bluuebunny/crossref_metadata_2025_split huggingface dataset:
P578 Exploring duration of corticosteroid withdrawal in definitions of corticosteroid-free remission endpoints in ustekinumab clinical trials: results from the IM-UNITI, UNIFI, and SEAVUE trials
Authors: Panés J , Panaccione R , Sands B , Gasink C , Marano C , Ma T , Hoops T 
Published: January 2023

Abstract

Background
Remission off steroids is a major treatment goal in inflammatory bowel disease. In the recent CORE-IBD consensus,1 the preferred definition of “corticosteroid-free” remission in clinical trials was withdrawal ≥12 weeks before the assessment timepoint. We evaluated the rates of corticosteroid-free remission according to three different definitions (ie, cross-sectional, ≥30, and ≥90 days) in the analysis of the corticosteroid-free remission endpoint using data from the IM-UNITI and SEAVUE trials of patients with Crohn’s disease (CD) and the UNIFI trial of patients with ulcerative colitis (UC).

Methods
In IM-UNITI and UNIFI, patients with moderate-to-severe CD and UC, respectively, who had previously responded to ustekinumab (UST) induction were randomized to placebo (PBO), UST 90mg SC q12w, or UST 90mg SC q8w. In SEAVUE, biologic naïve patients with moderate-to-severe CD were randomized to adalimumab 160mg SC at week 0, 80mg SC at week 2, and 40mg SC q2w or UST ~6mg/kg IV at week 0 and 90mg SC q8w. Each trial included protocols for mandatory corticosteroid tapering after the induction phase unless medically inappropriate (required in IM-UNITI and UNIFI starting at week 8 and recommended in SEAVUE starting at week 8 but required starting at week 16). Corticosteroid-free remission was defined as clinical remission (CDAI&lt;150 in IM-UNITI and SEAVUE and a Mayo score ≤2 with no individual subscore &gt;1 in UNIFI) and not receiving steroids at the assessment timepoint or ≥30 or ≥90 days before the assessment timepoint. Corticosteroid-free remission at week 44 was a major secondary endpoint in IM-UNITI and UNIFI (both cross-sectional). Corticosteroid-free remission (≥30 days before week 52) was a major secondary endpoint in SEAVUE.

Results
The proportions of patients who achieved corticosteroid-free remission were consistent, regardless of the corticosteroid-free duration used in the assessment (Tables 1 and 2). The results were consistent for both ustekinumab treatment groups (q12w and q8w) and placebo in the pivotal IM-UNITI and UNIFI studies (Table 1) and for both ustekinumab and adalimumab groups in the SEAVUE study (Table 2).

Conclusion
In CD and UC clinical trials of ustekinumab maintenance, which included protocol-mandated corticosteroid tapering regimens, corticosteroid-free remission results at 1 year were similar regardless of the corticosteroid-free duration used in the outcome definition.
References:
1) Ma C, Hanzel J, Panaccione R, et al. CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease. Gastroenterol 2022;4:950-64.
P584 Efficacy, safety, and tolerability of AMT-101, a gut selective oral IL-10 fusion, in the Phase 2 FILLMORE trial of patients with chronic pouchitis
Authors: Jairath V , Bressler B , Silverberg M S , Lee L Y , Lugo K A , Mayoral Monibas R , Annamalai T , Whitney J A , Weng E Y , Kanwar B , Danese S , Feagan B 
Published: January 2023

Abstract

Background
Chronic pouchitis can occur in up to half of patients within 10 years of ileal pouch-anal anastomosis (IPAA) after proctocolectomy for ulcerative colitis (UC). There is a large unmet need for medical treatments.

