bluuebunny/crossref_metadata_2025_split huggingface dataset:
P546 Comparative efficacy and safety of upadacitinib versus ustekinumab as induction therapy in patients with moderately to severely active ulcerative colitis: A matching-adjusted indirect comparison
Authors: Reinisch W , Panaccione R , Duijvestein M , Ceballos Santos D , Melmed G Y , Xuan S , Wegrzyn L , Levy G , Ilo D , Sanchez Gonzalez Y 
Published: January 2023

Abstract

Background
Upadacitinib (UPA), an oral Janus kinase inhibitor, and ustekinumab (UST), a parenteral IL-12/23 inhibitor, are approved therapies for patients (pts) with moderately to severely active Ulcerative Colitis (UC). In the absence of head-to-head data, we conducted a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) to compare efficacy and safety of UPA vs UST during induction.

Methods
Pts received UPA 45 mg oral, once daily for 8 weeks or PBO in the phase 3 studies U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026), and UST 6 mg/kg IV at week 0 with 8-week follow up or PBO in the phase 3 study UNIFI (NCT02407236). Efficacy outcomes were stratified by previous biologic exposure (ie, no prior exposure [bio-naïve] or inadequate response, loss of response, or intolerance to biologics [bio-failed]). Baseline characteristics for age, gender, extent and duration of disease, total Inflammatory Bowel Disease Questionnaire score, total Mayo score, high-sensitivity CRP, faecal calprotectin levels, weight, and UC medication use from the UPA trials were weighted to match the UNIFI trial. Efficacy outcomes at Week 8 were clinical remission per full Mayo score (FMS; FMS ≤2 with no subscore &gt;1), clinical response (decrease in FMS ≥3 points and ≥30%, plus a decrease in rectal bleeding score [RBS] of ≥1 or an absolute RBS of 0 or 1), endoscopic improvement (endoscopic subscore 0 or 1), and histologic-endoscopic mucosal improvement (HEMI). Safety outcomes evaluated in the overall population were adverse events (AEs) and serious AEs (SAEs), comprising the only safety assessments consistently collected across trials. Numbers needed to treat/harm (NNT/NNH) were calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes between UPA and UST.

Results
The MAIC included 824 UPA and 625 UST pts with efficacy data and 839 UPA and 639 UST pts with safety data. A greater proportion of pts receiving UPA vs UST in bio-naïve and bio-failed groups achieved clinical remission, endoscopic improvement, and HEMI after weighting (p≤0.01, Table 1) with NNTs &lt;10. In bio-naïve pts, differences in the proportion of pts with clinical remission, clinical response, endoscopic improvement, and HEMI for UPA vs UST were 0.172, 0.146, 0.312, and 0.255, respectively, and 0.105, 0.235, 0.135, and 0.118 for bio-failed pts. AEs and SAEs were not statistically different between UPA and UST.

Conclusion
During induction, greater efficacy with similar safety was observed with UPA vs UST for pts with moderately to severely active UC based on MAIC. Potential bias due to unobserved confounders may exist with MAIC methodology. Further analyses to assess longer-term outcomes are warranted.
P567 How can we predict the development of antibodies to infliximab in Crohn’s disease?
Authors: Ferreira A I , Lima Capela T , Macedo Silva V , Xavier S , Arieira C , Cúrdia Gonçalves T , Dias de Castro F , Moreira M J , Cotter J 
Published: January 2023

Abstract

Background
Anti-tumour necrosis factor-α (anti-TNF-α) therapy is an effective treatment for Crohn’s disease (CD). However, treatment failure is common. Our aim was to identify predictors of anti-TNF-α therapy failure.

Methods
Retrospective single-center study including anti-TNF-α naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate(ESR), c-reactive protein(CRP), faecal calprotectin, infliximab serum concentrations and antibodies to infliximab(ATI). Anti-TNF-α therapy failure was defined as ATI development at 6 or 12 months, absence of clinical response at 6 months, absence of clinical remission or objective response at 12 months. Clinical response was defined as reduction in Harvey-Bradshaw index(HBI) of≥3points comparing with initial value or HBI&lt;5points if initial HBI≥7points and clinical remission as HBI≤4points. Objective response was assessed by endoscopic studies (improvement of mucosal inflammation and absence of deep ulcerations) or imaging (improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement).

