bluuebunny/crossref_metadata_2025 huggingface dataset:
P366 genomics analysis and differentiation of Crohn's Disease, Intestinal Tuberculosis and Primary Intestinal Iymphoma
Authors: Lin L , Qu Y , Zhao X
Published: January 2023

Background

Crohn’s disease(CD), intestinal tuberculosis(ITB) and primary Intestinal Lymphom(PIL) are very similar in many aspects, and differential diagnosis of them remains a major clinical challenge. The purpose of this study is to perform genomic analysis of tissue wax blocks in patients by DASL analysis and screen out potential diagnostic genes for diseases.

Methods

Tissue wax blocks from 31 patients with CD, 33 patients with ITB, 25 patients with PIL and 12 healthy controls were collected to detect the expression of genes in the samples by DASL analysis. The data were then normalized, followed by differential expression analysis and GO and KEGG enrichment analysis. Based on the above results, potential diagnostic genes are screened out and then verified by immunohistochemistry.

Results

We obtained the expression intensity of 19869 genes in the intestinal tissues of 4 groups of patients. By differential expression analysis, the differentially expressed genes(DEGs) between these four groups of samples were obtained. GO and KEGG enrichment analysis showed that these DEGs had different effects on metabolic function, immune response, chemotaxis, growth and development, etc. According to the DEGs between the groups screened earlier, combined with the results of KEGG enrichment analysis, a total of seven potential diagnostic genes were screened, included EPHB3, CD70, CHST10, CXCL13, CEL, SCGB2A1 and SCGLEC10. Finally, the significant upregulation of EPHB3 in the intestinal mucosa of CD patients was verified by immunohistochemistry.

Conclusion

CD, ITB and PIL have significant differences in genome expression, and EPHB3 has been confirmed to be significantly upregulated in CD, which is expected to become one of the indicators for disease differential diagnosis. At the same time, Based on the results of our GO enrichment analysis and the results of previous researchers, we believe that EPHB3 may participate in the occurrence and development of Crohn's disease through the regulation of the development of the digestive tract and digestive system, cell adhesion, and epithelial-to-mesenchymal transition.
P367 Significant impact on health care utilization upon implementation of an electronic IBD care management program.
Authors: Koppelman L , Roozemond S , Cornelissen L , Hommes D , Voorneveld P , Maljaars J , Kubben F , Verweij E , van der Meulen - de Jong A
Published: January 2023

Background

The management of Inflammatory Bowel Diseases (IBD) remains to be a significant challenge because of its unpredictable clinical course and high associated costs. Recently, we implemented an electronic IBD care management program, provided by DEARhealth BV, which offers care-pathways that configurate according to individual IBD risk profiles, called THINK. High-risk (HR) IBD patients (current biochemical disease activity) will receive more intense monitoring and provider interactions compared to Low-risk (LR) (>3 years in remission) and Intermediate-risk (IR) (other patients) individuals (figure 1). In this project, before implementation of THINK, we aimed to assess whether 1. Current healthcare utilisation (HCU) (consultations, lab tests, calprotectin) differs between risk groups and 2, what the effect of implementing THINK would be on HCU (focused on consultations and laboratory tests) in a retrospective-analysed population.

Methods

161 consecutive IBD patients in hospital A, categorized in either the HR or IR group, were studied prospectively during 1 year before implementation of THINK. HCU was captured using an electronical medical record (EMR) and included consultations, blood tests and calprotectin. Furthermore, HCU in the years 2018-2019 in the IBD population of hospital B was studied (extraction of EMR). This historical data was compared to the THINK care path (see figure 1) when optimal implemented. The analysis focused on the activities present in de THINK care pathway (consultations and laboratory tests) to uncover the potential of the electronic IBD care management program.

Results

Baseline characteristics for hospital A cohort (N=161) are summed in Table 1. We followed 102 patients (60 Crohn) in the IR group and 59 patients in the HR group (29 Crohn). As expected, significant more HCU was present in the HR group (table 2). In hospital B, the utilization impact assessment was performed in the IBD cohort of 543 Crohn and 495 colitis patients. A difference in clinic consults was observed of -52,7% (HR), -53.5% (IR) and -29,3% (LR). The difference in laboratory tests utilization was found -54,0% (HR), -27.8% (IR) and -3,1% (LR).

Conclusion

Our initial experiences with a novel IBD management program demonstrated the feasibility of accurate remote disease activity monitoring and significant impact on utilization patterns due to the risk-based care pathway configurations. However, the analysis shows the ideal fictive situation when using standardized care pathways which cannot fully be considered the real-time situation. In this analysis no unexpected events are included. Future research should investigate the realization of these predictions.
P371 Assessment Of Postoperative Complications Following Ileocecal Resection In Crohn’s Disease From A Low-To-Middle Income Country
Authors: Benammi S , Naddouri J , Bakkali Y , Alaoui M , Sebbah F , Raiss M , Hrora A
Published: January 2023

Background

Our study aims to assess risk factors of postoperative complications following ileocecal resection of Crohn’s disease from a low-to-middle income country perspective. We aimed to provide local data demonstrative of inner conditions and challenges.

