greater odds of achieving CR, EI, or ER at Wk 52; specifically, absence of BU, FI, and NBM were significantly associated with CR (OR 1.793, 1.722, 1.645), absence of BU and NBM were significantly associated with EI (OR 1.557, 1.563), and absence of FI, NBM, and SI were significantly associated with ER (OR 2.337, 2.318, 2.355). Similarly, pts who achieved endoscopic outcomes of EI/ER at induction Wk 12 had a significantly greater odds of achieving CR (OR 2.011/3.332) and maintaining EI (OR 2.278/5.974) and ER (OR 3.222/7.426) at Wk 52 (Figure). Pts achieving absence of BU, tenesmus, NBM, and ER at Wk 12 had significantly greater odds of achieving meaningful within-person change in QoL outcomes such as work time missed, impairment while working, and overall work and activity impairment at Wk 52 (Table).

Conclusion

Achieving early disease control with RZB treatment through symptom and specifically endoscopic outcome improvements at Wk 12 was generally associated with greater odds of achieving improved long-term clinical, endoscopic, and QoL outcomes at Wk 52.

References

1. Solitano V, et al. J Clin Med. 2020;9(8):2646.
P1095 Switching from Ustekinumab to Risankizumab Improves Outcomes in Crohn’s Disease: A Single-Centre Real-World Data Analysis
Authors: Qazi U , Padley J , Colwill M , Mehta S , Donovan F , Francisco Alves A M , Pollok R , Poullis A , Patel K , Honap S
Published: January 2025

Background

Ustekinumab is a mainstay of treatment for Crohn’s disease (CD) and has been shown to be effective and safe. The SEQUENCE(1) trial found risankizumab is superior to ustekinumab at inducing endoscopic remission and non-inferior with respect to clinical remission. However, there is a lack of real-world data investigating the effectiveness of risankizumab in ustekinumab-exposed patients with active CD and we therefore aimed to assess this.

Methods

A retrospective, observational study was performed at a tertiary inflammatory bowel disease centre. We included all patients diagnosed with CD whose treatment was switched from ustekinumab to risankizumab between December 2023 to November 2024. Electronic patient records were used to collect anonymised data on demographics, disease phenotype and previous advanced therapy. Clinical and biochemical markers of disease activity were assessed at baseline (prior to treatment switch to risankizumab), and at 3 and 6 months after switching. Statistical significance was assessed using a one-sided paired t-test.

Results

Patient demographics are summarised in table 1. 52 patients were included in the study; mean age 45 years, age range 19-82 years, mean disease duration 12.7 years. 10 patients were switched due to primary loss of response to ustekinumab, 41 due to secondary loss of response and 1 due to side effects. The mean duration of follow-up was 178 days. All patients had clinical (Harvey Bradshaw Index (HBI)), biochemical (faecal calprotectin (FCP) or C-reactive protein (CRP)), radiological or endoscopic evidence (Simple Endoscopic Score for CD (SESCD) of active disease at baseline. The mean HBI at baseline was 3.4 which significantly improved at 3 months to 2.6 (n=40, p=0.02) and 6 months (n=13, p=0.03). The mean FCP at baseline was 530, which significantly decreased at 3 months to 211 (n=26, p=0.04). The mean albumin at baseline was 37.3g/L which significantly increased to 38.3g/L at 3 months (n=44, p=0.01). Changes in CRP, FCP and albumin at 6 months were not statistically significant. SESCD was available for 3 patients at 6 months of which 1 improved, 1 worsened and 1 was unchanged. No new safety signals were identified.

Conclusion

This real-world study demonstrates that in patients with active CD switching from ustekinumab to risankizumab can, at least in the short term, significantly improve symptoms and biochemical markers of disease activity. Larger studies with longer-term outcomes are needed to understand the impact of switching to anti-IL23p19 therapies in ustekinumab-exposed patients.

References

1.Peyrin-Biroulet L, Chapman JC, Colombel JF, Caprioli F, D’Haens G, Ferrante M, et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med. 2024 Jul 18;391(3):213–23
P1096 The predictive value of intestinal ultrasound for treatment response in Inflammatory Bowel Disease: a systematic review and pooled data analysis
Authors: Vos H , Teichert C , de Voogd F , Pruijt M , D’Haens G , Benninga M , Koot B , Gecse K
Published: January 2025

Background

Intestinal ultrasound (IUS) is a promising tool in predicting treatment response in Inflammatory Bowel Disease (IBD). We aimed to systematically review current literature on the predictive value of IUS for treatment response.

