bluuebunny/crossref_metadata_2025 huggingface dataset:
P499 Anorectal Motility Disorders In Inflammatory Bowel Disease Patients
Authors: Costache R E , Dimitriu A , Gheorghe C
Published: January 2024

Background

In spite of prolonged disease remission of IBD patients, induced by the new biological molecules, a significant number of them suffer from persistent debilitating symptoms with major impact on the quality of life. Frequently, these symptoms are due to post-inflammatory motility changes and misinterpreted as functional disorders. Our aim is to identify and characterize the anorectal motility dysfunction in IBD patients.

Methods

We are conducting an ongoing prospective study started in August 2019, which includes the IBD patients admitted in a Tertiary Gastroenterology Centre in Bucharest, with specific symptoms (anorectal pain, incontinence, difficult defecation). We perform high resolution anorectal manometry using Sandhill Scientific systems, the parameters being analysed using InSIGHT software. The manometric testing comprise measurements of anorectal pressure at rest, during squeeze, simulated evacuation, rectoanal inhibitory reflex (RAIR) and rectal sensory testing, in compliance with International Anorectal Physiology Working Group protocol

Results

We studied 30 patients (18 patients with Ulcerative Colitis and 12 patients with Crohn’s Disease, 18 females and 12 males, mean age 40 (±12.85) years. Only 33% (10 patients) had rectal active involvement. Symptoms were reported by 87% (26) patients: anal incontinence (85%), difficult evacuation (35%) and urgency (46%); rectal inflammation was not correlated with the presence of symptoms in our study group (p=0.28). Perianal surgical interventions didn’t represent a risk factor for fecal incontinence (p=0.18), or for dyssinergic defecation (p=0.1). Modified manometric parameters were found in 23 patients (79%). Low resting pressures were registered in 48% of patients; 55% of them presented low squeeze pressures; during push maneuvers, 34% of patients had insufficient rectal propulsive force, presenting low rectal pressures and 59% of them lacked anal canal relaxation. We performed sensibility testing on 18 patients: 9 patients presented criteria for hypersensitivity, hence reduced rectal compliance; 7 patients presented rectal hyposensitivity, while only 2 patients had normal rectal sensation. Recto-anal inhibitory reflex (RAIR) was present only in 28% of the patients, reflecting the dysfunction of the enteric neural system.

Conclusion

Patients with inflammatory bowel disease (IBD) have significantly higher rates of functional anorectal disease. Therefore, pelvic floor investigation is an essential tool in the investigation and management of IBD patients with ongoing symptoms not thought to be related to an IBD flare.
P526 Handsewn versus Stapled Ileocolic Anastomosis for Crohn's: Comparable Outcomes Despite More Severe Disease Profile in the Handsewn Group
Authors: Alipouriani A , Uchino T , Erozkan K , Lipman J , Hull T , Steele S R , Holubar S
Published: January 2024

Background

Stapled anastomosis is the most common anastomotic method after ileocolic resection for Crohn's disease, whereas handsewn end-to-end (HS-ETE) anastomosis is less frequently performed. The optimal technique for ileocolic anastomosis in Crohn's patients remains controversial. Some studies have suggested potential benefits of HS-ETE over SSTS, including lower recurrence rates, whereas others have found no difference. We aimed to compare short-term postoperative outcomes and long-term recurrence-free survival between the HS-ETE and SSTS groups at our center.

Methods

This retrospective study included consecutive patients who underwent ileocolic resection for Crohn's disease between 2012-2022 with either HS-ETE or SSTS anastomosis. The primary outcomes were perianastomotic recurrence and need for surgical/endoscopic intervention. Cox regression and Kaplan-Meier curves were used to compare recurrence-free survival.

Results

A total of 764 patients were included: 162 (21%) with HS-ETE and 602 (79%) with SSTS anastomosis. The median age of the HS-ETE and SSTS groups was 39 and 38 years, respectively. Males comprised 43% of the HS-ETE group and 51% of the SSTS group. The median BMI was 24 kg/m2 in both groups. The HS-ETE group had a longer median disease duration (10 vs. 7 years, p=0.02) and a higher rate of previous abdominal surgery (35% vs. 22%, p=0.01) than the SSTS group did. The ileocolonic location (78% vs. 66%, p=0.03) and perforating disease (45% vs. 35%, p=0.04) were also more common in the HS-ETE group. The median operative time (207 min vs. 147 min, p<0.001) and estimated blood loss (150 mL vs. 75 mL, p<0.001) were greater in the HS-ETE group. There were no differences in 30-day outcomes between the groups. Perianastomotic recurrence rates were similar between the HS-ETE and SSTS groups (29.6% vs. 28.9%, p=0.93). The 5-year recurrence-free survival rates were also comparable (HS-ETE, 56.4% vs. SSTS, 59%; p=0.94). Also, we found that the risk of requiring surgical or endoscopic intervention for recurrence between HS-ETE and SSTS was comparable (HS-ETE, 65.2% vs. SSTS, 74.2%; p=0.273)

Conclusion

Although the HS-ETE group had worse baseline disease characteristics, including longer disease duration, higher previous surgery rates, and more aggressive disease location and behavior, HETE and SSTS anastomosis after ileocolic resection for Crohn’s disease yielded comparable perioperative and long-term outcomes in our patient cohort.
P532 The enhanced recovery after surgery protocol take its place in inflammatory bowel disease surgery
Authors: Barugola G , Bertocchi E , Masini G , Geccherle A , Variola A , Todeschini A
Published: January 2024

Background

The enhanced recovery after surgery (ERAS) protocol is an evidence-based standardised multimodal programme formulated to reduce surgical stress and optimise recovery after surgery. The ERAS represents the best care practice for patients undergoing colorectal surgery. To ensure high compliance with active ERAS elements, patients must be educated to actively participate in the perioperative care pathway. ERAS protocols were originally designed to treat patients with colorectal cancer (CRC), only few studies have assessed this protocol in IBD patients. The aim of this study was to investigate the adherence to ERAS in IBD patients.

