bluuebunny/crossref_metadata_2025 huggingface dataset:
P376 Efficacy of ozanimod in vedolizumab-exposed patients with ulcerative colitis: a phase 3 True North post hoc analysis
Authors: Sands B E , Jain A , Ahmad H A , Osterman M , Memaj A , Canavan J B , Axelrad J E
Published: January 2023

Background

Ozanimod (OZA), an oral sphingosine 1-phosphate receptor modulator that prevents lymphocyte migration to inflamed tissues, is approved for the treatment of patients with moderate to severe ulcerative colitis (UC) in the European Union and United States. The phase 3 True North (TN) randomised trial showed that OZA was effective and well tolerated in these patients. OZA efficacy in patients who have been exposed to vedolizumab (VDZ-exp), an integrin receptor antagonist that interferes with lymphocyte trafficking to the gut, has not yet been described. This post hoc analysis of TN examined OZA efficacy in VDZ-exp patients.

Methods

In TN, patients were randomised to oral once-daily OZA 0.92 mg (equivalent to OZA HCl 1 mg) or placebo (PBO; Cohort 1) or to open-label OZA (Cohort 2) during the induction period (IP). Patients with a clinical response to OZA at Week 10 were rerandomised to OZA or PBO in the maintenance period (MP). Efficacy at Week 10 (IP) and Week 52 (MP) in the VDZ-exp subgroup was calculated. Differences in proportions between OZA and PBO at Week 10 were based on the Cochran-Mantel-Haenszel (CMH) test, stratified by corticosteroid use at screening and prior anti-tumor necrosis factor (anti-TNF) use. Differences between OZA/OZA and OZA/PBO at Week 52 were based on the CMH test stratified by both remission status and corticosteroid use at Week 10.

Results

TN included a total of 185 VDZ-exp patients (Cohort 1: PBO, n=35; OZA, n=63; and Cohort 2: OZA, n=87). Baseline demographics and clinical characteristics were balanced across treatment groups. In the VDZ-exp subgroup, 52% of patients had extensive disease at baseline, 78% had a Mayo endoscopic score of 3, 85% were previously exposed to anti-TNF, and 61% were receiving corticosteroid at baseline. At Week 10, OZA (Cohort 1) was numerically more effective vs PBO for all endpoints in VDZ-exp pts (Figure 1A). Notably, in the subgroup of patients previously exposed to VDZ as a first-line advanced therapy, clinical response at Week 10 was achieved in 50% (6/12) of OZA pts in Cohort 1 and 42% (5/12) of OZA patients in Cohort 2. At Week 52, a higher proportion of VDZ-exp patients on continuous OZA achieved all efficacy endpoints vs the OZA/PBO group, with significant differences shown for most endpoints. OZA/OZA vs OZA/PBO differences at Week 52 were larger than OZA vs PBO differences at Week 10 (Figure 1B).

Conclusion

This post hoc analysis of the phase 3 TN study found that OZA was effective in UC patients who previously failed VDZ, including those who failed VDZ alone or following other advanced therapies. Future studies evaluating OZA in VDZ-exp patients are warranted.
P377 Changes over time in the Lémann Index and the Inflammatory Bowel Disease-Disability Index in patients with Crohn’s disease
Authors: Wils P , Cartier L , Azahaf M , Hambli S , Branche J , Gérard R , Desreumaux P , Louvet A , Nachury M
Published: January 2023

Background

Crohn’s disease (CD) is a progressive, transmural disorder that leads to intestinal damage (fistula, abscesses, stenosis) and worsens the patient’s quality of life. The Lémann Index (LI, assessing cumulative bowel damage in CD) and the Inflammatory Bowel Disease-Disability Index (IBD-DI) have recently been validated. The objective of the present study was to assess changes over time in the LI and the IBD-DI and to identify factors associated with these changes.

Methods

In a cohort of 130 patients with CD being followed up prospectively at Lille University Hospital (Lille, France), the LI and the IBD-DI were evaluated first in 2016 (assessment #1, results previously published) and then again between September 2020 and October 2021 (assessment #2). Factors associated with the differences in the LI and IBD-DI were probed with a Mann-Whitney test or a bivariate analysis of variance. Survival curves for the progression of CD (surgery, drug-related events) were plotted according to the Kaplan-Meier method. Spearman’s coefficient was calculated as a guide to the strength of the correlation between the LI and the IBD-DI.

Results

101 patients were included. More than half of the included patients had a long-standing disease (>15 years), 35% had ano-perineal involvement and 56% had a history of resection. Clinical activity was reported in 40% of patients at assessment#2. The median time interval between the two evaluations was 4.2 years. The LI (assessed in 61 patients) did not change significantly (median: 9.6 at #1 vs. 9.3 at #2; p = 0.14). The LI increased for 16 patients (26%), decreased for 26 (43%) and was stable for 19 (31%). Persistent clinical activity was the only factor significantly associated with worsening of the LI (p=0.01). A LI >7.9 was not associated with CD progression. The IBD-DI score (assessed in 98 patients), decreased significantly over time (median: 23.2 at #1 vs. 21.4 at #2; p = 0.006). The IBD-DI decreased for 59 patients (60.2%), increased for 37 (37.8%) and was stable for two (2%). Factors associated with improvement in the IBD-DI were younger age at diagnosis, a longer time interval before initiation of the first biologic, drug optimization, and exposure to combination therapy. There was no correlation between LI and the IBD-DI (r 0.125, p=0.27).