Methods

A literature search was performed across multiple databases from inception to 17th of September 2024 (figure 1). We included articles in IBD patients where IUS was used for the assessment of treatment response. Data were analysed for Crohn’s disease (CD), ulcerative colitis (UC) and acute severe ulcerative colitis (ASUC), separately. Timing of IUS follow-up for CD and UC was categorized as baseline, rapid (0-3 weeks), short-term (4-8 weeks), intermediate (12-16 weeks) and long-term (>16 weeks). For ASUC timing was categorized as ≤5 days or >5 days. Treatment outcomes included endoscopic or clinical scores and therapeutic outcomes (e.g. surgery, treatment escalation). The quality of the included studies was evaluated using the QUIPS tool. For pooled data analysis, all authors analysing anti-TNF treatment of CD patients were contacted for raw data.

Results

In total, 28 articles were included with 17 in CD, 7 in UC and 4 in ASUC (figure 1). In general, quality of the included studies was adequate. In CD, IUS parameters at week 4-8 first differentiated between responders and non-responders with bowel wall thickness (BWT) as the most important parameter. Across 7 studies (335 individual patients) responders demonstrated a change in BWT of -43% to 0% vs -15.3% to 2% in non-responders. For UC, after 1 week a decrease of 1mm BWT in the rectum resulted in an OR of 1.9 (p=0.001) for predicting clinical remission at week 8 in one study (n=100). From 6 weeks onwards, there was a significant difference BWT decrease in the sigmoid colon for having future endoscopic response (-37% vs -20%; p=0.002) and remission (-49% vs -17%; p=0.002) in one study (n=50). In ASUC, BWT measured 1-3 days after starting iv. steroid treatment in two cohorts (n=66) significantly differed between responders and non-responders, with a change in BWT ranging from -34 to -13% vs -5 to 2% respectively. In the pooled data analysis, 6/13 authors shared data on BWT (n=187, table 1). At week 12-16, overall responders had a higher percentual decrease in BWT than non-responders (Δ-26% vs. Δ-2%, p<0,001). When differentiating for outcome, there was a significant difference in BWT decrease between endoscopic responders and non-responders (Δ-35% vs Δ +2%, p<0.001).

Conclusion

IUS predicts response in both CD, UC en ASUC in the early stages of treatment. Based on our pooled data analysis, a decrease in BWT of 26% (AUROC 0.813, sens 93%, spec 54%) after anti-TNF induction predicts future treatment outcomes.
P1097 Phase 1/2 study to assess safety, tolerability, and efficacy of XmAb942 (anti-TL1A) in healthy participants and participants with ulcerative colitis
Authors: Hung K , Aggarwal S , Gargosky S , Peterson C , Ramanujan S , Banfield C , Manukyan Z , Hassan-Zahraee M , Kanodia J , Woo J , Szymkowski D , Visonneau S , Burington B , Trout C , Leone D , Dahiyat B , Gujrathi S , Desjarlais J
Published: January 2025

Background

Tumour necrosis factor-like ligand 1A (TL1A) mediates a broad spectrum of pro-inflammatory and pro-fibrotic effects that have been linked to the pathogenesis of inflammatory bowel disease (IBD), as well as other autoimmune disorders. Recent clinical trials have demonstrated that antagonist antibodies that interfere with the interaction between TL1A and its cognate receptor, Death Receptor 3, can result in clinical remission in the two primary variants of IBD, ulcerative colitis and Crohn’s disease. XmAb942 is an anti-TL1A IgG1 antibody with ablated Fc-mediated effector function that incorporates the Xtend™ half-life extension technology. XmAb942 binds trimeric TL1A with high affinity and specificity and is highly potent across multiple preclinical assays. Allometric scaling of the non-human primate half-life of 23 days predicts a half-life of ≥ 70 days in humans. Quantitative systems pharmacology modelling supports the potential for superior drug exposure with less frequent dosing as compared to first-generation anti-TL1A antibodies. We now present details of the ongoing seamless Phase 1/2 study in healthy participants and participants with ulcerative colitis.

Methods

Phase 1 (Parts A and B) is a single ascending dose administered intravenously or subcutaneously followed by repeat dosing in healthy participants. Phase 2 (Part C) is in participants with ulcerative colitis with emerging Phase 1 data to determine dosing.

