bluuebunny/crossref_metadata_2025 huggingface dataset:
P707 Real-world Long-term efficacy of ustekinumab in the treatment of Perianal Fistulizing Crohn's disease: Results from a single-center retrospective study
Authors: Chen Q , Gong Y , Yang F , Qiao L , Wang H , Zhang D , Wang C , Zhu Z , Yang B
Published: January 2024

Background

The efficacy of ustekinumab (UST) in treating perianal fistulizing Crohn's disease (PFCD) remains inconclusive. This study aimed to investigate the long-term efficacy and prognostic factors of UST in the treatment of PFCD patients.

Methods

This is a retrospective single-center analysis of PFCD patients who had at least one year of follow-up and began UST treatment between November 2020 and September 2022. The primary outcome was fistula clinical remission at any time point. Secondary outcomes included fistula clinical response, intestinal clinical remission, and response. Factors associated with long-term fistula clinica remission were screened using the univariate analysis, LASSO regression and extreme gradient boosting (XGBoost) model, and visualized using SHAP.

Results

A total of 131 patients were included in the study, the mean follow-up was 70.39 weeks. Among these patients, 51 (38.9%), 72 (55.0%), and 82 (62.6%) achieved clinical fistula remission at weeks 24, 52, and the last follow-up, respectively. 111 patients (84.7%) achieved intestinal clinical remission and 119 patients (90.8%) achieved intestinal clinical response. Ninety-one patients (69.5%) had prior exposure to other biologics. This study did not ascertain a significant difference in the outcome of UST for CD between biologics Naïve and biologics Exposure patients. The XGBoost model integrated eight independent variables: Montreal L3, Montreal A2, CDAI, PDAI, ESR, body mass index, simple fistula, and re-operation events. The model revealed a favourable discrimination ability with AUC was 0.798 in the internal cohorts.

Conclusion

This study defined the effectiveness and eight risk factors of UST in long-term clinical fistula remission in PFCD patients, which is helpful for early identification of UST beneficiaries.
P732 Lack of concordance between patient-reported, physician-reported and objective criteria-based identification of suboptimal control in IBD patients: IBD PODCAST study results
Authors: D'Amico F , Gomollón F , Bamias G , Magro F , Heatta-Speicher T , Michelena N , Leitner C , Dignass A
Published: January 2024

Background

Crohn’s disease (CD) and ulcerative Colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic inflammation of the digestive tract. Increasing evidence highlights the unmet need, the burden of disease, the progressive nature of the disease and subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management. The IBD-PODCAST study estimates the proportion of patients with CD and UC with suboptimal disease control (DC) in a real-world setting. Criteria for suboptimal control were largely based on STRIDE-II and modified by an expert panel (Tabel 1). We previously reported that a large proportion of patients were identified with suboptimal DC. The aim of the current analysis was to compare the patients’ and physicians’ opinion to these objective criteria of suboptimal DC in this cohort.

Methods

A non-interventional, cross-sectional, multi-center study was conducted. In total 2185 patients were recruited across 103 sites in 10 countries. Details on the subjective evaluation of DC from patients and physician questionnaires were compared to the objective disease criteria identifying patients with suboptimal DC.

Results

While 52.2% and 44.3% of patients with suboptimal DC in CD and UC, respectively, were identified based on objective criteria; only a limited proportion of patients with CD (10.9%) and UC (13.0%) reported their DC as suboptimal. Similarly, a suboptimal DC was identified by a low rate of physicians (15.7% in CD and 17.9% in UC). Impaired QoL was the main reason for suboptimal DC among CD (46.1%) and UC (51.9%) patients. Conversely, lack of biochemical lab parameter normalization was the main reason for suboptimal DC for physicians (46.6% in CD and 51.8% in UC). An aligned definition of suboptimal DC between physicians and patients was found in a quarter of patients with CD (22.3%) and in a third of cases with UC (33.0%). A concordance of suboptimal DC between patient-reported, physician-reported and objective criteria based on STRIDE-II was identified in 7.5% of CD and 12.0% of UC patients (Figure 1).

Conclusion

There is a high percentage of suboptimally-controlled IBD patients in this large multinational real-world cohort suggesting a large disease burden in IBD patients. There is a disconnect between objective criteria for suboptimal DC and the evaluation by the patient and the physician. Objective criteria (incl regular disease monitoring) may be essential to improve alignment in disease management and treat to target approaches. There is a strong need to improve patient-physician communication and to standardize the definition of disease control in order to improve patient management, patient-physician communication2 and the patients’ quality of life.
P735 JAK inhibitors and S1P receptor modulators for the treatment of antibiotic refractory chronic pouchitis: an ECCO CONFER Multicentre Case Series
Authors: Testa G , Ribaldone D G , Verstockt B , Molnar T , Savarino E , Schmidt C , Vieujean S , Teich N , Meianu C , Juillerat P , Grellier N , Lobaton T
Published: January 2024

Background

Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in chronic antibiotic refractory pouchitis (CARP) are lacking. This ECCO-CONFER project collected cases of CARP treated with JAK inhibitors or S1P receptor modulators.