Methods

This retrospective study enrolled adult patients who underwent elective colorectal surgery and the ERAS protocol at our institute between May 2020 and December 2022. The patients were divided into IBD and non-IBD group. Data on medical history were collected from electronic health records. Preoperative, intraoperative, and postoperative data were collected for each patient using a self-reported mobile application (iColon). Adherence was calculated for at least 75% of active ERAS items. Chi-square test was used to compare categorical variables.

Results

619 patients, 492 non-IBD and 127 IBD, were enrolled. The overall adherence to ERAS protocol items was similar between the two groups (84% vs 82%, p 0.2). Adherence was evaluated during the three ERAS phases in the groups: preoperative (92% vs 90%, p 0.11), hospitalization (63% vs 62%, p 0.8), post-discharge period (96% vs 93%, p 0.2). Moreover, focusing on the preoperative ERAS items adherence, there were significant difference between non-IBD and IBD group in nutritional optimization (84% vs 67%, p <0.001) but no difference were reported in the patient’s pre-habilitation adherence (74 % vs 71%, p 0.4).

Conclusion

The feasibility of ERAS protocol was good in colorectal surgery as well as in IBD surgery. We need to focus on a tailored nutritional optimization in order to improve adherence and compliance among IBD patient.
P536 Outcome of colorectal cancer surveillance in paediatric inflammatory bowel disease: Time for new guidelines?
Authors: Vermeer E , Palsma C J , Gorter R R , de Boer N K , de Jonge R , Roelofs J J , de Meij T G J
Published: January 2024

Background

Paediatric inflammatory bowel disease (IBD) patients have an increased risk of colorectal cancer (CRC). Current guidelines advise to conduct CRC surveillance colonoscopy eight years following IBD diagnosis, or more often in case other risk factors for CRC are present, such as previous findings of colorectal dysplasia, or a concomitant primary sclerosing cholangitis (PSC) diagnosis. However, these guidelines are based on adult data and with no regard to the patient’s age, while frequent endoscopies impose a significant burden on children. In this study, we aimed to estimate the risk of dysplasia and CRC in paediatric IBD patients before the ages of 18 and 27 years.

Methods

Using the Dutch Nationwide Pathology Databank (PALGA), we examined the incidence and prevalence of dysplasia and CRC in patients up to 27 years in all Dutch paediatric IBD patients diagnosed between 1991 and 2023. Additionally, we assessed the influence of PSC diagnosis on CRC risk.

Results

Out of the 7,873 patients with biopsy-proven paediatric IBD, 24 developed dysplasia (0.34%) and two (0.025%) developed CRC before the age of 18 years. Out of the 3,425 patients from this cohort currently aged over 26 years, eleven (0.3%) developed CRC between 17 and 27 years. Overall, 120 patients (1.5%) were diagnosed with concomitant PSC, seven (5.8%) of which developed dysplasia and two (1.6%) of which developed CRC before the age of 27 years. The median time between IBD diagnosis and CRC diagnosis was 9.5 years in this cohort. Overall, CRC incidence before the age of 27 years decreased between 1991 and 2023. Additional clinical data on IBD localisation, severity of the disease, and concomitant diagnoses could not reliably be obtained from this database.

Conclusion

In this retrospective study, we found low prevalence of dysplasia and CRC in paediatric IBD patients, both before the age of 18 years and before the age of 27 years. PSC prevalence was low in this cohort, since only biopsy-proven PSC was included. However, we showed that PSC significantly increased the risk of CRC in paediatric IBD patients. Based on our findings it could be proposed to initiate CRC surveillance beyond the age of 18 years by experienced adult gastroenterologists, except in case of a concomitant PSC diagnosis.
P543 Patients in trials of moderate-to-severe UC who are exposed to placebo are more likely to suffer harm than those receiving active treatment: The lack of clinical equipoise in traditional study designs
Authors: Fine Z , Fear E N , St-Pierre J , Klein J A , Choi N K , Rubin D T
Published: January 2024

Background

Ulcerative Colitis (UC) is a relapsing-remitting inflammatory disease of the colon and rectum. There are many challenges to the recruitment of eligible individuals into clinical trials for IBD, including the availability of multiple standard-of-care treatment options and patient refusal to participate in randomized placebo (PBO)-controlled trials due to fear of receiving PBO. Patient harm across clinical trials for moderate-to-severe UC has not been adequately examined. We sought to quantify the potential harm to patients recruited to PBO.

