bluuebunny/crossref_metadata_2025 huggingface dataset:
P094 Textbook outcome in Inflammatory Bowel Disease surgery
Authors: Burneikis D , Liska D , Lipman J , Valente M , Gorgun E , Kessler H , Hull T , Sklow B , Steele S , Lightner A , Holubar S
Published: May 2021

Background

Textbook outcome (TO) is a composite measure of quality representing the most ideal result that can be expected from a surgical encounter. TOs for hepatobiliary, bariatric and thoracic procedures have been described in the literature. The purpose of this study was to define and to benchmark the rates of TO for common procedures in patients with Inflammatory Bowel Disease (IBD).

Methods

The American College of Surgeons National Surgical Quality Improvement Project (NSQIP) participant user files (PUF) from 2011 to 2019 were examined. Adults undergoing surgery for Crohn’s disease or ulcerative colitis were included. Four index procedures were selected for the study using Current Procedural Terminology (CPT) codes: ileocolic resection (ICR), diverting loop ileostomy closure (DLIC), total abdominal colectomy (TAC), and ileal pouch construction (IPAA). Four criteria had to be satisfied completely to achieve TO: 1) no 30-day complications, 2) no unplanned return to operating room, 3) no 30-day readmission, and 4) length of hospital stay (LOS) less than or equal to a predetermined threshold for each procedure. The LOS thresholds were derived by surveying 12 colorectal surgeons at our institution about the ideal length of stay for each of index procedure. Relevant preoperative variables collected in the NSQIP PUF were analyzed with multivariable logistic regression to identify potential predictors of TO for each procedure.

Results

The study included 15,261 distinct surgical encounters containing 6,862 ICR, 1,149 DLIC, 3,835 TAC and 3,415 IPAA. The survey mean ideal LOS for each procedure was 3 days for ICR, 2 days for DLIC, 4 days for TAC, and 4 days for IPAA. Using the above definition, TO was achieved in 29% of ICR, 20% of DLIC, 46% of TAC, and 35% of IPAA. The rate of achieving TO increased over time for all four procedures studied (Figure 1). Multivariable logistic regression identified several unique positive and negative predictors of achieving TO. For ICR, male sex and ASA class 4 were significant negative predictors of TO (OR 0.73 [0.66–0.82] and 0.23 [0.07–0.86] respectively); while for TAC, older age and presence of wound infection [DL3] made TO less likely (OR 0.51 [0.35–0.75] and 0.45 [0.23–0.88] respectively); for IPAA, laparoscopic approach made TO much more likely [DL4] (OR 2.0; [1.62–2.46]). We identified no statistically significant predictors of TO for DLIC. Satisfying the LOS threshold was the greatest determinant of achieving TO for all four procedures studied.

Conclusion

In this study, we present the rates of TO for the four most common IBD operations as captured in NSQIP. TO has the advantage of being easy to interpret and can be followed over time to benchmark individual and institutional performance.
P121 The study of the hypercoagulable state in Crohn disease: Results of a prospective comparative study
Authors: Serghini M , Ben Youssef H , Laabidi A , Ben Mustapha N , Hafi M , Fekih M , Boubaker J
Published: May 2021

Background

The risk of thrombosis is increased in Crohn disease (CD). Abnormalities in hemostasis during CD have been evaluated in several studies but the results remain controversial. The thrombin generation assay (TGA) provides an overall assessment of hemostasis compared to traditional tests. The purpose of this work was to study the hypercoagulable state in patients with CD through TGA and to correlate it with the clinical and biological status of the disease.

Methods

This was a prospective comparative study, collating 50 patients diagnosed with CD and compared to 50 matched controls according with age and sex, between May 2016 and January 2020. TGA was effectuated in both groups. Data related to CD were collected. Parameters of lag time (min), time to peak (min), peak (nM), endogenous thrombin potential (ETP in nM.min) and velocity index (VI in nM/min) were analyzed. Laboratory parameters of inflammation, factor VIII and anti-coagulant factors were evaluated in patients.

Results

Median age of patients was 44.02 years (29 men and 21 women). The proportion of patients in remission was 66%. The mean levels of FVIII (285.1±175.2 vs 133.8±41.9; p=0.001), ProteinC (117±22.8 vs 103.2±13.6; p=0.003) and Antithrombin (97.1±16.9 vs 80.65±13.2; p=0.001) were significantly higher in patients with CD compared to controls. No significant difference was found for the rates of ProteinS. Thrombin generation was faster in patients with CD compared to controls (IV: 163.9±41.9 vs 138.2±67.4; p=0.04) and in cases of fistulizing or stenosing phenotype compared to the inflammatory phenotype. Thrombin generation was higher in patients: hospitalized compared to those seen as outpatients (ETP: 1515±406.6 vs 1248.2 + 380.8; p=0.05), treated with corticosteroids (ETP=1718.7 + 126.9) compared to the rest of the patients (p=0.03), with CRP> 6 mg/L compared to those with normal CRP (ETP= 1515 + 384.8 vs 1245 + 348.2) (p=0.02) and with hyperfibrinogenemia level compared to those with normal fibrinogen (Peak = 351.6±74.1 vs 294.9 ±64.4) (p= 0.03). A significant positive correlation was noted between the parameters of TGT, CRP and fibrinogen. ETP value was significantly correlated with CRP (r=0.45; p=0.001) and fibrinogen (r=0.35; p=0.02). This allowed us to determine two biological scores correlating ETP and CRP (ETP=1384 + 2.9 x CRP), as well as fibrinogen level (ETP=1060.7 + 130.5 x Fibrinogen)