Methods

This retrospective multicentre study collected cases across Europe through the ECCO-CONFER project, including patients with ulcerative colitis (UC) diagnosis who underwent proctocolectomy with ileal pouch anal anastomosis (IPAA), treated with JAK inhibitors or S1P receptor modulators for CARP and at least three months of follow up. Main outcomes were steroid and antibiotics-free clinical response at three months (T3) for each drug, defined as clinical part of modified Pouchitis Disease Activity Index (mPDAI) reduction by ≥1 points, steroid and antibiotics-free clinical response at 1 year (T12) assessment, defined as mPDAI reduction by ≥2 points, steroid and antibiotics-free clinical remission (mPDAI=0) at T3 and T12, endoscopic response at T12 (improvement in PDAI Endoscopic Inflammation subscore reaching <3) and endoscopic remission at T12 (endoscopic PDAI ≤1). Non-response imputation was applied.

Results

Seventeen treatments with small molecules of CARP in 15 patients were collected from nine centres in seven countries. Eight patients were treated with tofacitinib; steroid and antibiotics-free clinical response at T3 was achieved in six patients (75%) and steroid and antibiotics-free clinical remission was achieved in five patients (62.5%). One patient discontinued tofacitinib for loss of response after eight months. Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50.0% of patients, steroid and antibiotics-free clinical remission in one patient (16.7%), endoscopic response in 50.0% and endoscopic remission in 50.0%. One patient was treated with filgotinib, neither steroid and antibiotics-free clinical response nor steroid and antibiotics-free clinical remission were achieved. Six treatments with upadacitinib were collected: at T3 steroid and antibiotics-free clinical response was achieved in 33.3% and steroid and antibiotics-free clinical remission was achieved in 16.7% of cases. Two cases were treated with ozanimod. At T3 steroid and antibiotics-free clinical response was achieved in one patient (50.0%) and steroid and antibiotics-free clinical remission was not achieved. No side effects were reported. Baseline characteristics and results are summarized respectively in figure 1 and table 2.

Conclusion

In a multiple biologic-refractory population, small molecules might be a suitable treatment option for CARP. Based on current limited data, the use of JAK inhibitors should be further investigated.
P747 Assessment of a microlearning programme for patients with Inflammatory Bowel Disease (The ADEII project) on ansiety/depression status and illness perception
Authors: De Castro Parga M L , Hernández V , Sanromán L , Martínez-Cadilla J , Figueira M , Rodriguez-Prada I
Published: January 2024

Background

Information and communication technologies (ICTs) represent a novel approach to chronic disease management. However, their use in Inflammatory Bowel Disease (IBD) is lacking and their results as far unknown, because no specific tools are available, The prevalence of anxiety and/or depression in IBD ranges from 30-35% in clinically inactive phases. Furthermore, negative perceptions of the disease in the dimensions of consequences and emotions have been related to depression and anxiety. We aim to evaluate the outcomes of a novel microlearning programme for IBD patients in.anxiety/depression status and illness perception.

Methods

Prospective cohort study in adult patients with IBD (18 to 70 years old) who underwent a microlearning programme over a 2-month period, throught 4-minute videos organised in individualised video pathways that were sent via mobile phone using a Telegram bot. All patients received the 4-video main pack, consisting of 2 videos with information about their disease (ulcerative colitis or Crohn's disease), 1 video on adherence and another one on steroid treatment. To these were added as many videos as the number of drugs used by the patient to control IBD. Before starting the programme and at 6 months, patients completed the Hospital Anxiety and Depression Scale (HADS) and the Brief Illness Perception Questionnaire (BIPQ).

Results

Between June and October 2022, 1226 videos were sent to 200 IBD patients: 51.5% female (103), UC 52.5% (105), mean age 46.1 (13.2) years (Table 1). Median number of videos per patient was 6 (6-7). Attendance to ADEII programme ranged between 78% and 90%.The median score on the HAD anxiety subscale was 8.1 (4.3), while the median score on the HAD depression subscale was 6(4-8), Initially, anxiety was diagnosed in 60 patients (30%) and depressión in 16 (8%) as subescales scores>11. We found significant differences between the pre-intervention versus post-intervention medians and IQR in anxiety score 8(5-11) vs 7(4-11) (p=0.008) but no in depression. Regarding BIPQ test post -intervention there were significant decreases in P8 negative emotions 6(3-8) vs. 5(3-7) (p=0,003) and P5 identity 6(4-8) vs 5(3-7) (p=0,003) as well as a significant increase in P7 comprehensibility of disease 7(5-9) vs. 8(7-9) (p=0,003).