Methods

We reviewed phase 3 clinical trials of therapies for moderate-to-severe UC including anti-TNF-alpha (infliximab, adalimumab, golimumab), anti-integrin (vedolizumab), anti-interleukin (IL) 12/23 (ustekinumab), anti-IL23 (mirikizumab, guselkumab), Janus kinase inhibitors (tofacitinib, upadacitinib), and sphingosine-1 phosphate receptor modulators (ozanimod, etrazimod). We analyzed the proportions (# of pts. with events/cohort size) of adverse events (AEs), serious adverse events (SAEs), disease exacerbation AEs (DEAEs), and disease exacerbation SAEs (DESAEs). We calculated Number Needed to Harm (NNH = 1/Incidence rate in cohort) for PBO (NNHPBO) and experimental therapy (NNHRx) in each trial. Maintenance phase NNHs were categorized as treat-through (TT) or re-randomized (RR).

Results

We identified an increased probability of AEs in the PBO arm of 7/11 induction (NNHPBO= 2.18-11.06; NNHRx=2.47-16.52), 1/8 TT maintenance, and 5/11 RR maintenance (NNHTTPBO = 1.2-3.1; NNHTTRx =1.1-16.4; NNHRRPBO = 1.3-10.8). We identified an increased probability of SAEs for 8/11 induction (NNHPBO=14.5-58.0; NNHRx=22.13-101.0), 4/8 TT, and 5/11 RR (NNHTTPBO = 3.9-23.3; NNHTTRx =4.2-29.9; NNHRRPBO = 8.8-35.0). Patients were at increased probability of DEAEs in the PBO arm of 8/11 induction (NNHPBO=7.38-43.20; NNHRx=12.50-106.33), 7/8 TT, and 7/10 RR (NNHTTPBO = 3.0-11.1; NNHTTRx =4.3-15.0; NNHRRPBO = 2.7-25.2). DESAEs were at increased probability of harm in the PBO arm of 8/9 induction (NNHPBO=29.00-116.00; NNHRx=47.43-119.75), 3/5 TT, and 7/10 RR (NNHTTPBO = 14.4-52.0; NNHTTRx =13.2-230.0; NNHRRPBO = 11.2-25.2).

Conclusion

In PBO-controlled clinical trials of therapies for moderate-to-severe UC, there are increased AEs and SAEs for patients who receive PBO, especially for DEAEs and DESAEs. Induction treatment responders re-randomized for maintenance to PBO experienced greater harms (i.e. lower NNH) than TT PBO patients. These findings raise concern about clinical equipoise in moderate-to-severe UC clinical trials and support ongoing efforts to design trials with active comparator arms and adaptive or platform methodologies.
P551 Benefit–risk trade-offs and patient preferences for therapy selection in Ulcerative Colitis: a multi-country preference study
Authors: Gisbert J P , Schreiber S , Siegel C A , Magro F , Jus A , Whichello C , Michaels-Igbokwe C , Heidenreich S , Oortwijn A , Vermeire S
Published: January 2024

Background

The treatment landscape of ulcerative colitis (UC) is increasingly complex. In the absence of predictive biomarkers and objective parameters, shared treatment decision-making is advocated in clinical practice. This study quantified the benefit–risk trade-offs that patients with UC are willing to make when choosing a treatment. A patient-centric benefit–risk assessment of filgotinib, an oral, Janus kinase 1 preferential inhibitor, was also conducted to show how measured trade-offs can be used.

Methods

Patients recruited through databases, panels, social media and patient associations completed an online discrete choice experiment (DCE). Eligible patients were aged ≥18 years, had a diagnosis of UC for ≥6 months and resided in France, Germany, Italy, Spain or the UK. DCE treatment attributes were identified using a literature review, clinical data and patient interviews. Patients completed the DCE by choosing between a series of two hypothetical treatment options with varying attributes which were systematically varied to ensure trade-offs were made. Data were analysed using a mixed logit model. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. Preference data were combined with SELECTION clinical trial data to evaluate the desirability of filgotinib 200 mg versus placebo from the patients’ perspective.1

Results

Among 631 patients who completed the survey (8997 patients invited), 75.3% were male and the mean age (standard deviation) was 42.2 (7.7) years. Patients preferred a daily oral pill over self-injection or intravenous treatment, and a treatment that avoided steroid use (Figure). Achieving and maintaining remission (RAI 32.4%; 95% confidence interval [CI] 29.5–35.2%) was considered the most important factor when choosing treatment. To achieve a 20% increase in the chance of remission, patients were willing to accept a 1.4% (95% CI 1.2–1.6%) increase in the risk of blood clots, a 2.0% (95% CI 1.7–2.3%) increase in the risk of serious infections, and a 0.7% (95% CI 0.6–0.8%) increase in the risk of malignancies (Table). Analysing patient preference and clinical data suggests filgotinib has a 70.1% chance of being preferred over placebo (p<0.001).

Conclusion

Treatment preferences of patients were mostly driven by the likelihood of achieving and maintaining remission. To achieve this, they were willing to accept some increase in the risks of blood clots, serious infections and malignancies. Patients also valued avoiding steroids. A patient-centric benefit–risk assessment indicated that patients are significantly more likely to prefer filgotinib over placebo, illustrating how preference data can be used with clinical data to inform decision-making.

1. Feagan BG et al. Lancet 2021;397:2372–84.
P553 The safety and efficacy of adalimumab 80mg weekly as maintenance therapy in pediatric Crohn’s Disease
Authors: Cohen-Sela E , Weintraub Y , Yerushalmy-Feler A , Orlanski-Meyer E , Nassar R , Magen-Rimon R , Shamir R , Shouval D S , Matar M
Published: January 2024

Background

Intensification of adalimumab (ADL) dosing to weekly 40 mg injections, in response to low drug levels, has been shown to provide beneficial outcomes in pediatric patients with Crohn’s disease (CD). Our study aimed to evaluate the safety and efficacy of weekly 80 mg ADL administration in children with CD.

