bluuebunny/crossref_metadata_2025 huggingface dataset:
P937 A Retropective Analysis of Micronutrient Status in Inflammatory Bowel Disease
Authors: Ruan G , Zhang Y , Yu S , Yang H
Published: January 2024

Background

Researchers are increasingly focusing on the influence of micronutrient levels on the initiation and prognosis of Inflammatory Bowel Disease (IBD). Earlier investigations have highlighted a connection between deficiencies in zinc and selenium and an elevated risk of IBD development and unfavorable outcomes. This study seeks to investigate the existing micronutrient status among Chinese patients with IBD and assess whether deficiencies in trace elements are associated with disease activity, extent of intestinal involvement, and the use of biological treatments.

Methods

This cross-sectional study included patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) who underwent plasma micronutrient testing during outpatient or inpatient visits to the Department of Gastroenterology at Peking Union Medical College Hospital from May 2022 to October 2023. Baseline data, the history of biological agent use, and laboratory inflammation parameters such as hsCRP, ESR, and Alb were extracted from the Electronic Medical Record System. Colonoscopy images were examined to assess the extent of intestinal involvement and endoscopic activity. The distribution of micronutrient deficiency among patients with varying disease statuses was explored using the Pearson chi-square test and Mann-Whitney U-test.

Results

Among the 168 participants with IBD in this study (77 with CD, 91 with UC), a frequent occurrence of deficiencies in copper, selenium, strontium, and zinc was noted. In CD patients in the endoscopic active phase, there was a higher incidence of selenium and zinc deficiencies compared to the remission phase (selenium 0% vs. 11.3%, p=0.17; zinc 4.2% vs. 24.5%, p=0.052). In UC patients during the endoscopic active phase, strontium (14.5% vs. 0%, p=0.053) and zinc (17.7% vs. 3.4%, p=0.094) deficiencies were more likely to occur. CD patients with zinc deficiency and UC patients lacking zinc or selenium showed higher levels of blood hsCRP and ESR but lower levels of serum albumin. UC patients with E3 type involvement were more prone to selenium and strontium deficiencies compared to those with only left colon involvement (selenium 18.5% vs. 2.7%, p=0.025; strontium 14.8% vs. 5.0%, p=0.078).

Conclusion

This study identified a notable prevalence of micronutrient deficiencies in individuals with IBD, particularly during active phases. Specifically, patients with CD in an inflammatory state are inclined to exhibit zinc deficiency. In the case of UC, the absence of selenium, strontium, and zinc signals a higher level of inflammation. UC patients with involvement of the entire colon are more prone to experiencing deficiencies in selenium and strontium. These findings warrant validation through multi-center study and mechanism invetigation.
P943 Real world Effectiveness and safety of tofacitinib in patients with Ulcerative Colitis: 6 months follow-up of the French TOFAST study
Authors: Fumery M , Bouhnik Y , Faure P , Bouzidi A , Brault Y , Peyrin-Boroulet L , Laharie D
Published: January 2024

Background

TOFAST is an observational, prospective, multicenter cohort study aiming to describe the real-life clinical benefit of tofacitinib in moderate-to-severe Ulcerative Colitis (UC).

Methods

We report the results of the interim analysis after 6 months of follow-up, describing patient's characteristics, effectiveness, including change in daily PRO2 scores [RB and stool frequency (SF)] during the first 14 days and the median time to relief, and safety.

Clinical response was defined as a decrease in partial Mayo score (PMS) (≥ 3 points and ≥30%) from inclusion with a concomitant decrease in rectal bleeding (RB) subscore ≥ 1 point (absolute subscore of 0 or 1). Clinical remission was defined as PMS ≤2 with no subscore >1.

Symptomatic relief was reported by patients as the time in days from initiation of tofacitinib to improvement of their symptoms. Safety has been been reported as the % of Adverse Events (AE), serious AE and AE of special interest.

Results

88 patients were included in the safety analysis (one patient was excluded from the effectiveness analysis as he did not meet the eligibility criteria) with a median exposure duration of 11.7 [Q1; Q3: 6.0; 22.1] months. Of these patients, 67 completed a 6-month follow-up visit by 15/07/2023 and were included in the effectiveness analysis.

At inclusion 59.8% of patients were male with a mean (± SD) age of 37.5 ±13.2 years, a median disease duration of 5.9 years [Q1; Q3: 2.7; 13.1]. 46.5% of patients had pancolitis. The mean total Mayo Score was 8.1 ±2.4.

94.3% of patients had previously received at least one anti-TNF agent, 67.8% vedolizumab and 35.6% ustekinumab.

Tofacitinib was initiated at 10 mg b.i.d, in combination with corticosteroids for 35.6% of patients.

At 6 months, 53 (77.9%) patients were still treated with tofacitinib, 58.5% at 10 mg BID dose. Corticosteroids were ongoing in 22.9% of patients.

Clinical response and remission were observed in 64.2% and 61.2% of patients, respectively.

For the 68 (78.2%), patients who reported improvement the median time to relief was 7 days [Q1; Q3: 3.5 ;14.5].