Conclusion

This is the first cohort study assessing changes over time in both the LI and the IBD-DI in CD patients. After more than 4 years of follow-up, the LI appeared to be stable and the IBD-DI decreased, without correlation between the indices. Persistent clinical activity was associated with worsening LI reinforcing the interest in monitoring these patients.
P381 Ustekinumab trough levels are associated with sonographic transmural healing in Pediatric Inflammatory Bowel Disease
Authors: Kellar A , Aronskyy I , Dubinsky M C , Dolinger M T
Published: January 2023

Background

Transmural healing (TH) assessed by intestinal ultrasound (IUS) is associated with improved inflammatory bowel disease (IBD) outcomes. This study evaluates the relationship between ustekinumab trough levels (UTL) and sonographic TH in children with IBD treated with ustekinumab (UST).

Methods

Children (<18 years) with IBD treated with maintenance UST and undergoing IUS examination and serum UTL (Prometheus Labs, CA) at a single tertiary center between July 2020 and October 2022 were prospectively recruited. Children who underwent IUS and UTL on 2 events >6 months apart were included in a per-event analysis. Primary outcome was the comparison of UTL between children with and without TH, defined as bowel wall thickness (BWT) ≤3 mm and no hyperemia (BWH) on color Doppler, using the Mann-Whitney U test. Area under the receiver operating curve (AUROC) determined the optimal UTL cut-point to detect TH. Secondary outcome was the comparison of UTL for each IUS parameter. Descriptive statistics summarized the data as frequencies and percentages for categorical variables and median [interquartile range] for continuous variables. A p-value of significance was set to <0.05.

Results

Overall, 50 IUS exams on 129 bowel segments were performed in 44 children with IBD, 34:10 Crohn’s disease (CD):ulcerative colitis (UC)/IBD-U treated with UST, median [IQR] age 14.9[13.2-16.6] years, 22(50%) female, and disease duration 3.83[1.98-5.32] years (Table 1). 18(41%) children were treated with standard dose UST of 90mg every 8 weeks and had significantly lower UTL compared to 26(59%) treated with escalated dosing of 90 mg every 4 or 6 weeks (7.4[4.8-12.7] ug/ml vs. 11.6[6.1-19.3] ug/ml, p=0.002). Median time between UTL and IUS was 0 days [0-11.25]. Overall, 24(55%) children (18(53%) CD, 6(60%) UC/IBD-U) achieved TH. Higher UTL was associated with TH (13.1[6.1-17.5] ug/ml) compared to children without TH (5.7[4.2-13.9] ug/ml; p=0.010) (Figure 1A). Higher UTL was also associated with TH in children with CD (11.7[5.3-17.0] ug/ml) compared to children with CD without TH (5.5[4.2-11.0] ug/ml; p=0.013) (Figure 1B). Optimal UTL cut-point to detect TH was 11.4 ug/ml for all children (AUROC=0.647, sensitivity=62%, and specificity=69%) and children with CD (AUROC=0.661, sensitivity=59%, specificity=79%). Median UTL for all children was associated with lymphadenopathy (p=0.02) but no other individual IUS parameters (Table 2).

Conclusion

Higher maintenance UTL are associated with sonographic TH in children with IBD. Future prospective studies are needed to determine if targeting higher UTL levels during induction and maintenance UST therapy promotes TH.
P388 Shear wave elastography predicts short-term response to induction therapy in patients with Crohn’s disease
Authors: Sagami S , Morikubo H , Miyatani Y , Fukuda T , Asonuma K , Maeda M , Yoko Y , Karashima R , Hojo A , Nakano M , Hibi T , Kobayashi T
Published: January 2023

Background

Endoscopy has been used to assess the disease activity of Crohn's disease (CD) but may not be sufficient considering the transmural nature of its inflammation. Bowel ultrasonography (BUS) has been reported to reflect disease activity of CD and long-term outcomes. We performed a prospective study to determine whether BUS can predict short-term clinical response to induction therapy.

Methods

Consecutive CD patients with active ulcers in endoscopy requiring induction therapy (Anti-TNF antibody, IL-12/23 p40 antibody, integrin inhibitor, prednisolone) were prospectively enrolled at a single center from October 2018 to July 2022. Short-term clinical response was defined by a reduction of Crohn’s disease activity index > 70 at week 8. Ultrasonographic findings (bowel wall thickness (BWT), colour Doppler signal (CDS), and shear wave elastography (SWE) were recorded for the most severely affected segment at baseline, week 1, and 8 and compared between responders and non-responders.

Results

Seventeen out of 29 patients were classified as responders at week 8. There was no difference in BWT and CDS at baseline, week 1, and 8 between responders and non-responders (Table 1). In contrast, responders had lower baseline SWE compared with non-responders (2.7±0.3 vs. 3.8±0.3, p=0.02). Adjusted by the prior exposure to biologics, the lower SWE at baseline was associated with clinical response at week 8 (adjusted odds ratio associated with 0.1 m/s increase: 0.9, p=0.018) (Table 2). SWE did not change over time regardless of response for 8 weeks.