Methods

This was a retrospective study conducted in a referral colorectal center in a low-to-middle income country from 2014 to 2020. We included all patients with Crohn’s disease admitted to our department for ileocecal resection. Patient’s and Crohn’s disease, surgical and postoperative characteristics were collected using chart review. We excluded all patients with missing data. We defined perioperative hemorrhage as blood loss≥200cc. Our primary outcome was immediate<90-days post-operative complications risk factors assessment.

Results

We included 83 patients with complete data. The median age was 34(18-75) and 54.2%(n=45) were female. Patients were 94.6%from urban areas and 5.4%(n=4) rural. Among all included surgeries, 83.1%(n=69) were elective and 16.9%(n=14) were emergency cases. Open surgery was conducted in 46 cases(55.4%), 30patients had laparoscopic ileocecal resection (36.1%), and 7(8.4%) had conversion. Immediate postoperative complications were reported in 16.9%(n=14);anastomotic leak 2(2.4%), surgical site infection 8(9.6%), entero-cutaneous fistula 2(2.4%), and postoperative hemorrhage 2(2.4%). Long-term outcomes with surgical reoperation were conducted in 5 cases(5.8%) excluding stoma removal. The total length of stay median was 6 days (4-31). Immediate postoperative complications were associated with postoperative bleeding(OR=27.8; 95% CI[1.26-614];p=0.001,Fisher’s=0.027), required transfusion during surgery or at postoperative follow-up(OR=18.3;95% CI[3.09-109];p<0.001,Fisher’s=0.001), hospital length of stay(t-test<0.001), pre-operative hemoglobin(t-test0.031).

Conclusion

Considering the accessibility of hemoglobin management in a low-to-middle income country, it represents an impactful tool in surgical quality enhancement.
P385 Risk-benefit assessment of IBD drugs: a physicians and patients survey
Authors: D'Amico F , Caron B , Vieujean S , Peyrin-Biroulet L , Danese S
Published: January 2023

Background

Treatment choices for patients with inflammatory bowel disease (IBD) are based on the balance between risks and benefits. To date, there are no globally accepted methods for assessing the risk-benefit ratio. Our aim was to compare the perspectives of patients and physicians in evaluating the risks and benefits before initiating therapy for IBD.

Methods

An anonymous survey was conducted between March and August 2022. Multiple choice questions, similar for physicians and patients, were formulated. The questionnaire was developed in English and was later translated in Italian and French by native speakers. All patients with a confirmed diagnosis of IBD who were followed up at the IRCCS San Raffaele Hospital (Italy), Nancy University Hospital (France), and University Hospital CHU of Liège (Belgium) were invited to participate. All physicians who attended an IBDscope webinar were invited to participate by email.

Results

In total, 367 patients and 146 physicians participated in the survey from 34 countries worldwide (Tables 1 and 2). For most patients (71.4%) and physicians (89.0%), efficacy and safety were equally important in choosing a therapy. Clinical improvement and clinical remission were the most relevant outcomes for patients (90.9 and 88.4 Likert scales), while clinical remission and endoscopic remission were for physicians (90.0 and 87.6 Likert scales). The main factors in the benefit-risk assessment for patients were quality of life (95.1%), disease activity (87.5%), and presence of comorbidities (84.5%). The main factors for physicians were presence of comorbidities (99.3%), disease activity (97.9%), prior failure to biologics or small molecules (96.6%). Disease duration, family history of IBD, administration interval, therapy duration, and administration route had a limited role for both physicians and patients. Based on patients' and physicians’ opinions, the risk of serious infections (90.5% and 98.6%), malignancies (90.5% and 100.0%), cardiovascular events (88.8% and 98.6%), death (86.4% and 91.8%), relapse (86.1% and 94.5%), all infections (86.1% and 100.0%), surgery (83.1% and 93.1%), and hospitalization (76.6% and 88.4%) should be included in the benefit-risk assessment. The risk percentages considered acceptable by patients and physicians are reported in Figures 1 and 2. Infliximab was the most effective drug for physicians in inducing and maintaining disease remission in both Crohn’s disease and ulcerative colitis, while ustekinumab and vedolizumab were equally considered the safest drugs.