PRO2 scores normalization during the first 14 days is shown in the figure.

84.1% of patients reported at least one adverse event (AE) and 21.6% reported at least one serious AE. Seventeen (19.3%) infections and 3 (3.4%) cases of herpes zoster were observed as well as one non-invasive low-grade urothelial carcinoma. No major cardiovascular or venous thromboembolic event, nor malignancy or death were observed (Table).

Conclusion

In this real-life cohort of patients with refractory UC, tofacitinib induced a clinical response and remission in over 60% of patients, with symptoms relief observed as early as the first two weeks. AEs were consistent with the known tofacitinib safety profile.
P956 Pregnancy outcomes after maternal or paternal exposure in the tofacitinib ulcerative colitis clinical programme
Authors: Mahadevan U , Chaparro M , Segovia Medina M , Kulisek N , Guo X , Wu J , Vranic I , Diehl A , Dubinsky M C
Published: January 2024

Background

Pregnant women with ulcerative colitis (UC) have a higher risk of adverse pregnancy outcomes vs age-matched controls.1 Tofacitinib is an oral Janus kinase inhibitor for the treatment of UC. There are no well-controlled studies on tofacitinib use in pregnant women. It was shown to be teratogenic in rats and rabbits at approximately 73 and 6.3 times, respectively, the maximum recommended human dose of 10 mg twice daily. Tofacitinib affects female fertility, parturition and peri/postnatal development in rats and was secreted into the milk of lactating rats; it had no effects on male fertility or sperm motility/concentration.

Methods

We report pregnancy outcomes in the tofacitinib UC clinical programme: 4 randomised, placebo-controlled Phase (P)2/3 studies (NCT00787202/NCT01465763/NCT01458951/NCT01458574),2,3 an open-label, long-term extension study (NCT01470612)4 and a randomised P3b/4 study (NCT03281304) were analysed.5 Study protocols excluded pregnant women, required females of childbearing potential to use effective contraception and regularly tested for urine β-hCG. Study drug was discontinued in female patients who became pregnant. Pregnancy outcomes after maternal or paternal tofacitinib exposure were identified from Pfizer’s internal safety database up to March 2023 and categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up.

Results

There were 40 pregnancies with exposure to tofacitinib: 16 cases of maternal exposure (median age 29.5 [range: 24−41] years), all during the 1st trimester (10 [62.5%] healthy newborns, 2 [12.5%] medical terminations, 2 [12.5%] spontaneous abortions, 2 [12.5%] lost to followup); and 24 cases of paternal exposure (18 [75.0%] healthy newborns, 2 [8.3%] spontaneous abortions, 4 [16.7%] lost to follow-up). There were no cases of foetal death or congenital malformation.

Conclusion

Most known outcomes for maternal and paternal tofacitinib exposure were healthy newborns, similar to previous analyses in other tofacitinib clinical study populations and the general UC population.6,7 Limitations included the low number of reported pregnancies and available follow-up. Tofacitinib should not be used during pregnancy unless necessary.

References:

1. Cornish et al. Gut 2007;56:830−7

2. Sandborn et al. N Engl J Med 2012;367:616−24

3. Sandborn et al. N Engl J Med 2017;376:1723−36

4. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–78

5. Vermeire et al. J Crohns Colitis 2021;15:1130–41

6. Mahadevan et al. Inflamm Bowel Dis 2018;24:2494–500

7. Selinger et al. Frontline Gastroenterol 2021;12:214–24

Study sponsored by Pfizer. Medical writing support provided by S Leneghan, CMC Connect; funded by Pfizer
P961 Achieving treatment targets in Ulcerative Colitis and reasons for failing to do so: Real world experience in a multi-ethnic asian population
Authors: Tan Y B , Ang T L , Ong J P L , Wang L M , Fock K M , Li J W , Kwek A B E , Tan C K
Published: January 2024

Background

In ulcerative colitis (UC), endoscopic remission (ER) is recommended as a long-term treatment target as it predicts favourable outcomes. We performed this study to identify the proportion of patients who achieved treatment targets as set out in the Selecting Therapeutic Targets in Inflammatory Bowel disease (STRIDE II) consensus. Secondly, we aim to identify the reasons for failing to meet treatment targets.

Methods

This is a retrospective analysis of all UC patients who were seen at Changi General Hospital, Singapore from 1 January 2000 to 31 December 2022. Patients were identified from an existing IBD registry. All patients with confirmed diagnosis of UC were included in the analysis. Those with follow up period less than 1 year or no repeat endoscopy were excluded. We collected baseline demographics, disease characteristics, medications, clinical activity scoring, biomarkers, endoscopic findings and histologic reports.

We defined biomarker normalization, ER and histological remission as outlined in the STRIDE II consensus. Next, we compared factors associated with ER. We also assessed possible reasons for failure to achieve ER. SPSS version 26 was used for data analysis.