Results
Totally 53 CD patients were included, 49.1%treated with combination of anti-TNF-α and immunomodulatory therapy. Anti-TNF-α therapy failure occurred in 21 patients(39.6%). At 6 months, ATI development occurred in 6 patients(11.3%) and absence of clinical response in 9(17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0%.
At 6 months, ATI development was significantly higher in patients with lower infliximab serum concentrations at week 14 (with ATI 5.9±3.2 vs without 14.3±7.7, p&lt;0.001). Additionally, ATI development was significantly higher in patients with a higher initial value of ESR (with ATI median 35 vs without median 13, p=0.045). The infliximab serum concentrations at week 14 (AUC 0.828;p=0.009; sensitivity 0.833, specificity 0.404 for values≤11.6) and the initial value of ESR (AUC 0.754;p=0.045; sensitivity 0.833, specificity 0.468 for values≥15) had very good and good discriminative capacity, respectively, in predicting ATI development. No statistically significant differences were found in initial values of CRP and faecal calprotectin. The other definers of anti-TNF-α therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of biochemical parameters.

Conclusion
Infliximab serum concentration after induction is the most important factor in ATI development, influencing treatment response, regardless of the combination with immunomodulatory therapy. Higher initial value of ESR can also predict the development of ATI.
P571 Frequency and risk factors of advanced neoplasia in Korean IBD patients with Low Grade Dysplasia in previous surveillance
Authors: Park Y E , Kim D H , Park S K , Lee Y J , Lee C K , Kim E S , Kim K O 
Published: January 2023

Abstract

Background
There are insufficient studies on clinical outcome after surveillance of low grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD). We aimed to evaluate the clinical feature, frequency and risk factors of advanced neoplasia in IBD patients after diagnosis of LGD

Methods
From 2003 to 2020, medical records of 166 IBD patients from 6 university hospitals in Korea were reviewed retrospectively. All of the patients were diagnosed as LGD in surveillance. Patents’ baseline characteristics, disease status, polyp characteristics and treatment were evaluated. The frequency and risk factors of advanced neoplasia were also analyzed.

Results
Disease duration was 11.47 years (7.85-14.50), and follow-up duration was 3.74 years (1.95-7.58). Colitis associated LGD was noted in 56 cases (33.7%), Advanced neoplasia developed in 12 cases (6 large LGD, 3 tubulovillous adenoma, 3 high grade dysplasia) and all the cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo score and colitis-related dysplasia were more common than sporadic lesions (83.3% vs. 29.9%; P&lt;0.001). In multivariate analysis, colitis-associated LGD significantly increased the risk of developing advanced neoplasia (Odds ratio [OR], 10.516; 95% confidence interval [CI], 2.064-53.577; P=0.005). Among patients with colitis-associated lesions, a significant risk factor for advanced neoplasia was a history of LGD (OR, 9.429; 95% CI, 1.330-66.863; P=0.025).

Conclusion
Advanced neoplasia developed in 7.2% of IBD patients with LGD. Because most of advanced neoplasia developed from colitis-associated lesions, more careful examination is suggested in patients with colitis -associated LGD, especially with previous history, in surveillance colonoscopy.
P595 Time of Therapeutic Drug Monitoring of infliximab during induction and its relationship with clinical remission in Inflammatory Bowel Disease
Authors: Muñoz-Villafranca C , Arreba P , Gomez M , Ispizua Madariaga N , Buendia L , Lopez M L , Ugarte A , de la Fuente I , Prado N , Irusta L , Jimenez M A , Santa Cruz M , Gonzalez M , Bilbao A , Ortiz de Zárate J 
Published: January 2023

Abstract

Background
The usefulness of therapeutic drug monitoring(TDM) of infliximab during induction and its relationship with clinical outcome in patients with inflammatory bowel disease(IBD) is well established. However, the optimal time of monitoring in terms of clinical outcomes remains unclear.
The aim is to evaluate the TDM at various times during induction and its association with clinical remission.

Methods
An observational, retrospective and single-centre study of patients with active disease ,Crohn’s disease (CD) or ulcerative colitis(UC), was performed. Induction treatment with infliximab 0, 2, 6 weeks was conducted and if there was response, maintenance therapy was provided.
Antibody levels were measured in serum samples at week 2 and week 14 by using an enzyme-linked immunosorbent assay, within the therapeutic range(3-8 µg/ml). Patients were followed at least for one year or until loss of response. The clinical response was assessed in week 14 and week 52 by Harvey-Bradshaw Index in CD and Mayo Partial Index in UC.