Conclusion

Thrombin generation appears to be more accelerated in patients with CD than in controls. This hypercoagulability is associated with hospitalization, stenosing and fistulizing phenotypes, elevated CRP and fibrinogen and corticosteroid therapy. The determination of ETP from CRP and fibrinogen would be a valuable tool for assessing the state of coagulability in these patients.
P133 Clinical and ultrasonographic enthesitis in inflammatory bowel disease patients with and without psoriasis
Authors: Soriano A , Bertolini E , Bertani A , Beltrami M , Macchioni P
Published: May 2021

Background

Previous studies have reported the association between psoriasis (PsO) and inflammatory bowel disease (IBD). Coexistence of IBD and PsO has been associated with significant higher prevalence of enthesitis and dactylitis.

The aim of the study was to compare the prevalence of clinical and ultrasonographic peripheral enthesis abnormalities in a consecutive series of patients with IBD and psoriasis (PsO) as compared to a group of IBD patients without psoriasis (IBD).

Methods

174 IBD consecutive patients [36 PsO and 138 IBD, M/F 91/83, mean age 42.6±14.7 years, mean disease duration 110 ±12.3 months] were recruited. A complete clinical examination, MASES and LEI scores, BASDAI, and dactylitis count, was performed at study entry. Laboratory markers (namely ESR, CPR, Hb, fecal calprotectin) were collected. Axial or peripheral spondyloarthritis (SpA) diagnosis was made using ASAS criteria. US examination was performed by a rheumatologist blind to clinical data. Lateral epicondyle of the humerus, distal quadriceps femoris insertion into the patella, inferior pole of the patella, tibial distal insertion of the patellar tendon, calcaneal insertion of the Achilles tendon, and plantar aponeurosis insertion were examined bilaterally. Knee and ankle joints were evaluated for synovial hypertrophy, PD signal and fluid effusion. Enthesitis was defined according to OMERACT and scored as 0–36 for GUESS and 0–136 for MASEI.

Results

146 patients (83.4%) showed structural damage at > 1 enthesis, 44 patients (25%) had at least 1 active enthesitis, with no significant difference between the two groups. PsO group showcased a significantly increased prevalence of patients having > 1 thickened enthesis (86.1% vs 63.9%, p=0.009) and of PD signal at knee examination (11.1% vs 2.2%, p= 0.034). Enthesis thickness was significantly increased in PsO, in every examined site. Enthesophyte length was significantly increased in PsO group at quadriceps tendon, patellar distal insertion and Achilles tendon.

Conclusion

Presence of PsO and/or familiar history of PsO in IBD patients might represent a predisposing factor for the development of subclinical enthesytis as an extra-intestinal manifestation of IBD, during the disease course.
P141 IBUS-SAS for Crohn’s disease ultrasound activity: initial validation and research of the optimal cut-off score
Authors: Dragoni G , Innocenti T , Lynch E N , Fiorini C , Parisio L , Roselli J , Bagnoli S , Macrì G , Rogai F , Milani S , Galli A , Milla M
Published: May 2021

Background

Intestinal ultrasound (IUS) is being widely accepted as a reliable tool to objectively monitor Crohn’s disease (CD) activity. Recently, an international panel of experts developed an IUS score, called IBUS-SAS (International Bowel Ultrasound Segmental Activity Score). Our aim was to validate this index in a real-life cohort and find a cut-off score that correlates with common lab results of intestinal inflammation.

Methods

All CD patients referred to our unit for IUS examination between November 2020 and February 2021 were scored with the IBUS-SAS. Clinical activity at the time of presentation using Harvey-Bradshaw Index (HBI) was recorded, with remission defined as HBI<5. Faecal calprotectin (FC) and C-reactive protein (CRP) within 8 weeks from IUS were also included. Upper limits of normal for CRP and FC were set at 0.5 mg/dL and 150 µg/g, respectively. Combined biomarkers remission (CBR) was defined as both negative CRP and FC. Pearson’s correlation (rho = ρ) was performed between IBUS-SAS and the other parameters. ROC analyses were carried out to find a predictive cut-off value of IBUS-SAS for CBR.