Results

After excluding 23 patients, a total of 139 patients were analysed with a mean follow-up time of 13.5 years. Figure 1 demonstrates the baseline demographics, disease characteristics, treatment modalities, remission targets and reasons for failure of ER. 96.4% of patients achieved clinical remission with a median time of 8 weeks (IQR: 4). Faecal calprotectin (FC) was not routinely measured at baseline but its use increase significantly after the STRIDE consensus. 53.4% of patients achieved biomarker normalization. ER was achieved in 58.3%. Of the 81 patients who achieved endoscopic remission, 49.4% also achieved histological remission. For patients who had repeat endoscopy within 1 year of diagnosis (35.3%, 49/139), 8.16% had achieved ER with a median time of 34 weeks (IQR: 4).

Lower baseline C-reactive protein (CRP), follow-up FC, partial mayo score (PMS) at follow-up and biomarker normalization were associated with ER (Table 1). Interestingly more extensive disease was also associated with ER.

The main reason for failing to achieve ER was non-compliance to treatment in 58% of the patients. A smaller proportion of patients refused treatment escalation due to absence of symptoms, cost concerns or repeating endoscopy after treatment escalation.

Conclusion

More than half of all patients with UC achieve long term target of ER in our population and baseline and follow-up biomarkers and PMS are associated with ER. Patients’ compliance is the key reason for failing to achieve ER. Thus, patient education should be reinforced to improve treatment outcomes.
P976 Treatment with exclusive enteral nutrition (EEN) impacts the peripheral blood mononuclear cell profile of paediatric patients with Crohn’s disease
Authors: White B , Curle J , Gervais L , Wands D , Nichols B , Hansen R , Russell R , Gerasmidis K , Milling S
Published: January 2024

Background

Background: Despite its established clinical efficacy, the immunological effects of exclusive enteral nutrition (EEN) in Crohn’s disease (CD) are yet to be elucidated. This study investigated the impact of EEN on circulating peripheral blood mononuclear cells (PBMCs) and how any effects observed varied according to clinical response to treatment.

Methods

Methods: Children with active CD received EEN for eight weeks as their sole induction treatment. Blood and faecal samples were collected prior to EEN and upon EEN completion. PBMCs were isolated, stained and analysed using flow cytometry. Differences in PBMCs types were compared during EEN. Faecal calprotectin was measured with ELISA. Absence of gluten immunogenic peptide (GIP) in faeces was used as a proxy marker of EEN compliance.

Results

Results: Nine participants were recruited (Table 1), three of whom initiated azathioprine during their course of EEN. Following treatment with EEN a decrease in the relative number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA (TEMRA) was observed with a corresponding increase in the frequency of circulating central and effector memory CD8+ T cells (Fig. 1). When we excluded participants that commenced thiopurines during their course of EEN a decrease in the relative number of circulating TEMRA CD8+ T cells persisted and a decrease in naïve CD8+ T cells in the blood was also observed. Participants who demonstrated a decrease in faecal calprotectin 50% following treatment with EEN (n= 5) also demonstrated an increase in the frequency of circulating central memory CD8+ T cells. When focussing on participants (n=7) within our cohort who demonstrated a high-level of compliance (undetected GIP in faeces) during EEN, we again observed a decrease in number of TEMRA CD8+ T cells in blood alongside an increase in the frequency of circulating central and effector memory CD8+ T cells.

Conclusion

Conclusion: We observed significant changes in CD8+ T cell populations in the peripheral blood of children following treatment with EEN. These changes were observed irrespective of background immunomodulator use and persisted in participants which achieved >50% decrease in FC or demonstrated compliance to EEN. Our observed changes in CD8+ T cell populations, particularly the consistent increases in circulating effector and memory CD8+ T cells, are likely a consequence of the actions of EEN in decreasing the diversity and composition of the gut bacteria, therefore reducing the recruitment of effector/memory cells from the blood into the intestine.
P983 Treatment of patients with moderate-to-severe Crohn’s disease with subcutaneous infliximab leads to an endoscopic response across all segments of the colon and terminal ileum: A post hoc analysis of the LIBERTY-CD study
Authors: Sands B E , Dubinsky M C , D’Haens G , Schreiber S , Danese S , Hanauer S B , Kim D H , Lee Y N , Colombel J F
Published: January 2024

Background

Mucosal healing (MH) has been associated with positive long-term clinical and surgical outcomes in patients (pts) with Crohn’s disease (CD).1 Patterns of MH vary by therapeutic agent, with limited efficacy in the terminal ileum.2–4 This post hoc analysis aimed to investigate the pattern of endoscopic MH across intestinal segments in pts who received subcutaneous (SC) infliximab (IFX) maintenance treatment in the Phase 3 LIBERTY-CD study.

Methods

LIBERTY-CD demonstrated superior efficacy of SC CT-P13 120 mg every 2 weeks (Q2W) vs placebo (PBO) after IV IFX induction for clinical remission and endoscopic response at Week (W) 54.5 This post hoc analysis evaluated centrally read and batch analysed Simple Endoscopic Score for Crohn's Disease (SES-CD) values obtained at screening, W22 and W54 for 5 ileocolonic segments (rectum; left, transverse and right colon; and terminal ileum). Pts with missing data or who underwent dose escalation to SC IFX 240 mg Q2W upon loss of response from W22 were imputed as non-responders. Endoscopic complete MH (CMH; defined as SES-CD=0) or partial MH (PMH; defined as ≥50% decrease in the SES-CD from screening) were evaluated for segments that had endoscopic abnormalities at screening (segmental SES-CD ≥1 at screening). Results were analysed descriptively.

