bluuebunny/crossref_metadata_2025_split huggingface dataset:
P433 Efficacy of risankizumab by baseline clinical, biochemical, and endoscopic disease severity in moderately to severely active Crohn's disease
Authors: Panaccione R , D'Haens G , Seenan J P , Caprioli F , Siegel C , Nakamura M , Wei S C , Kligys K , Zhang Y , Zambrano J , Song A P , Ferrante M 
Published: January 2023

Abstract

Background
Risankizumab (RZB), a p19-anti-interleukin-23 monoclonal antibody, has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Crohn’s disease (CD). This post hoc analysis evaluates the efficacy of induction and maintenance RZB therapy by baseline clinical, biochemical, and endoscopic disease severity.

Methods
In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance/inadequate response to ≥ 1 biologic (both studies) and/or conventional therapy (ADVANCE) were randomized to receive intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving stool frequency and/or abdominal pain score clinical response to 12 weeks of induction therapy were rerandomized in the FORTIFY (NCT03105102) study to receive subcutaneous (SC) maintenance RZB (180 mg or 360 mg) or PBO (withdrawal). Clinical and endoscopic endpoints were evaluated by baseline disease characteristics (Crohn’s Disease Activity Index [CDAI: ≤ 300, &gt; 300], highsensitivity C-reactive protein [hs-CRP: &lt; 10 mg/L, ≥ 10 mg/L], and Simple Endoscopic Score for Crohn’s Disease [SES-CD: 6−15, &gt; 15]). Induction analyses included patients who received RZB 600 mg or PBO; data from the ADVANCE and MOTIVATE studies were pooled. Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.

Results
The induction analysis included 527 patients who received RZB 600 mg IV and 362 patients who received PBO. Patients treated with RZB 600 mg IV achieved significantly higher response rates vs PBO at week 12, regardless of subgroup (P &lt; .05 for all; Figure 1). In the maintenance study, patients treated with SC RZB continued to achieve higher response rates vs the PBO (withdrawal) group at week 52 regardless of subgroup (P was not &lt; .05 for all; Figure 2). Improvements in clinical and endoscopic outcomes were generally observed from weeks 12 to 52 with RZB treatment across all subgroups. Response rates were generally similar across subgroups in both induction and maintenance studies; endoscopic remission and ulcer-free endoscopy (resolution of ulcer) rates were numerically lower for patients with increased inflammation (hs-CRP &gt; 10 mg/mL) and higher endoscopic activity (SES-CD &gt; 15).

Conclusion
RZB induction therapy resulted in higher response rates for clinical and endoscopic outcomes compared with PBO at week 12, regardless of baseline clinical, biochemical, and endoscopic disease severity. RZB also showed durable efficacy with continued RZB maintenance therapy, supporting the long-term use of RZB for patients across a range of baseline disease severity and activity.
P435 Real-world comparison of effectiveness between ustekinumab and a second anti-TNF agent in patients with symptomatic stenosing Crohn's disease after failure of a first anti-TNF agent: results of the USTEKNOSIS study
Authors: Buisson A , Jammet A , Pereira B , Fumery M 
Published: January 2023

Abstract

Background
While surgery was considered as the reference for stricturing Crohn's disease (CD), anti-TNF agents are now the first-line treatment thanks to the CREOLE study.
However, there is no efficacy data after anti-TNF failure.
We aimed to compare the effectiveness of ustekinumab and a second anti-TNF agent after failure of a first anti-TNF in symptomatic stricturing Crohn’s disease (CD).

Methods
In this multicenter study, we retrospectively included all adult patients with CD treated with ustekinumab or anti-TNF for symptomatic stricture (confirmed on imaging or endoscopy) after prior exposure ≥ one anti-TNF for the current stricture, without surgery between the failure of the last anti-TNF and the study.
The primary endpoint was clinical remission (composite endpoint) at 6 months was defined as no pain, no vomiting, no food restriction, no sub-occlusive episode, no steroid, no surgery or discontinuation of treatment.
The long-term endpoints were discontinuation of treatment for failure, bowel damage progression and surgery.
The comparisons were performed after using propensity score analysis adjusted on potential confounders.