Results

In total, 40 CD patients were included. The characteristics of the cohort are reported in Table 1. In patients in clinical remission, IBUS-SAS was 27.52±17.42 (mean ±SD); in patients with clinical activity, it was 59.23±22.36. In individuals with negative FC, IBUS-SAS mean value was 26.59±16.85; in case of FC >150 µg/g, it was 50.13±22.16. IBUS-SAS score directly correlated with all parameters considered: clinical activity (ρ=0.38, P=0.01), CRP (ρ=0.33, P=0.04) and FC (ρ=0.42, P=0.007). ROC analysis of IBUS-SAS for CBR revealed an area under the curve of 0.92 (95% CI 0.86–0.97), with a sensitivity of 83.3% and a specificity of 91.3% for a cut-off value of 42.9.

Conclusion

This pilot analysis of IBUS-SAS confirmed its potential to precisely define CD activity, correlating both with clinical scores and biomarkers. An IBUS-SAS cut-off value of 42.9 has demonstrated the highest sensitivity and specificity in predicting normal values of both CRP and FC. A comparison of IBUS-SAS with endoscopic activity and a larger cohort are needed to confirm these findings.
P142 Role of e-health in the management of Inflammatory Bowel Disease: A systematic review and meta-analysis
Authors: Kuriakose Kuzhiyanjal A J , Nigam G B , Antoniou G A , Cross R K , Farraye F A , Limdi J K
Published: May 2021

Background

The increasing incidence and prevalence of inflammatory bowel disease (IBD), has fuelled the need for innovative models of care.

We aimed to compare effectiveness of e-health interventions (virtual clinics, telephone consultation, remote monitoring or any web-based health platform) with standard care in management of IBD. Our primary outcomes were to assess the difference in disease activity and percentage of patients in clinical remission at the end of follow up. Our secondary outcomes were to investigate differences in quality of life (QoL), IBD-knowledge & rate ratios (RR) for endoscopic procedures, total healthcare encounters, corticosteroid use, and IBD related hospitalisation or surgery.

Methods

We searched Medline, Embase, PubMed, CINAHL, PsychInfo, Clinical trials registry and Cochrane databases for randomised controlled trials (RCT) published in the English language until November 2020, comparing e-health interventions to standard care for patients with IBD. Pooled estimates of dichotomous outcomes were calculated using the odds ratio (OR) and 95% confidence interval (CI) using the Mantel-Haenszel statistical method. For continuous data, the standardised mean difference (SMD) and 95% CI were calculated using the inverse variance statistical method. Event data were analysed and expressed as RR with 95% CI using the inverse variance statistical method. Random effects model was used.

Results

Nine studies involving 1841 participants (991 e-health group and 850 controls) were identified. There was no statistically significant difference between the mean disease activity scores for UC (SMD 0.22, 95% CI: -0.04–0.48) and CD (SMD 0.02, 95% CI: -0.18–0.22) in the e-health and standard care groups and no statistically significant difference in the percentage of patients in clinical remission at the end of follow up between both groups (OR -1.05, 95% CI: 0.76–1.45). Higher QoL (SMD 0.19, 95% CI: 0.05–0.34) and IBD knowledge (SMD 0.25, 95% CI: 0.12–0.37) scores were noted in the e-health group compared to standard care. There were no statistically significant differences noted in the RR for endoscopic procedures (RR 1.01, 95% CI: 0.81–1.26), total healthcare encounters (RR 1.03, 95% CI: 0.93–1.15;), IBD related, corticosteroid use (RR 0.99, 95% CI: 0.51–1.92), and IBD related hospitalisation (RR 0.81, 95% CI: 0.53–1.25) or surgery (RR 0.87, 95% CI: 0.49–1.55) between both groups.

Conclusion

E-health interventions are comparable with standard care for impact on disease activity, remission, endoscopy utilisation, total healthcare encounters, corticosteroid use, and IBD related hospitalisation or surgery. QoL and IBD related knowledge were higher in the e-health compared to the standard care group.
P150 Histologic features predicting prognosis and their relationship with endoscopic findings in Ulcerative Colitis patients with mucosal healing
Authors: Shin S , Choi C W , Moon J M , Kim H S , Choi C H
Published: May 2021

Background

Mucosal healing (MH) is one of the treatment targets in patients with ulcerative colitis (UC). However, it has been suggested that even in patients with MH, disease prognosis depends on histologic activity. This study aimed to evaluate histologic features predicting disease prognosis and their relationship with endoscopic findings in UC patients with MH.

Methods

We retrospectively reviewed the data of patients with UC who underwent colonoscopy or sigmoidoscopy with biopsy and evaluated eight histological features, including chronic inflammatory infiltrate, neutrophils in epithelium, ulceration, acute inflammatory cell infiltrate, basal plasmacytosis and serrated architectural abnormalities, as well as Nancy index (NI). Histologic variables predicting disease progression defined as starting corticosteroid, biologics, or small molecule agent, or undergoing clinical relapse or surgical operation were evaluated, and correlated with endoscopic findings.