Conclusion

Lower intestinal wall stiffness as measured by SWE is an independent predictor of short-term clinical response.
P390 Ustekinumab modulates IL-12 and IL-23-related cell type-specific inflammatory transcriptional states in Ulcerative Colitis induction therapy
Authors: Richards D , Venkat S , Freeman T C , Mcrae B , Hoops T , Marano C , Branigan P
Published: January 2023

Background

Ustekinumab (UST) is a monoclonal antibody specific for the p40 subunit of interleukin (IL)-12 and IL-23. In a randomised phase 3 trial (UNIFI; NCT02407236) in patients with moderate-to-severe ulcerative colitis (UC), UST was shown to be more effective for inducing and maintaining clinical remission than placebo. There has yet to be a mechanistic understanding of p40 blockade in inflammatory bowel disease. Here, we investigated the underlying molecular mechanism of action of UST in UC.

Methods

Paired colon biopsies for transcriptomic analysis were obtained at screening and week 8 in patients who received a single intravenous induction treatment of placebo (n=145 subjects), UST 130 mg (n=155 subjects), or a weight-range-based dose (approximated to UST 6 mg/kg of body weight; n=171 subjects). Tissue transcriptional profiles were determined using Affymetrix microarrays. Transcriptional changes were analysed in the context of cell type-specific co-expression modules derived from single cell UC data. Gene set variation analysis (GSVA) was used to quantitatively assess changes in specific biologic modules in the context of endoscopic and histologic-endoscopic mucosal improvement (HEMI) responder and non-responder analyses. Nichenet, which predicts ligand–target gene links, was used with single cell UC data to identify ligands that are predicted to be associated with our cell type-specific modules.

Results

By week 8, both UST treatment arms induced a greater magnitude of transcriptional changes associated with Th17, Th1 cytotoxicity, myeloid inflammatory, epithelial inflammatory, and inflammatory fibroblast modules compared with placebo. Ligand-target gene predictions indicate IL-12 and IL-23 are associated with changes in the Th1 cytotoxicity and Th17 module expression, respectively. Population level molecular changes in both UST treatment arms are consistent with endoscopic and HEMI response at week 8. When evaluating sub-groups stratified by endoscopic improvement or HEMI status, significant changes were observed in transcriptional modules in both UST responders and UST non-responders identifying mechanistic processes associated with dual blockade of IL-12 and IL-23 following exposure to UST. Placebo non-responders showed no significant changes.

Conclusion

Molecular analysis of colon biopsies from UC patients after UST induction revealed IL-12 and IL-23-related transcriptional changes associated with Th1 cytotoxicity and Th17 biology. By leveraging UC single cell derived transcriptional modules, we have identified key disease-relevant processes that significantly changed with UST treatment, regardless of response status and have extended the mechanistic understanding of p40 blockade in UC.
P394 Long-term perineal reoperation and wound healing after proctectomy or ileal pouch-anal anastomosis extirpation in patients with Inflammatory Bowel Disease – a retrospective multicentre study
Authors: Berghog J , Hermansson M , Risto A , Strömbäck J , Unger D , Gustafsson H , Hagavall M , Landerholm K , Buchwald P , Nordenvall C , Myrelid P , Block M ,   Swedish Organization for the study of IBD (SOIBD)
Published: January 2023

Background

Patients with inflammatory bowel disease (IBD) may need to undergo proctectomy or ileal pouch-anal anastomosis (IPAA) extirpation with known short- and long-term perineal complications such as wound dehiscence, delayed healing, sinus formation and fistulas. This study aimed to examine perineal complications after proctectomy or IPAA extirpation.

Methods

This Swedish retrospective, multicentre study included IBD patients ≥18 years undergoing proctectomy or IPAA-extirpation between January 1st 2000 and December 31st 2019 at four hospitals. Medical records were reviewed and perineal wound healing was assessed at 3, 6, 12 and 24 months. Primary endpoint was need for perineal re-operation due to complications. Predefined factors associated with reoperation was assessed.

Results

Four hundred and fifty-one patients (257 males) were included in the study. After 3, 6, 12 and 24 months 70%, 75%, 80% and 88% had healed. Forty-nine (11%) patients underwent re-operation for perineal wound complication. Low age and short duration of IBD were significantly associated with the risk of reoperation (p<0.001 and p=0.032). Crohn′s disease was more common (55%) in the group that underwent re-operation compared to 41% in the no-reoperation group but not statistically significant (p=0.06). Most patients that underwent re-operation demonstrated a wound complication or perineal wound secretion within 30 days of surgery; 90% vs 48% ;p<0.001[KL1] and 80% vs 37%; p<0.001 [KL2] respectively. Following re-operation, the perineal wound healed in 45% (22/49).

Conclusion

At long-term follow-up 88% had healed perineal wound and only 11% had required perineal reoperation. Wound complications and secretion within 30 days of surgery seem unfavourable and predict reoperation and incomplete perineal healing.
P400 Identifying Nutritional targets in Crohn’s disease: INTICO1: a time-limited trial of exclusive enteral nutrition during adult CD remission
Authors: McDonnell M , Westoby C , Sartain S , Giannasca P , Corthésy J , Grzywinski Y , Frézal A , Capt P , Cummings F , Wootton S
Published: January 2023

Background

During clinical remission in adult Crohn’s disease (CD), impaired health reacted quality of life and fatigue is common, and the nutritional state may be affected by factors such as restrictive eating and altered anatomy from previous inflammation or surgeries. Adults with CD in clinical remission do not routinely undergo nutritional assessments or intervention. The INTICO1 study used a time-limited trial of exclusive enteral nutrition (EEN) to expose and explore nutritionally sensitive aspects of in adults with CD during remission. The extent to which the nutritional state relates to the quality of CD remission and the potential role for nutritional therapies is neither well described nor understood.