Conclusion

An ICT-based educational program was widely accepted by IBD patients and showed a decrease in anxiety and negative emotions and representations, along with improvement in the understanding of disease.
P749 Comparison of bowel preparations for colonoscopy in inflammatory bowel disease- A systematic review and network meta-analysis of randomized trials
Authors: Chatterjee A , Kaur S , Jena A , Patil A , Dutta U , Sebastian S , Sharma V
Published: January 2024

Background

Colonoscopy is important in the management inflammatory bowel disease. Adequate bowel preparation (IBD) is a prerequisite for colonoscopy and may be difficult to achieve in setting of IBD

Methods

We performed a systematic review and network meta-analysis of randomised trials of various bowel preparations used before colonoscopy in IBD. Various electronic databases were searched to identify eligible studies. A frequentist network meta-analysis was done to compare the effectiveness of various bowel preparations. Risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcomes were assessed qualitatively.

Results

We included 7 trials including 960 patients. All bowel preparation had a similar effectiveness of bowel preparation as compared to 4 litres of polyethylene glycol (PEG) (OR when compared with PEG4L: OSS- 1.1043 95% CI 0.6553-1.8610; PEG/Ascorbate 2L- 0.9838, 0.6519-1.4848; PEG 1L -1.0011, 0.5522-1.8150; PEG2L plus bisacodyl -1.0864, 0.7130-1.6554; PEG 4L plus simethicone -1.0069, 0.6721-1.5084; PEG/SPMC 1.5L -0.9966, 0.5569-1.7835; SPMC 2L -1.0996, 0.6123-1.9745 had a similar effectiveness. Low-volume preparations had better compliance, tolerance, and acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcome after colonoscopy like cecal intubation rate, and change in electrolyte levels were found.

Conclusion

Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.
P752 Difficult-to-treat inflammatory bowel disease: effectiveness and safety of 4th and 5th lines
Authors: Caron B , Habert A , Bonsack O , Camara H , Jeanbert E , Parigi T L , Netter P , Danese S , Peyrin-Biroulet L
Published: January 2024

Background

Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined difficult-to-treat IBD. The objective of this study was to investigate for the first time treatment persistence, efficacy and safety of biologics or small molecules used in 4th or 5th line therapy.

Methods

We reviewed all consecutive patients with IBD treated at Nancy University Hospital between July 2022 and April 2023 with the 4th or 5th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4th and 5th line therapy.

Results

We enrolled 82 patients with IBD (4th line: 44; 5th line: 38). On Kaplan-Meier analysis the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p>0.05) as 4th and 5th line treatment. The restricted mean survival time analysis showed that persistence rate of risankizumab was the highest as 4th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks respectively, p=0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks respectively, p=0.035). In multivariate regression, Crohn’s disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence.

Conclusion

In this first real-world setting, risankizumab could have longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn’s disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.
P768 Appropriateness of small molecule agents for patients with IBD of childbearing age – a RAND appropriateness panel
Authors: Selinger C P , Laube R , Fraser A , Headley K , Kent A , Kok K , Lee V , Limdi J , Ludlow H , Rees F , Sagar N , Walker E
Published: January 2024

Background

Many women of childbearing age with IBD require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules Tofacitinib, Filgotinib, Upadacitinib and Ozanimod (TFUO) have shown concerning reproductive results in animal studies. Therefore, their use in women of childbearing age needs careful consideration.

Methods

We convened a RAND appropriateness panel of 6 gastroenterologists, 2 IBD nurses, 1 IBD pharmacist and 3 expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds.

Results

13 statements were voted on in two rounds. All statements were deemed appropriate after one round of revisions. Here we present a selection of key statements:

1. Women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception. Counselling regarding the risk of TFUO in unplanned pregnancies should be provided.

2. For women using contraception while on JAK therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception over combined oestrogen-progesterone formulations to reduce the risk of venous thromboembolism.

3. TFUO are contraindicated during pregnancy due to serious teratogenicity concerns.

4. Regardless of physical wash out periods, we recommend that women currently receiving TFUO cease therapy with enough time to establish clinical remission ideally for at least 3 months prior to conception. This window allows to safely establish whether the alternative (or no) therapy can maintain remission.

5. Therapies other than TFUO should be considered as first line therapy in women with IBD of childbearing age, with the exception of select individual social or medical circumstances, or women who have completed family planning and agree to use effective contraception.