Results

A total 194 biopsy specimens of 103 patients were evaluated. The highest grades of each histologic item were analyzed when biopsies were performed at multiple sites in one patient. 30.6% showed NI ≤ 1 (no acute inflammatory infiltrate) in 49 patients with endoscopic remission. Among 68 patients with MH, only 24.8% achieved NI ≤ 1. Mucosal friability in endoscopic findings was significantly associated with moderate-to-severe active histologic status (NI ≥3) (46.2% vs 80.0%, P=0.013), and patients with NI ≥3 showed significantly higher rates of disease progression during 13.7-month follow-up period (5.1% vs 19.0%, P=0.21). Ulceration and serrated architectural abnormalities were significantly associated with disease progression, and serrated architectural abnormalities was an independent risk factor in multivariate analysis (odds ratio 2.691 (95% confidence interval: 1.047–6.915), P=0.04).

Conclusion

Mucosal friability in endoscopic findings reflects moderate-to-severe active histologic status, and presence of serrated architectural abnormalities predicts disease progression in UC patients with MH. These findings may help identify patients need closer monitoring.
P153 IBD patients’ treatment preferences are heterogeneous, but largely affected by the avoidance of abdominal pain and side effects (P-POWER IBD study)
Authors: Louis E , Siegel C A , James B , Heidenreich S , Krucien N , Ghosh S
Published: May 2021

Background

Multiple treatments are approved for inflammatory bowel disease (IBD), each offering unique attribute profiles. Therapeutic targets historically included clinical and endoscopic outcomes, but updated guidelines1 also include absence of disability and restoration of quality of life (QoL). Optimising QoL requires understanding patient priorities and considering their preferences in treatment selection. This patient preference study (P-POWER IBD) quantified the tradeoffs patients would make between treatment attributes.

Methods

Adults with self-confirmed Crohn’s disease (CD) or ulcerative colitis (UC) who were receiving IBD treatment took part in an online cross-sectional survey. In a discrete choice experiment (DCE), patients were asked to choose between hypothetical treatments described by six attributes: administration, risk of mild or moderate side effects, risk of serious infections, and impact on abdominal pain, bowel urgency and fatigue. Attributes were selected based on foundational qualitative research and literature review.2 Qualitative and quantitative pilots were used to pre-test the DCE. Relative Attribute Importance (RAI) scores and maximum acceptable risk (MAR) of mild-to-moderate side effects were estimated from a mixed multinomial logit model.

Results

A total of 400 patients (CD: 54%; UC: 46%; female: 38%; mean age: 41 years [range: 18–78]) were recruited. All attributes significantly affected treatment preferences with preference heterogeneity observed (Figure 1). While all attributes were important, their relative importance differed (Figure 2). Avoiding abdominal pain was most important (RAI 33%) followed by the risk of mild or moderate side effects (RAI 27%), risk of serious infections (RAI 16%), treatment administration (RAI 10%), fatigue (RAI 9%), and bowel urgency (RAI 6%). CD patients placed greater importance on abdominal pain (p<0.05) than UC patients and UC patients greater importance on bowel urgency than CD patients (p<0.05). MAR indicated the increased risks of side effects patients would accept to improve other attributes (Figure 3). Notably, to reduce abdominal pain from severe to moderate, patients would accept an additional 19% risk of mild or moderate side effects and 31% if the pain was reduced to mild.

Conclusion

Patients with IBD had strong preferences that varied greatly and were willing and able to make tradeoffs between various important treatment attributes, in particular abdominal pain. Individual preferences should be considered in clinical practice as they may impact long-term targets and QoL.

References
P204 Elevated Fecal Calprotectin Levels Predict Flare-up in Patients with Inflammatory Bowel Disease During International Air Travel
Authors: Park J , Hyuk Y
Published: May 2021

Background

Inflammatory bowel disease (IBD) patients often experience disease flare-ups during international air travel. We aimed to evaluate the proportion of patients that experiences IBD flares during international air travel and identify risk factors associated with enhanced disease activity.

Methods

Patients with scheduled international air travel were enrolled in the study from the Seoul National University Bundang Hospital IBD clinic. Flight information and clinical data were collected via questionnaires and personal interviews, and risk factors associated with IBD flares were determined.

Results

Between May 2018 and February 2020, 94 patients were enrolled in the study (mean age, 33.0 years; males, 53.2%; mean disease duration, 56.7 months), including 56 (59.6%) with ulcerative colitis and 38 (40.4%) with Crohn’s disease. Of the 94 patients enrolled, 15 (16.0%) experienced an IBD flare-up and 79 (84.0%) remained in remission throughout travel. Logistic regression analysis revealed that high fecal calprotectin levels before travel (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.001, p = 0.016), the presence of a comorbidity (OR: 6.334, 95% CI: 1.129–35.526, p = 0.036), and a prior emergency room visit (OR: 5.283, 95% CI: 1.085–25.724, p = 0.039) were positively associated with disease flare-up. The previous and current use of immunomodulators and biologics, time of flight, altitude, number countries visited, travel duration, objective of visit, and previous medical consultations were not associated with disease flare-up.