Results
Overall, 70 patients were analyzed, including 34 in the ustekinumab group and 36 in the anti-TNF group (29 on infliximab and 7 on adalimumab). The two groups were similar for age (38.5 vs 37.6 years), CD duration (12.2 vs 13.5 years), female gender (41.2% vs 51.8%), CD location (p=0.43) and CD phenotype (p=0.38). Concomitant immunosuppressant was observed in 63.9% with an anti-TNF versus 8.8% with ustekinumab. The number (p=0.56) and the length (p=0.10) of stricture were also similar. The proportion of patients ≥ 2 prior biologics was higher in the ustekinumab group (41.2% vs 8.3%; p=0.001). The rate of primary failure to anti-TNF agent was comparable (16.7% vs 20.6%).
After adjustment based on propensity scores, the rate of clinical remission at 6 months was 73.9% and 42.7% (p = 0.24), under ustekinumab and anti-TNF, respectively. The predictive factors of remission in patients receiving ustekinumab were prior bowel resection (p=0.001) and length of stricture &lt; 12 cm (p=0.042), while no predictor was found in those treated with anti-TNF agent. The risk of treatment discontinuation for failure (HR =2.86 [1.33-6.15]; p=0.008) or bowel damage progression (HR=3.90 [1.64-9.24]; p=0.003) were significantly greater in patients receiving another anti-TNF agent compared to those on ustekinumab. We did not observe any significant difference concerning the risk of surgery (HR=2.60 [0.70-9.61]; p=0.15).

Conclusion
Ustekinumab seems to be more effective than a 2nd anti-TNF to treat symptomatic stricturing CD after failure of a first anti-TNF. However, these data need to be confirmed by independent prospective data.
P439 Induction of endoscopic response, remission and ulcer-free endoscopy with upadacitinib is associated with improved quality of life in patients with Crohn’s disease
Authors: Panés J , Louis E , Bossuyt P , Joshi N , Lee W J , Lacerda A , Remple V , Xuan S , Loftus Jr. E V 
Published: January 2023

Abstract

Background
Patients with Crohn’s disease (CD) experience reduced quality of life (QoL), and disease-related impact on work productivity, contributing to a high disease burden. This study evaluated the association of achieving endoscopic outcomes at week 12 and associated QoL at week 52 in patients with CD treated with upadacitinib (UPA).

Methods
This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and one maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Meaningful improvement in QoL outcomes (Inflammatory Bowel Disease Questionnaire [IBDQ] remission ≥170, IBDQ response increase ≥16, Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F] response increase ≥9, Short Form 36 [SF-36] Physical Component Score [PCS] and Mental Component Score [MCS] change ≥5, and Work Productivity and Activity Impairment Questionnaire [WPAI] change ≥7%) was evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test.

Results
Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.2%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained a meaningful improvement in PROs by week 52 (IBDQ remission, 52.6% vs 30.3%; IBDQ response, 56.6% vs 36.8%; FACIT-F response, 46.7% vs 25.9%; SF-36 PCS 49.3% vs 30.8% and MCS 39.5% vs 25.9%; all P≤0.01, Table 1). Additionally, patients who achieved endoscopic response (vs those who did not) at the end of induction were more likely to attain meaningful improvement in WPAI overall work impairment by week 52 (47.1% vs 26.5%, P≤0.01, Table 1). Similar findings were observed in patients who achieved endoscopic remission (P≤0.01, Table 1) and ulcer-free endoscopy (P≤0.05, Table 1) vs those who did not at end of induction.

Conclusion
Achieving endoscopic outcomes at end of induction treatment was associated with meaningful improvement in quality of life and overall work productivity at 52 weeks for patients with CD receiving UPA. Endoscopic remission and ulcer-free endoscopy were associated with very similar long-term benefit.
P441 Long-term CD treatment failure and dose modification rates with vedolizumab and other biologics: Results from a large prospective observational study
Authors: Siegmund B , Siegel C A , Sebastian S , Zhou J , Jones S , Adsul S , Louis E 
Published: January 2023

Abstract

Background
Durable treatment effectiveness is an important consideration in the long-term management of patients with Crohn’s disease (CD) receiving biologic therapy. The aim of this analysis was to evaluate rates of failure and dose modification for biologic treatment over time in patients with CD using data from a large long-term observational study evaluating secondary outcomes in patients initiating treatment on vedolizumab (VDZ) and other biologics.