Results
Out of 93 patients that were evaluated, 23 with UC(24.73%) and 70 with CD(75.27%,), 65 (69.89%) and 58 patients(62.37%) achieved remission at week 14 and week 52 respectively. Infliximab levels at week 14 but not at week 2 were significantly higher in patients who achieved clinical remission in both week 14 (5.8 vs 2.1 µg/ml; p=0.0002) as in week 52 (6.4 vs 1.9 µg/ml; p=0.0001).
The levels at week 14, but not at week 2 had predictive value of remission, in both week 14 [OR 1,4 (CI 1.14-1.76) p=0.001] and week 52 [OR 1.4 (CI 1.15-1.87); p=0.001]. The patients with immunosuppressants at week 14 presented the highest rate of remission in week 52 (77.78 vs 52.63; p=0.014). The intensification of treatment was a negative factor to achieve remission both in week 14 and at week 52.

Conclusion
The levels of infliximab in week 14 are higher and have predictive value of clinical remission both in early (week 14) and long-term (week 52). Levels of infliximab in week 2 did not provide significant predictive value of clinical response. The use of immunosuppressants could be a favourable factor of clinical outcome.
P598 The utility of the “Low Anterior Resection Syndrome SCORE” in assessing the postoperative outcomes of patients undergoing restorative proctocolectomy with ileal pouch anal-anastomosis for Ulcerative Colitis
Authors: Perotti S , Mineccia M , Daperno M , Massucco P , Gonella F , Ferrero A 
Published: January 2023

Abstract

Background
Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) in a J-pouch configuration is the treatment of choice for patients with ulcerative colitis. Some patients who have undergone this surgery present symptoms including fecal or gas incontinence, urgency, clustering, and frequency, that occurs after anal sphincter-sparing surgery for the treatment of rectal cancer. There is a lack in standardization and evaluation of functional outcomes. Our aim is to evaluate the effectiveness of the LARS (low anterior resection syndrome) score in this cohort of patients.

Methods
We conducted a retrospective analysis of a prospectively maintained single center database. We assessed the quality of life by using the Inflammatory Bowel Disease Questionnaire (IBDQ-32). The functional bowel complaints were assessed using the LARS score.

Results
Between 2015 and 2020, 70 patients with ulcerative colitis underwent total colectomy and subsequent IPAA with J-Pouch configuration. Among these, 49 patients who closed the ileostomy and were followed for at least 6 months, were selected for the present study. Nineteen patients did not have the LARS; among 30 who complained the LARS, 17 had a major LARS (tab.1). The latter had a worse quality of life on the IBDQ-32 questionnaire, especially in relation to urgency and frequency (Fig.1). We compared the two scores using Spearman's test correlation coefficient, detecting a significant correlation (rho -0.7664185; p-value &lt;0.005); a significant correlation between the urgency sub-category with LARS score (rho -0.6515759; p-value &lt;0.005) and frequency (rho -0.6744705; p-value &lt;0.005) was evaluated.
Tab 1: Patients characteristics:

Fig.1:IBDQ-32 value in different LARS categories

Conclusion
In our experience LARS score appears to be a useful, effective and simple tool to predict functional outcomes and QoL not only in oncological rectal sphincter-sparing surgery but also in functional surgery for ulcerative colitis.
P615 The safety and efficacy of ustekinumab combined with sphincter-preserving surgery for perianal fistulizing Crohn’s disease:a single-center retrospective study
Authors: Li Y , Gu Y 
Published: January 2023

Abstract

Background
To assess the clinical efficacy and safety of ustekinumab(UST) combined with sphincter-preserving surgery in the treatment of perianal fistulizing Crohn’s disease(pfCD).

Methods
A single-center retrospective study. The baseline data of pfCD patients who met the inclusion and exclusion criteria and visited the Anorectal Department of the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2020 to March 2022 were collected. Patients were assessed for fistula response and remission by rectal magnetic resonance image(MRI) and perianal disease activity index(PDAI). Patients' fistula response and remission were assessed by rectal MRI and PDAI. Patients were assessed for clinical response and remission by using Crohn's disease activity Index( CDAI). Patients' anal function was assessed by using the Wexner score. The differences in CDAI,PDAI and inflammatory parameters, including C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR), at 0 week, 8 weeks and 16 weeks were statistically analyzed.

Results
A total of 64 pfCD patients were included. Fistula response was 23.4% (8 weeks), 40.6% (16 weeks), and 51.6% (follow-up endpoint); fistula remission was 21.9% (follow-up endpoint); fistula MRI remission was 9.3% (follow-up endpoint); clinical response was 68.8% (8 weeks) and 79.7% (16 weeks); and clinical remission was 46.9% (8 weeks) and 59.4% (16 weeks). CDAI, PDAI and inflammatory parameters at the 8th and 16th week of treatment were significantly lower than those before treatment (p&lt;0.05). There was no significant difference in postoperative anal function (p&lt;0.05). The incidence of adverse events was 1.6%.