6. TFUO may be appropriate choices for women of childbearing age after failure of, intolerance of or contraindications to one biological agent licensed for IBD.

7. In women who wish to have children in the future, a minimum treatment period for TFUO should be considered. Where the wish to start a family is less than 1 year in the future it is recommended to consider agents other than TFUO.

8. TFUO are contraindicated during breastfeeding.

9. If a woman conceives while taking TFUO, the medication should be ceased, she should receive counselling about potential known and unknown maternofoetal complications, and alternative IBD therapy may be commenced if required.

Conclusion

We developed 13 practice statements derived from a RAND appropriateness panel of clinicians and patients to guide decision making for women of childbearing age regarding TFUO small molecules therapies for IBD.
P770 Proactive Infliximab monitoring improves the rates of transmural remission in Crohn’s disease – a propensity score matched analysis
Authors: Fernandes S R , Tubal Bronze S M , Saraiva S , Bernardo S , Gonçalves A , Moura Santos P , Valente A , Correia L , Cortez-Pinto H , Magro F
Published: January 2024

Background

Few patients can reach transmural remission in Crohn’s disease (CD) with currently available therapies. Proactive optimization of Infliximab (IFX) based on trough levels may potentially improve these results.

Methods

Retrospective cohort study including consecutive CD patients starting treatment with IFX. Rates of transmural remission were compared between patients with and without therapeutic drug monitoring (target level: 5-7 µg/mL). A propensity score matched analysis was performed to adjust for potential confounders (figure).

Results

195 CD patients were included, 57.9% receiving proactive therapeutic drug monitoring. The rates of transmural remission were higher in patients under proactive therapeutic drug monitoring (37.2% vs 18.3%, P=0.004) with similar results in the propensity score matched analysis (34.2% vs 17.1%, P=0.025). In multivariate analysis, proactive therapeutic drug monitoring was independently associated with transmural remission: OR 2.95 95%CI(1.44-6.06), P=0.003.

Conclusion

Proactive optimization of IFX based on trough levels increases the rates of transmural remission in CD.
P771 Comparing obstructive symptoms and dietary restrictions with Crohn's disease stricture severity
Authors: Saunders B , Lesack K , Rosentreter R , Macci A , Novak K , Ma C , Kaplan G , Ingram R J , Seow C , Panaccione- R , Lu C
Published: January 2024

Background

Stricturing Crohn’s Disease (CD) is characterized by bowel narrowing often leading to obstruction. Obstructive symptoms (OS) have been evaluated in patients with CD strictures using OS scores (STRIDENT). Clinical observations suggest that OS are generally associated with end-stage strictures requiring dietary restrictions and surgery. Evaluating the prevalence of symptoms in strictures is important as regulatory agencies require symptom response to therapies in trials. Intestinal ultrasound (IUS) accurately assesses CD strictures. IUS criteria for ileal strictures includes: 1) bowel wall thickness (BWT) > 3mm, 2) luminal narrowing, and 3) pre-stenotic dilation (PSD) > 2.5 cm. It remains unclear whether stricture severity is correlated with OS (nausea, vomiting, bloating, abdominal pain). We aim to assess if OS and dietary restrictions occur more often in those with more severe strictures (pre-stenotic dilation size).

Methods

In this pilot study, prospective ileal CD patients with inflammatory (non-stricture) phenotype versus definitive or probable strictures were surveyed. OS for the past 2 months were queried in patients with definitive (BWT >3mm, luminal narrowing < 1cm, PSD ≥ 2.5cm), and probable strictures (definitive with PSD < 2.5cm) as identified on IUS. OS queried included nausea, vomiting, bloating, abdominal pain, and dietary restrictions. Chi-squared tests for categorical symptoms and one-way ANOVA (Kruskal Wallis) was used to compare symptom prevalence within the non-stricture or stricture category.

Results

39 patients were recruited with a median diagnosis age of 23.5 years (range 24-69) with 12 non-stricture phenotype (30.8%), 13 definitive (33.3%), and 14 probable stricture (35.9%). Patients with definitive strictures (35.3%) have significantly more nausea than those without strictures (11.8%) (p = 0.01), and no difference with probable strictures. Nausea with probable strictures (41.2%) was not significantly different from non-stricture patients (11.7%) (p = 0.07). In those with definitive versus non strictures, bloating (53.6 % vs 61.5 %, p = 0.69), post prandial pain (57.6 % vs 25.0 %, p = 0.14), and vomiting (10.0% vs. 20.0%, p = 0.47) were not significantly different. No difference was found in obstructive pain (F=2.27, p=0.12) among all groups. Dietary restrictions occurred in 40% (5/12) without strictures, 43.8% (7/12) with probable strictures, and 69.2% (9/13) with definitive strictures.