Methods

In this retrospective cohort study conducted across five Israeli centers, we reviewed the medical records of pediatric CD patients who received a high dose of ADL 80 mg weekly injections between 2016 and 2023. Collected data included demographic characteristics, disease features, laboratory studies, and treatment outcomes.

Results

Thirty-two children with CD were included: mean age 15.8 (±1.7) years at intensification, 21 male (66%), 18 (56%) with L3 phenotype. The median time to ADL 80 mg intensification from ADL induction was 48.4 weeks (IQR 23.1-122.5). The mean weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was 28.5 (±16.9) at the time of intensification and the median calprotectin and C-reactive protein levels were 937 μg/g (IQR 540-1410) and 1.3 mg/dL (IQR 0.6-5.2), respectively. Clinically active disease was the main reason for ADL intensification (30, 94%). Baseline ADL levels were available in 30 patients (94%) with a median of 3.8 μg/mL (IQR 2.4-7.2). Among these, 23 children (77%) failed to achieve a target of ≥ 7.5 μg/mL. The median follow-up duration from the intensification dose was 91.2 weeks (IQR 53.6-149.1). Corticosteroids were required in 5/32 (15.6%) children, with a median time of 32.3 weeks (IQR 10.7-51.3) from intensification. There was no statistically significant difference in steroid utilization rates between children who achieved a target baseline drug level of ≥ 7.5 μg/mL and those who did not (p=0.934). Thirteen individuals (41%) discontinued ADL treatment, within a median of 24.7 weeks (IQR 11.7-57.1) from intensification. CD-related exacerbation, hospitalization, and surgery rates were 9 (28%), 4 (13%), and 2 (6%), respectively. No statistically significant differences were found in exacerbation (p=0.406), hospitalization (p=0.322), or surgery rates (p=0.427) between children who achieved a baseline ADL trough concentration level of ≥ 7.5 μg/mL and those who did not. Overall, ADL intensification was safe, but 3 (9%) patients developed new-onset psoriasis.

Conclusion

Our findings support the safety and efficacy of administering ADL at a weekly dosage of 80 mg as maintenance therapy in pediatric patients with moderate to severe CD.
P556 Immunomodulator and advanced therapies for Induction of clinical remission and response in Crohn’s disease: A systematic review and network meta-analysis
Authors: Sinopoulou V , Gordon M , Vuyyuru S , Darie A M , Radford S , Shale M , Moran G
Published: January 2024

Background

Several effective advanced therapies have been approved for the treatment of Crohn’s disease (CD) in the past two decades. Many have used synthesis techniques to study this area, but these rarely consider both advanced and immunomodulator therapy together in the same analysis. Network meta-analysis enables the direct and indirect comparison of these different therapeutic agents, aiding in determining their relative positioning within the treatment algorithm.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). The outcomes included were clinical remission and response, adverse events (AE), withdrawal due to AE, total and serious AE. We performed random-effects meta-analysis and network meta-analysis (frequentist approach), and estimated relative risk (RRs), 95%CI values. We used GRADE to ascertain certainty of evidence.

Results

A total of 83 RCTs comprising 19214 patients were eligible. A total of 28 interventions were included in the analysis. Combination of anti-tumor necrosis factor (TNF) and immunomodulators, anti-TNF monotherapy (adalimumab [ADA], infliximab [IFX], BI695501), IL-23 antagonists (ustekinumab [UST], guselkumab, risankizumab [RIS], mirikizumab), anti-integrins (vedolizumab, natalizumab) and upadacitinib were effective in inducing clinical remission compared to placebo (Figure 1). There was moderate certainty of evidence for combination of ADA and azathioprine (AZA) (RR 3.1, 95%CI [2.0-4.8]; risk difference [RD]: 40.1%), IFX+AZA (RR 2.5, 95%CI [1.7-3.8]; RD: 28.9%), ADA (RR 2.5, 95%CI [1.8-3.5]; RD:28.5%), and UST (RR 2.0 95%CI, [1.6-2.5]; RD: 19.2%) in induction of clinical remission compared to placebo. For induction of clinical response, there was moderate certainty of evidence for IFX+AZA (RR 2.8, 95%CI [1.6-4.8]), ADA (RR 2.5, 95%CI [1.7-3.9]), IFX (RR 2.8, 95%CI [1.6-4.8]), RIS (RR 1.9, 95%CI [1.3-2.6]). On analysis of serious adverse events all therapies were of no difference to placebo (very low certainty). On sensitivity analysis, the impact of concomitant immunomodulator use and the biological naivety of patients had little effect on these results.

Conclusion

On network meta-analysis, combination of anti-TNFs and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for the induction of clinical remission. More novel therapies appear to have examples of similarly important effect sizes, but are currently limited due to the imprecision of the limited evidence base at present and future research should target these therapies in study.
P557 Data communication practices for reporting health care outcomes to improve quality of care: A scoping review
Authors: Ali M , Visser E , West R , Noord D V , Woude C J V D , Deen W V
Published: January 2024

Background

Value-based health care (VBHC) aims to improve care quality while minimizing costs. An important mechanism of VBHC involves monitoring and reporting health care outcomes to health care providers (HCPs) through data communication (DC) or data feedback. For complex diseases like Inflammatory Bowel Disease (IBD), unwarranted variation in care practices is ubiquitous. Health care data can be used to improve care by showing insights about achieved outcomes and practice variation to HCPs. While some tentative best practices for DC exist, a comprehensive overview is needed to gain a better understanding of how to effectively report health care outcomes to HCPs. This scoping review addresses this gap by examining the use and effectiveness of DC practices not only within the specific realm of IBD but also drawing insights from other clinical fields.