Conclusion

Factors including fecal calprotectin levels, prior visit(s) to the ER, and the presence of a comorbidity predicted IBD flare-up during international travel.
P216 Comparative Assessment C-reactive Protein Between a Point-of-Care Testing and Current Standard of Care (Immunonephelometric testing)
Authors: Lorenzon G , Marsilio I , Maniero D , Rigo A , Barberio B , Zingone F , Bahur B , Bray K R , Savarino E V
Published: May 2021

Background

C-reactive protein (CRP) is widely used as a biomarker of inflammatory disease activity in hospitalized and non-hospitalized patients. In particular, CRP is commonly used in patients suspected to have an inflammatory bowel disease (IBD) or with a confirmed diagnosis of IBD diagnosis in order to drive the diagnostic approach, to monitor disease activity and to guide therapeutic adjustments. However, standard laboratory CRP testing (Immunonephelometric assays) present some drawbacks, including a turnaround time of 1–2 hours, and the need of specialized equipment, offices and laboratory personnel. Because of that, point-of care testing (POCT) was recently developed in order to provide results within 2 minutes from blood collection, enabling a rapid response to clinical condition.

Aim

To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) using capillary whole blood and the comparative Immunonephelometric assay using serum samples.

Methods

From October to November 2020, consecutive patients hospitalized at Gastroenterology Unit, Padua University Hospital, aged > 18 years and with clinical evidence of active inflammatory disease or infection, who underwent to a standard of care CRP test (Dimension Vista – Siemens Healthineers) were included in the study (range 2.9–340 g/L). Within 1 hour from blood collection, in each patient, CRP quantitation from capillary whole blood collected by finger stick was performed using the ProciseDx CRP assay, with reportable range between 3.6–100 g/L. A Deming regression test was used to identify the correlation between the two methods.

Results

Eighty-three patients were enrolled (62.5% males with mean age ± SD: 60±18). The most common indications for hospitalisation were liver disease (34.9%), pancreatic disturbance (27.7%) and suspicious or recurrence of IBD (16.7%). ProciseDx POCT with finger prick samples required a turnaround time of 2±0.2 minutes, whereas serum samples analyzed in clinical laboratory with the reference method required a turnaround time of about 180±15 minutes (p<0.001). Overall, the correlation between the two tests was high (R squared of 0.899 (95% CI 0.916–0.968)). In particular, the correlation between the methods was even higher with CRP values between 0–100 g/L with R squared of 0.961 (95% CI 0.958–0.986).

Conclusion

The ProciseDx POCT allows a more rapid and comparable accuracy of CRP assessment in hospitalized patients as compared to the standard laboratory measurement. Moreover, the ProciseDx POCT does not require specialised personnel to be performed. The use of ProciseDx POCT may improve and accelerate the decision-making approach, further reducing the resources required for CRP assessment.
P238 Enteropathy associated T-cell lymphoma as a diagnostic challenge in young patient with Crohn’s disease
Authors: Biscanin A , Tomasic V , Dorosulic Z , Kralj D , Lerotic I , Cacic P , Ogresta D , Hrabar D
Published: May 2021

Background

The diagnosis of Crohn’s disease (CD) can sometimes be challenging. Enteropathy associated T cell lymphoma (EATL) is a rare aggressive lymphoma highly associated with celiac disease1. It usually affects small bowel, with signs and symptoms which may mimic CD.

Methods

We present a case of a 37-year-old male patient with coeliac disease, CD and (mis)diagnosed EATL in proximal jejunum.

Results

Patient was referred to our clinic with a constant epigastric pain, weight loss (BMI 17.5), intermittent temperatures, joint pain and diarrhoea. Laboratory tests were normal. Serology for coeliac disease was highly positive. Abdominal ultrasound showed small amount of ascites. EGD showed small shallow stomach ulcers and aphthous mucosal changes of postbulbar part of duodenum. Histology suggested coexisting CD and celiac disease. CT scan detected thickened duodenal wall and suspected duodenal stenosis and enteroscopy was performed. Approximately 80 cm from pyloric ring multiple jejunal ulcers were found. Unfortunately, biopsy was not performed. Colonoscopy showed small ulcers of terminal ileum and histology was nonspecific. Diagnosis of coexisting CD and coeliac disease was established. Therapy with PPI, systemic glucocorticoids and azatioprine was introduced. Three months later patient was in a good clinical condition, but EGD showed multiple gastric and duodenal small ulcers. Dose of azathioprine was optimized because patient refused biologics. After six months of asymptomatic period EGD showed mucosal healing. Azatioprine was continued. One year after the diagnosis of CD he was admitted again to our hospital because of intermittent fevers, severe periumbilical pain, weight loss and dehydration. Laboratory tests showed anemia (Hb 111 g/L), leucocytosis (L12.6/L) an elevated CRP (168 mg/L). CT scan detected jejunal perforation with multiple liver and spleen abscesses. He went under surgery with jejunal resection and histological findings from resected jejunum suggested EATL. In two postoperative days, the patient had progressive liver injury and suppression of bone marrow activity, and despite all supportive treatments he died.

