bluuebunny/crossref_metadata_2025_split huggingface dataset:
P610 Real-world effectiveness and safety of advanced therapies for the treatment of moderate-to-severe ulcerative colitis (UC): evidence from a systematic literature review (SLR)
Authors: Irving P M , Hur P , Gautam R , Guo X , Vermeire S 
Published: January 2023

Abstract

Background
Since advanced therapies (ATs) for moderate to severe UC are increasing, their effectiveness and safety in real-world (RW) settings should be assessed.

Methods
A SLR was done as per method described by Cochrane Collaboration and PRISMA guidelines, using Embase, MEDLINE and MEDLINE-In Process databases to find RW studies of biologics (adalimumab/ADA, golimumab/GOL, infliximab/IFX, vedolizumab/VEDO and ustekinumab/UST) or small molecules (filgotinib/FIL, ozanimod/OZA and tofacitinib/TOFA) in patients (pts) with UC. Only products approved at the time of search were included. Studies published in English as full papers (Jan-2005–Feb-2022) or congress abstracts (Jan-2019–Feb-2022) were included. Studies with &lt;30 pts or with only bio-naïve pts were excluded.

Results
Of 3930 results, 139 studies were included (18 comparative and 121 single AT). 13% of studies had only bio-exposed pts, 63% had &gt;50% bio-exposed pts and 28% had subanalysis for bio-exposed pts.
Comparative studies of VEDO vs TNF inhibitors (TNFIs; n=10); TOFA vs VEDO (4), TNFIs (3) or UST (1). In comparative effectiveness studies (16), rates of clinical remission (CR) with VEDO were numerically higher vs TNFIs (Fig1). For TOFA vs VEDO, the effectiveness of TOFA in multiple outcomes was numerically (occasionally significantly) greater (Fig2). The study of UST vs TOFA showed similar rates of steroid-free CR (Dalal 2021). In 2 studies, IFX was the most effective TNFI.
Comparative safety studies (14) mostly reported % pts with any/serious adverse events (AEs/SAEs) with limited reporting of incidence of MACE and malignancy. A study showed no significant differences in the risk of SAEs (HR0.899;95%CI0.502–1.612) or serious infections (HR1.235;95%CI0.608–2.511) for VEDO vs TNFIs (Lukin 2022). Two studies showed comparable AE rates for TOFA and VEDO. One study showed that VEDO pts had higher chance of experiencing AEs than TOFA pts (OR1.83;95%CI1.10–3.03) but similar number of SAEs (OR0.39;95%CI0.03–4.33; Straatmijer 2022). A study of TOFA vs UST showed similar overall AE rates (Dalal 2021). AE rates for TNFIs were comparable.
In single AT studies (VEDO n=50, TOFA 24, ADA 18, GOL 14, IFX 10, and UST 5), % of pts with CR and AEs/SAEs varied widely.
No studies were found for FIL and OZA.

Conclusion
In comparative studies of largely bio-exposed pts, CR rates with TOFA were generally numerically higher vs VEDO and comparable with UST; and numerically higher for VEDO vs TNFIs. IFX was most effective TNFI. SAE rates were similar across ATs. The results should be interpreted cautiously due to varied baseline characteristics though few studies were propensity scores matched. More comparative studies are needed as CR in single AT studies varied widely.
P619 Inflammatory bowel disease meets fertility: a physicians and patients survey
Authors: Vieujean S , De Vos M , D’Amico F , Paridaens K , Daftary G , Peyrin-Biroulet L , Danese S 
Published: January 2023

Abstract

Background
Inflammatory bowel diseases (IBD) affect patients during their childbearing years. Literature evidence is scarce regarding the level of knowledge among health care professionals (HCPs) and patients out the impact of IBD on fertility. The aim of this survey was to investigate HCPs' and patients' knowledge on fertility, pregnancy, and sexual function, to evaluate how HCPs approach this topic and to report patients’ reproductive outcomes.

Methods
Subjects were invited to anonymously complete an online questionnaire collecting data on demographics, patients' disease characteristics, Crohn's and colitis pregnancy-specific disease-related knowledge (CCPKnow), family planning, reason of childlessness, pregnancy outcomes, need for assisted reproductive technology, impact on sexual function, and availability of patients’ information regarding IBD and pregnancy.