Results

The primary objectives of Parts A and B are to assess the safety and tolerability of single and repeat doses of XmAb942. Secondary objectives include assessment of pharmacokinetics (PK). Exploratory objectives include assessment of immunogenicity and pharmacodynamics. The primary objective of Part C is to evaluate the effect of repeat doses of XmAb942 on clinical remission in participants with moderately to severely active ulcerative colitis. Secondary objectives include evaluation of endoscopic improvement, endoscopic remission, clinical response, histologic-endoscopic improvement, histologic-endoscopic remission, as well as safety and PK assessments. Exploratory objectives include assessment of immunogenicity and pharmacodynamic effects.

Conclusion

The seamless Phase 1/2 study is designed to assess XmAb942 as a next-generation, potent, and long-acting anti-TL1A antibody therapeutic with potential best-in-class drug exposure and less frequent dosing. This study is currently enrolling in Australia, with Phase 2 to be expanded globally. Interim data are expected in the first half of 2025.

References

Clinical trials identification: NCT06619990
P1099 Simple magnetic resonance imaging markers are non-inferior measures of treatment response compared to complex disease activity scores in patients with active Crohn’s disease
Authors: Nejatbakhsh E , Rafaelsen S R , Brodersen J B , Knudsen T , Kjeldsen J , Juel M A , Jensen M D
Published: January 2025

Background

Minimally invasive modalities have shown significant potential for monitoring disease severity and treatment response in Crohn’s disease (CD). Several magnetic resonance imaging (MRI) scoring systems have been validated in research settings. However, these calculations are time-consuming, which limit their widespread adoption in clinical practice. This analysis evaluated treatment response in patients with active CD using simple imaging markers and compared them to complex multifactorial scores.

Methods

A post-hoc analysis was conducted using data from a prospective, blinded, multicenter study (ClinicalTrials.gov: NCT03435016). The study included patients with endoscopically active CD and a clinical indication for medical treatment. All patients completed ileocolonoscopy (IC) and MRI-enterocolonography with intravenous contrast and diffusion-weighted sequences before and after treatment. IC served as the gold standard. Response was defined as a ≥ 50% reduction of Simple Endoscopic Score for Crohn’s Disease (SES-CD). The simple markers evaluated were bowel wall thickness (BWT) and the apparent diffusion coefficient (ADC). Measurements were performed on the most severely affected ileocolonic segment and were compared to Magnetic Resonance Index of Activity (MaRIA), Simplified MaRIA (sMaRIA), and the Clermont score.

Results

Forty-two patients with known CD were included in the analysis. Patient characteristics are shown in Table 1. Endoscopic response was achieved in 19 patients (45.2%) with a median SES-CD of 11.5 (interquartile range [IQR] 9-17) and 7.0 (IQR 0-13) before and after medical treatment, both P < 0.001. MaRIA, sMaRIA, Clermont score, BWT, and ADC all significantly improved in patients with endoscopic response compared to non-responders (P < 0.05). Receiver operating characteristics are shown in Figure 1. The diagnostic accuracy for the absolute difference in BTW (AUC 0.735, 95% CI 0.583-0.886) and ADC (AUC 0.753, 95% CI 0.602-0.904) appeared to be higher than MaRIA (AUC 0.595, 95% CI 0.415-0.775), P = 0.12 and P = 0.13, respectively. The relative reduction of BTW (AUC 0.761, 95% CI 0.611-0.911) trended towards higher diagnostic accuracy compared to MaRIA (AUC 0.627, 95% CI 0.448-0.806, P = 0.098). A > 17% relative reduction of BWT resulted in an optimal sensitivity and specificity of 73.7% (95% CI 48.8-90.9) and 82.6% (95% CI 61.2-95.0), respectively.

Conclusion

Repeated measurements of BWT or ADC in the most diseased ileocolonic segment appear to be non-inferior to validated scores like MaRIA and sMaRIA at determining response to medical treatment in patients with active CD. These measurements are simple to perform and do not require intravenous contrast.
P1104 Endo-histologic outcomes in patients with ulcerative colitis responding to tofacitinib
Authors: Singh D.M. A , Bhardwaj A , Jain D , Sharma R , Singh D , Mahajan R , Kaur K , Singh A , Narang V , Kaur H , Singh M , Gupta P , Sehgal T , Midha V , Sood A
Published: January 2025

Background

The therapeutic landscape for ulcerative colitis (UC) has shifted toward deeper disease control. The real-world data on efficacy of tofacitinib in inducing histologic remission (HR) remains limited. We evaluated the real-world efficacy of tofacitinib in achieving endoscopic remission (ER) and HR.