Conclusion

Nausea was the sole indicator distinguishing definitive from probable strictures. Pain, vomiting, and bloating did not differentiate those with severe from probable strictures, possibly due to dietary restrictions. More recruitment will refine these findings and enable comparison with specific IUS parameters.
P786 Evaluation of the efficacy and safety of the use of subcutaneous infliximab in the treatment of inflammatory bowel disease in naïve patients
Authors: Escobar J , Pérez J , Plaza R , Castillo M , Sáez O , Ponferrada Á
Published: January 2024

Background

The use of intravenous (IV) infliximab in inflammatory bowel disease (IBD) is an established treatment with a demonstrated safety and efficacy profile. Subcutaneous (SC) infliximab is currently available, showing comparable results in disease maintenance, but lacking studies in naïve patients. This study aims to determine whether initial treatment with SC infliximab is as effective and safe in real clinical practice.

Methods

This is a single-center observational study that included patients with clinically active IBD who directly initiated SC infliximab after IV induction (IV 5 mg/kg 0-2 weeks and SC 120 mg/2 weeks at week 6). The primary objective of the study was to evaluate the response to SC treatment at 3 and 9 months in patients naïve for infliximab. Secondary objectives included the need for intensification, rescue treatments (corticosteroids, change of biologic or surgery), the occurrence of adverse effects and pharmacokinetic aspects (blood levels, development of antibodies to infliximab or ATIs). Clinical activity was assessed using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and Partial Mayo Score (PMS) for ulcerative colitis (UC). In addition, biochemical parameters (hemoglobin, albumin, C-reactive protein, and fecal calprotectin) were monitored.

Results

A total of 19 patients were included, 14 with CD and 5 with UC (Table 1). Among them, 16/19 had not received previous biological treatment and 3/19 had received another anti-TNF other than infliximab. They were followed at 3 (18/19) and 9 months (18/19) (Figure 1). Significant improvement (p<0.05) was observed in the parameters of clinical activity (6/18 persisting with mild-moderate activity at 9 months) and biochemical activity (fecal calprotectin). Infliximab levels were adequate at 3 (median 12; range 3.2-39) and 9 months (median 15.9; range 0.3-51). In total, 31.6% of patients (6/19) discontinued treatment: 1/19 due to mild acute urticaria at baseline, 2/19 due to the development of ATIs (one also developed lung abscesses requiring hospitalization) and 3/19 due to loss of secondary response requiring a change of biologic. Of the latter, one also needed treatment with oral corticosteroids. In none of the patients was the treatment intensified or surgery required.

Conclusion

Treatment with SC infliximab in naïve patients seems to be an effective and safe alternative with results comparable to IV infliximab in real clinical practice. In our 9-month study, clinical scores and fecal calprotectin improved significantly, with low immunogenicity rates. Only 31.6% of patients discontinued treatment due to adverse effects or loss of response.

Table 1. Baseline characteristics of patients
P797 Assessment of pharmacokinetics and clinical response in patients transitioning from intravenous to subcutaneous vedolizumab
Authors: Amor Costa C , Garcia Ramirez L , Suarez Ferrer C , Martin-Arranz E , Rueda Garcia J L , Sanchez Azofra M , Poza Cordon J , Gonzalez Diaz I , Amiama Roig C , Martin-Arranz M D
Published: January 2024

Background

Vedolizumab is a humanized monoclonal antibody directed against α4β7 integrin used in inflammatory bowel disease (IBS) patients1. The usual dosage of Vedolizumab is 300 mg intravenously (iv). Recently the subcutaneous (sc) formulation (108 mg every 2 weeks) has been approved, which provides more independence for the patient, avoiding visits to the hospital and possible inconveniences associated with it2.

Methods

The aim of the study is to evaluate the clinical and biochemical response of IBS patients treated with vedolizumab, 16 weeks after transitioning from iv to sc. An observational, prospective, single-center cohort study was performed. Patients with IBS and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. Clinical index as Harvey-Bradshaw Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) and questionaries (IBDQ-9 and TSQM) were performed on each visit.

Results

43 patients were included, 12 of them (27.9%) chose to transition to sc formulation. Baseline characteristics of both groups are shown in Table 1. 34 (79.1%) patients were prescribed vedolizumab due to previous biologic failure, 7 (16.3%) in first line due to comorbidities and 2 (4.7%) because of adverse effects in prior treatment.