Methods
This was a phase 2, randomized double-blind, parallel-group, 2 active-arm trial of the combined phase 2/3 trial in adults (18-75 years) with a prior history of UC with proctocolectomy and subsequent IPAA, who presented with chronic or recurrent pouchitis. The trial was conducted in US, Canada, and Western Europe. Approximately 20 patients were planned to be randomized 1:1 to either 3 mg or 10 mg AMT-101 doses administered once daily, orally, for 12 weeks. The key efficacy endpoints were: 1) the proportion of patients with symptomatic improvement, as measured by stool frequency response, and 2) the proportion of patients with histologic healing, as measured by Geboes scores. Histology and endoscopy were centrally read.

Results
22 patients were randomized to receive AMT-101 3 mg (n=10) or 10 mg (n=12). The mean (SD) baseline absolute stool frequency was 13.4 (4.5). Overall, 36.4% (8/22) of patients achieved stool frequency response, defined as either a reduction of ≥ 3 stools and a ≥ 30% reduction in number of stools from baseline, or a return to post-IPAA number of stools or lower, at Week 12. 40% (4/10) and 33% (4/12) of patients dosed with 3 mg or 10 mg, respectively, achieved stool frequency response at Week 12. Rapidity of stool frequency response was demonstrated as early as Week 2 in both arms and was substantially maintained through Week 12.
Patients had a median (IQR) baseline Geboes score of 5.1 (3.2 to 5.2), representing severe pouchitis with ulceration and tissue destruction. Across both arms, 22.7% (5/22) [20.0% (3 mg) and 25.0% (10 mg)] of patients met the histologic healing response of Geboes score ≤ 3.1, an objective assessment of disease improvement. Endoscopic assessments (SES-CD, ≥50% reduction) were also performed, with modest improvements [10% (3 mg) and 8.3% (10 mg)] at Week 12.
There was no systemic AMT-101 PK (by design) nor anti-drug antibodies detected. Translational analysis revealed IL-10 biological responses in both arms. In tissue, IHC results showed increases in anti-inflammatory FOXP3+ (Tregs) and CD163+ (M2-macrophages) cells in the lamina propria.
Treatment emergent adverse events were mostly mild to moderate, with only one treatment-unrelated serious adverse event.

Conclusion
AMT-101 3 mg and 10 mg both appeared to be safe and generally well tolerated. PK and translational data confirmed AMT-101’s gut-restricted profile over the 12-week treatment with tissue-level PD effects and no systemic exposure. The AMT-101 3 mg dose is advancing into a Phase 3 trial for chronic pouchitis.
P586 Vedolizumab in Mild to Moderate Crohn’s Disease Patients Naïve to Biological Therapy: a Multicentric Observational Study
Authors: Dotti A Z , Vilela E G , Chebli J M F , Chebli L A , Magro D O , Steinwurz F , Argollo M , Carvalho N S , Parente J M L , Parra R S , Perin R L , Flores C , Morsoletto E M , Ferreira S D C , Ludvig J C , Kaiser Jr R L , Queiroz N S F , Faria M A G , Nicollelli G M , Andrade A R , Kotze P G 
Published: January 2023

Abstract

Background
Vedolizumab, a human monoclonal antibody that blocks integrin α4-β7, was approved for the management of Inflammatory Bowel Diseases. In real-world experience the number of patients using vedolizumab as first-line biological therapy was low, mainly in Crohn′s Disease (CD). This study aimed to evaluate the efficacy of vedolizumab exclusively in CD patients who were naïve to previous biologics, with mild to moderate disease. Additionally, we aimed to analyze the safety profile of vedolizumab, rates of mucosal healing, need for abdominal surgery and drug discontinuation over time in this specific population.

Methods
We performed a retrospective multicentric cohort study with patients with mild to moderate CD treated with VDZ who were naïve to previous biologics agents. These patients had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52 as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab over time.

Results
From a total of 72 patients (6 excluded) 53% (35/66) reached clinical remission at week 12. This percentage increased to 71.9% (46/64) at week 26, 88.1% (52/59) at week 52 and 81.8% (54/66) at the last follow-up visit. Clinical response was achieved in 72.7% (48/66), 92.2% (59/64), 95,1% (58/61) and 83.3% (55/66) in the same periods, respectively. Mucosal healing was achieved in 62.3% (33/57) of patients. Vedolizumab was well-tolerated and most adverse events were minor; 89.3% remained on vedolizumab after 52 weeks. During vedolizumab treatment, 3/66 patients underwent surgery.