Methods

This was a single arm longitudinal observation study with a dietary intervention. 24 adults in CD remission (Harvey Bradshaw <5, faecal calprotectin <250) underwent assessment of nutritional state at 3 time points; after habitual diet (assessment 1), after 7 days of polymeric EEN (assessment 2) and after a 2-week gradual return to habitual diet (assessment3). Assessments comprised food diary analysis, anthropometry, bio-electrical impedance analysis, routine pathology measures of micronutrient concentration, and patient reported outcome measures (PROMs).

Results

Assessment 1 (habitual diet) identified individuals with multiple inadequacies of intake (7% (26/368)) micronutrients bloods below the normal laboratory range (see table for analytes) reduced lean mass, low phase angle (PhA) and excessive fatigue (reduced SF-36 vitality). At assessment 2 (post EEN), subjects had fewer deficiencies 4% (16/368), with significant increases seen in Vitamins A, D, E, B2, B6, B9 and the minerals Ca, Cu, Po4 and Se. At visit 3 (return to free diet), micronutrient concentrations reverted toward assessment 1 level, although B6 and B9 remained significantly higher (pairwise comparison visit 1 vs visit 3). BIA measures of nutritional status (PhA) and the SF36 physical function score improved 1 and 2 (5.2 vs 5.4 p<0.01 and 95 v100 p<0.05) and returned to baseline levels on return to free diet (Assessment 3).

Conclusion

A time-limited trial (7 days) of EEN, given in this setting of adults in CD remission led to changes in micronutrient biochemistry, objective improvement in the bioelectrical properties of the body (increased phase angle) and an improvement in fatigue among the subjects as captured by the SF36-PF. The study suggests that impaired nutritional state and excessive fatigue is likely to be prevalent among adults with CD during remission and may be sensitive to nutritional intervention.
P402 A Pilot Study on the Effect of Colesevelam on the Microbiome in Primary Terminal Ileal Resected Crohn’s Disease
Authors: Kumar A , Quraishi M N , Al-Hassi H O , Elasrag M , Segal J P , Jain M , Steed H , Butterworth J , Farmer A , McLaughlin J , Beggs A , Brookes M
Published: January 2023

Background

Surgery plays a pivotal role in ileal Crohn’s disease despite the risk of endoscopic recurrence following an ileocaecal resection greater than 65% within 12 months of surgery. More than 90% of Crohn’s patients have a concomitant diagnosis of bile acid diarrhoea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in post-operative Crohn’s patients with bile acid diarrhoea can alter the microbiome and prevent disease recurrence.

Methods

Post-operative Crohn’s patients with symptoms of diarrhoea underwent 75SeHCAT testing for bile acid diarrhoea. If positive (75SeHCAT < 15%), patients were treated with colesevelam and stool samples were collected at 4-weeks, 8-weeks and 6-12 months post-treatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in clinic as per local guidelines. Patients underwent a 6-12 months post-operative colonoscopy where mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert’s score, with disease remission defined as Rutgeerts score < i2 and disease recurrence ³ i2. Faecal and mucosal 16S ribosomal RNA gene analysis was undertaken to assess a/b-diversity and microbial composition.

Results

A total of 44 faecal samples and 44 mucosal biopsies were sequenced from 14 patients. 1/10 patients on colesevelam and 2/4 patients not on colesevelam demonstrated disease recurrence. There was no significant difference in a/b-diversity pre- and post-treatment. Pre-treatment, the three most abundant bacterial classes in all patients were Bacteroidia, Clostridia and Gammaproteobacteria (Figure 1). Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the two patients not given colesevelam, ½ (50%) showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria.

Conclusion

This small pilot study demonstrated that patients who were given colesevelam, a bile acid sequestrant, were more likely to be in disease remission at their 6-12 months colonoscopy review. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in post-operative Crohn’s disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance.
P413 Withdrawal versus continuation of thiopurine in vedolizumab-treated patients with Ulcerative Colitis (VIEWS): a multi-centre randomised controlled trial
Authors: Pudipeddi A , Paramsothy S , Kariyawasam V , Paramsothy R , Ghaly S , Haifer C , An Y K , Begun J , Connor S , Corte C , Ward M , De Cruz P , Fung C , Redmond D , Leong R W
Published: January 2023

Background

The benefit of continuing thiopurine in ulcerative colitis (UC) responders to vedolizumab (VED) is unclear. We aimed to determine the effect of thiopurine withdrawal in VED-treated UC patients on combination therapy.

Methods

This prospective multi-centre, single-blind, randomised controlled trial recruited UC patients on VED 300mg IV every 8 weeks and a thiopurine for ≥6 months. Patients in steroid-free clinical remission (partial Mayo score[pMS]≤2, no subscore>1) and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomised 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 VED trough levels. Secondary outcomes were disease relapse (pMS≥3 and faecal calprotectin>150μg/g or increase in MES≥1 from baseline), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission, faecal calprotectin (remission<150μg/g) and adverse events.