Results

Among all randomised pts (N=343; SC CT-P13: n=231, PBO: n=112), the most frequently affected segment at screening was the left colon (187/343; 54.5%), followed by the right colon (185/343; 53.9%), rectum (163/343; 47.5%), terminal ileum (156/343; 45.5%) and transverse colon (134/343; 39.1%). In an analysis of all affected segments, endoscopic CMH rates were higher with SC CT-P13 vs PBO (Figure 1A). Endoscopic CMH rates in the terminal ileum at W54 were 46.7% and 19.6% in the SC CT-P13 and PBO arm, respectively (p=0.0014). PMH rates were also significantly higher in the SC CT-P13 arm across all segments at W22 and W54 (Figure 1B), with rates in the terminal ileum of 64.8% and 33.3% in the SC CT-P13 and PBO arm, respectively (p=0.0003).

Conclusion

SC IFX 120 mg Q2W led to high and consistent endoscopic MH rates across all segments, including the terminal ileum. Early observation of endoscopic MH (at W22) underscores the potency of SC IFX treatment. Further studies are warranted to investigate the association between segmental MH and long-term outcomes.

1Otte ML et al. World J Gastroenterol 2023;29:1157–72.

2Danese S et al. Gastroenterology 2019;157:1007–18.

3Reinisch W et al. J Crohns Colitis 2017;11:425–34.

4Wu Y et al. Therap Adv Gastroenterol 2020;13:1756284820976923.

5Hanauer SB et al. Gastroenterology 2023;164(S6):S220–1.
P985 Efficacy and safety of de-escalation from 50 mg to 25 mg of oral, once-daily, obefazimod for the third and fifth year of open-label maintenance treatment in patients with moderately to severely active ulcerative colitis (UC): An interim analysis
Authors: Dulai P , Sands B E , Danese S , Peyrin-Biroulet L , Dubinsky M , Tilg H , Siegmund B , Sloan S , Ploncard P , Rabbat C , Vermeire S
Published: January 2024

Background

Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a Phase 2a and Phase 2b, double-blind, placebo-controlled induction trials [2] and their subsequent open-label maintenance (OLM) studies [3].

Methods

Patients with UC who received 50 mg of oral, once-daily, obefazimod for approximately four years in the Phase 2a OLM study and approximately two years in the Phase 2b OLM study, provided they met the eligibility criteria (Mayo Endoscopic subscore = 0 or 1), were given the option to transition to a subsequent open-label maintenance study in which they were administered a daily dose of 25 mg of obefazimod for up to 2 years. This interim analysis, conducted with cut-off date of July 31, 2023, reports the findings of a cohort of patients who completed their week 48 visit.

Results

As of the cut-off date, there were 71 eligible patients, of whom 8 (11%) discontinued prior to week 48 and 63 (89%) completed their 48-week visit. An as observed analysis indicated a disease control rate of 84% (defined as a stable or improved Modified Mayo Score) (Table 1).

The levels of fecal calprotectin were <250 and <150 µg/g for 93% (42/45) and 82% (37/45) of patients with available FCP values, respectively.

In total, 39/76 subjects (51.3%) reported at least one treatment emergent adverse event (TEAE). The most frequent TEAEs (≥ 5%) were COVID-19 (7.9%) and ulcerative colitis (6.6%). No new safety findings were identified over these 48 weeks.

Conclusion

One year after dose de-escalation to a daily regimen of 25 mg of obefazimod, favorable outcomes in disease control were observed among patients with UC who demonstrated endoscopic improvement (ES<1) after 2-4 years of 50 mg od. No new safety signals have emerged for a duration of up to five years of treatment with once-daily obefazimod.

References:

1. Vermeire S, et al. J Crohns Colitis. 2023; doi: 10.1093/ecco-jcc/jjad067; 2. . 2021; 3. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022.
P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Alshiwanna B , Mcnamara J , Wilson W , Pipicella J L , Ghaly S , Gearry R , Begun J , Williams A , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Connor S J , Andrews J M
Published: January 2024

Background

Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort.

Methods

We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval <8 weeks and/or dosing >5mg/kg. We examined IBD outcomes prior to and 12 months post DE.

Results

A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml).

Faecal calprotectin (FCP) remission rate (FCP <250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p<0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p<0.001) and radiological investigations (243 vs 343; p<0.001).

Conclusion

Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.
P1012 Dose escalated Ustekinumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Barnett M , Mcnamara J , Wilson W , Pipicella J , Ghaly S , Gearry R , Begun J , Williams A , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Connor S J , Andrews J M
Published: January 2024

Background

Ustekinumab is a human monoclonal antibody targeting interleukin-12 and 23 with established efficacy in inflammatory bowel disease (IBD). Many people receiving ustekinumab do not achieve adequate or sustained response to standard dosing and require dose escalation (DE). We aimed to investigate the frequency and outcomes of escalated dosing regimens in an Australasian cohort.