Conclusion
Vedolizumab was effective in the management of patients with mild to moderate CD as first biological agent, with a remission rate of 88.1% after one year. Mucosal healing was observed in 62.3% of patients and major abdominal surgery was needed in only 4.5% of patients. This is one of the first international studies focused on the use of vedolizumab as a first-line biological treatment option in clinical practice in mild to moderate CD.
P599 Similar efficacy of mesalazine in adult and elderly patients: post-hoc analysis of randomised non-inferiority trial of 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis
Authors: Safroneeva E , Gerstner O , Laoun R 
Published: January 2023

Abstract

Background
Ulcerative colitis (UC) incidence has bimodal age distribution with a peak in the second to fourth decade and a second smaller peak in the sixth to eighth decade. We assessed the difference in rates of clinical and endoscopic response and remission in adult (≤60 years of age) and elderly (&gt;60 years of age) mild-to-moderate (Mayo Clinic Score ≥5) UC patients treated with mesalazine.

Methods
We performed a post-hoc analysis of data from a phase 3 non-inferiority trial of 817 UC patients treated with mesalazine for 8 and additional 38 weeks in a double-blind and open label study, respectively (D’Haens et al. Aliment Pharmacol Ther.2017;46:292–302). The differences between groups were analysed using Wilcoxon rank sum or chi-square test with continuity correction. P-value of &lt;0.05 was considered to be statistically significant.

Results
Elderly patients had longer disease duration, higher body mass index, higher number of co-morbiditities and concomitant medications recorded prior and during the trial, when compared with adults participating in the study (Table 1). These patients also had higher baseline Mayo endoscopic score (2.38±0.486 standard deviation [SD] in elderly vs. 2.26±0.439 SD in adult patients; p-value=0.0077). No difference in rates of combined clinical and endoscopic remission, clinical remission and response, endoscopic remission and response were observed at week 8 and 38 (Table 2).

Conclusion
We observed similar rates of clinical and endoscopic response and remission in adult and elderly mild-to-moderate UC patients treated with mesalazine for 8 and 38 weeks.
P600 Democratic deliberation to assess Veteran preferences for biosimilar medication switching for the treatment of Inflammatory Bowel Disease in a resource-conscious setting.
Authors: Ryan K , Hou J K , Baker J , Krenz C , De Vries R , Waljee A K 
Published: January 2023

Abstract

Background
Optimizing care while being resource-conscious, the Veterans Health Administration (VHA) must develop equitable policies incorporating Veterans’ values and beliefs. Switching patients with Inflammatory Bowel Disease (IBD) from biologic medications (originators) to less expensive biosimilars offers opportunities to explore potential policies. Unlike originators, the FDA did not require disease-specific randomized controlled trials for approval of biosimilars, raising provider and patient concerns about the safety of switching to these medications. Deliberative democratic (DD) methods allow us to assess Veteran views of switching programs, a necessary step in creating equitable policies.

Methods
We carried out two 2-day sessions with Veterans from the Ann Arbor VA (n=17) and Houston VA (n=12). Deliberation began with education about IBD, the use of biologics (including biosimilars), and related implementation challenges. Participants engaged in facilitated small group discussions to 1) identify Veterans views about biosimilar switching and Veteran preferences about switching, and 2) evaluate five approaches for switching: (a) “status quo”–switching policies vary by VHA facility, (b) “sickest last”–Veterans with severe IBD are switched last, (c) “opt-out”–Veterans may opt-out of switching, (d) “next appointment”–Veterans are switched at follow-up, and (e) “lottery”–patients are switched based on random selection. Participants ranked options (1=most preferred, 5=least preferred) and proposed modifications to these approaches. Participants completed pre- and post-DD session surveys. Transcripts were analysed using qualitative methods.