Methods
We analysed data from a multicentre, prospective, observational, post-authorisation safety study (PASS; NCT02674308, EUPAS6469) following VDZ or other biologic treatment cohorts under routine standard of care. Longitudinal data on treatment failure (including biologic discontinuation†, IBD non-surgical hospitalization, primary IBD surgery and corticosteroid initiation) up to 36 months and dose modification at any time during the study were analysed in biologic-naïve and biologic-experienced patients with CD in the treatment cohorts.

Results
The cohort comprised 1338 biologic-naïve patients (pts) (VDZ, n=312; other biologics, n=1026) and 1543 biologic-experienced pts (VDZ, n=829; other biologics, n=714). Baseline pt characteristics (Table 1) were broadly similar across different treatment cohorts, although there were some notable differences with respect to fistulising disease and age at CD diagnosis.

Treatment failure rates for biologic-naïve and biologic-experienced pts cumulatively over time at specific time points are shown in Table 2. The proportion of pts continuing biologic treatment with dose modification at any time during the study period for biologic-naïve pts was 13/312 (4.2%) in VDZ-treated pts vs 502/1026 (48.9%) in the group treated with other biologics and 34/829 (4.1%) vs 433/714 (60.6%), respectively for biologic-experienced pts.

Conclusion
This large observational study reported rates of treatment failure, hospitalization, and IBD-related surgeries during long-term follow-up of biologic-naïve and biologic-experienced pts with CD. Dose modification occurred less frequently in biologic-naïve and biologic-experienced pts treated with VDZ compared with pts receiving other biologic treatments during the study.
P442 Endoscopic resection of visible precancerous lesions in patients with colonic Inflammatory Bowel Disease
Authors: Busacca A , De Sire R , Capogreco A , Dal Buono A , Gabbiadini R , Loy L , Finati E , Spadaccini M , Maselli R , Hassan C , Repici A , Armuzzi A 
Published: January 2023

Abstract

Background
IBD patients have an increased risk of reporting a colorectal cancer. According to SCENIC, endoscopic resection (ER) should be preferred to biopsies for visible precancerous lesions in absence of stigmata of invasive cancer or submucosal fibrosis. However, the evidence is still lacking on specific outcomes of ER for the management of dysplastic lesions in IBD. Aim of this study was to evaluate the effectiveness and safety of ER of visible precancerous lesions in IBD patients.

Methods
In this retrospective study, we included consecutive IBD patients referred to an Endoscopy Unit (2016-2022) to undergo a ER, including endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and hybrid EMR-ESD (hESD), of visible precancerous lesions. The primary outcome was the assessment of rates of en bloc resection, R0 resection and adverse events (AEs). The secondary outcome was the rate of post-ER surgery and surgery for refractory IBD. En bloc resection was defined as excision of the targeted lesion in a single specimen. R0 resection was defined as resection with lateral and deep margins free of dysplasia/neoplasia on histopathology. Among AEs, we considered bleeding and perforation.

Results
A total of 67 visible lesions (64.18% non-polypoid, 53.73% left-side colon, median size 25 mm±20 mm, 65.67% neoplastic pit-pattern) in 67 patients with colonic IBD (56.72% male, median age 58 yrs±15 yrs, 68.66% ulcerative colitis, median disease duration 160 months±98 months, 58.21% active disease) were included. ESD, hESD, and EMR was performed in 20.9%, 6%, and 73.1% of cases. The final histopathological diagnoses after ER were inflammatory polyp in 32.84%, SSL in 8.96%, LGD in 40.30%, HGD in 13.42%, adenocarcinoma in 2.99%, and squamous cell carcinoma in 1.49% of cases. Excluding inflammatory polyps, en bloc resection was achieved in 14/14(100%), 3/4(75%), and 15/27(55%) lesions in case of ESD, hESD, and EMR (ESD+hESD vs EMR p&lt;0.05). R0 resection was achieved in 12/14(86%), 3/4(75%), and 15/27(55%) lesions in case of ESD, hESD, and EMR (ESD+hESD vs EMR p=0.05). AEs occurred in 21% (2 bleedings and 1 perforation), 0%, and 3% (1 perforation) of patients treated by ESD, hESD and EMR (ESD+hESD vs EMR p=N.S.). Post-ER surgery rate was 21%, 25%, and 3% for patients treated by ESD, hESD, and EMR. Surgery for refractory IBD rate was 7%, 0%, and 18% for patients treated by ESD, hESD, and EMR.