Results
A total of 257 HCPs from 40 countries and 793 patients (615 females, 176 males and 2 who preferred not to disclose their gender; 396 (50%) with ulcerative colitis, 381 (48%) with Crohn’s disease, 14 (1.8%) with undetermined IBD) from 4 countries completed the survey. The characteristics of participants are listed in Table 1. In total, 98.4% of HCPs had good or very good pregnancy-specific knowledge according to CCPKnow score, compared to only 29.3% of patients. Of the women surveyed, 56.3% had no children (14.1% due to a voluntary choice). A total of 427 pregnancies and 401 live births were reported in 266 women. Twenty-four pregnancies (5.6%) in 22 women required assisted reproductive technologies (ART). There were no more complications in pregnancies resulting from ART compared with spontaneous conception (5/24; 20.8% vs 211/401; 52.6%). Three quarters of IBD patients (75.6%) had breastfed. An impaired sexual function was found in one-fifth (21.9%) of men with IBD, while two-thirds (66.1%) of the women reported sexual function impairment. Surprisingly, 63% of patients reported not having received any information about IBD and pregnancy, and only 10% of patients had received information from their IBD specialist. In addition, 42.1% and 36% of HCPs had already referred a patients to a medically assisted reproduction centre to receive general information about their reproductive health and about options of fertility preservation (e.g., cryopreservation), respectively.

Conclusion
IBD patients have a poor knowledge about the impact of IBD on fertility and pregnancy and HCPs does not sufficiently inform their patients. More information on these topics is needed for IBD patients.
P620 Can ustekinumab trough and antidrug antibody levels post induction predict treatment failure?
Authors: Mccrossan M , O’Moráin N , Kumar L , Rowan C , Sheridan J , Cullen G , Doherty G , Mulcahy H 
Published: January 2023

Abstract

Background
Ustekinumab (UST), a monoclonal antibody that blocks interleukins IL-12 and IL-23, is increasingly used in the treatment of Crohn’s disease and Ulcerative Colitis. While therapeutic drug monitoring (TDM) is used with increasing frequency in other biologic agents, there is a paucity of data regarding the clinical utility of TDM for UST. This pilot study aimed to determine whether loss of response (LOR) and treatment failure (TF) can be predicted by post UST-induction serum trough concentrations and antibody levels.

Methods
A pilot retrospective observational study of patients who received subcutaneous (SC) induction of UST, following LOR to anti-TNF, for treatment of Crohn’s disease in 2016 was performed. We previously demonstrated comparable drug trough levels following SC rather than intravenous UST induction. Patients with available 74 month follow up data were included. Frozen serum samples used for this measurement were retrospectively tested for antibody levels using ELISA. Our IBD database and admissions data were analysed from 2016-2022. We recorded treatment duration, interval shortening, and treatment failure. Treatment failure was defined as switch to another biologic agent and/or surgery. Data were analysed using SPSS software [IBM], with Wilcoxon Rank Sum Test used for hypothesis testing.

Results
In this pilot study, a total of 10 patients (female=1, mean age 38.5 y) met the inclusion criteria. During the 74 month follow-up period, 3 patients failed treatment (mean age 30 y) while 7 remained on UST (mean age 42 y). All patients required interval shortening (4 weekly dosing). There was no difference in Crohn’s phenotype or smoking status between groups. All TF patients were switched to alternative biologic agents, with 1 patient requiring surgery. The patients who failed treatment were noted to have higher antibody levels (median 6.57 Au/ml vs 5.87 AU/ml, p=0.03) [Fig 1]. Two of these patients were noted to have lower trough levels than those who continued on UST, with one having a higher trough level (median 2.9mcg/ml vs 5.8mcg/ml, p=0.52) [Fig 2].

Conclusion
Shortening of dose interval with UST therapy in Crohn’s disease is frequently required. This pilot study suggests an association between treatment failure and higher antidrug antibody levels 8 weeks post induction of UST. There was no significant difference in drug trough levels between groups. The patient with the highest trough level in the cohort failed treatment – This raises the possibility of multiple mechanisms of failure; however, it is impossible to draw conclusions given the sample size. Further studies are required to assess whether measurement of post induction antibody and drug trough levels has clinical utility in guiding treatment decisions.
P622 Change in Dietary Inflammatory Index Score in patients with Crohn’s disease and healthy volunteers following the Groningen Anti Inflammatory Diet (GrAID)
Authors: Barth I , Stevens C L , Dijkstra G , Campmans-Kuijpers M J E 
Published: January 2023

Abstract

Background
Dietary patterns play an important role in Inflammatory Bowel Disease (IBD). The Dietary Inflammatory Index (DII) is a diet quality score that estimates the inflammatory potential of a dietary pattern on inflammatory markers. Recently, the Groningen Anti-Inflammatory Diet (GrAID) was developed to improve disease course in patients with IBD. The aim of this study is to investigate whether following the GrAID improves diet quality based on the DII compared to baseline intake in patients with Crohn’s disease (CD) and healthy volunteers (HV).