Methods

Studies that implemented and evaluated DC to engage HCPs with data and improve outcomes with qualitative or quantitative designs were sought. Medline, CINAHL, Scopus, Web of Science, Embase, the Cochrane Register of Controlled Trials and PsycINFO were searched for publications in English between 2010 - April 2023. Two researchers reviewed titles, abstracts and extracted data from eligible full texts.

Results

We screened 5,857 studies and included 239: 51 randomized controlled trials, 28 quasi-experimental, 121 pre-post intervention, and 39 qualitative studies. In 35% of those, feedback was implemented in acute care, 30% in primary care, 25% in tertiary care and 10% in other settings. Most interventions (76%) combined DC with co-interventions targeting HCPs’ intrinsic (providing education, post-feedback discussions) and/or extrinsic motivation (incentives, social influence). Additionally, 80 (33%) studies included nudges as part of co-interventions: action toolbox (n=38), reminders (n=28), posters to visualize compliance (n=12) and commitment messages (n=2). Best practices used in DC design included ‘benchmarking with peers’ (n=131), ‘timely feedback’ (n=141), and ‘active delivery of feedback’ (n=147). Most pre-post studies showed positive outcomes (96%), while only 63% of the studies with controlled designs showed positive improvements in outcomes.

Conclusion

The findings of our study highlight the use of DC (co-)interventions in various clinical fields. Additionally, we identified only few studies with controlled designs. In the future, studies with controlled designs testing the effectiveness of DC strategies and additive effects of different co-interventions are warranted to facilitate targeted improvements, particularly in the care of IBD patients, where care practices vary widely.
P561 Reasons for low use of topical 5-ASA formulations in patients treated for ulcerative colitis: comparison of doctors and patients perspectives
Authors: Pittet V , Rogler G , Seibold F
Published: January 2024

Background

Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. In patients with proctitis or left sided colitis, topical application of 5-ASA as suppository, enema or foam preparation has been shown more effective as compared to systemic treatment. In a study conducted 10 years ago, we observed an underuse of topical therapy in patients with UC.

Objectives

to assess the current use of topical 5-ASA for UC and compare it with previous findings. To evaluate perspectives on use of topical therapies, among physician and patients.

Methods

The study had two parts. We first conducted a retrospective cohort data analysis, among adult UC patients included in the SIBDCS. We included patients enrolled since 2012 (not included in our previous study), and to compare the results of the use of 5-ASA therapies from 2021-2021. We then conducted two parallel surveys: with patient and with gastroenterologists. The survey was independent from the cohort data analysis. We assessed potential reasons for low use of topical therapies.

Results

721 patients were included in the retrospective study (329 (45.6%) females, age at diagnostic (median, IQR): 31 (23-42), disease duration: 6 (2-15)). Disease extension at last FU was 18.0% proctitis, 26.3% proctosigmoiditis; clinical activity was low to moderate in 18.6%, and high in 1.8% of patients. 16.4% of patients with proctitis received topical 5-ASA only (5-ASA top+oral (5ASA): 42.2%), 5.9% with proctosigmoiditis (16.6% 5ASA), 0% in left-sided colitis (9.3% 5ASA) (figure 1). Exclusive 5-ASA topical use was lower than observed 10 years ago (23.3%) in proctitis. The survey was completed by 142 patients: 89 females (63%), mean (SD) age 46 (13) and disease duration 15 (10), 15% had proctitis/proctosigmoiditis and 29% left-sided colitis. 63 gastroenterologists participated in the survey; 25% were females, 36.5% had a professional experience up to 10 years, 55% were in single/group practice. 76% of patients reported having ever been prescribed suppositories (S), 74% foam (F), 61% enema (E). Patients-reported top reasons for stopping topical therapy prematurely (1/3 of cases) were unpleasantness (51.3% F/E, 13.9% S), ineffectiveness (41.1% F/E, 60.5% S), and preference for tablets (51.3% F/E, 37.8% S). Physicians’ perspectives on compliance difficulties were unpleasantness (83.7% F/E, 56.3% S), and preference for tablets (76.4% F/E, 63.7% S). 85% of patients were well informed on rectal therapies, 76% of doctors would be open for training/update on rectal therapies.

Conclusion

The use of rectal therapies in UC patients that should benefit from is still low. Reasons for non-compliance were discordant between doctors and patients.
P567 Impact of recent thiopurine use on ozanimod safety in patients with ulcerative colitis: a post hoc analysis of the phase 3 True North study
Authors: Battat R , Panaccione R , Hart A , Hisamatsu T , Ahmad H A , Osterman M T , Wu H , Jain A , Rosen M , Siegmund B
Published: January 2024

Background

Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P1 and S1P5, is approved for the treatment of moderately to severely active ulcerative colitis (UC) in adults based on results from the phase 3 True North study (NCT02435992). Reductions in absolute lymphocyte count (ALC) are expected with ozanimod but not associated with treatment-emergent adverse events (TEAEs). This post hoc analysis explored the effect of recent use of thiopurines on ALC and safety outcomes in patients treated with ozanimod.