Methods

A prospective cohort study was conducted from January 2022 to June 2024. Adult patients with moderate-to-severe UC (Mayo score ≥6, endoscopic subscore ≥2), who responded to tofacitinib induction were included. Paired endoscopic and histologic assessments were performed at baseline and week 48. Endoscopic disease activity was graded using the Mayo endoscopic score (MES), while histologic activity was evaluated using the Nancy index. The primary outcome was combined endoscopic-histologic remission (EHR), defined as MES of 0 and a Nancy index of 0, at week 48. The secondary outcomes included ER, HR, histologic endoscopic mucosal improvement (HEMI) and endoscopic improvement histologic remission (EIHR).

Results

Seventy-seven patients were analyzed. Clinical response at week 8 was seen in 66 (85.7%) patients, with 43 (65.2%) of these patients maintaining clinical response through week 48. At week 48, combined EHR was achieved in 22 (28.6%) patients, while ER and HR were observed in 30 (38.9%) and 29 (37.6%) patients, respectively. HEMI was noted in 32 (41.6%) patients, while EIHR was seen in 27 (35.1%) patients. (Figure 1) The endoscopic and histological outcomes did not differ with concomitant administration of corticosteroids during induction, previous exposure to thiopurines and the time of achievement of symptomatic remission (8 weeks vs 16 weeks). (Figure 2) No significant predictors of ER, HR, or combined EHR were identified. No serious adverse effects were reported.

Conclusion

Tofacitinib is effective in achieving combined HER, ER, and HR. These findings support the potential for histologic healing as a therapeutic target for UC in real world.
P1106 Early surgical treatment after diagnosis of anal lesions of CD may reduce risk of and colostomy and rectal amputation
Authors: Sako M , Okamoto K
Published: January 2025

Background

Anal fistulas in Crohn’s disease (CD) are often indicated for surgical treatment. We examined the possibility of surgical treatment at early stage after the occurrence of anal lesions without extensive lesions or anal strictures, which can lead to earlier remission and longer maintenance.

Methods

113 CD patients (age 30.0 ± 9.0 years at the time of surgery, 86 males and 27 females) who continued to visit the hospital after surgery for anal fistula from 2003 to 2019 at the Department of Colorectal Surgery at Tokyo Yamate Medical Center were included. Surgery was performed for the purpose of drainage of abscess and removal of infected granulation tissue, and induction of biologics were decided by the physician and the anal surgeon in cases of postoperative wound healing was prolonged, except in cases which biologics had already been started for intestinal lesions. Remission of anal lesions was defined as the epithelialization and disappearance of drainage of the wound, and the rate of colostomy or rectal amputation due to continued activity of postoperative anal lesions was investigated in patients who underwent surgery within 1 year of diagnosis of anal lesions (31 cases, early group) and in cases that were performed after 1 year (82 patients, non-early group).

Results

Colostomy and rectal amputation were performed in 14.3% (4/28) in the early group and 37.8% (28/74) in the non-early group (p<0.05). Biologics were used in 61.1% (69/113) in total, (IFX36, ADA24, UST9, VDZ1), 35.5% (11/31) in the early group and 70.7% (58/82) in the non-early group. The rate of colostomy and rectal amputation was 18.2% (2/11) in the early and bio group, 0% (0/20) in the early and non-bio group, 20.7% (12/58) in the non-early and bio group, and 29.2% (7/24) in the non-early and non-bio group. The rate of colostomy and rectal amputation was relatively low in early group and the risk was not reduced by biologics in non-early group.

Conclusion

In CD, early surgical treatment after diagnosis of anal lesions may contribute to reduced risk of and colostomy and rectal amputation.
P1115 Short- and Mid-term Effectiveness and Safety of Risankizumab in Refractory Crohn’s Disease: A Retrospective Study
Authors: Elosua Gonzalez A , Ramoneda G , Villalonga L , Pérez Ó , Zabalza L , Vicuña M , Nantes Ó , Rubio S , Rodriguez C
Published: January 2025

Background

Risankizumab (RSK) is the first anti-IL-23 drug approved in 2022 for moderate-to-severe Crohn’s disease (CD). Data on its real-world effectiveness and safety remain limited. This study assesses the short- and mid-term effectiveness of RSK and its safety profile in a clinical practice setting.