Conclusion

Physicians and patients have different priorities in evaluating the benefit-risk balance of a new therapy. Treatment decisions should be discussed and shared with patients.
P392 Risk factors for postoperative recurrence after ileocolic resection for Crohn’s Disease: long-term results from a population-based cohort.
Authors: van Renterghem A , van der Holst A , van Kuijk S , Pierik M , Belgers E , Romberg-Camps M , Jeuring S , Demandt D , Stassen L
Published: January 2023

Background

Crohn’s disease (CD) patients often require surgical interventions and post operative recurrence is common. Data regarding risk factors for recurrence in representative cohorts are scarce. We assessed the risk-factors of recurrence of CD after ileocolic resection (ICR) in a population based cohort.

Methods

Patients who underwent a primary or re-resection for ileocolic CD between 2003 and 2017 were included. The primary endpoint was clinical recurrence. The secondary outcome was surgical recurrence. A Cox regression model was used to assess recurrence free survival.

Results

289 patients were included of which 120 male (41.5%). Most common indication for ICR was stricturing (B2) disease in 146 (50.5)%), followed by penetrating (B3) disease in 101 (34.9%). Recurrence occurred in 189/289 patients (65.4%) after a median follow up of 2.3 years and surgical recurrence in 22 (7.6%) after median follow up of 4.8 years. Multivariate analysis showed a significant higher chance of clinical recurrence in smokers (HR: 1.659 (95% CI: 1.230; 2.238)) (p<0.05), patients with prior resections (HR: 1.514 (95% CI: 1.014; 2.261)) (p<0.05), perianal involvement (HR: 1.453 (95% CI: 1.033; 2.044)) (p<0.05) and isolated involved proximal resection margin (HR: 1.615 (95% CI: 1.039; 2.509)) (p<0.05). B2 and B3 disease behaviour and post-operative medication was associated with less recurrence, respectively (HR 0.397 (95% CI: 0.253; 0.624)) (p<0.05), (HR 0.443 (95% CI: 0.282; 0.696)), (p<0.05) and (HR: 0.658 (95% CI: 0.473; 0.916)) (p<0.05). Considering surgical recurrence, underweight and overweight BMI and open surgery decreased the chance on recurrence.

Conclusion

Our study in a population based cohort confirmed risk factors for recurrence consistent with current evidence, but also identifies novel and less frequently found risk factors. Medical therapy reduces the risk for recurrence on a population level. We found an association between involved resection margin and recurrence. Differences between studies may be caused by differences in patient selection or definition of recurrence. Confirmation of this finding in independent representative cohort is necessary. This indicates a need for a standardised scientific database for future prospective research.
P395 Short-term clinical efficacy and safety of teduglutide for Crohn’s disease patients with short bowel syndrome
Authors: Kaku K , Sato T , Takeuchi J , Uchino M , Fujihira Y , Shimizu K , Yokoyama K , Yagi S , Takashima Y , Ikenouchi M , Kojima K , Kawai M , Nagase K , Kamikozuru K , Yokoyama Y , Takagawa T , Ikeuchi H , Watanabe K , Shinzaki S
Published: January 2023

Background

The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS–IF) in patients with Crohn’s disease (CD) remain unknown and real-world data have not been scarce. This study aimed to investigate the short-term efficacy and safety of TED in CD patients on parenteral support (PS) for SBS–IF.

Methods

We retrospectively investigated the medical records of CD patients with SBS–IF who initiated TED between January 2020 and October 2022 in Hyogo Medical University hospital. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥20% at week 4. Secondary outcomes were the changes in body mass index (BMI), estimated glomerular filtration rate (eGFR), albumin, hematocrit (Ht), PS calorie requirements, withdrawal from PS, and adverse events during the observation period.

Results

Of 605 CD patients, 23 who underwent home PS for SBS–IF were included in this study. Twenty patients continued TED throughout the observation period. The median PS duration was 11.6 (range 1.0-20.0) years and the observation period after starting TED was 48.0 (7.0-60.0) weeks. TED significantly reduced the PS volume from 17989(570-49000) mL/week to 14257(0-42000) mL/week at week 4 (p = 0.0013), and the PS volume decreased by ≥20% in 8 patients (40.0%) at week 4 and in 16 patients (80.0%) during the observation period after TED administration. The BMI significantly increased from 17.9 (12.9–23.9) kg/m2 before TED administration and 18.9 (14.6–25.4) kg/m2 after TED administration (p = 0.014). Although there were no significant differences in albumin (p = 0.53), eGFR (p = 0.66), and Ht (p = 0.089), the PS calorie /week was significantly decreased from 6581 (244–14000) kcal to 3747(0– 8820) kcal after TED administration (p = 0.0001). Ten patients (50.0%) experienced gastrointestinal stoma complications, including stoma swelling and/or prolapse during the observation period. Abdominal pain occurred in 7 cases (35.0%), catheter-related infection in five patients (25.0%), oedema in 4 patients (20.0%), nausea in 2 patients (10.0%), abdominal distension in 3 patients (15.0%), and upper respiratory tract infection in 1 patient (5.0%). All the symptoms were transient and tolerable. Although 3 patients discontinued TED due to nausea and abdominal pain and were excluded from this analysis, these symptoms improved after the discontinuation.