Results

Sixty-two consecutive patients (58% males, median follow-up 23.0 months) were randomised to withdraw (n=42) or continue (n=20) thiopurine. Randomisation was balanced. Complete data was available for 58 patients. There was a non-significant trend toward increased disease relapse in the withdrawal group (P=0.12, Fig. 1). In the withdrawal group, baseline histologic activity significantly increased disease relapse (HR:5.8, 95%CI:1.6-20.8, P=0.007, Fig. 2). There was a trend towards higher relapse rates in the withdrawal versus continue groups for bio-exposed patients (50.0% [6/12] vs 0.0% [0/4], P=0.07) but not bio-naïve patients (20.0% [6/30] vs 12.5% [2/16], P=0.52). At week 48, the continue group had significantly higher histologic remission (OR:4.6, 95%CI:1.1-18.9, P=0.03) and histo-endoscopic remission rates (OR:4.6, 95%CI:1.3-16.1, P=0.01, Fig. 3) versus the withdrawal group, but similar endoscopic remission rates (P=0.09, Fig. 3). Faecal calprotectin remission was significantly higher in the continue (94% [16/17]) versus withdrawal group (70% [28/40], P=0.047) with mean calprotectin 44.5μg/g±SD56.2 vs 209.6μg/g±SD344.2 (P=0.003) respectively. On multivariate analysis, histologic activity at baseline (HR:5.3, 95%CI:1.1-26.2,P=0.04) predicted disease relapse. Week 48 median VED levels were 15.9µg/mL (IQR:10.1-22.7) in the withdrawal group versus 14.7µg/mL (IQR:12.1-18.7) in the continue group (P=0.43). No patients had anti-VED antibodies. There was no significant difference in adverse events between groups.

Conclusion

Although thiopurine withdrawal did not affect VED trough level, it increased calprotectin, histologic and histo-endoscopic activity in UC. In patients with histological activity despite deep remission, thiopurine withdrawal significantly increased the risk of disease relapse.
P415 Real-world data in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional LISTEN II study
Authors: Stallmach A , Schulze H , Teich N , Cavlar T , Jana K , Henneberger S
Published: January 2023

Background

Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking integrin antibody and is approved for treating patients with moderately to severely active UC (ulcerative colitis) and CD (Crohn’s disease) intravenously (IV) or subcutaneously (SC). The LISTEN II study aims to determine patient characteristics and effectiveness in patients treated with VDZ in a real-world setting.

Methods

LISTEN II is a multicentre, prospective non-interventional study in Germany. Adult patients with UC or CD, for whom the physician has decided to either initiate VDZ IV or switch from IV to SC, are included. Data on patient characteristics, modalities of VDZ use and disease activity (pMayo, HBI) are followed up quarterly for up to one year per routine practice. In addition, patient reported outcomes (PROs) confirmed as relevant in the previous LISTEN I study (e.g. rectal bleeding and general wellbeing) are recorded via an app (ePRO).

Results

Data of 198 UC patients (50% female, 6.0 years median disease duration) and 116 CD patients (56% female, 10.9 years median disease duration) with a mean age of 40 years were included in this interim analysis. VDZ treatment was newly initiated IV in 164 UC patients and 98 CD patients (start) and switched from IV to SC by 34 UC and 18 CD patients (switch) at study inclusion. At baseline corticosteroids were documented as used in 70% and 56% of UC and CD start-patients in the year prior to enrollment.

Burden of disease was classified as high (pMayo>4) in 51% of UC patients at baseline and decreased to 15% at 3 months. For CD patients, proportion of high burdened patients (HBI>7) was 27% at baseline and 12% at month 3 (Figure 1). In this period, total mean pMayo score decreased in UC patients from 4.3±2.5 (start: 4.9±2.1; switch: 1.0±1.3) to 2.2±2.2 (start: 2.5±2.2; switch:1.0±1.6) and total mean HBI score from 5.4±4.4 (start: 5.8±4.5; switch: 3.5±3.7) to 3.3±3.4 (start: 3.4±3.4, switch: 2.8±3.3) in CD patients (Figure 2).

UC patients using the ePRO (N=152, mean age: 39 years, 49% female) reported from ePRO initiation up to month 3 a mean score decrease for rectal bleeding (range 0-3) from 1.3 to 0.6, for general well-being (range 0-4) from 1.7 to 1.3 and for impact on work productivity (range 0-10) from 3.7 to 2.3 points.

Conclusion

LISTEN II real-world data support the effectiveness of VDZ treatment in UC and CD patients. Patients starting VDZ IV showed a higher disease activity at baseline which decreased under VDZ treatment. Switching of VDZ IV to SC was mainly performed in patients with low disease burden under VDZ treatment, resulting in maintained therapeutic effectiveness. Also PROs of UC patients show an improvement supporting benefit with VDZ treatment.
P416 The impact of remission on healthcare resource utilisation and costs amongst patients with inflammatory bowel disease in France, Germany, Italy, Spain, and the United Kingdom
Authors: Patel K V , Salmon P , Marin-Jiménez I , Thessen M , Kligys K , Sharma D , Sanchez Gonzalez Y , Kershaw J
Published: January 2023

Background

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) with increasing healthcare resource utilisation (HCRU) and associated costs. Optimal management of CD and UC aims to induce and maintain remission which may subsequently lower HCRU and costs. This study reports on the potential impact on HCRU and associated direct HCRU costs (excluding drug costs) from achieving CD or UC remission in France, Germany, Italy, Spain and the United Kingdom (EU5).

Methods

Data were drawn from an Adelphi Real World IBD Disease Specific ProgrammeTM, a point in time survey collected from gastroenterologists and their IBD patients in EU5 in Sep 2020-Jan 2021. GEs completed a patient record form for their next 5-10 consulting IBD patients covering demographics, remission status, healthcare professional visits, tests used to diagnose and monitor CD/UC, hospitalisations and surgeries related to IBD. Patients were stratified into two groups based on GE stated remission status from set categories: remission (RE) vs non-remission (NR). Associated HCRU costs were sourced from published healthcare system reports per country. Outcomes and costs were compared between patients in RE vs NR using inverse probability weighted regression statistical analysis (α=0.05), adjusting for age, sex, BMI, smoking status, disease location, and current treatment.