Conclusion

EATL is a serious complication of coeliac disease, it rarely develops in young people and presents diagnostic challenge especially in CD patients. The aim of this report was to raise awareness of the importance of endoscopy with tissue sampling and cross sectional imaging especially in refractory coeliac disease and CD patients.
P297 HLA-DQA1*05 allele and its association with the secondary loss of response to infliximab in patients with Inflammatory Bowel Disease
Authors: Angulo Mcgrath I , Bracho González M , Ocaña Ledesma A , Olmedo Martín R V
Published: May 2021

Background

It is estimated that around 40-50% of patients with Inflamatory Bowel Disease (IBD) will experience a secondary loss of response (SLR) to infliximab, being the immunogenicity a fundamental mechanism. The HLA class II allele, DQA1*05, that codifies the adaptative immune response, is present in approximately 40% of patients treated with anti-TNF, and has been recently associated with a higher probability of immunogenicity, secondary loss of response and discontinuation of anti-TNF therapy.

The aim of this study was to evaluate if the presence of one o more copies of this allele is associated with a higher chance of SLR in patients with IBD treated with infliximab in our project study area.

Methods

Retrospective observational cohort study. We conducted a review of our unit’s database, including in the study patients with IDB treated with infliximab that responded to the induction, in which the presence of HLA-DQA1*05 had been tested. SLR was defined as the recurrence or worsening of symptoms that entailed a treatment change or intensification, hospitalization or surgery. The predictive factors for SLR were identified through a uni and multivariate Cox regression analysis.

Results

88 patients with IDB were included (63 with Crohn’s Disease and 25 with Ulcerative Colitis), followed up to the SLR (52,3%) or a median of 35 months (IQR=58). 42% of these patients were carriers of the HLA-DQA1*05 allele. Patients’ clinical features are gathered in table 1. In the univariate analysis the disease duration in years (HR=0,9, IC 95% 0,85-0,97, p=0,008) and the presence of HLA-DQA1*05 (HR=2,27, IC 95% 1,07-4.83, P=0,03) were associated with the SLR. In the multivariate analysis, adjusted for smoking, previous restrictive surgery, years of evolution of the disease and the presence of combined immunosuppressive therapy, only the presence of HLA-DQA1*05 remained associated to the SLR (HR=2,32, IC 95% 1,07-5,02, p=0,03). Figure 1.

Conclusion

The presence of the HLA-DQA1*05 allele is frequent in patients with IBD, and it is associated with a secondary loss of response to infliximab. If confirmed with prospectively designed studies, the determination of this allele could guide physicians on the therapeutic decision making, advancing towards a more accurate medicine.
P358 An observational, prospective cohort study to evaluate the long term safety and effectiveness of intravenous CT-P13 (biosimilar of infliximab) in patients with Crohn’s Disease or Ulcerative Colitis
Authors: Cheon J H , Kang H W , Lee S J , Kim S H
Published: May 2021

Background

CT-P13 is the world’s first approved biosimilar infliximab for all indications of the reference infliximab. The purpose of this study was to assess long term safety and effectiveness of CT-P13 intravenous (IV) in patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC). We now present the result of safety and effectiveness of CT-P13 in patient with CD, UC for up to 5 years from this longitudinal, observational, prospective cohort Phase IV study.

Methods

The study was conducted from 17 April 2014 to 28 February 2020 in 22 and 21 study centres, in Korea and European Union, respectively. Patients were administered 5 mg/kg of CT-P13 by IV at weeks 0, 2 and 6 and every 8 weeks thereafter. The primary objective was to evaluate adverse events of special interest (AESI) including HBV reactivation, congestive heart failure, opportunistic infections, serious infection including sepsis, tuberculosis, serum sickness (delayed hypersensitivity reactions), hematologic reactions, systemic lupus erythematosus/lupus like syndrome, demyelinating disorders, lymphoma, hepatobiliary events, hepatosplenic T cell lymphoma (HSTCL), intestinal or perianal abscess (in CD), serious infusion reactions during a re-induction regimen following disease flare, sarcoidosis/sarcoid-like reactions, paediatric malignancy, leukaemia, malignancy, colon carcinoma, dysplasia (in UC), skin cancer, pregnancy exposure and bowel stenosis, stricture and obstruction (in CD).

Results

A total of 470 patients with inflammatory bowel disease (IBD) were analysed. Overall 352 (74.9%) patients have been continuously treated for more than 1 year and the mean duration of drug exposure was 26.3 months. The safety profile of CT-P13 and switching from the reference infliximab to CT-P13 was well-tolerated. A total of 329 (70.0%) patients experienced at least one treatment-emergent adverse event (TEAE). Adverse events of special interest of CT-P13 were analysed by safety analysis set (Table 1). Immunogenicity testing was optional and 72 (15.3%) patients had at least one ADA positive after first infusion of study drug. The incidence of TEAEs in ADA positive subset (83.3%) were slightly higher compared to the incidence of TEAEs in ADA negative subset (76.6%). The effectiveness results of clinical remission for each indication was generally well maintained after the study drug administration (Table 2).