Conclusion

TED reduced PS volume at week 4 in CD patients with SBS–IF, and the BMI and the PS calorie requirement were improved during the observational period without serious adverse events.
P399 Detection of iron restricted erythropoiesis in patients with IBD: How can we disentangle effects of inflammation?
Authors: Aksan A , Mangold C , Stötzel J , Tessmer L , Schröder O , Stein J M
Published: January 2023

Background

Iron deficiency and anaemia are among the most common complications of IBD. While the distinction between functional and absolute iron deficiency (AID) is vital for therapeutic decision-making, inflammation is a frequent confounder in their diagnosis: An indirect indicator of body iron stores, serum ferritin is the most specific biomarker of AID. However, it is also an acute-phase reactant and can thus be obscured by IBD-related inflammation. Patients with active IBD often have anaemia of inflammation (AOI), i.e., reduced availability of iron for erythropoiesis (iron-restricted erythropoiesis, IRE) despite adequate stores. ECCO guidelines suggest adding biomarkers to distinguish functional from absolute ID in AOI. Here, we compared the utility of red cell indices and biochemical markers to detect IRE in IBD and define a decision threshold for the selection of biomarkers to discriminate AID and iron sequestration.

Methods

In an observational cross-sectional study, routine blood samples of patients with IBD were collected. CBC, iron status (serum ferritin, SF; transferrin saturation, TSAT; serum iron % of hypochromic red cells, %HYPO; reticulocyte haemoglobin content, CHr; soluble transferrin receptor, sTfR) and high sensitivity CRP (hsCRP) as inflammatory marker were determined by standard methods. sTfR-F index was calculated (sTfR (mg/L)/log10 SF(μg/L)). Patients with SF<30μg/L were assigned as AID-consistent controls to define decision thresholds for iron markers in patients with SF≥30μg/L which were then used to evaluate IRE in patients with SF≥30μg/L. The accuracy of the markers in the presence/absence of inflammation were assessed and contextual diagnostic thresholds determined.

Results

Samples were collected from 312 patients with IBD (159f/153m;163CD/149UC;42.7±14.5y), of whom 122(39.1%) had inflammation. 43 patients with SF<30μg/L were selected as AID-control group. Results in this group were: TSAT (cut-off 20%; AUCROC 0.730; sens.65%, spe.34%), %HYPO (3.5%; 0.733; 42%, 93%), CHr (32pg; 0.713; 51%, 86%), sTfR (2.70mg/L; 0.775; 81%, 63%), sTfR-F (2.01; 0.914; 88%, 88%). sTfR-F was used as reference for IRE in patients with SF ≥30μg/L. Accuracy of the markers as detectors of IRE is shown in Table 1.

Conclusion

sTfR was the most accurate sole marker of IRE in patients both with and without inflammation, its cut-off being higher in the presence of inflammation. In patients without inflammation, SF was a valuable additional parameter. Relative cost-effectiveness of the markers alone or in combination is under investigation.
P403 Therapeutic compliance in patients with chronic inflammatory bowel disease.
Authors: Hajlaoui A , Sabbah M , Bibani N , Jlassi H , Bellil N , Lassoued K , Trad D , Gargouri D
Published: January 2023

Background

The World Health Organization estimates that half of all patients do not take their treatment as agreedwith the prescriber. Thus, the evaluation of compliance is essential in the management of patients withchronic diseases, particularly chronic inflammatory bowel diseases (IBD). This evaluation cansometimes be variable. Hence, it is of clinical significance to develop objective scales unifying compliance assessment methods.

The aim of our study was to assess therapeutic compliance in IBD patients and to identify predictivefactors of non compliance.

Methods

A cross-sectional study over a period of six months (from June to November 2022) including all IBD patients from our department was conducted.The data collection was carried out by one investigator. We used an analytical chart containingdemographic and clinical questions, the Perceived Stress Scale (PSS) questionnaire in its French version to evaluate the degree of stress and the "Morisky medication adherence scale -8 MMAS" and the "Girerd" questionnaires to evaluate compliance to treatment.