Methods

Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in routine care across Australia and New Zealand. Data feeds continuously into a de-identified clinical quality registry (CQR). Data were interrogated in November 2023 comparing outcomes and healthcare utilisation prior to and at 12 months post ustekinumab DE. DE was defined as maintenance dosing >90mg subcutaneously Q8 weekly and/or additional induction doses.

Results

A total of 790 people received ustekinumab, with 43.4% on DE therapy. Most of the cohort had Crohn’s disease (86.1%), followed by ulcerative colitis (11.3%) and IBD-unclassified (1.6%). The median age for the total cohort was 40 years (IQR 30-52) with an even gender distribution (50.3% female). The median age at diagnosis was 25 (IQR 18-38) with a median time to DE of 6 months (IQR 1-15). Age, age at diagnosis and disease duration did not significantly differ between DE and standard dose cohorts. Almost all people with IBD on DE ustekinumab continued on therapy beyond 12 months (84.5%).

Rates of faecal calprotectin remission (<250ug/g), endoscopic remission and patient reported outcome (PRO2) remission were higher 12 months post DE (Table 1). Systemic steroid requirements fell significantly 12 months post DE. The number of endoscopies and radiological investigations fell at 12 months post DE, while the rates of hospital admissions did not significantly differ between the DE and standard cohorts. Clinical assessments (per person) reduced from 1.2 pre-DE to 0.9 post DE.

Conclusion

In a large real-world Australasian cohort of people receiving ustekinumab for IBD, close to half required DE. DE led to reduced systemic steroid use and improved endoscopic, PRO2 and FCP remission rates at 12 months. These data can be used to perform health economy analysis to determine the price points at which DE is cost effective, with additional data on quality of life and indirect healthcare costs being important to include for a robust holistic assessment of value in care.
P1023 Variability in Mesalazine Management for Ulcerative Proctitis Include Doses, Route of Administration and Use of Fecal Calprotectin: Insights from Clinical Practice Across Spain Beyond Clinical Guidelines
Authors: Bastida Paz G , Ceballos D , Ricart E , Marín-Jiménez I , Menchén L , Carpio D , Ginard D , Muñoz F , González-Lama Y
Published: January 2024

Background

Despite universal use of mesalazine in ulcerative colitis treatment, many aspects of clinical practice remain unclear or are not even addressed in clinical guidelines, leading to significant variations in mesalazine management among clinicians. We aimed to gather different approaches of mesalazine use in ulcerative proctitis (UP).

Methods

After discussion of a clinical case, a predefined questionnaire was anonymously answered throughout a series of meetings held at 10 different locations in Spain. Results were categorized according to experience levels and inflammatory bowel disease (IBD) focus.

Results

259 IBD treating gastroenterologists were engaged; 84% had <10 years of experience and 25% had a specific focus on IBD.

Most participants (84%) manage UP based on clinical symptoms (i.e. fecal urgency). In case of a clinically moderate-severe UP, 81% would initiate treatment with high dose of combined mesalazine, while 11% proposed only suppositories. 60% of participants would assess response at 4 weeks. If clinical remission achieved, 85% would use fecal calprotectin (FC) to assess deep remission.

Upon initial failure of combined mesalazine treatment at standard dose, 59% attempt optimizing mesalazine doses, while 38% add beclomethasone dipropionate. Younger physicians without specific focus on IBD prefer modifying mesalazine doses (70.5% vs 37.1%), (P=0,006), whereas more experienced physicians with monographic dedication prefer adding beclomethasone dipropionate (60% vs 29.4%), (P=0,006).

For maintenance therapy (oral or topical mesalazine) the most important drivers in therapeutic decision-making were severity of the initial flare (40%) and patient preferences (36%). After a moderate-severe flare of UP, 80% would recommend maintenance therapy with high dose oral mesalazine and 3 suppositories/week.

For monitoring, less experienced physicians and those not working in IBD units more frequently relied only on clinical parameters (26.6% vs. 8.7%, p=0.01), using FC to a lesser extent (73% vs. 88%, p=0.1) compared to more experienced and IBD focused physicians. In the case of elevated FC in asymptomatic patients, 49% would prefer to scope, while 47% increase mesalazine dose directly.

The preferred high dose of mesalazine was 4g (55%) or 4-5g (44%). 73% would not reduce the dose upon achieving remission. Only 75% actively investigate therapeutic adherence.

Conclusion

Management of mesalazine in UP patients is highly heterogeneous, and clinical guidelines do not address all issues arising in clinical practice. Nevertheless, clinicians in our setting often use high oral and rectal mesalazine doses for both induction and maintenance and they commonly monitor patients using FC.
P1026 Clinical decision support tool for vedolizumab could not predict outcome in ulcerative colitis patients – a retrospective real-life single-centre cohort study
Authors: Molinari N , Maček P , Ocepek A
Published: January 2024

Background

Early intervention with biologics can slow the progression of ulcerative colitis (UC), thus improving long-term outcomes. As treatment options in UC expand, the positioning of advanced therapies is becoming more important. The ability to identify patients with UC who are more likely to respond well to a specific drug before initiation of treatment could help physicians navigate within the proposed treatment algorithm. Dulai et al. derived and validated a clinical decision support tool (CDST) for the prediction of response to vedolizumab (VDZ) in UC.