Conclusion

The results show that CT-P13 was well-tolerated and efficacious in IBD patients. There was no new safety and effectiveness findings in patients who have been exposed to CT-P13 or patients who have switched treatment from the reference infliximab to CT-P13.
P391 Antibiotics in pediatric Inflammatory Bowel Diseases: a systematic review
Authors: Verburgt C , Heutink W P , Kuilboer L I M , Dickmann J D , van Etten-Jamaludin F S , Benninga M A , de Jonge W J , Van Limbergen J E , Tabbers M M
Published: May 2021

Background

Dysbiosis is the central concept in the current thinking regarding IBD pathogenesis. Current available therapies in pediatric Inflammatory Bowel Disease (IBD) focus on targeting the immune system by suppressing the immune response and often fail to sustain long term remission. Antibiotics directly target bacteria but are underrepresented in current (pediatric and adult) IBD treatment guidelines. We aimed to describe available evidence concerning the use of antibiotics in the treatment of pediatric IBD.

Methods

We systematically assessed efficacy and safety of antibiotics in pediatric IBD. CENTRAL, EMBASE (Ovid) and Medline (Pubmed) were searched for Randomized Controlled Trials (RCTs). Quality assessment of included articles was conducted with the Cochrane risk-of-bias tool.

Results

Two RCT’s (n=101, 4.4-18 years, 43% male) were included. Both studies had overall low risk of bias. In mild-to-moderate Crohn’s disease, azithromycin+metronidazole (AZ+MET) (n=35) compared to metronidazole (MET) alone (n=38) did not induce a significantly different response (PCDAI drop ≥12.5 points or remission) (p=0.07). For induction of remission (PCDAI≤10), AZ+MET was more effective than MET (p=0.025). In Acute Severe Colitis, the mean 5-day PUCAI was significantly lower in the antibiotic (vancomycin, amoxicillin, metronidazole, doxycycline)+intravenous corticosteroids (IVCS) group (n=16) compared to IVCS (n=12) alone (p=0.037), whereas remission (PUCAI<10) did not differ (p=0.61). No significant drug-related adverse events were reported.

Conclusion

Our results highlight the lack of evidence in pediatric IBD. More evidence is needed to assess if implementation in daily practice is necessary.
P422 COVID 19 infection in IBD patients treated with biologic therapy-experience from tertiary center in Serbia
Authors: Sokic Milutinovic A , Jevtovic M , Jovicic I
Published: May 2021

Background

COVID 19 pandemic is caused by newly discovered coronavirus that started end of December 2019 and is ongoing. Patients with severe forms of Crohn’s disease (CD) and ulcerative colitis (UC) treated with biologic therapy are considered to be at increased risk of infectious diseases due to the immunosuppressive effect of biologic drugs. Available guidelines recommend that biologic therapy is continued during the pandemic. Since data on COVID 19 infection in this subgroup of IBD patients is limited we aimed to assess presence of risk factors related to virus transmission, incidence and severity of COVID 19 infection in patients on biologic therapy in tertiary center in Serbia.

Methods

Study was conducted in Clinic for Gastroenterology and Hepatology, Clinical center of Serbia. We included 263 IBD patients on biologic therapy in the study (mean age 41±13, 142 males). There were 162 CD and 101 UC patients. Standardized questionnaire was used to assess presence of different risk factors relevant for virus transmission and also symptoms and severity of disease if patient was infected with COVID 19.

Results

Out of 263 patients 41 (22 CD, 19 UC) was COVID 19 positive. Mean age of COVID 19 positive patients was 43±14, 19 were males and 22 females. In COVID 19 positive group 26 patients were on anti-TNF therapy (15 on infliximab and 6 on adalimumab), while 15 were treated with vedolizumab. Risk factors for COVID 19 infection were use of public transportation (p<0.05), active disease (p<0.05), residency in capital city (p<0.05) and presence of COVID 19 infection in a household member (p<0.05). Other factors such as age, sex, blood type, use of conventional immunosuppressive therapy and class of biologic drug did not differ between infected and uninfected group. Pneumonia was diagnosed in 7 patients (17%) and hospital admission was necessary in 4 cases (9.75%). All hospitalized patients were using corticosteroids due to relapse of IBD. Most common symptoms of infection were fever in 26 (63.4%), tiredness in 19 (46.3%) and loss of taste and smell in 17 (41.4%) patients. All patients recovered successfully and none needed mechanical ventilation.

Conclusion

Use of biologic therapy during COVID 19 pandemic is safe in IBD patients. Since we did not observe any fatal outcomes and all patients had mild to moderate COVID 19 presentation it is possible that biologic therapy, especially anti-TNF, has a protective role in preventing cytokine storm during COVID 19 infection.
P427 Efficacy and safety of vedolizumab and adalimumab in Asian adults with moderately to severely active ulcerative colitis: Post-hoc analysis of the VARSITY trial
Authors: Kim J S , Leung W K , Wu D C , Lindner D , Fadeeva O , Demuth D
Published: May 2021

Background

The VARSITY trial, the first head-to-head study comparing the efficacy and safety of biologics in patients with moderately to severely active ulcerative colitis (UC), demonstrated superior clinical remission with vedolizumab (VDZ) versus adalimumab (ADA) at week 52. This post-hoc analysis describes outcomes in patients from Asia included in the VARSITY trial.