All included patients remained in remission during follow-up. At week 16 (w16), no significant differences were found in calprotectin levels in patients on iv treatment (mean 146.6 ± SD 45.9) vs sc (159.26 ± 53.9) (p 0.9). Vedolizumab serum levels at w16 were higher in the sc group (22364.3 ± 5141.6) vs. iv (11425.9 ± 1514.2), with statistically significant differences (p 0.009). At w16, 9 (75%) of the patients in the SC group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. 1 patient (8.3%) in the sc group returned to iv treatment. 4 patients (12.9%) in iv and 2 (16.6%) in sc treatment presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site.

Conclusion

In our experience, vedolizumab sc is a safe and convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.

1. Smith, Michael A et al. "Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases." The Annals of pharmacotherapy vol. 48,12 (2014): 1629-35.

2. Vermeire, Séverine et al. "Efficacy and Safety of Subcutaneous Vedolizumab in Patients With Moderately to Severely Active Crohn's Disease: Results From the VISIBLE 2 Randomised Trial." Journal of Crohn's & colitis vol. 16,1 (2022): 27-38.
P806 Development of a clinical model to predict secondary non-response of anti-TNFα treatment on Crohn's disease
Authors: Xiang L , Xiaomei S , Yan L , Wei T , Hong G
Published: January 2024

Background

Secondary non-response to anti-tumor necrosis factor-α (including Infliximab and Adalimumab) in patients with Crohn’s disease (CD) is common. Prediction of secondary non-response is essential for treatment decision for individual patients.

Methods

The clinical model was constructed in a training cohort. Clinical features, serological parameters, genetic biomarkers etc. were obtained as predictors after anti- TNFα therapy. Univariate analysis was performed to eliminate irrelevant predictors with secondary non-response. A logistic regression model was developed using genetic biomarkers and predictors with P < 0.1 in the univariate analysis. Finally, the model was validated with reference to its calibration and clinical decision curve.

Results

In a univariate analysis, infliximab antibodies,white blood cell(WBC), albumin(Alb), previous use of immunosuppressant, switching to other drugs, immunological preparation were found associated with secondary non-response to IFX. Logistic regression analysis with stepwise backward selection P < 0.01 and a clinical model was developed based on the above predictors.

Conclusion

The study presents a model to predict secondary non-response to anti-TNFα in CD. This model can be used to help clinicians adjust the therapeutic strategy for CD patients.
P810 Fecal microbiota transplantation in Ulcerative rectocolitis
Authors: Ferreira F , Sousa M , Melado M , Pacheco M , Trindade L , Lorentz F , Carmo L , Clara A
Published: January 2024

Background

The objective of this work was to carry out a systematic review of the literature to evaluate interventional trials that compare fecal microbiofa transplantation (FMT) with a control group and evaluate the incidence of remission of ulcerative colitis as an outcome.

Methods

The search was conducted using the database from PubMed, from February 2021 to April 2023. In all, 303 articles were found. After reading the titles, 43 articles were selected for the abstract reading. After all the analysis with inclusion and exclusion criteria, 7 articles were fully analyzed in the present study. Of the 7 selected studies, 71% (5/7) performed clinical trials.

Results

In all the studies, a total of 352 patients were submitted to the FMT, with a average of 63 participants per study. The age of the participants vary from 18 to 75 years old, with all the studies having an average age in the third or fourth decade. All articles included patients with clinical disease activity, and 85.7% used the Mayo severity index. Regarding the stool administered, in 71.4% of the studies the participants received frozen stool and the preparation was carried out with saline solution. The infusion was performed with colonoscopy on 85% (6/7) of the studies, however there was no standardized approach to the transplant protocol or preparation of the patients before the FMT. The association between the FMT and the clinical remission has been positive in 85% (6/7) of the studies. 4 of the 5 articles that evaluated the clinical response pointed to an improvement of the patients submitted to the transplant over the placebo group. The endoscopic remission were analyzed in all the 7 studies showing positive results in 43% (3/7) of them. The laboratory were performed in just 1 of the studies and they reported substantial improvement of the evaluated parameters of the FMT group. There was no significant difference between the risk of developing adverse effects between the FMT and the placebo groups.

Conclusion

The FMT has been shown to be effective on the induction of clinical remission of Ulcerative Colitis, however, clinical studies with greater scientific impact are needed to implement this new therapeutic modality.
P834 Choosing wisely: Ustekinumab in Elderly Crohn’s Patients – A Comparative Study
Authors: Dar Antaki L , Shani U , Dotan A , Ukashi O , Ben-Horin S , Kopylov U , Levartovsky A
Published: January 2024

Background

The burden of Inflammatory Bowel Disease (IBD) in elderly patients derives from background comorbidities and the elevated risk associated with immunosuppressive treatments. In the present study, we aimed to assess the efficacy and safety of ustekinumab (UST) in elderly patients with Crohn's disease (CD).