Methods

We performed a retrospective single-centre cohort study based on UR-CARE registry data. Data for 72 UC patients treated with VDZ from July 2016 until April 2023 were analysed. CDST for UC was calculated using four variables: absence of exposure to a tumour necrosis factor (TNF) alpha inhibitor, disease duration of ≥ 2 years, moderate baseline endoscopic activity and baseline albumin concentration. Patients were then stratified into three probability groups: group 0 with low (≤ 26 points), group 1 with intermediate (27 to ≤ 32 points) and group 2 with high (> 32 points) probability of response. To test the association between CDST, clinical remission (CR) (defined as PRO2 £ 1 with rectal bleeding score 0), corticosteroid-free remission (CSFR) and endoscopic activity (defined as no change in endoscopic activity, endoscopic improvement (EI) (change of endoscopic Mayo of ≥1), or endoscopic remission (ER) (endoscopic Mayo ≤ 1)) chi2 test was used. The difference in faecal calprotectin (FC), depending on whether VDZ was continued or not, was tested by the Mann-Whitney U test.

Results

In our cohort, 59.7% of patients were male, the median age was 32.1 years, the median duration of disease until VDZ was 2.6 years, and 63.9% had pancolitis. 34.7% of patients had concomitant corticosteroid treatment at baseline, and 52.8% had been exposed to a TNF-alpha inhibitor. We found no statistically significant association between the CDST group and CR or CSFR at weeks 14 and 52 nor endoscopic activity at follow-up endoscopy. All patients in group 2 responded with lowering of FC 3-6 months after initiating VDZ and continued treatment. Also, patients in CDST group 1 who experienced lowering of FC continued VDZ therapy. In contrast, all patients in CDST group 0 and patients in group 1, who had persistently elevated FC, eventually failed VDZ regardless of optimisation. The difference in FC between those who discontinued VDZ and those who did not was statistically significant (p=0.004).

Conclusion

Our results did not confirm the predictive value of existing CDST for VDZ in UC patients. Novel prediction tools in UC are needed.
P1032 Ileoanal Pouch Salvage Rates with Endoluminal Vacuum Therapy for Early vs. Late Anastomotic Leaks
Authors: Alipouriani A , Lavryk O , Lipman J , Hull T , Steele S , Liska D , Holubar S
Published: January 2024

Background

Anastomotic leakage is a dreaded complication after ileal pouch-anal anastomosis (IPAA) that occurs in 5-10% of cases. Endoluminal vacuum (EndoVac) therapy has emerged as a minimally invasive option that promotes healing by applying negative pressure to the associated abscess cavity through the anastomotic defect but is typically applied only to early IPAA leaks. We hypothesized that EndoVac for early compared with late leaks would be associated with a higher pouch survival rate.

Methods

We retrospectively reviewed the medical records of consecutive patients who developed a pouch anastomotic leak after IPAA and were treated with EndoVac therapy at our institution between 2005-2023. Patients were stratified into early (30 days) and late (>30 days) leaks. Anastomotic healing was defined as complete closure of the leak site, as evidenced by resolution of symptoms, normal endoscopic and radiographic evaluation, and no further drainage from the presacral space or abdominal wall. Pouch failure was defined as a permanent ileostomy or pouch excision. Figures represent frequency (proportion) or median (range). The probability of pouch survival over time was estimated using the Kaplan-Meier method.

Results

A total of 13 pouch patients underwent EndoVac therapy for leaks by six surgeons (median age, 34 years; 62% male; median body mass index 25.8 kg/m2. Diagnoses: ulcerative colitis (n=11), and familial adenomatous polyposis (n=2). The median time to leak diagnosis was 32 (12- 340) days; of these 6 (46%) were early and 7 (54%) were late. All (100%) patients were diverted at the time of EndoVac therapy, 10 (77%) patients were still diverted, and 3 (23%) were rediverted. Patients underwent a median of 5 EndoVac changes (2-22) over a median duration of 34.5 (21-125) days. After EndoVac therapy, complete/near-complete defect healing occurred in 9 (69%), 1 whom required suturing of a small residual defect. Of those with incomplete healing (n=4), 3 (23%) underwent pouch excision and 1 (7.7%) a redo pouch. Comparing early and late leaks, defect healing (66.7% vs 71.4%, p=0.72) and pouch survival (83.3% vs 71.4%, p=0.65) were similar. The overall pouch salvage rate was 77% (10/13).

Conclusion

EndoVac therapy is effective for postoperative pouch leaks and achieves a high rate of pouch salvage in both early and late leaks.