Conclusion
Our findings showed that ER (including ESD, hESD, and EMR) of visible precancerous lesions performed in a tertiary center might be considered feasible, safe and effective in IBD patients, despite the presence of submucosal fibrosis. These data should be confirmed in a wider IBD population referring from different specialized Endoscopy Units.
P452 Fecal Microbiota Transplantation Leads to Lower IBD Related Complications in Hospitalized Inflammatory Bowel Disease Patients with Clostridioides difficile Infection: A retrospective cohort study
Authors: Le P H , Chiu C H , Chiu C T , Kuo C J , Yeh P J , Chen C C , Pan Y B 
Published: January 2023

Abstract

Background
Clostridioides difficile (C. difficile) infection (CDI) increases the risks of hospitalization, colectomy, and mortality in inflammatory bowel disease (IBD). There has been no study comprehensively evaluating the risk factors, clinical characteristics, and outcomes of CDI in IBD.

Methods
In this retrospective cohort study, we enrolled hospitalized IBD patients with toxin A/B results for C. difficile in a medical center between April 2007 and April 2021. They were divided into CDI group and control groups. The risk factors, clinical presentations and outcomes were analyzed.

Results
A total of 144 IBD inpatients (45 CDI group and 99 control group) were enrolled for analysis. The median follow-up duration was 15.5 months. The incidence of CDI in IBD inpatients was 31%. The risk factors of CDI included longer IBD duration, biological failure, and biological user. More patients presented as abdominal pain in CDI group (77.8% vs 55.6%, P=0.011). After antibiotics treatment and fecal microbiota transplantation, 83.3% patients had negative result, and 61.9% had improved clinical symptoms. Regarding clinical outcomes, CDI led to more hospitalizations (median 2 times (range 0-12 times) vs median 1 time (range 0-19 times), P=0.008), lower steroid free remission rate (46.7% vs 67.7%, P=0.017) and higher Mayo score (median 5 points (range 2-12 points) vs median 3 points (range 0-12 points)). Compared to antibiotics treatment, the patients receiving fecal microbiota transplantation (FMT) had less times of hospitalization and less IBD related complications during follow-up.

Conclusion
CDI led to more hospitalizations, lower steroid free remission rate and higher Mayo score in IBD inpatients. FMT should be considered in refractory or recurrent CDI in IBD to improve the clinical outcomes.
P465 Health-related quality of life from the Inflammatory Bowel Disease Questionnaire in patients with ulcerative colitis treated with etrasimod in the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials
Authors: Armuzzi A , Rubin D T , Schreiber S , Panés J , Fellmann M , Bartolome L , Goetsch M , Bhattacharjee A , Wu J , Chaparro M , Dubinsky M C 
Published: January 2023

Abstract

Background
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5) in development for the treatment of moderately to severely active ulcerative colitis (UC). ELEVATE UC 52 and ELEVATE UC 12 were two phase 3 studies that demonstrated efficacy and safety of etrasimod in patients with UC in which several patient-reported outcomes were collected. Health-related quality of life (HRQoL) was assessed in a post hoc analysis of the ELEVATE programme with the validated Inflammatory Bowel Disease Questionnaire (IBDQ).1

Methods
In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). Patients in the full analysis set with modified Mayo Scores 5-9 with a completed 32-item IBDQ questionnaire at baseline, week 12 (both trials) and week 52 (ELEVATE UC 52 only) were included in this analysis. Least squares mean (LSM) change from baseline for IBDQ total score and IBDQ domain scores were compared between etrasimod and PBO arms in both trials at each time point (data as observed), along with the proportion of patients who achieved IBDQ remission (IBDQ total score ≥170; nonresponder imputation).