Results

A total of 1,526 CD patients were analysed and split into patients in RE (n=1,021) and NR (n=505; Figure 1). Compared with CD patients in NR, patients in RE experienced a lower risk of at least one hospitalization (12.8% vs 29.8%; p<0.001) and surgery (13.8% vs 26.0%; p<0.0001) (Figure 2), and fewer visits to HCPs in the last 12 months (6.5 vs 7.4; p=0.005) (Figure 3). Furthermore, total HCRU cost was 53% less for patients in RE vs NR (€1410.4 vs €2153.4; p=0.0002), with 16% lower HCP visit and test costs (€637.1 vs €737.3; p<0.001) and 83% lower hospitalisation and surgery costs (€773.3 vs €1416.2; p=0.001) (Figure 3). In addition, 1,447 UC patients were analysed and split into patients in RE (n=968) and NR (n=479; Figure 1). Compared to UC patients in NR, patients in RE experienced a lower risk of at least one hospitalization (11.4% vs 24.3%; p<0.0001) and surgery (1.8% vs 5.0%; p=0.004 (Figure 1), and fewer HCP visits (6.0 vs 7.1; p<0.001) (Figure 3). Total HCRU cost trended lower amongst patients in RE vs NR (€1219.6 vs €1443.0; p=0.085), with 19% lower costs of HCP visit and test costs (€617.3 vs €734.7; p<0.0001).

Conclusion

Patients with IBD who achieve remission present lower HCRU burden, lower risk of hospital and surgery, and ultimately lower associated direct HCRU costs to healthcare systems in EU5.
P419 Outcomes at one year after sequential use of high-dose tofacitinib following infliximab in Acute Severe Ulcerative Colitis
Authors: Eqbal A , Hilley P , Gilmore R , Li Wai Suen C , Choy M , De Cruz P
Published: January 2023

Background

Acute Severe Ulcerative Colitis (ASUC) remains a significant cause of morbidity faced by up to 25% of patients with ulcerative colitis at some point during their disease course. We present the outcomes up to 1 year after the novel use of high dose tofacitinib, in patients with steroid refractory ASUC after failing to respond to infliximab.

Methods

Eleven patients with ASUC who were treated with high dose sequential tofacitinib [10mg three times daily (TDS)] after failing to respond to infliximab between 2019-2021 were identified at an Australian tertiary centre.

Results

Nine of 11 patients demonstrated a clinical and biochemical response to treatment during admission. All 9 patients remained colectomy free at both 6 and 12 months. At 6 months the median Mayo score was 1 [range 0-7]. At 12 months the median Mayo score was 1 [range 0-6]. No patients experienced venous thromboembolic events or major infective complications.

Conclusion

High dose tofacitinib may be a safe and effective agent in the treatment of steroid refractory ASUC after failing to respond to infliximab. Prospective studies are required to explore the use of tofacitinib in ASUC before it can be routinely recommended as salvage therapy.
P425 The utility of intestinal ultrasound to inform clinical decision making
Authors: Yeaman F , Panaccione R , Ma C , Lu C , Seow C , Kaplan G , Maracle B , Novak K
Published: January 2023

Background

Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease leading to progressive bowel damage. Objective monitoring is essential to improve outcomes. Intestinal ultrasound (IUS) is an accurate, repeatable modality preferred by patients. The aim of this study was to evaluate changes in medical therapy and further tests requested, when IUS is used routinely to follow patients in an expert centre.

Methods

This is a single centre, prospective observational cohort study. All recruited provided informed consent with ethics approval through the University of Calgary. Patients over the age of 18 years were recruited via convenience sampling from October 1, 2020 to September 31, 2022. Patients were part of a registry where clinic-based IUS is standard of care. Patient demographics, medical treatment changes and further investigations were recorded.

IUS were performed by an IBD gastroenterologist trained in advanced IUS. Patients were classified as symptomatic (Harvey Bradshaw Index [HBI] ≥5) or asymptomatic (HBI<5). IUS were categorised as inactive if the bowel wall thickness (BWT) was <3mm without colour Doppler and inflammatory mesenteric fat) or active (BWT ≥3mm, colour Doppler ≥2 and presence of inflammatory fat). Data were reviewed regarding management: medication changes were defined as dose change, addition of corticosteroids or other medication and medication change. Referral for surgical opinion was recorded. Further outcomes included faecal calprotectin, stool for infection, blood tests, endoscopy, imaging or hospital admission.

Results

138 episodes of care were logged including 103(74%) with Crohn’s disease, 16(12%) with ulcerative colitis, 2(1.4%) with IBD-unclassified, 13(9.4%) without IBD investigated for symptoms and 4(2.9%) not recorded. Figure 1 shows symptomatic and active episodes compared to asymptomatic and inactive. IUS were performed: for flare symptoms in 22(16%); for monitoring in 107(78%); or to investigate symptoms in 9(6.5%). IBD medication was escalated in 22(52%) patients with active IUS disease plus symptoms and in 9(39%) asymptomatic patients with active IUS. Medication escalation was performed in 4(16%) symptomatic patients with inactive IUS and 2(4.2%) asymptomatic patients with inactive IUS based on low drug level or adverse events. One patient had medication reduced in frequency due to the IUS findings(Table 1). No hospital admissions occurred following IUS.