Results
Participant demographics are in Table 1. Most Veterans sessions preferred the “sickest last” (mean rank: 1.8, standard deviation: 0.9) or “opt-out” (2.4,1.4) approaches over the “status quo” (3.1,1.0) or “lottery” (4.6,0.9); preferences did not significantly change after deliberation (Figure 1). Preferences reflected Veterans’ concerns about the risk of switching to biosimilars for the most vulnerable Veterans and their strong preference for transparency around biosimilar switching. Participants emphasized the importance of informed choice, prioritizing based on health status, personalization, and shared decision-making.

Conclusion
DD methods are effective for soliciting Veterans' opinions and preferences for health policies. Veterans favoured policies that provided information and control, promoted shared decision-making, and reduced risk to vulnerable patients. Incorporating patient preferences and insights is critical when implementing health policies in the VHA and other resource-limited settings.
P608 Time to onset of effect of biologics and small molecules in moderate-to-severe or acute severe ulcerative colitis – a systematic review and network meta-analysis
Authors: Attauabi M , Dahl E K , Burisch J , Gubatan J , Nielsen O H , Seidelin J B 
Published: January 2023

Abstract

Background
Time to response of advanced therapies is an important parameter due to the symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. We aimed to assess the comparative onset of effectiveness of biological therapies and small molecules for this patient population.

Methods
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomized controlled trials or open-label studies assessing the effectiveness of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.

Results
The systematic literature search identified 20,406 citations, of which 28 studies comprising 11,155 patients fulfilled the eligibility criteria (Figure 1). All agents were superior to placebo for the induction of a clinical response at week 2 (Figure 2). Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest (Figures 3-4). Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Ustekinumab, and ozanimod ranked lowest across all endpoints.

Figure 1: Flow diagram of assessment of studies identified in the systematic review

Figure 2: Forest plot for achievement of clinical response at week 2 among patients with moderate to severe ulcerative colitis

Figure 3: Indirect comparison of biologics and small molecule drugs for the induction of clinical response at week 2 in patients with moderate-to-severe ulcerative colitis

Figure 4: Indirect comparison of biologics and small molecule drugs for the induction of clinical remission at week 2 in patients with moderate-to-severe ulcerative colitis

Conclusion
In this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of effectiveness of advanced therapies.
P617 Dual biologic therapy in pediatric Inflammatory Bowel Disease
Authors: Abbas R , Ibrahim N , Elawad M , Al-Mudahka F , Abdelrhman H , Akobeng A K 
Published: January 2023

Abstract

Background
There is paucity of data on the effectiveness of combination biologic agents as an option for children with refractory inflammatory bowel disease (IBD) that is inadequately controlled by biologic monotherapy. The aims of this study were to determine the effectiveness and safety of combination biologic use in pediatrics IBD.

Methods
A retrospective cohort study of children with IBD seen at Sidra Medicine and who received combination biologic therapy from October 2018 to April 2022. The diagnosis of IBD was established according to the revised Porto criteria. Children with IBD on two or more biologics were identified from our IBD database and their electronic medical records were reviewed. Patients included in the study must have been on combination biologic therapy for at least two months. Relevant clinical and demographic data were collected.

Results
Out of the 211 patients in our IBD database, we identified a total of 14 patients who had received dual biologic therapy within the study period. 3 patients were excluded because they had received dual biologic therapy for less than 2 months. 11 patients with IBD met our inclusion criteria and were included in this study. All 11 patients had Crohn’s disease. Overall, 7 patients (63%) were male, the median age at the start of starting combination therapy was 15.1 years (IQR 13.9 to 17.4), and the median disease duration was 2.3 years (IQR 1.4 to 3.2). Patients had been on the first biologic for a median of 20.3 months (IQR 13.0 to 32.3) before the addition of the second biologic. The reasons for dual biologic therapy included active disease, failure of single biological therapy, and development of complications. The patients had failed therapy with a median of two (range 1-3) prior biological medications. Concomitant dermatological disease (psoriasis) was present in one patient (9.1%). After a median follow-up of 5.2 months (IQR 2.9-5.5), median PCDAI significantly reduced from 22.5(IQR 16.75-30) to 5(1.25-13.75) {P&lt;0.001}…Figure 1. Median fecal calprotectin reduced from 1534 (1361-1612) to 489 (379-658) {P&lt;0.001}. No adverse events were noted.