Figure 1. CONSORT-style flowchart of IPAA leaks treated with EndoVac therapy.
P1041 Coconut water modulates dietary potassium and gut microbiome to induce remission in ulcerative colitis: randomized controlled trial
Authors: Kedia S , Virmani S , Bajaj A , Markandey M , Singh N , Madan D , Kaushal K , Sahu P , Vuyyuru S , Kante B , Kumar P , Thomas D , Mundhra S , Singh M , Verma M , Sharma R , Das P , Dash N , Monga N , Awasthi A , Makharia G , Ahuja V
Published: January 2024

Background

High potassium intake is associated with decreased risk of inflammatory bowel disease(IBD), urinary potassium has been correlated with disease activity in ulcerative colitis(UC), and gut microbiome modulation improves outcomes in UC. We evaluated coconut water as potassium rich diet and gut microbiome modulator in patients with mild-moderate UC.

Methods

This single-center double-blind placebo-controlled trial randomized patients with mild-moderate (simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC (ulcerative colitis endoscopic index of severity-UCEIS>1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water (200-250mg potassium/100ml) was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤ 2) and secondary outcome measures were clinical response (SCCAI decline ≥ 3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks.

Results

Of 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2 ± 11.2years; males-54.1%; disease duration-48 (IQR:24–90) months; pancolitis - 26.1%; SCCAI-5 (IQR:4 – 6); UCEIS-4 (IQR:3 – 5)]. There was significant increase in dietary potassium and decline in sodium/potassium ratio at 8 weeks in CW. Clinical response [57.1% vs 28.3%, p=0.01, OR-3.4 (95%CI:1.4 – 7.9)], remission [53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin (FCP)<150μg/g [53.6% vs 14.3%, p=0.01, OR-6.9(95%CI:1.6 – 28.9)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8 weeks in CW. Adverse events were comparable and no patient developed hyperkalemia.

Conclusion

Coconut water increased dietary potassium, modulated the gut microbiome and was more effective than placebo for induction of remission in mild-moderate UC.
P1042 Serum N-glycan Biomarkers Predict Patient Response to Biologics for Crohn’s Disease
Authors: Elgood Hunt G , Spencer D , Senard T , Gardner R , Satsangi J , Adams A , Noble A , D’Haens G , Joustra V , Li Yim A , de Jonge W J
Published: January 2024

Background

Several therapeutic antibodies are approved to treat Crohn’s Disease (CD), for example, Vedolizumab (anti-α4β7), Ustekinumab (targets IL-12 and IL-23), Adalimumab and Infliximab (anti-TNF). Glycosylation alterations have been associated with CD, but have not been thoroughly investigated as potential predictors of disease remission¹. A comparison of serum N-glycan profiles between responders and non-responders prior to each therapy was used to detect potential biomarkers to response. The N-glycan composition after treatment was used to distinguish the different mechanisms of the biologics. In addition, a comparison of glycomic profiles across the different therapies could highlight the distinct biological pathways involved in response.

Methods

Serum samples, before (t1) and after (t2) treatment, were taken from 166 patients, containing the four sub-cohorts of patients under different biologics with CD. Treatment response, observed in 100 patients, was assessed by a combination of clinical and endoscopic outcomes. Firstly, the Serum N-glycans were detected by hydrophilic interaction liquid chromatography to produce a 62-peak chromatogram. Followed by quantifying the relative area of 62 glycan peaks via HappyTools². Logistic regression was used to determine which glycan peaks at t1 are predictive of response (p-value <0.05) and which are markers of response (p-value<0.05). 5 fold cross-validation tested on a variety of classifiers was used to derive the optimal predictor of response. The glycomic profiles across the four biologics, at both t1 and t2, were compared through the Kruskal test. The significant peaks (p-value < 0.05) were then combined to generate a multiclass model to predict response in each therapeutic.

Results

The N-glycan classification models for all four sub-cohorts under different biologics, Ustekinumab (0.78 AUC), Adalimumab (0.82 AUC), Infliximab (0.75 AUC), Vedolizumab (0.75 AUC), performed moderately well at predicting therapy response prior to treatment(figure 1A). In turn, patients could be identified as responders after treatment by N-glycan based classification models, Ustekinumab (0.70 AUC), Adalimumab (0.86 AUC), Infliximab (0.85 AUC), Vedolizumab (0.84 AUC). Prior to treatment, patients who responded were strongly distinguished by the therapy type (0.96 AUC) through a combination of 13 significant glycan peaks (figure 1B).

Conclusion

This study has demonstrated multiple N-glycans are potential predictors of biological response, with the possibility to guide clinicians in the most appropriate form of treatment. These results require the integration of mass spectrometry and validation by larger cohorts.
P1048 Mirikizumab administration experience from Ulcerative Colitis patients: Survey data from the LUCENT clinical program
Authors: Clemow D , Radawski C , Milata J , Alaka K , Hunter Gibble T , Schaum A , Ezennia O , Martinez N , Szaloki T , Ito Y , Rodriguez D , Kirk K
Published: January 2024

Background

Mirikizumab (MIRI) is an anti-IL-p19 antibody approved for moderately-to-severely active ulcerative colitis (UC). The recommended dose regimen has 2 parts: MIRI administration begins with intravenous (IV) infusion every 4 weeks (Q4W; 3 total) and is followed by maintenance dosing of subcutaneous (SC) injections (2 injections per dose) Q4W. Self-injection of SC MIRI is allowed after patient training. This study investigated patient satisfaction with and acceptability of MIRI IV infusions and SC injections during the LUCENT program.