Conclusion

Active IUS triggered treatment modification in almost 40% of patients, regardless of symptoms. Future studies will assess benefits of timely treatment changes for long term outcome. IUS supports a clinician at the bedside to make timely clinical decisions that may avoid invasive testing and decrease resource limited endoscopy.
P431 A Pan-European Real-World Study of SB5 biosimilar following transition from reference adalimumab: The PROPER study; 48-week analysis of persistence
Authors: Dignass A , Gisbert J P , Bossa F , Kelly O , Rahman M , Lobatón T , Addison J
Published: January 2023

Background

SB5, a biosimilar to reference adalimumab (ADL) received marketing authorisation in 2017 (EU) and 2019 (US) based on pre-clinical and clinical phase I and III study data demonstrating bioequivalence and comparable efficacy, safety and immunogenicity to ADL. The real-world study “Pan-EU Real-World Experience with Imraldi” (PROPER) was designed to provide insights into outcomes, including predictors of persistence, following transition from ADL to SB5 outside the randomised, controlled trial setting.

Methods

Under an umbrella design, 1040 patients with immune-mediated inflammatory disease (rheumatoid arthritis [RA], axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], Crohn’s disease [CD] or ulcerative colitis [UC]) who had received at least 16 weeks of treatment with ADL prior to transition to SB5 were enrolled at centres in Belgium, Germany, Ireland, Italy, Spain and the UK and followed for 48 weeks post-transition. Candidate predictors of persistence on SB5 included sex, medical history, age, duration of disease, disease score and concomitant therapy, all as recorded at time of SB5 initiation. Variables of clinical relevance reported for at least 15% of each cohort were selected as candidate predictors and fitted into a univariate Cox regression model. Persistence on SB5, i.e., time to SB5 discontinuation up to Week 48 post-transition was estimated using the Kaplan-Meier method. This abstract presents results for the CD cohort.

Results

Of 447 CD patients included, 433 completed 48 weeks’ follow-up; 316 of those (70.7%) remained on SB5 throughout. The probability of persistence (95% Confidence Interval [CI]) at Week 48 was 71.8% (67%, 76%) (Figure 1).

Figure 1. Persistence on SB5

Table 1 shows the six variables qualifying as candidate predictors in the CD cohort and the probability of each to predict persistence at Week 48. Being female was the only variable shown to be associated with non-persistence of SB5: Hazard ratio (95% CI) 2.21 (1.54, 3.18). The 95% CIs of the other variables all crossed 1.0.

Table 1. Probability of candidate variable to predict persistence on SB5

Conclusion

The majority of the CD cohort remained on SB5 at 48 weeks after transition from reference ADL. Of the candidate predictors of persistence, only female sex was found to have an association with increased risk for SB5 discontinuation. A limitation of this finding is the low proportion of subjects discontinuing SB5 prior to Week 48, hence a low incidence of potential candidate predictors. When anticipating persistence, results suggest no evidence to mitigate against transition, within the baseline categories explored.
P432 Patient satisfaction and patient costs associated with telephone clinic appointments in Inflammatory Bowel Disease (IBD) following the pandemic
Authors: Matini L , Stokes E A , Parra Mujica F , Kormilitzin A , Kantschuster R , Punj Sharda A , Dunbar G , Song K , White L , Travis S P L , Walsh A
Published: January 2023

Background

Prior to the COVID-19 pandemic, conventional management of outpatient care in IBD predominantly revolved around face-to-face clinic appointments. In the changing landscape of care provision during the pandemic, appointments were conducted almost exclusively through telephone consultation. An electronic questionnaire was developed to assess patient satisfaction and patient costs.

Methods

A pilot was carried out with 15 patients to identify any technical issues with e-mail delivery of the questionnaire and gauge face validity of the questionnaire content. 1400 patients registered with the TrueColours-IBD remote digital monitoring system were sent the questionnaire link via e-mail in May 2021. No demographic data were collected by design, in order to avoid the perception of bias and ensure freedom of expression through anonymity.

Results

506 responses were received including 21 duplicates which were excluded, totalling 485 valid responses. 408/485 patients reported having a telephone appointment with the IBD service since March 2020, 484/485 reported having had a face-to-face appointment in the past. 348/408 (86%) were either ‘very satisfied’ or ‘somewhat satisfied’ with their most recent telephone consultation, while 22 (6%) were either ‘very dissatisfied’ or ‘somewhat dissatisfied’. 247/408 (61%) were also either ‘very satisfied’ or ‘somewhat satisfied’ with the ease of accessing further care if required, compared to 33/408 (8%) who were either ‘very dissatisfied’ or ‘somewhat dissatisfied’. Given the choice, 195/408 (48%) patients preferred to receive a telephone appointment in the future; 147/408 (36%) would opt for face-to-face and 66/408 (16%) stated no preference, all with the option of changing that choice if needed. Telephone appointments were associated with a mean total patient time off-work or leisure of 23 minutes (S.D. 51, n=408) compared to 190 minutes (S.D. 96, n=484) for face-to-face appointments. The average cost of time off work or leisure associated with telephone appointments was £5.55 (S.D. = £15.74, n=408), compared to £43.42 (S.D. = £31.27, n=484) for face-to-face appointments (Table 1). Costs of transport add further to face-to-face appointment costs. Greater proportions of patients had a companion for their face-to-face appointment and required childcare compared to telephone consultations (Table 2), which again increases the difference in costs.