Results

Forty-seven patients were included, with a mean age of 43 years [20-71 years] and a M/F sex ratio of0.59. Forty patients had Crohn's disease and seven had ulcerative colitis. Only 19 patients were recently (less than two years) diagnosed of IBD. Whereas, 20 patients were followed for more than 10years. All were undergoing maintainance therapy with azathioprine in 34%, anti TNF in 19%, combotherapy in 19%, 5 ASA in 8.5%. Among our population, 17% presented a flare and were under corticosteroids during our study.Most of our patients did not have a secondary or a university degree (n= 22). When it comes to patients’ perceptions of the disease, 14 patients showed a good understanding while seven showed poor knowledge. The remaining 26 patients had average knowledge about the disease and its management.Regarding the level of stress caused by their disease, 40% were able to cope with it, while 25.5% had major difficulty in stress management.Fifty-one patients were considered to be well compliant according to the MMAS-8, 32% were moderately compliant and 17% were not compliant. The results were comparable using both scores(Morisky and Girerd). The main predictors of poor compliance were level of education (p=0.042),degree of knowledge of the disease (p=0.011) and poor stress coping (p=0.001).

Conclusion

Adherence to treatment is the most important predictor of success or failure of therapeutic care. It isimportant to educate patients about the importance of compliance both at treatment initiation andduring periodic visits. It is also important to identify and act on the factors that lead to non-adherence.
P408 Dual therapy with vedolizumab and tofacitinib in refractory ulcerative colitis patients – single centre experience
Authors: Kolar M , Kastylova K , Lukas M , Duricova D , Hruba V , Machkova N , Cerna K , Jirsa J , Kubickova K , Vojtechova G , Lukás M
Published: January 2023

Background

Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with non-response to multiple drugs. Beside dose optimization and selection of agents with different mechanism of action, combination of two different targeted molecules has recently been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients.

Methods

Patients with complicated refractory or acute severe colitis, in whom combined treatment with vedolizumab and tofacitinib based on shared clinical decision was started, were included. Data on demographics, treatment details, persistence and disease activity including laboratory markers, clinical activity index (partial Mayo score) during regular visits every 2 months up to one year after treatment initiation were collected. Currently available data were analyzed at 6 months. Endoscopic disease activity before and 2-6 months after dual therapy start was evaluated.

Results

In total, 21 UC patients who were started on vedolizumab and tofacitinib dual therapy between Oct 2020 and Sep 2022 were included. Tofacitinib dose was 10mg bid in all patients and all patients on vedolizumab maintenance treatment had intensified dosing regimen. Mean patients age was 36.4±8.1 years, 47.6% were males and 52.4% females. Mean disease duration at baseline was 7.5±5.8 years. All patients had advanced disease including 61.9% with extensive colitis and 38.1% with left-sided colitis. At least 2 previous biologics in monotherapy were used in 85.7% of patients. Mean pMayo score at baseline was 5.6±1.9 and decreased to 0.5±0.9 at 6 months (p=0.0020). Initial fecal calprotectin in the cohort was 1829±2520µg/g vs. 225±257µg/g at 6 months (p=0.0068) and mean CRP changed from 11.4±17.1 to 5.4±7.2mg/l (p=ns). Endoscopic Mayo score before dual treatment initiation averaged 2.8±0.5 indicating mostly severe disease activity and decreased to 1.4±1.2 during follow-up endoscopy (p=0.0005) with half of the patients having only no to mild activity (eMayo 0-1). Up to now, dual therapy had to be terminated in 7 patients – 4 patients failed on the treatment, 1 refused to continue with dual therapy, 1 patient experienced adverse event (liver lesion) and 1 was discontinued for reimbursement reasons.

Conclusion

In the presented small cohort of patients with refractory ulcerative colitis, in whom other modalities were depleted or colectomy was considered, combined vedolizumab and tofacitinib treatment has proven to be efficient with half of the patients reaching mucosal healing after 6 months and without raising significant safety concerns.
P418 Dose escalation of oral 5-aminosalicylic acid for ulcerative colitis with Mayo endoscopic subscore of one improves long-term prognosis: a one-year multicentre, open-label, randomized controlled trial.
Authors: Aoki Y , Fukuda T , Kiyohara H , Yokoyama A , Nakazawa A , Yoshimatsu Y , Sugimoto S , Nanki K , Mikami Y , Fukuhara K , Mizuno S , Sujino T , Mutaguchi M , Takabayashi K , Morohoshi Y , Hosoda Y , Ogata H , Iwao Y , Naganuma M , Kanai T
Published: January 2023

Background

Endoscopic healing, one of the treatment targets for ulcerative colitis (UC), is commonly defined as Mayo endoscopic sub-score (MES) ≤1. Furthermore, patients in whom MES of 0 is achieved are at a lower risk of relapse than those with MES of 1. However, it is unclarified whether the therapeutic intervention of dose escalation of oral 5-aminosalicylic acid (5-ASA) improves the prognosis of UC patients in clinical remission with MES of 1.