Methods

This study was designed as a retrospective-cohort study including patients ≥ 60 years old (elderly) and patients < 60 years (non-elderly) who commenced UST for CD at a large, tertiary medical center. Outcomes were assessed by clinical response evaluation through parameters such as physician global assessment (PGA) and the Harvey-Bradshaw index (HBI), alongside assessment of clinical biomarkers, hospitalization rates, treatment persistence, and the necessity for surgical interventions. A secondary analysis was conducted of elderly patients treated with UST compared to elderly patients treated with vedolizumab (VDZ).

Results

In total, the primary analysis included 99 patients treated with UST (34 elderly patients and 65 non-elderly patients). Duration of follow-up was a median of 12 months (IQR 0). Elderly patients had predominantly an isolated ileal disease (68%) compared to an ileo-colonic disease (36%) in non-elderly patients (p = 0.017). The median age of onset was 68 years (IQR 64-75), and 34 years (IQR 28-42), respectively. Furthermore, elderly individuals were more likely to receive corticosteroids as their initial treatment (44% vs. 14%, <0.001). No differences were demonstrated in disease duration, EIM, phenotype, or previous biological therapy. Following six months of therapy, elderly patients were more likely to achieve complete clinical remission (31% vs. 12%, p = 0.035) as assessed by PGA. The elderly group experienced higher hospitalization rates during the 6-month (21% vs 4.6%, p = 0.029) and the 12-month follow-up period (15% vs. 3.1%, p = 0.045), while surgery rates were comparable between non-elderly and elderly groups (table 1). Concerning elderly UST vs elderly VDZ patients (n=69), no significant differences were observed in clinical response and remission rates between the groups after 6 and 12 months of follow up. In addition, no significant differences were shown in regard to safety (hospitalizations, surgery or therapy cessation rates).

Conclusion

UST is an effective treatment option in elderly CD patients. However, this population had higher hospitalization rates compared to non-elderly patients, greatly owing to age and comorbidities.
P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic review
Authors: Forss A , Flis P , Sotoodeh A , Kapraali M , Rosenborg S
Published: January 2024

Background

Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN.

Methods

We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database.

Results

Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN.

Conclusion

In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.
P845 Vedolizumab induces endoscopic healing uniformly irrespective of disease location: post-hoc analysis of the LOVE-CD trial
Authors: Hens B , Oldenburg L , Molnár T , Baert F , Clasquin E , Vermeire S , Löwenberg M , D'Haens G
Published: January 2024

Background

Vedolizumab (VDZ) is a gut-selective anti–α4β7-integrin monoclonal antibody approved for the treatment of Crohn's disease (CD). We performed a post-hoc analysis of the LOVE-CD trial to evaluate the effect of disease location on endoscopic healing.

Methods

LOVE-CD is a prospective multicentre study of VDZ therapy in adult patients with moderate-severe CD (Crohn's Disease Activity Index (CDAI) >220 and presence of ulcers at endoscopy). Patients received VDZ 300 mg infusions at weeks 0-2-6 followed by 8 weekly infusions up to week 52. An additional infusion at week 10 was given to patients without clinical response (CDAI decrease <70 points). Corticosteroids had to be withdrawn by week 26. Ileocolonoscopies were performed at weeks 0, 26, and 52, recorded, and centrally scored by 2 independent readers using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The primary endpoint for this analysis was the proportion of patients, stratified by disease location (according to Montreal classification), with ulcer-free endoscopy (absence of any ulceration; SES-CD ulcer score 0) at week 52. Key secondary endpoints at week 52 were the proportion of patients, stratified by disease location, with endoscopic remission (SES-CD <4 for L2/L3 CD or <2 for L1 CD, and no subscores >1), with combined steroid-free clinical and endoscopic remission (CDAI<150 and endoscopic remission), the segmental healing rates, and ulcer healing rates stratified by disease duration.

Results

186 patients were included in this intention to treat (ITT) analysis: 42 (22.6%) with L1, 52 (28.0%) with L2, and 92 (49.5%) with L3 disease. Baseline characteristics are shown in table 1. At week 52, the primary endpoint (absence of all ulcerations) was attained in 15/42 patients with L1 (35.7%), 20/52 with L2 (38.5%) and 25/92 with L3 CD (27.2%) (ITT, NRI (p=0.327)). Endoscopic remission was observed in 12/42 patients with L1 (28.6%), 20/52 with L2 (38.5%), and 29/92 with L3 disease (31.5%) (ITT, NRI (p=0.558)). The combined endpoint of clinical-endoscopic remission was reached in 9/42 L1 (21.4%), 16/52 L2 (30.8%), and 23/92 L3 patients (25.0%) (ITT, NRI (p=0.571)). Resolution of ileal ulcers was achieved in 15/40 L1 patients (37.5%) and 37/90 L3 patients (41.1%) (ITT, NRI (p=0.698)), resolution of colonic ulcers in 21/52 L2 (40.4%) and 45/90 L3 patients (50.0%) (ITT, NRI (p=0.268). Patients with early CD (disease duration <2 years) had higher ulcer healing rates than patients with late CD (47.5% versus 24.8%) (ITT, NRI (p=0.002)).