Methods
Between October 2021 and October 2022, patients with CD and HV completed a 12-week GrAID intervention as part of an ongoing trial: VITA-GrAID (NCT04913467). In this sub analysis, nutrient intake from a 3-day food diary was calculated at baseline (T0; habitual diet) and after 12 weeks (T3; following the GrAID), using Evry software (version 2.3.7.0). From both intakes the DII score according to the Shivappa method was calculated, based on 28 food parameters. Next, both scores were compared to the DII score of the GrAID, calculated assuming complete adherence to the GrAID. A lower DII score is regarded to having a higher anti-inflammatory potential. Paired nonparametric tests (Wilcoxon signed-rank) were performed to calculate differences between T0 and T3. Data were analysed using R (2021.09.0) and IBM SPSS Statistics 28.

Results
Eighteen individuals completed the 12-week GrAID intervention (12 patients with CD; and 6 HV) (table 1). Between T0 and T3, significant increases were found in fibre (16.5g), total protein (21g), total plant protein (14g), vitamin B2 (0.29ug) and beta carotene (1837ug) intake. Significant decreases were found in mono- and disaccharides (-18g), alcohol (- 5.3g), and sodium (-875mg) intake (Table 2). The median DII score at T0 was -0.112, IQR: [-1.269; 1.362] and was significantly lower at T3 (median: -2.040; IQR [-2.588; -1.417], p&lt;0.05) (figure 1). Median DII score in patients with CD differed significant between T0 and T3 (0.323, IQR [-1.3897; 1.523] and -2.040, IQR [-2.665; -1.549] respectively, p&lt;0.05), but not in HV (-0.692, IQR [-1.127; 0.566] and -1.998, IQR [-2.441; -1.336] respectively, p=0.09) (Figure 2).

Conclusion
These preliminary results show that diet quality improved in patients with CD after following the GrAID for 12 weeks. For HV, probably more participants are needed. Further research is necessary to determine whether a lower DII score will actually improve the disease course of patients with CD and the diversity of the microbiome in HV.
P626 Safety of recombinant zoster vaccine in patients with Inflammatory Bowel Disease: a single centre experience
Authors: Todeschini A , Geccherle A , Signoretto P , Variola A 
Published: January 2023

Abstract

Background
Patients with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. However, vaccination rates for HZ are low among IBD patients. Although the safety of recombinant zoster vaccine (RZV) are high among immunocompetent individuals, there are only few data in IBD patients treated with immunomodulating drugs. This study aims to evaluate safety of recombinant zoster vaccine in IBD patients.

Methods
This is a retrospective study among IBD patients after RZV vaccination. RZV was administrated to 31 IBD patients. Afterwards completed vaccination, telephone or in-person interviews were conducted to report adverse events (AEs) related to vaccination. Data on medical history and treatment was collected from electronic health records.

Results
32 patients, 12 CD and 20 UC, were enrolled. 77% received a complete RZV vaccination cycle. The vast majority of patients (97%) were in biological or immunomodulatory therapy and 80% had previous HZ infection. About 30% of patients had at least one side effect. Local pain at site of injection (27%) and fever (47%) were the most common AEs. Flares of the underlying IBD were not reported. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported.

Conclusion
The short-term vaccine reactions experienced in this cohort of IBD patients were self-limited, including local pain at the injection site and fever. We found a good safety profile of RZV vaccination in our cohort.
P627 HLA DQA1*05 was not associated to primary non-response or loss of response to first anti-TNF in real world Inflammatory Bowel Disease patients.
Authors: Pascual Oliver A , Cuarán C , Casas-Deza D , García-López S , Corsino-Roche P , Sierra Moros E , Julián-Gomara A B , Vicente-Lidón R 
Published: January 2023

Abstract

Background
Biologics have been a breakthrough in the management of patients with inflammatory bowel disease (IBD). However, we lack predictors of response to these drugs. A recent study has shown a significant association between HLA DQA*105 mutations and the development of loss of response to anti-TNF mediated by immunogenicity. The high quality of the study and the wide differences found, have led to its quick practical implementation in the choice of biological agent. However, the supporting evidence is limited in clinical practice.