Methods

True North was a phase 3 trial of ozanimod induction and maintenance therapy in moderately to severely active UC. Patients in Cohort 1 were randomised to once-daily double-blind treatment with ozanimod 0.92 mg or placebo; patients in Cohort 2 received open-label ozanimod for a 10-week induction period. Patients on concomitant thiopurines were required to stop therapy at study start without a washout period. In this post hoc analysis, patients were stratified by recent prior thiopurine use (within 90 days of ozanimod initiation). ALC was assessed at baseline; ALC, TEAEs, and infectious outcomes were assessed during the induction period at Weeks 5 and 10.

Results

Of the 1012 patients in True North, 796 were treated with ozanimod and analysed (n=57 with recent thiopurine exposure; n=739 without recent thiopurine exposure). At baseline, mean ALC (×109/L [SD]) was slightly lower in patients with than without recent thiopurine use (Table). Both groups had similar baseline incidence of ALC <200 cells/µL (0%) and <500 cells/µL (range 0.0–0.3%). While ALC <200 cells/µL and <500 cells/µL were more prevalent among patients with than without recent thiopurine use (Figure), the reductions from baseline to Week 10 in ALC were similar in both groups (Table). Rates of infection were also similar in patients with recent thiopurine use (14.7% in Cohort 1 and 13.0% in Cohort 2) and without recent thiopurine use (10.4% and 12.5%, respectively). The most frequent infection was nasopharyngitis in both groups: 8.8% in Cohort 1 and 0% in Cohort 2 in patients with recent thiopurine use; 3.0% and 2.9%, respectively, in patients without recent thiopurine use. There were no serious adverse events (AEs) related to ozanimod treatment, and treatment discontinuations were similar in patients with and without recent thiopurine exposure.

Conclusion

Lower ALC was observed in patients starting ozanimod within 90 days of thiopurine use but was not associated with an increased incidence of infection or serious AEs. The findings suggest switching from thiopurines to ozanimod without a washout period may be safe and tolerable.
P580 Iron deficiency anaemia and quality of life in Inflammatory Bowel Disease: Prospective cohort study of ferric derisomaltose on quality of life and work productivity in patients with IBD
Authors: Goodhand J R , Parkinson M , Bewshea C , Ahmad T , Kennedy N A
Published: January 2024

Background

Iron-deficiency anaemia is a frequent complication of inflammatory bowel disease (IBD), affecting approximately 10% of patients at any one time. Quality of life scores in patients with IBD and anaemia are similar to those reported in malignancy. ECCO guidelines recommend assessment and treatment of iron deficiency anaemia, with a goal of normalising haemoglobin and iron stores.

Methods

We conducted a prospective observational cohort study of patients with IBD being treated for iron deficiency anaemia with ferric derisomaltose. Patients were included who were anaemic as per World Health Organisation criteria with a ferritin of <30 µg/L and/or a transferrin saturation of <18%. Variables collected included haematological parameters, the 12-item Short Form survey (SF-12) as a generic health-related quality of life measure, the Work Productivity and Activity Impairment (WPAI) questionnaire and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) as a disease-specific quality of life measure. Patients were assessed at baseline, 12 weeks and 52 weeks. We present here the outcomes at week 12. Comparative statistics have been conducted using Wilcoxon signed rank tests and Pearson’s correlation coefficient.

Results

We recruited 124 patients given between 700 and 1900 mg of ferric derisomaltose, each as a single infusion. Of these, 60% (74/124) were female and the median age was 43 years (IQR 31 – 58). Just under half (46%) of participants had Crohn’s disease, the remainder had ulcerative colitis (49%) or IBD unclassified (5%). Median (IQR) baseline haemoglobin was 114 (109 – 123) g/L in men and 110 (104 – 116) g/L in women.

By week 12, haemoglobin, ferritin, SIBDQ, the WPAI, and both the mental and physical component scores of the SF-12 had improved significantly (all p values <0.0001; see Figure 1). Change in the physical score of SF-12 correlated positively with change in haemoglobin (r = 0.38, p<0.0001), while the change in WPAI correlated negatively with change in haemoglobin (r = -0.30, p=0.013).

Conclusion

Treatment with intravenous ferric derisomaltose in patients with iron deficiency anaemia and IBD was associated with significant improvements in haematological, work productivity, and quality of life parameters.
P582 Combination of granulocyte–monocyte apheresis and ustekinumab: multicentre and retrospective study
Authors: Rodríguez-Lago I , Herrera-deGuise C , Boscá-Watts M , Rodríguez C , Leo E , Calvo M , Cañete F , Chacón S , Cuarán C , Elorza A , Guerra E , Iglesias E , Sánchez D , Barreiro-de Acosta M , Ginard D , Cabriada J L
Published: January 2024

Background

Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports have also described its combination with biologics, mainly with anti-TNF.