Methods

This was a cross-sectional, 30-min, web-based survey. Patients were eligible if they were enrolled in LUCENT-3, a phase 3, open-label, long-term extension study of MIRI. Patients entered LUCENT-3 from the AMAC phase 2 study, or the LUCENT-1 and LUCENT-2 phase 3 studies. The survey covered patient satisfaction with and acceptability of IV infusions during the AMAC, LUCENT-1, or LUCENT-2 (extended or reinduction) studies and SC injections during the AMAC, LUCENT-2, or LUCENT-3 studies (Figure 1). Survey questions had responses based on 5-point Likert scales (Table 1). The survey was completed during LUCENT-3; MIRI SC injection experience at the time of survey varied from >2 yrs to ≥3 yrs. Subgroup analyses (primary: age and sex) were made using Fisher's exact tests.

Results

The survey was completed by 93 patients from 11 countries (mean age, 42.9 yrs; 54.8% male; 69.9% White). Most patients were satisfied or very satisfied with IV infusions (82.8%) and SC injections (91.4%). More than 89% of patients retrospectively reported that their satisfaction with either administration method remained the same or improved over time. Most patients indicated receiving 2 SC injections (96.8%) and receiving SC injections Q4W (97.8%) were somewhat or completely acceptable. Patients (95.1%) agreed that the self-injection device was easy to use. 97.8% were satisfied or very satisfied with the administration of MIRI overall, 96.8% agreed or strongly agreed that they would recommend MIRI to someone with UC, and 90.3% agreed or strongly agreed that improvements in their UC outweighed any dissatisfaction with the administration method. Acceptability of MIRI administration differed by age (p=0.0369). More patients aged ≥40 yrs than <40 yrs found the MIRI administration completely acceptable (98.2% vs. 89.2%). Overall satisfaction with the IV infusions differed by sex (p=0.0159). More females than males were satisfied or very satisfied with the IV infusions (92.9% vs.74.5%).

Conclusion

Most UC patients were satisfied with and acceptable of receiving MIRI by IV infusions and SC injections and found the dosing of 2 SC injections Q4W acceptable.
P1055 Intravenous to subcutaneous infliximab switch may reduce the risk of immunogenicity related treatment failure and can be used to facilitate immunomodulator withdrawal
Authors: Campbell I , Brownson E , Bailey E , Nowell E , Laird S , Seenan J P , MacDonald J
Published: January 2024

Background

Infliximab (IFX) is an effective treatment option for many patients with inflammatory bowel disease. Immunogenicity mediated treatment failure (IMTF) is a common clinical problem usually tackled by addition of an immunomodulator (IMM) and/or IFX dose escalation.

Switching stable patients on IV IFX maintenance therapy to SC IFX has been shown to be safe and effective.1 It is hypothesised that SC IFX may reduce the risk of IMTF but there is little data to support this. We aimed to explore whether switching selected patients at risk of IMTF from IV to SC IFX was safe and effective and assess whether this strategy can facilitate treatment de-escalation and IMM withdrawal.

Methods

The local IBD database was used to identify potentially suitable patients at higher risk of IMTF. This included those on escalated doses of IV IFX, those who had developed low level anti-drug antibodies (ADA), and those on combination therapy in whom it was felt desirable to withdraw IMM. Those who agreed to switch were commenced on SC IFX 120mg fortnightly and followed up clinically and with IFX drug levels (DLs) and ADA at week 8, 24 and 52.

Results

29 eligible patients underwent IV to SC IFX switch. Two patients were excluded: one returned to IV IFX and the other stopped IFX completely within 8 weeks of switch.

Outcomes for 27 patients were evaluated: 10 with UC, 14 CD, 3 IBD-unclassified. Median age was 38 (IQR 31-49). Median duration of IV IFX was 34 months (IQR 24-54 months). 17 patients were on accelerated IV IFX dosing.

All 27 patients remained on SC IFX at one year. Two required a course of steroids for disease flare. Of the 19 patients who had faecal calprotectin (FCP) data available, the mean FCP prior to switch was 66.1 (30-317) and post initiation of SC IFX was 189.6 (30 – 1800), but this did not reach statistical significance (p=0.172).

12/27 patients were on IV IFX plus IMM therapy. 9/12 successfully stopped IMM after switch to SC IFX.

Mean DL prior to switch was 7.13 (2.7-12.5) and post switch was 12.07 (1.6-14.5). In those who were on accelerated IV IFX dosing, 15/17 saw an increase in DLs post switch. In the 8 patients who had ADAs prior to switch, all saw a reduction, with 6 having no detectable ADAs post switch.

Conclusion

Switching from IV to SC IFX in this cohort was safe and effective. Most patients maintained steroid free remission at one year. All those who stopped IMM were successfully maintained on monotherapy at 1 year. 15/17 people treated with escalated IV dosing were successfully switched to standard SC IFX dosing with improvement in mean IFX DLs and without loss of clinical effect.