Conclusion

Almost half of surveyed patients stated a preference for telephone appointments, although a third still preferred traditional follow-up. An evolution of care pathways is supported by patient preference and the statistically significant time and cost savings to patients receiving telephone appointments.
P438 Efficacy and safety of ustekinumab for Ulcerative Colitis through 4 years in Asian patients: Final results from the sub-population of UNIFI long-term extension
Authors: Hisamatsu T , Kim H J , Motoya S , Suzuki Y , Ohnishi Y , Marano C , Imai Y , Saadoun C , Zhuo J , Kawamura S ,   UNIFI Investigators
Published: January 2023

Background

Ustekinumab (UST) is an interleukin-12/23 p40 antagonist approved for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the final efficacy and safety results of UST in the Asian subpopulation in the UNIFI long-term extension (LTE) through 4 years (Week [WK] 200).

Methods

Overall, 87 intravenous (IV) UST induction WK8 responders were randomised to subcutaneous (SC) maintenance therapy: 34 placebo (PBO); 24 UST 90 mg every 12 weeks (q12w); 29 UST 90 mg q8w. The nonrandomised patients (pts) included 22 IV UST induction nonresponders who received SC UST at WK8, responded at WK16, and continued on SC UST q8w; and 12 responders to IV PBO induction who received SC PBO.1,2 Pts who completed WK44 continued on SC UST q8w or PBO treatment in the LTE, and PBO pts were discontinued after unblinding. Starting at WK56, randomised pts with UC worsening could adjust to SC UST 90 mg q8w. Efficacy was evaluated in UST-randomised pts (n=53) using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0). Safety was evaluated for all pts treated in the LTE, including randomised and nonrandomised populations until WK220.

Results

Among all UST-randomised pts at maintenance baseline WK0 (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 49.1% were in symptomatic remission at WK200 (biologic naïve 77.8.%; failures 34.4%); 49.1% of pts were in corticosteroid-free symptomatic remission at WK200 (Table 1; Fig. 1-2). Overall, 43.5% of biologic failure and 0% of biologic naïve pts who were randomised to UST and treated in the LTE discontinued treatment between WK44 and WK200. Among randomised pts who continued UST in the LTE, 63.4% were in symptomatic remission at WK200; 78.6% of pts with observed data at WK200 were in symptomatic remission (Table 1; Fig. 3); and 80.0% of those in clinical remission at WK44 were in symptomatic remission at WK200. Safety events were similar among UST-treated pts compared with PBO. From maintenance baseline WK0 through WK220, pts receiving UST (combined UST) and PBO had 241.8 and 56.5 total pt-years of follow-up, respectively. Safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 222.48 vs 320.29, SAEs: 11.58 vs 7.08, and serious infections: 1.65 vs 1.77. During the final year of the LTE, no deaths or major cardiovascular events were reported in UST-treated Asian pts.

Conclusion

Consistent with the overall study population in UNIFI LTE1,2, Asian pts receiving SC UST generally maintained clinical benefit through 4 years. No new safety signals were observed.

1Afif W, et al. UEGW. Vienna, Austria, October 8-11, 2022. 2Sands BE, et al. ACG. Charlotte, NC, October 21-26, 2022
P445 Network meta-analysis to evaluate the comparative efficacy of intravenous and subcutaneous infliximab and vedolizumab in the maintenance treatment of adult patients with Crohn’s Disease and Ulcerative Colitis
Authors: Peyrin-Biroulet L , Bossuyt P , Bettenworth D , Loftus Jr. E V , Anjie S , D’Haens G , Saruta M , Arkkila P , Kim D H , Choi D , Reinisch W
Published: January 2023

Background

Network meta-analysis (NMA) using randomised controlled trial (RCT) data can provide indirect evidence on comparative efficacy of various treatments.1 The NMA reported herein was conducted to evaluate infliximab (IFX) and vedolizumab (VDZ) comparative efficacy during maintenance treatment of moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), covering various dosing regimens and administration routes for each biologic.

Methods

Studies were identified by literature searches that included publications up to 1 November 2022. Parallel-group RCTs evaluating IFX or VDZ (intravenous [IV] or subcutaneous [SC]) for maintenance treatment of adult patients with moderate-to-severe CD or UC that reported clinical remission rates were included. Eligible studies treated patients for a minimum of 22 weeks, with follow-up of 30–60 weeks for maintenance. Clinical remission rates in tumour necrosis factor inhibitor (TNFi)-naïve patients from each study were analysed in a Bayesian NMA fixed-effect model.

Results

Overall, 13 RCTs were identified and included in the analysis (Table 1 for CD and Table 2 for UC). The difference in study design between IFX (treat-through) and VDZ (re-randomisation of induction responders only) was noted. A connected network of evidence could be generated using CD and UC studies (Figures 1A and 1B, respectively). In both CD and UC, IFX SC 120 mg had the highest odds ratio (95% confidence interval [CI]) vs. placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90–18.2]; UC: 5.45 [1.94–15.3]), albeit with the CIs overlapping with the CIs of the other tested regimens (Figures 2A and 2B). In both CD and UC, IFX SC 120 mg ranked highest for clinical remission among the biological agents, dosing regimens, and routes of administration tested.

Conclusion

In both CD and UC, IFX SC showed a favourable efficacy profile for achieving clinical remission during maintenance treatment of TNFi-naïve adult patients, when compared with the other IFX IV or VDZ IV/SC regimens tested.

References:

1 Rouse B et al., Intern Emerg Med 2017;12(1):103-111.