Results
At baseline, a total of 237 and 191 etrasimod-treated patients and 112 and 96 PBO-treated patients completed the IBDQ for ELEVATE UC 52 and ELEVATE UC 12, respectively. LSM change from baseline in IBDQ total scores for etrasimod vs PBO were 42.8 vs 27.4 (difference [95% CI] 15.4 [6.5, 24.4]; P&lt;0.001) and 55.8 vs 38.1 (difference [95% CI] 17.7 [6.6, 28.6]; P=0.002) at week 12 and week 52, respectively, in ELEVATE UC 52, and 47.5 vs 30.2 (difference [95% CI] 17.3 [8.5, 26.2]; P&lt;0.001) at week 12 in ELEVATE UC 12 (Figure 1A). A greater proportion of etrasimod-treated patients achieved IBDQ remission at week 12 in both trials and week 52 in ELEVATE UC 52 (Figure 1B). Etrasimod-treated patients demonstrated significant improvements from baseline vs PBO in all 4 IBDQ domains in both trials (Figure 2). Across all IBDQ domains, improvements were seen at 12 weeks and the LSM change from baseline was greatest among etrasimod-treated patients at all time points.

Conclusion
Patients treated with etrasimod demonstrated greater improvement from baseline in total and all 4 domain scores of the IBDQ at the end of the 12-week induction phase and 52-week maintenance phase in comparison with PBO. These findings demonstrate the benefits of etrasimod on disease-specific HRQoL and support the clinical findings from the ELEVATE programme.
Reference:
1. Chen XL, et al. Health Qual Life Outcomes. 2017;15:1-13.
P469 Effect of mirikizumab on clinical and endoscopic outcomes based on prior advanced therapy failure in patients with moderately to severely active ulcerative colitis
Authors: Navabi S , D’Haens G , Samaan K H , Li X , Arora V , Redondo I , Danese S 
Published: January 2023

Abstract

Background
In Phase 3 induction (LUCENT-1) and maintenance (LUCENT-2) studies, mirikizumab (miri), was well-tolerated and efficacious in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response, loss of response or intolerance to conventional or advanced therapy. This analysis evaluated clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy based on number and types of prior targeted immune modulator (TIMs) failures, where TIMs include biologics (anti-TNFs, vedolizumab (VDZ)) and tofacitinib.

Methods
Patients were randomized at induction baseline to receive 3 intravenous doses of 300mg miri or PBO every 4 weeks (Q4W). Responders to miri induction at Week 12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W40 (52 weeks of continuous therapy). Endpoints evaluated were clinical remission, clinical response, symptomatic remission, and endoscopic remission at Week 12 of LUCENT-1, and clinical remission, corticosteroid (CS)-free remission, endoscopic remission, and histologic-endoscopic mucosal remission (HEMR) at Week 40 of LUCENT-2. Efficacy in the subgroup of patients who failed 0, 1, ≥2 prior TIMs, anti-TNFs, VDZ, or both anti-TNF and either VDZ or tofacitinib (anti-TNF+1) were assessed. There were not enough patients with prior tofacitinib failure alone for statistical significance analysis.

Results
At LUCENT-1 baseline, 58.8%, 21.1%, and 20.2% of patients failed 0, 1, and ≥ 2 prior TIMs, respectively. 36.3% failed anti-TNFs, 18.8% failed vedolizumab (VDZ), and 15.2% failed an anti-TNF +1 other TIM. At Week 12 of LUCENT-1 and Week 40 of LUCENT-2, a greater proportion of miri-treated patients achieved efficacy endpoints compared with placebo for all subgroups (Table 1). The treatment differences [95% CI] were significant for all subgroup analyses except for some subgroups from two endpoints: clinical remission at Week 12 of induction and HEMR at week 40 of maintenance (Figure 1). Three subgroups in the Week 12 clinical remission analysis did not achieve significant treatment differences: 1 prior TIM failure (6.5% [-2.9%, 15.8%]), ≥2 prior TIM failures (7.6% [-0.3%, 15.5%]), and anti-TNF failure (6.4% [-0.6%, 13.4%]). For the HEMR endpoint all subgroups achieved significant treatment differences except for the 1 prior TIM failure subgroup (15.3% [-1%, 31.6%]).

Conclusion
Regardless of the number and types of failed prior advanced therapies, mirikizumab is efficacious for both induction and maintenance therapy in patients with moderately to severely active UC.