Methods

A retrospective analysis was conducted on patients with refractory luminal CD treated with RSK at our tertiary centre between March 2022 and July 2024 who completed induction therapy. The primary endpoint was clinical remission at weeks 12 and 24, assessed via the Physician Global Assessment (PGA) based on symptoms, laboratory data and endoscopy/imaging if available. Secondary endpoints included at least clinical response, steroid-free remission and response, adverse events, and drug persistence.

Results

Sixty-three patients were included (65% male, median age 31 years, median disease duration 9.8 years), with 95.2% previously exposed to anti-TNF, 82.5% to ustekinumab, and 52.4% to vedolizumab; 60% had prior exposure to three biologics, 25.4% to four, and 44% had undergone intestinal resection. Induction (600 mg) was administered intravenously in 88.9% of cases.

At week 12, remission and at least partial response rates were 25.4 % and 76.2%, respectively, while steroid-free remission and response rates were 22% and 65.1%. By week 24, 35 patients remained in the study, achieving remission/response rates of 25.7% and 62.8%, respectively, and steroid-free rates of 18.2% and 48.5%. No significant differences were found regarding prior ustekinumab exposure or response/remission outcomes between weeks 12 and 24. RSK persistence was 93%, with four patients discontinuing due to nonresponse. Additionally, by week 24, four patients had required reinduction with 1200 mg administered intravenously. Three adverse events (headache, insomnia, arthralgia) were mild and did not require treatment discontinuation.

Conclusion

Risankizumab demonstrated encouraging effectiveness in treating refractory Crohn’s disease, achieving clinical responses and steroid-free remission in the short- to mid-term. High drug persistence and a favorable safety profile highlight its potential as a valuable treatment option in real-world settings.
P1136 Mesenteric excision and endoscopic recurrence in ileocaecal Crohn’s Disease: a single centre experience
Authors: Jones T , Jayasooriya N , Thoua N , Ghanbari A
Published: January 2025

Background

Endoscopic recurrence of Crohn’s disease after ileocaecal resection is a major concern and has been linked to multiple factors. Endoscopic evidence of postoperative recurrence (ePOR) in the first 6 months ranging between 40-70%.1 Effects of mesenteric sparing versus extended resection in ileocaecal resection is thought to be one of the factors contributing to ePOR.2

Methods

All ileocacecal resections for Crohn’s Disease performed between March 2018 and December 2023 and with surveillance ileocolonoscopy were included in this retrospective analysis. Surgical procedure was standardised with ligation of the ileocolic pedicle at 2-3cm from the origin. Mesentery was excised from the point of vessel ligation directly to the limits of bowel resection. Extracorporeal ileocolonic anastomosis was performed in a stapled, side-to-side, antiperistaltic configuration with closure of the mesenteric defect. Principles of Enhanced Recovery After Surgery were adhered to. All specimens received histological analysis. Surveillance colonoscopy was performed with Modified Rutgeerts Score assigned by the endoscopist with retrospective review by a second endoscopist.

Results

Seventeen patients were eligible for inclusion. Median age was 36 years. Eleven patients (65%) received biologic therapy prior to surgery. Twelve patients (71%) received laparoscopic surgery. Median operative duration was 129 minutes. One patient (6%) had a Clavien-Dindo grade 3+ morbidity (radiological drainage of a collection) with no anastomotic leaks. Median length of stay was 7 days. Histological analysis demonstrated clear margins in all specimens. Six patients (35%) received biologic therapy after surgery. First endoscopic surveillance was performed at a median 18 months. Modified Rutgeerts Score was 0 in 2 (12%), 1 in 9 (53%), 2a in 1 (6%), 2b in 4 (24%) and 3 in 1 (6%) of patients. One patient underwent further surgery for proximal stricture >5cm from the anastomosis. Median follow up was 98 months.

Conclusion

Mesenteric excision comparable to that of D2 lympadenectomy for colorectal cancer is safe. Furthermore, it may confer benefit with lower ePOR, compared to recent literature. Further research is needed to confirm the benefit of mesenteric excision in ileocaecal resection for Crohn’s Disease.

References

1.Nardone OM, Calabrese G, Barberio B, et al. Rates of Endoscopic Recurrence In Postoperative Crohn’s Disease Based on Anastomotic Techniques: A Systematic Review And Meta-Analysis. Inflamm Bowel Dis. 2024;30(10):1877–87.

2.Brown SR. How can the surgeon reduce recurrence after surgery for ileocolic Crohn’s disease? Semin Colon Rectal Surg. 2023;34(4):100985.