Methods

A multicentre, open-label, randomized, controlled trial was conducted among 5 hospitals in Japan from March 2018 to June 2022. Patients with UC, aged 16 years or older, treated with 5-ASA, in clinical remission and confirmed MES of 1 were enrolled. Patients receiving maintenance therapy other than oral 5-ASA and thiopurine (e.g., topical therapy, biologics) were excluded. Patients were randomly assigned to either the therapeutic intervention group (increased the dose of 5-ASA) or the control group (without any intervention). Concomitant use of immunomodulator (IM) was used for the stratification factor in the randomization. The primary endpoint was clinical relapse within one year. Relapse was defined as both (1) pMayo ≥3 or rectal bleeding sub-score ≥1, and (2) addition of any induction treatments for UC including topical agents. Predictive factors for relapse and adverse events (AEs) were investigated as the secondary outcomes. The predictive factors were explored in the multivariable Cox regression analysis.

Results

Eighty-one patients were enrolled and randomly assigned into the therapeutic intervention or the control group, and two patients were excluded due to important protocol violations after the randomization. Finally, 79 patients (n=39; therapeutic intervention, n=40; control) were included in the full analysis set (FAS). In the FAS, 46 (58.2%) patients were male, and 20 (25.3%) patients were treated with IMs. The relapse within one year was less in the therapeutic intervention group (6/39; 15.4%) than the control group (15/40; 37.5%), significantly (P =0.026) (Fig.1). In the exploratory analysis for the predictors, concomitant use of IM was associated with relapse (hazard ratio, 2.52; 95% confidence interval, 1.04-6.12, P =0.041). There were three AEs in the therapeutic intervention group. Two patients complained of nausea, and the other complained of diarrhea and melena. All the AEs were improved after turning back the treatment to that before the intervention.

Fig. 1. The proportion of patients relapsed within one year in the full analysis set (primary analysis).

Conclusion

The dose escalation of oral 5-ASA reduced the relapse within one year in UC patients in clinical remission with MES of 1.
P421 Real-world effectiveness and safety of vedolizumab induction therapy for Crohn’s disease in Poland – a prospective, observational POLONEZ II study considering patients reported outcomes
Authors: Liebert A , Kłopocka M , Cichoż-Lach H , Michalak A , Talar-Wojnarowska R , Domżał-Magrowska D , Filipiuk A , Krogulecki M , Kopertowska-Majchrzak M , Eder P , Stawczyk-Eder K , Waszak K , Zagórowicz E , Wojciechowski K , Drygała S
Published: January 2023

Background

Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking drug, used to treat ulcerative colitis (UC) and Crohn’s disease (CD), lifelong conditions with unknown aetiology with frequent relapses and remitting course which are a burden for patients and a challenge for health care systems. We aimed to evaluate the real-world effectiveness of VDZ induction therapy for Polish patients with CD.

Methods

This was a multicenter, observational, prospective study involving patients with moderately to severely active CD qualified for reimbursed treatment with VDZ in 10 Polish centers between Apr 2020 and Nov 2021. The primary endpoints were clinical response (≥ 70-point reduction in Crohn's Disease Activity Index, CDAI) and remission rate (CDAI ≤ 150) at week 14. Other endpoints included changes from baseline (week 0, first dose of VDZ) to week 14 for patient-reported outcomes (PROs): quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), fatigue (Inflammatory Bowel Disease-Fatigue Self-assessment Scale, IBD-F), stool frequency (SF score) and abdominal pain score (APS).

Results

A total of 98 patients with CD were enrolled in the study. At baseline, the most common disease location in the cohort was ileocolonic CD (n=70/98, 72.9%). Fifty patients (51%) were on corticosteroids at week 0. Nine patients discontinued VDZ therapy before or at week 14, mainly due to lack of response (n=6/9, 66.7%). At week 14, 63.3% of patients (n=62/98) achieved clinical remission and 30% (n=15/50) steroid-free remission. Clinical response rate in overall study population was 90.8% (n=89/98). Median CDAI score decreased from 336.5 to 108.0 (p<0.001) at week 14 (Fig. 1). Declines from baseline were also observed in median CDAI sub-scores: SF score (38.0 vs 10.0; p<0.001) and APS (18.0 vs 2.0; p<0.001) (Fig. 1). At week 14, median changes from baseline scores on the IBDQ (total and all subscales) were statistically significant (p<0.001) (Fig. 2). Improvement was also observed after the VDZ 14-week treatment period in fatigue severity and frequency (p<0.01) as well as its impact on daily activities (p<0.001) based on IBD-F (Fig. 3). The percentage of patients without concomitant corticosteroids increased more than 1.5-fold from week 0 (49.0%) to week 14 (76.3%).