Methods

The aim of our study was to evaluate the clinical efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. A retrospective, multicentric study was performed in 12 IBD Units, including all patients with refractory UC who received combined GMA plus UST. The number of GMA sessions, its frequency, filtered blood volume and time of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing the GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding UST intensification, need for new immunomodulators/biologics and surgery were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results

Nineteen patients were included (15 UC, 2 Crohn’s disease, 2 unclassified IBD; median age 48 years (IQR, 36-63); 68% male). At baseline, 78% were receiving steroids and 23% immunomodulators. Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab. Baseline Mayo score was 6.5 (IQR, 5-7), with a median CRP of 9 mg/L (IQR, 4.8-20.8) and faecal calprotectin 1,612 mg/kg (IQR, 873-4,152). GMA was started mostly after PNR in 83%, the median number of GMA sessions was 16 (IQR, 11-27) and 50% of patients started maintenance GMA. Partial Mayo score significantly decreased 6 months after the last GMA session (p=0.019). During follow-up, 27% started a new biologic therapy and 13% required surgery. 64% of patients under steroids at baseline were able to stop them. Adverse events were reported in 5% of patients.

Conclusion

GMA can safely recapture the response to UST in refractory patients after PNR or LOR to this drug.
P585 Effectiveness of Switching to Subcutaneous Infliximab in Ulcerative Colitis Patients Experiencing Intravenous Infliximab Failure
Authors: Bae J H , Park J B , Baek J E , Hong S W , Park S H , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Hwang S W
Published: January 2024

Background

Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment.

Methods

This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC.

Results

Twenty-three patients met the inclusion criteria: 15 in group A and 8 in group B. The serum infliximab levels significantly increased after SC switching in both groups. Electively switched group also exhibited increased infliximab levels after SC switching. Group A showed improved partial Mayo score with a significant decrease in faecal calprotectin (FC) and C-reactive protein after switching. In group B, the FC level significantly decreased without clinical relapse after switching. A high proportion of patients (≥ 80%) in both groups achieved clinical and/or biochemical response at last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction.

Conclusion

In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of its efficacy and safety.
P595 Assessment of mucosal healing after exclusive elemental diet using small bowel capsule endoscopy in paediatric Crohn’s disease
Authors: Kim Y E , Choi H J , Jang J Y , Lee S H , Kim D Y , Oh S H , Kim K M
Published: January 2024

Background

Exclusive elemental nutrition (EEN) is an effective treatment for induction of remission and is recommended as first-line induction therapy in children with active luminal Crohn’s disease (CD). Evaluating treatment response is important because endoscopic or mucosal healing is associated with long-term outcomes, but it is difficult to perform repeated colonoscopies in children. Small bowel capsule endoscopy (SBCE) is used to diagnose small bowel lesions and is more convenient than colonoscopy. This study aimed to evaluate the improvement of small bowel mucosal lesions using SBCE in paediatric CD patients treated with EEN as induction therapy.

Methods

We retrospectively reviewed data from patients under 18 years of age who were newly diagnosed with CD and commenced EEN as induction therapy between May 2018 and April 2023. Among these patients, we included those who completed EEN for more than 6 weeks and underwent SBCE at both the time of diagnosis and within 2 weeks of completion of EEN. We analysed the proportion (%) of patients who achieved mucosal healing (defined as the Lewis score < 135) and patients exhibiting improvement in ulcers on the follow-up SBCE after EEN. We also compared the Lewis score, laboratory tests, and BMI z-score before and after EEN using the paired t-test.

Results

A total of 71 patients (57 males, 14 females) were included with a mean age of 13.3 ± 2.27 years (range 7-17 years). After 6 to 8 weeks of EEN, 64 patients (90.1%) showed improvement in ulcers on follow-up SBCE, including 35 patients (49.3%) with complete disappearance of ulcers and 29 patients (40.8%) with partial disappearance of ulcers. Seven patients (9.9%) showed no improvement. The Lewis score was significantly decreased (p < 0.001). In addition, mucosal healing, defined as the Lewis score < 135, was achieved in 28 patients (38%). When comparing laboratory tests before and after EEN, haemoglobin and albumin increased (p < 0.001), and ESR, CRP, and fecal calprotectin decreased significantly (p < 0.001). However, BMI z-score was not improved after EEN (p = 0.46).

Conclusion

Most patients showed improvement in ulceration on SBCE after EEN. Additionally, improvements in blood test and fecal calprotectin levels were noted following EEN. It is suggested that SBCE is a useful tool to evaluate mucosal healing after EEN in paediatric Crohn's disease.
P615 Clinical efficacy of accelerated 4-weekly vs. Conventional 8-weekly ustekinumab dosing in Inflammatory Bowel Disease: A single centre experience
Authors: Lloyd A , Quarry S , Sugrue K , Gleeson S , O'Sullivan G , O'Sullivan C , Forde G , Doyle M , Moran C , Mcdonald C , Sheehan D , Buckley M , Iacucci M , McCarthy J
Published: January 2024

Background

8-weekly dosing regimen of ustekinumab in the treatment of moderate-to-severe Inflammatory Bowel Disease (IBD) is the current standard of care. Accelerated 4-weekly dosing has been suggested to be efficacious, however not licensed, in ‘non-responders’. The aim of this study is to determine how 4-weekly accelerated dosing regimen in ustekinumab drug levels correlate with response to treatment in patients with IBD.

Methods

Patients for inclusion were identified retrospectively utilising online prescription records at Mercy University Hospital, Cork. Inclusion criteria consisted of IBD patients commenced on ustekinumab with a treatment duration of at least 6 months. Participants were separated into 4-weekly and 8-weekly treatment groups. Faecal calprotectin (FCP) levels/ustekinumab drug levels were recorded from the 12-week check in post initiation and at the 2nd assessment. Symptoms were scored at these visits and further quantified using the Harvey Bradshaw index for Crohn’s Disease and the partial mayo score for Ulcerative Colitis.