Conclusion
Dual biologic therapy was associated with clinical and biomarker improvements in patients with Crohn’s disease who previously failed at least one single biologic. Dual biologic treatment was not associated with adverse events during the study period. Dual biologic therapy may be an attractive strategy but the lack of randomized controlled trials as well as long-term safety concerns means that there is a need for further trials on this subject. Future studies should assess risk: benefit ratios, safety, and efficacy of specific combinations of biologic use in IBD.
P625 Randomized controlled trial on the effect of megaboluses of intravenous corticosteroids added to oral corticosteroids in the treatment of moderately active ulcerative colitis
Authors: Llaó J , Martín-Arranz E , Zabana Y , Navarro-Llavat M , Garcia-Planella E , Busquets D , Monfort D , Pineda J R , Gutiérrez A , Villoria A , Menchén L , Bastida G , García-Alonso F J , Rivero M , Chaparro M , Riestra S , Merino O , Rodríguez-Lago I , Barreiro-de-Acosta M , Domènech Moral PhD E 
Published: January 2023

Abstract

Background
Oral corticosteroids remain as the first-line treatment for moderately active ulcerative colitis (UC). In controlled studies, they achieved clinical remission in 30-60% of patients at 30 days. In severe systemic diseases, intravenous bolus administration of methyl-prednisolone accelerates the clinical response and increases the therapeutic efficacy of corticosteroids.

Aims
To assess the additive effect of IV boluses of methyl-prednisolone in an outpatient Schedule on the remission rate of moderately active UC.

Methods
Randomized, controlled, open study. Inclusion criteria: 1) moderately active (complete May 6-10) distal or extensive UC; 2) never exposed to immunosuppressants or biologicals; 3) without corticosteroid therapy within the last 6 months. Randomization to oral prednisone 60mg/day (ORAL arm) or the same regimen preceded by intravenous boluses of 500mg methyl-prednisolone for 3 days (BOLUS arm). Primary endpoint: clinical and endoscopic remission at week 8 as defined by a complete Mayo score &lt;3 with no subscore &gt;1. Results are expressed in frequencies, medians and interquartile range.

Results
75 patients (39 ORAL, 36 BOLUS) were included, 24% at diesease onset, 49% extensive UC, 68% were on maintenance with oral 5ASA, and 31% had ever received systemic corticosteroids. At baseline, complete Mayo score was 9 (7-9), with C-reactive protein 9.25 mg/L (3.85-20.17) and fecal calprotectin 1430 ug/g (501-2702), with no differences in the baseline clinical-epidemiological characteristics between both treatment arms. At 8 weeks, 37% of patients achieved clinical-endoscopic remission (47% BOLUS vs 28% ORAL; p=0.089), 52% mucosal healing -Mayo endoscopic subscore &lt;2- (61% BOLUS vs 44% ORAL; p=0.129), 24% endoscopic remission -Mayo endoscopic=0- (31% BOLUS vs 18% ORAL; p=0.202) and 55% clinical remission - partial Mayo score &lt;2- (61% BOLUS vs 49% ORAL; p=0.281). No associated factors with clinical-endoscopic remission were identified.

Conclusion
The addition of three intravenous megaboluses at the beginning of a conventional regimen of oral prednisone achieves a non-significant increase in clinical-endoscopic remission rates at the end of corticosteroid treatment in patients with moderately active UC.