Methods
Retrospective cohort study, carried out at the Miguel Servet Hospital, Zaragoza, Spain. We included IBD patients who had received anti-TNF therapy as first biologic and whose HLA DQA1*05 had been determined. Primary non-response and secondary failure (assessed by survival analysis) has been evaluated as well as safety outcomes.

Results
199 IBD patients [161 (81%) Crohn′s disease (CD) 38 (19%) ulcerative colitis (UC)] were included. 42.4% had HLA DQA1*05 mutation and 60% received combination therapy with immunomodulators at the start of anti-TNF treatment. Median follow-up was 24 months (IQR 11-66). No statistically significant differences were found in primary non-response to anti-TNF (87,8% vs 12,2%, p = 0,825), depending on the presence or absence of HLA mutation. No differences in secondary loss of response according to HLA mutation in any of the analyses performed (full cohort, according to IBD or anti TNF type) were observed (Figure 1). Secondary loss of response has also been assessed according to the use or non-use of concomitant immunomodulator. Again, no differences were observed in this analysis (Figure 2). Multivariate analysis, like the univariate analyses, showed that the presence of the HLA-DQA1*05 mutation was not associated with a higher rate of secondary loss of response or shorter time to failure. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events between carrier and non-carrier patients.

Conclusion
In our real-life cohort of IBD patients treated for the first time with anti-TNF, the presence of the HLA-DQA1*05 mutation did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the mutation. More data is needed to incorporate HLA DQA1*05 determination into routine clinical practice as a key factor in individual decision making.
P641 Bowel Doppler Signal, the most important ultrasonographic feature in clinical practice in managing Inflammatory Bowel Diseases patients
Authors: Les A , Cotruta B , Iacob R , Saizu R , Gheorghe L , Gheorghe C 
Published: January 2023

Abstract

Background
IBD are chronic diseases that require multiple endoscopic and imaging assessments, being diseases that not only involve a multitude of medical resources but patient compliance too. Bowel ultrasound (BUS) is a useful imaging tool in monitoring inflammatory bowel diseases (IBD) patients. Current guidelines recommend BUS altogether with other cross-sectional imaging methods to diagnose, monitor IBD patients and also for detecting complications and post-surgery recurrence. A multitude of ultrasonographic features are used to describe pathologic findings related to IBD but not all of them are easy to integrate in clinical practice, especially in unexperienced hands.

Methods
Our study included 117 IBD patients of which 28 were diagnosed with ulcerative colitis and 89 with Crohn’s disease. Diagnosis was established endoscopically and histologically and both patients with active and inactive disease were included. Exclusion criteria consisted in patients with other causes of inflammatory syndrome, patients with solely rectal localization of the disease or a surgical history. Subjects were prospectively evaluated using BUS and several sonographic aspects of the bowel wall were monitored: bowel wall thickness, bowel echo pattern, Doppler signal (DS) presence, hypertrophic mesenteric fat, and the presence of lymph nodes. Biological markers of inflammation were obtained including faecal calprotectin. Patients were followed up for the next 6 months and data regarding treatment intensification was noted. All patients signed an informed consent, and the study was approved by the Ethics Committee of the Fundeni Clinical Institute.

Results
Significantly higher values of clinical and biological markers were associated with the presence of parietal DS (p&lt;0.0001) suggesting that this BUS feature is an important bowel wall inflammation surrogate. Higher Limberg scores (a subjective Doppler signal score used in BUS) correlated with increased values of biological markers of inflammation (p=0.002). A multivariate analysis showed that DS and a thicker than 5 mm bowel wall were independent predictors of step-up therapy. The presence of parietal DS raised the patient risk of switching therapy 7.6 times, while bowel wall thickness only 2.4 times, making DS the most useful BUS feature in evaluating inflammatory activity and predicting the need for step-up therapy.

Conclusion
DS is one of the most important BUS features to use in evaluating and monitoring IBD patients and could have a role in disease decision making. This finding should advocate for this imaging method in clinical practice, and even low BUS-experience practitioners are encouraged to use it.
P644 Leucine-rich alpha 2 glycoprotein- A useful biomarker to discriminate small intestinal mucosal healing in asymptomatic CRP-negative Crohn’s disease
Authors: Tanaka A , Kanmura S , Maeda N , Kuwazuru K , Komaki F , Komaki Y , Ido A 
Published: January 2023

Abstract

Background
The long-term treatment goals for inflammatory bowel disease including Crohn’s disease (CD) have shifted from clinical remission to mucosal healing. However, frequent endoscopies are a great burden on the patients. Leucine-rich alpha 2 glycoprotein (LRG) is produced by hepatocytes, neutrophils, and the intestinal epithelium. Therefore, it is speculated to be more gut-specific than C-reactive protein (CRP) level. This study examined whether LRG could be used as a biomarker to determine the presence or absence of small intestinal mucosal healing in asymptomatic patients with CRP-negative CD.