Results

101 patients at the Mercy University Hospital Cork were identified utilising a database of prescriptions and physical charts (4-weekly: 27; 8-weekly: 74). A statistically significant decrease in FCP levels at 2nd assessment was noted in patients with 4-weekly dosing (p=0.028). There was no statistically significant relationship between dosing interval and symptoms (p=0.735). Individual patient factors including age, gender, type of IBD, and concurrent IBD medications did not have a statistically significant effect on faecal calprotectin levels or symptoms.

Conclusion

The greater percentage decrease in faecal calprotectin provides objective evidence supporting the escalated dosing interval at the Mercy University Hospital IBD centre. However, further study is necessary to justify increasing the dosing interval for all patients treated with ustekinumab for IBD.
P619 Sleep disruption is associated with reduced quality of life in inflammatory bowel disease through its interaction with pain
Authors: Barnes A , Mountifield R
Published: January 2024

Background

Quality of life is reduced in people with inflammatory bowel disease. Poor sleep is prevalent in people with inflammatory bowel disease. This study aimed to investigate the influence of sleep on quality of life in people with inflammatory bowel disease.

Methods

An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn’s Colitis Australia. The questionnaire included the EQ-5D-5L measures of health-related quality of including EQ-5D utility score, EQVAS – visual analogue scale from 0-100 of quality of life and domains mobility, selfcare, activities, pain and depression and anxiety. Measures of sleep included the insomnia severity index (ISI), and the Pittsburgh sleep quality index (PSQI). IBD activity was assessed using validated patient reported scores. Demographic data and mental health scores were also obtained.

Results

Quality of life was lower in people IBD than the general South Australian population (utility score mean (SD) 0.79 (0.15) v 0.91(0.14)). Poor sleep and clinically significant insomnia were associated with lower quality of life (utility score 0.77 (0.15) and 0.71 (0.16) respectively, cohort 0.79 (0.15), p<0.0001). Sleep quality scores moderately correlated with EQ-5D domains pain (Ro=0.35), usual activities (Ro=0.32), and depression-anxiety (Ro=0.37) but not domains self-care or mobility. After adjusting for demographic variables, IBD anxiety, depression, and anxiety the pain domain continued to be influenced by sleep quality, sleep disturbance and sleep duration, and the usual activities domain continued to be influenced by daytime dysfunction (see table 1).

Clinically significant insomnia was associated with a reduction of 13.6 (10.42-16.91) (univariate regression) in quality of life measured by EQVAS. Following introduction of demographic and IBD activity the reduction in EQVAS for clinically significant insomnia remained significant (10.11 (6.96-13.27)). Health related quality of life scores (EQVAS) were significantly worse in those with clinically significant insomnia and active IBD than with active IBD alone (see Figure 1).

Conclusion

Health related quality of life in IBD is influenced by aspects of sleep quality irrespective of IBD activity and mental health conditions. The presence of insomnia is associated with a significant decline health related quality of life. Consideration should be given to sleep targeting interventional studies in an IBD population.
P623 Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn’s disease
Authors: Schreiber S W , Danese S , Colombel J F , Hisamatsu T , Irving P M , Park H , Kim D H , Lee Y N , Hanauer S B
Published: January 2024

Background

Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD).1 Given the rapidly expanding therapeutic armamentarium for CD and lack of direct comparative evidence,2 an updated network meta-analysis (NMA) of data from Phase 3 randomised controlled trials (RCTs) was performed to evaluate the comparative efficacy of advanced CD therapies licensed in Europe or the US.

Methods

Eligible studies, identified by systematic literature review (PROSPERO no.: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate-to-severe CD who responded to induction therapy. Head-to-head studies (including with treat-through designs) comparing licensed advanced therapies were also eligible. Studies were placebo- (PBO) or active-controlled and included 52–64 weeks of follow-up. Patients had not received prior tumour necrosis factor inhibitors, other biologics or Janus kinase inhibitors, thus each drug was received as first-line advanced therapy. Clinical remission and endoscopic response rates achieved with maintenance treatment were synthesised and analysed in a frequentist NMA random-effects model.

Results

There were 9 eligible RCTs (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY, U-ENDURE). Among 14 compared treatment arms, SC infliximab 120 mg every 2 weeks (Q2W) showed the highest risk difference (RD) versus PBO for achieving clinical remission during the maintenance phase (0.38 [95% confidence interval (CI): 0.23, 0.53]), followed by SC adalimumab 40 mg QW (0.32 [0.17, 0.48]) and oral upadacitinib 30 mg once daily (0.30 [0.08, 0.53]) (Figure A). Endoscopic response data were available from LIBERTY-CD, FORTIFY and U-ENDURE: among 5 treatment arms, SC infliximab 120 mg Q2W showed the highest RD (95% CI) versus PBO for achieving endoscopic response (0.39 [0.29, 0.49]), followed by SC risankizumab 180 mg Q8W (0.37 [0.17, 0.56]) and SC risankizumab 360 mg Q8W (0.27 [0.06, 0.48]) (Figure B).

Conclusion

In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favourable efficacy profile in terms of achieving clinical remission and endoscopic response, when administered as a first-line advanced therapy for maintenance treatment of patients with moderate-to-severe CD.

1Remsima summary of product characteristics (https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf). Accessed 1 November 2023.

2Barberio B et al. Gut 2023;72:264–74.