Conclusion
UST combined with sphincter-preserving surgery is safe and effective in the treatment of pfCD.This therapy can effectively improve the fistula condition and systemic manifestations.
P616 Fatigue in pediatric inflammatory bowel diseases – systematic review and rates in a prospective cohort
Authors: Focht G , Turner S , Carmon N , Lev-Tzion R , Orlanski-Meyer E , Ledder O , Yogev D , Assa A , Turner D 
Published: January 2023

Abstract

Background
Studies in adults suggest that fatigue is amongst the most commonly reported symptoms, reaching ~50% of patients, often even while the patients enter clinical remission. However, fatigue has been rarely discussed in children and no study hitherto determined the rate of fatigue in pediatric IBD (PIBD). We aimed to perform a systematic review of the literature in children with either CD or UC and to explore the rate of fatigue in a prospective inception cohort of PIBD.

Methods
A systematic review of the literature was conducted for pediatric studies of any design reporting fatigue as an outcome. Manuscripts were reviewed by 2 authors, inclusion was based on consensus. Next, children with new onset IBD were asked to complete the IMPACT-III, a health-related quality of life (QOL) questionnaire at 4 months after diagnosis, to capture response to treatment. Children &lt;9 years who are unable to reliably report fatigue by themselves were excluded. Four fatigue-related questions were analyzed (Table 1). Each question has 5 response options each assigning 25 points according to the users’ guide (i.e. 0, 25, 50, 75, 100 points when the latter implies higher QOL and lack of fatigue). Remission was defined as wPCDAI&lt;12.5 for CD and PUCAI&lt;10 for UC. Explicit clinical and demographic data were prospectively recorded.

Results
In the systematic review only 12 studies reported on fatigue in pediatric IBD were identified,8 of which reported fatigue as primary outcome and 1 was an intervention trial. None provided rate of fatigue,also since unlike in adults,no PIBD-specific fatigue measuring scale was available. A total of 86 children were included in the inception cohort (median age 14.5[IQR 12.8-15.9] years,39[45%] females;59[69%] CD,27[31%] UC;47(55%) in clinical remission). At 4 months, only 4 patients (4.6%) selected the highest score (100) for all 4 questions, i.e. no fatigue). Forty four children (53%) had min 2 questions with a score &lt;100,of whom 27 (61%) were in clinical remission. Twenty-eight children (33%) did not score 100 in neither of the 4 questions and 12(14%) had scored all 4 questions≤50. Of the 47 children who were in clinical remission,33(70%) had at least 2 of the 4 questions scored&lt;100.

Conclusion
The reporting and assessment of fatigue among pediatric IBD literature is extremely limited. This study is the first to report fatigue rate in children. We show that after induction treatment fatigue rate of any severity may be as high as 53%, moderate fatigue as 33% and severe fatigue as 14%. Fatigue was common also in those in clinical remission. Our results call for a more standardized tool of measuring fatigue in PIBD since its quantification can facilitate a more methodical management of this disabling and underreported symptom.
P629 Real-life treatment persistence and treatment outcomes of Finnish patients with Inflammatory Bowel Disease receiving vedolizumab as first-line biological treatment
Authors: Ylisaukko-oja T , Af Björkesten C G , Erbel A , Nuutinen H , Jussila A , Molander P , Koskela R , Blomster T , Pajala M , Ilus T , Haiko P , Kovac B , Silvola S , Smith S , Jokelainen J , Sipponen T 
Published: January 2023

Abstract

Background
Vedolizumab is a gut selective anti-lymphocyte trafficking monoclonal antibody directed towards the integrin α 4β 7. The efficacy and safety of vedolizumab in the treatment of adults with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC) are well-established in randomized clinical trials and real-world evidence studies. However, real-world data are limited on vedolizumab therapy used on biological naïve CD and UC patients. Here, we analyse treatment persistence, treatment outcomes, and reasons for treatment discontinuation of vedolizumab as a first-line biological treatment in CD and UC patients in a Finnish real-world setting.

Methods
This was an observational, retrospective, multi-centre registry study. The cohort included all adult (≥ 18 years of age) patients with a diagnosis of CD or UC who initiated vedolizumab as a first-line biological treatment between May 2014, and June 2020, in the five Finnish university hospital districts. Clinical data were collected from electronic health records. The Prescription Register by the Finnish Social Insurance Institution was the data source for prescribed IBD treatments. Treatment persistence was defined as the time from initiation to discontinuation of therapy. P-values were calculated by using paired t-test.