Conclusion

VDZ is effective in induction therapy and has significant impact on disease activity and Health-Related Quality of Life (HRQL) including fatigue in patients with CD.
P422 Transition from intravenous to subcutaneous infliximab and vedolizumab: adherence, satisfaction and safety profile in a cohort of patients with Inflammatory Bowel Disease
Authors: Todeschini A , Geccherle A , Signoretto P , Fasoli E , Variola A
Published: January 2023

Background

Inflammatory Bowel Disease (IBD), Ulcerative Colitis (UC) and Crohn’s Disease (CD), is a group of chronic inflammatory disorders. Biologics are indicated for patients failing conventional maintenance therapy with moderate to severe activity. Different routes of administration, intravenous (IV), subcutaneous (SC) or oral have been approved. For chronic diseases such as IBD, some patients may prefer self-administered SC dosing to IV dosing as a less time-intensive and more convenient treatment option. This aims to assess acceptance, safety and satisfaction of transition from IV to SC administration of infliximab (IFX) and vedolizumab (VDZ) in cohort of patients with IBD.

Methods

The transition from IV to SC administration was proposed to 91 patients. All patients were given two questionnaire: (a) before the switch, focused on the impact of the IV administration on their life and (b) 8 weeks after the switch focused on the level of satisfaction and onset of adverse event (AE). Data on medical history and treatment was collected from electronic health records.

Results

Overall, 91 patients were enrolled for switching from IV to SC therapy. All patients filled the first questionnaire. The IV therapy did not or minimally burden on patients’ life in 71% and 15 patients (16%) refused the transition. The main reasons why patients preferred to stay on IV administration were the fear of reducing follow-up visit with IBD staff and the fear of doing the therapy outside the hospital. On the other hand, 76 patients accepted and 8 weeks after the transition they completed the second questionnaire. of these 76, 39 CD and 51 male, 41 (53%) were treated with VDZ and the majority of patients (53%) were at the first line of treatment. Most of patients (67%) did not experience any difficulties in handling the device but “only” the 65% respected the correct time-table of administration. 20% of patients report at least one AE, the most common were erythema, swelling and pain in the injection site. Only the 5% should switch back to IV treament. 8 patients (10%) were switched back to IV administration due to AEs and 1 swaped to Ustekinumab.

Conclusion

In this cohort of IBD patients, we found a good acceptance rate (83.5%). The vast majority of patients (95%) was satisfied of transition from IV to SC. Moreover, we reported a good safety profile of SC therapy, AEs were mostly self-limited and local.
P427 One Year Follow up of Three Phase IB/IIA Clinical Trials of Ex Vivo Expanded Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulizing Crohn’s Disease
Authors: Lightner A , Otero Pineiro A , Reese J , Ream J , Nachand D , Obi M , Adams A , VanDenBossche A , Dadgar N , Hull T
Published: January 2023

Background

Mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, to date, studies have excluded patients with proctitis, anal canal involvement, vaginal involvement, and an ileal pouch in situ. We sought to assess the safety and efficacy of a direct injection of MSCs for the treatment of perianal, rectovaginal, and peripouch Crohn’s fistula(s).

Methods

Three phase IB/IIA randomized control trials of perianal (n=23), rectovaginal (n=19) and peripouch (n=22) Crohn’s related fistulas were conducted to determine safety and efficacy of MSCs for refractory phenotypes of perianal Crohn’s disease. Crohn’s patients with perianal, rectovaginal, and peripouch Crohn’s fistulizing disease were offered enrollment into a clinical trial. A total of 75 million MSCs were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million MSCs was administered at 3 months if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events were collected at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes were assessed at the same time points.

Results

A total of 64 patients were enrolled and treated; 49 were treatment and 15 were control. There were no adverse or serious adverse events reported related to investigational product. At twelve months, overall combined clinical and radiographic healing was achieved in 70% of perianal, 37.5% of rectovaginal, and 46.2% of ileal pouch fistulas, respectfully. In the control cohorts, 12 month healing was 0%, 0%, and 0% in the three clincial trials respectively. The perianal Crohn’s disease activity index and VanAssche score all significantly decreased in treatment patients at six and twelve months, but not in the control groups.

Conclusion

Allogeneic bone marrow derived MSCs offer a safe and effective alternative treatment approach for severe phenotypes of perianal fistulizing Crohn’s disease.
P429 Patient skeletal muscle area and postoperative clinical recurrence in Crohn’s disease: a retrospective study
Authors: Inniss S , Simpson K , Fragkos K , Wood C , Smith A , Rahman F
Published: January 2023

Background

Sarcopenia, a reduction in muscle mass and function, is a poorly recognised phenomenon in Crohn’s disease (CD) despite occurring in 16%-68% of CD patients [1-5]. It has been linked to both an increased need for surgery and increased risk of postoperative complications. However, the role of sarcopenia in CD and its long-term impact on surgical outcomes are unknown. We aimed to assess the link between sarcopenia and postoperative clinical recurrence.