Conclusion

This post-hoc analysis of LOVE-CD shows that disease location does not affect endoscopic healing rates with VDZ in CD. However, early CD is associated with significantly higher endoscopic remission rates compared to late CD.
P847 Effectiveness of tofacitinib in ulcerative proctitis compared to left sided colitis and pancolitis
Authors: Singh A , Mahajan R , Midha V , Kaur K , Singh D , Bansal N , Sood A
Published: January 2024

Background

Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC).

Methods

This was a prospective observational cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure.

Results

Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 55%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. (Figure 1) Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary non-response at week 48. The median fecal calprotectin values at week 8 were 119.5 (53.75-611.25), 134 (63-456) and 208 (48.25-876) in patients with UP, LSC and PC, respectively. Similarly at week 48, the median fecal calprotectin values were the lowest in patients with UP (57[36-99]) as compared to patients with LSC (113[41-572]) and PC (150[89-1562]). The endoscopic remission rates at week 48 were similar in all the three groups (31%, 21% and 18% in groups UP, LSC and PC, respectively (UP vs LSC, p=0.25; UP vs PC, p=0.18; LSC vs PC, p=0.68). The probability of sustained clinical response was highest in patients with UP (cumulative probability of maintaining response 0.88) followed by groups LSC (cumulative probability of maintaining response 0.74) and PC (cumulative probability of maintaining response 0.60). The between group difference, was significant (Log Rank, p=0.03). (Figure 2) Patients with UP had the lowest incidence of adverse effects.

Conclusion

The effectiveness of tofacitinib in inducing and maintaining remission is greater in patients with UP compared to LSC and PC.
P849 Bayesian network meta-analysis of the efficacy of advanced therapies for patients with moderately to severely active ulcerative colitis naïve to advanced therapy
Authors: Jairath V , Leahy T P , Potluri R , Wosik K , Gruben D , Cappelleri J C , Bartolome L
Published: January 2024

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In the absence of head-to-head randomised controlled trials (RCTs), network meta-analyses (NMA) offer insight into the comparative effectiveness of treatment options. NMA were conducted to examine the relative efficacy of etrasimod vs other advanced therapies (AT) with licensed dosing (European Medicines Agency) for the treatment of UC in patients naïve to biologic agents and/or Janus kinase inhibitors.

Methods

A systematic literature review (SLR) was performed on 15 November 2022, and covered all available records without time limit, using NICE DSU and PRISMA guidelines. NMA were conducted under a Bayesian framework, and a multinomial fixed-effect approach was used to model outcomes, clinical response and clinical remission, in the induction phase and among induction phase responders in the maintenance phase, in patients naïve to AT. Reported outcomes from trials with a treat-through design, such as ELEVATE UC 52, were recalculated to mimic those of a responder re-randomisation design; only responders in the induction phase were analysed in the maintenance phase. Data are presented as median relative risk (RR) of the treatment vs its comparator, along with corresponding 95% credible intervals (CrI). Prespecified sensitivity analyses were performed.

Results

Of 81 studies identified from the SLR, 21 and 11 RCTs were included in the induction and maintenance networks, respectively. For induction and maintenance phases, all therapies demonstrated benefit over placebo, consistent with phase 3 clinical trial data. In the NMA for clinical remission in the induction phase, etrasimod 2 mg had a statistically significant benefit over adalimumab 80/40 mg and 160/80 mg (RR [95% CrI] for treatment vs etrasimod 0.49 [0.29–0.78] and 0.67 [0.50–0.92], respectively), filgotinib 100 mg (0.55 [0.37–0.84]) and placebo; conversely, upadacitinib 45 mg had statistically significant benefit vs etrasimod (1.47 [1.07–2.03]; Table). There were no statistically significant differences for etrasimod vs other comparators. Similar results were observed for clinical response. In the maintenance phase, there were no statistically significant differences between etrasimod 2 mg and other treatments for clinical remission and clinical response (Table).

Conclusion

With respect to clinical remission and clinical response during induction and maintenance phases, etrasimod efficacy was similar to most comparators as a first-line AT. Differences in trial design and risk-benefit profiles of AT should be considered when interpreting NMA results.