Methods
The subjects of this study were asymptomatic CRP-negative CD patients who visited our department from May 2021 to October 2022, had their LRG measured, and underwent imaging evaluation by capsule endoscopy or balloon-assisted endoscopy. We analysed the patients’ clinical background, the ROC-AUC of LRG for mucosal healing, the cut-off value of LRG to discriminate mucosal healing. Endoscopic evaluation was performed within 3 months before and after the LRG measurement. Mucosal healing was defined as the absence of open ulcers. Clinical remission (no subjective symptoms) was defined as a Harvey-Bradshaw index (HBI) ≤4 points. The upper limit of the normal CRP value was set to &lt;3 mg/L.

Results
A total of 28 cases were analysed; 13 (46%) were men. The median age (range) of onset was 21.2 years (7-52 years). The median disease duration (range) was 6.4 years (0-27). B1 was established in 13 (45%) cases, B2 in 7 (25%) cases and B3 of Montreal Classification in 8 (29%) cases. The median (range) of the HBI score was 2 (0-4). The median (range) of LRG was 12.3 g/ml (7.6-20.5 μg/ml). The ROC-AUC of LRG for mucosal healing was 0.743 (95% confidence interval 0.559-0.927). The cut-off value of LRG for discriminating mucosal healing was 12.2 μg/ml (sensitivity 0.769, specificity 0.682).

Conclusion
In asymptomatic CRP-negative CD patients, when LRG was 12.2 μg/ml or more, it was suggested that they might have small intestinal ulcers.
P648 Effectiveness of Biologic Therapies in Decreasing Risk of Hospitalization and Surgery, Maintaining Steroid Free Remission and Achieving Mucosal Healing in Inflammatory Bowel Disease; Real World Data.
Authors: Shehab M , Abdullah I , Alostad W , Marei A , Alfadhli A 
Published: January 2023

Abstract

Background
Several biologic therapies are currently available for the management of inflammatory bowel disease (IBD) rendering the choice and sequencing between them as a first line under question. In our study, we evaluated the effectiveness of biologic therapies in achieving important clinical and endoscopic outcomes in biologic naïve patients with IBD.

Methods
Electronic medical records of patients with moderate to severe IBD, who were previously naïve to biologics, were reviewed and evaluated retrospectively in a tertiary care gastroenterology center, Haya Alhabib Center. Patients who were on infliximab, adalimumab, ustekinumab and vedolizumab for 12 months were included. The primary end points were percentage of hospitalization, surgery, steroid free remission, and mucosal healing, defined as Mayo score less than 1 in ulcerative colitis and SES-CD score less than 3 in Crohn’s disease. Descriptive analysis was performed to measure outcomes.

Results
A total of 335 biologic naïve patients with IBD were included; 262 (78.2%) patients with ulcerative colitis and 73 (21.8%) patients with Crohn’s disease. Regarding hospitalization, 25 (14.7%) out of 170 on adalimumab,12 (10.7%) out of 112 on infliximab, and one (6.25%) on vedolizumab were hospitalized. None of the patients on ustekinumab were hospitalized. 9 out of 171 (4.7%) patients on adalimumab underwent surgery, while none of the patients on the other biologics underwent IBD related surgery. Regarding steroid free remission, 29 (16.9%) out of 171 patients on adalimumab received steroid courses, 15 (13.3%) out of 113 patients on infliximab, 4 (11.4%) out of 35 patients on ustekinumab, and 1 (6.3%) out of 16 patients on vedolizumab. A total of 159 out of 171 patients (93.0%) on adalimumab achieved mucosal healing. While 100 out of 113 patients (88.5%) on infliximab, 26 out of 35 patients (74.3%) on ustekinumab, and 7 out of 16 patients (43.8%) on vedolizumab achieved mucosal healing.

Conclusion
Adalimumab, infliximab, and ustekinumab and vedolizumab were all effective in inducing steroid free remission. However, patients on vedolizumab had numerically lower percentages of mucosal healing than other biologics. Percentage of hospitalizations and IBD related surgeries were higher in patients on infliximab and adalimumab. Future Larger prospective comparative studies are needed.