Methods

Retrospective data was collected between 2015 and 2021 from CD patients who had undergone gastrointestinal surgery and a MR or CT scan within 3 months prior to surgery. Follow up data was retrospectively collected for 6 months. MR and CT scans were used to determine skeletal muscle area (SMA) from the cross-sectional L3 vertebrae, which was used to identify patients as sarcopenic or not. Clinical recurrence was defined as a Harvey-Bradshaw Index of 5 or more. Statistical analysis included demographics and inferential analyses. Missing data was attributed to the absence in clinic notes.

Results

This single centre study included 64 CD patients [56.3% male, median age of 30.0 (18.0-76.0), 87.7% non-smokers] who had undergone gastrointestinal surgery. Most patients had ileocolonic CD (74.6%, 47/63) and either stricturing (46.9%, 30/64) or penetrating (31.3%, 20/64) disease behaviour, and 23.4% (15/64) had perianal disease. 45.3% (29/64) of patients had had at least one previous surgery. Preoperatively, 20.6% (13/63) of patients were on steroids and 55.6% (35/63) were on combined drug therapy. Patient median SMA was 113.6 (61.8 – 281.7) cm2 with sarcopenia found in 74.1% (43/58) of patients. SMA was lower in females (females: 92.1±19.3 cm2 vs males: 137±39.5 cm2, p<0.001) and patients with a BMI<18.5 kg/m2 (BMI<18.5 kg/m2: 91.8±19.1 cm2 vs BMI≥18.5 kg /m2: 120.3±33.3 cm2, p=0.004) (figure 1). Postoperative clinical recurrence was observed in 17.8% (8/45) of patients at 6 months. Patients with clinical recurrence had a significantly lower SMA (87.4 ± 18.5 cm2) compared to those without clinical recurrence (120.9 ± 39.2 cm2) (p=0.001) (figure 2). Patients with a lower SMA were 1.1 times more likely to have clinical recurrence at 6 months compared to patients with a higher SMA (OR 1.05 (CI 1.01-1.10)(p=0.022)).

Conclusion

Sarcopenia is highly prevalent in preoperative CD patients. Patients with early clinical recurrence had a significantly lower SMA. SMA may be useful in predicting CD patients at risk of early postoperative clinical recurrence. However, more research is needed to confirm study findings.
P430 Mesalazine dose modification based on fecal calprotectin levels in ulcerative colitis patients in clinical remission
Authors: Piñero G S , Mañosa M , Cañete F , Calafat M , González L , Ruffinengo O , Domènech E
Published: January 2023

Background

Mesalazine is the most widely used maintenance therapy for ulcerative colitis (UC). The lowest effective dose recommended is 2g/day, although higher doses are often prescribed. Fecal calprotectin (FC) is a monitoring biomarker that correlates well with endoscopic remission and predicts clinical relapse. Our aim was to evaluate the suitability of mesalazine dose modification based on FC levels in asymptomatic UC patients.

Methods

Retrospective study in asymptomatic UC patients treated with oral mesalazine therapy which dose was modified in clinical practice according to FC levels between 2016-2022. Sustained clinical remission, clinical relapse and treatment escalation (increase in dose or introduction of rescue therapy) after dose change were assessed during follow-up.

Results

Mesalazine dose was reduced in 47 patients because of persistent low FC (mean 36ug/g; IQR 22-85); 51% extensive UC, median age of 55 years (IQR 43-63), median duration of clinical remission before dose-reduction 17 months (IQR 8-32) and mean baseline dose 3.2g/day (IQR 2-4). Mesalazine was reduced to 2g/day (IQR 0-2.4). A FC value >250 ug/g was observed at least once in 10% of subjects during follow-up. The cumulative probability of maintaining clinical remission after dose reduction was 90% and 82% at 12 and 24 months, respectively. Rescue therapy was used in 27%, 17% being corticosteroids.

In 17 patients, mesalazine dose was increased due to high FC levels (mean 524ug/g; IQR 393-739); 47% extensive UC, median age 54 years (IQR 39-72), median duration of clinical remission before dose increase 16 months (IQR 11-33) and mean baseline dose 2.4g/day (IQR 1.5 -2.4). Dose was increased to 3.2g/day (IQR 3-4.4) and 58% presented FC <250 ug/g at least once during the follow-up. The cumulative probability of clinical recurrence after dose escalation was 14% and 28% at 12 and 24 months, respectively, and 29% needed rescue therapy (6% steroids).

Conclusion

Mesalazine dose modification based on CF levels in asymptomatic patients with UC appears to be a safe strategy and is followed by a low probability of clinical recurrence in the mid-term.
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

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, > 300], highsensitivity C-reactive protein [hs-CRP: < 10 mg/L, ≥ 10 mg/L], and Simple Endoscopic Score for Crohn’s Disease [SES-CD: 6−15, > 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 < .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 < .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 > 10 mg/mL) and higher endoscopic activity (SES-CD > 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

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 < 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.