Results
The cohort consisted of 54 CD and 69 UC patients treated with vedolizumab as a first-line biological treatment. The mean ages were 61.9 and 56.8 years for CD and UC at the time of vedolizumab start, respectively. Disease duration was 10.9 years in CD and 10.5 years in UC. Altogether, 35.8% of patients had a history of cancer. At month 12, treatment persistence was 84.9% (n=44) in CD and 64.7% (n=41) in UC cohorts (Figure 1). Most vedolizumab discontinuations (CD, n=11; UC, n=26) were due to lack of efficacy, and treatment discontinuations due to adverse events were rare (n&lt;5). Vedolizumab was associated with favourable treatment outcomes, as indicated by efficacy improvements at 12 months compared with baseline in Harvey-Bradshaw Index (CD, 3.2 vs 4.9, p=0.025), Partial Mayo Score (UC, 3.8 vs 5.1, p=0.021), Physician’s Global Assessment (CD, 0.9 vs 1.8, p&lt;0.001; and UC, 0.4 vs 2.1, p&lt;0.001) scores, and positive endoscopic Mayo Score (UC, 0.7 vs 2.2, p&lt;0.001) and biochemical outcomes.

Conclusion
Vedolizumab showed high treatment persistence and positive treatment outcomes such as improvements in efficacy, endoscopic activity, and biochemical parameters when used as the first-line biological treatment.
P630 Upadacitinib Improves Clinical Outcomes in Patients with Moderate to Severely Active Crohn’s Disease Irrespective of Previous Failure to Respond to Biologics or Conventional Therapies
Authors: Schreiber S W , Lim A , Lacerda A P , Allegretti J R , Watanabe K , Lukin D , Dubenco E , Ford S , Oomen J , Zhou Q , Liu J , Louis E 
Published: January 2023

Abstract

Background
Upadacitinib (UPA), an oral, selective Janus kinase inhibitor, demonstrated significantly greater efficacy compared with placebo (PBO) in patients (pts) with moderately to severely active Crohn’s disease (CD) in phase 3 multicentre, double-blind, PBO-controlled induction U-EXCEL and U-EXCEED, and maintenance U-ENDURE trials.1-3 This analysis compared clinical outcomes in pts treated with UPA vs PBO once daily (QD) among pts without or with a history of biologic failure.

Methods
Eligible pts with an average daily very soft/liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2, plus a Simple Endoscopic Score for CD (excluding the narrowing component) ≥6 (≥4 for pts with isolated ileal disease) were randomized (2:1) to UPA 45 mg (UPA45) or PBO in U-EXCEL and U-EXCEED. Induction responders (≥30% decrease in average daily very soft/liquid SF and/or APS, neither worse than baseline) to 12-week (wk) UPA45 were re-randomized 1:1:1 for maintenance to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO QD in U-ENDURE. Clinical remission, response (CR-100), and maintenance of clinical remission, along with adverse events (AEs) were assessed through maintenance wk 52.

Results
Baseline demographics/characteristics were similar for all treatment groups; pts with prior biologic failure were 71.5% PBO and 72.0% UPA45 in induction and 76.4% PBO, 73.4% UPA15 and 75.6% UPA30 in maintenance. Among pts without/with biologic failure history, those treated with UPA45 exhibited higher rates for clinical remission at wk 12 (CDAI: UPA45 54.1%/40.5% vs PBO 39.4%/19.4%; SF/APS: UPA45 54.0%/42.2% vs PBO 28.3%/14.1%, Fig. 1A). Similar results were observed at wk 52 with UPA15 and UPA30 vs PBO (Fig. 1B). Irrespective of biologic failure status, a higher proportion of patients on either UPA dose maintained clinical remission from maintenance wk 0 to wk 52 (Fig. 1C). Higher proportions of pts with prior biologic failure achieved CR-100 with UPA45 vs PBO at wk 12 (53.2% vs 26. 9%); at wk 52 differences from PBO were found for either UPA dose in pts without or with prior biologic failure (Fig. 1D). Serious AEs and serious infections were similar across treatment groups (Tables 1-2). No tuberculosis or adjudicated cardiovascular events were reported. Malignancy, opportunistic infections, thrombotic events, and gastrointestinal perforations were infrequent (&lt;1.0% or 10 E/100PY).

Conclusion
All upadacitinib doses achieved greater clinical efficacy than placebo during induction and maintenance periods, irrespective of patient prior exposure to biologic therapy, with an acceptable safety profile.