Methods

Adult patients with moderately to severely active UC (Mayo score 6–12; endoscopic sub-score ≥2), refractory to conventional therapies and anti–tumour necrosis factor-naïve or -experienced (exposure capped at 25%) were included. This analysis focussed on patients from Hong Kong, Taiwan and South Korea. Patients were randomised (1:1) to receive intravenous (IV) VDZ (300mg) and subcutaneous (SC) placebo on day 1 of weeks 2, 6, 14, 22, 30, 38 and 46 or SC ADA, at weeks 1 (total dose:160mg) and 2 (80mg) and every 2 weeks (40mg) plus IV placebo thereafter until week 50. The primary endpoint was clinical remission at week 52. Secondary endpoints included rates of endoscopic improvement, corticosteroid (CS)-free remission and histological remission at week 52. Patients with missing endpoint assessment at week 52 were considered non-responders. Data were analysed descriptively.

Results

A total of 45 patients (VDZ: n=21; ADA: n=24) were included. At baseline (VDZ and ADA, respectively), the mostly male population (71.4% and 58.3%) had a mean (SD) age of 46.4 (14.7) and 40.4 (15.1) years; severe disease: 33.3% and 54.2%; mean (SD) disease duration: 6.8 (5.5) and 5.4 (3.5) years; and were biologic-naïve: 85.7% and 79.2%. At week 52, a higher rate of clinical remission was achieved in VDZ- vs. ADA-treated patients (28.6% vs. 16.7%; Table). Adverse events (AEs) occurred in 71.4% (VDZ) and 87.5% (ADA) of patients; serious AEs occurred in 4.8% (VDZ) and 16.7% (ADA) of patients. AEs led to study drug discontinuation in 4.8% (VDZ) and 8.3% (ADA) of patients; no deaths occurred.

Conclusion

Patients from Asian countries with moderately to severely active UC achieved higher rates of clinical, CS-free, and histological remission as well as endoscopic improvement with VDZ vs. ADA. VDZ and ADA were both generally safe and well tolerated. Descriptive trends were consistent with findings in the larger VARSITY cohort.
P431 Teduglutide use and nutritional outcomes in short bowel syndrome with intestinal failure: a real-world claims database analysis
Authors: Micic D , Jiang J , Chen L , Fan T , Mu F , Satija A , Downes N , Shrestha S , Wu E , Swallow E , Wojtowicz A , Raphael B P
Published: May 2021

Background

Teduglutide (TED) is a glucagon-like peptide 2 analogue approved for the treatment of patients with short bowel syndrome (SBS) requiring parenteral support (PS). SBS is a rare condition resulting from a reduced absorptive surface area of the small intestine, most commonly due to inflammatory bowel disease (IBD). Patients with SBS with intestinal failure (SBS-IF) remain dependent on PS to maintain adequate calorie, fluid, electrolyte and micronutrient stability. In phase 3 clinical trials, TED reduced PS requirements in patients with SBS-IF. This study aimed to assess PS use and discontinuation rates among patients with SBS on TED using real-world data.

Methods

This retrospective cohort study of adults with SBS-IF (≥18 years) with ≥1 TED pharmacy claim(s) used the US-based administrative healthcare claims IBM MarketScan database (2009–2019). The first TED claim was defined as the index date. Patients required ≥6 months of continuous enrolment prior to index date (baseline period) and no history of malignancy. Primary analysis was conducted during the follow-up period (index date to earliest of continuous enrolment end or 2 years post-index). A sensitivity analysis was also conducted among the cohort during the TED utilization period (index date to the earliest of continuous enrolment end or TED discontinuation). Patients required PS use during both baseline and follow-up/TED utilization periods (primary and sensitivity analyses). PS discontinuation was defined as a PS utilization gap of ≥30 days. A generalized estimating equation linear regression model evaluated if PS use (days/week) changed significantly from baseline to selected time points post-index.

Results

Of 110 identified patients with SBS-IF, mean age was 53.4 (SD 13.2) years and 77 (70%) were women. Included were 51 (46%) patients with Crohn’s disease and 20 (18%) with ulcerative colitis. The main comorbidities were renal disease (23%) and liver disease (15%). PS frequency was 4.6 (2.5), 3.3 (2.9), 2.9 (3.0) and 3.6 (3.0) days/week at baseline and months 6 (p<0.0001), 12 (p<0.0001), and 24 (p=0.0267), respectively. PS discontinuation increased over time to 34.4%, 46.7% and 65.2% at 3, 6, and 12 months, respectively. The sensitivity analysis demonstrated similar rates of PS use and discontinuation.

Conclusion

In this real-world study of adults with SBS-IF, including >50% with IBD, TED was associated with PS reductions comparable to those achieved in clinical trials and higher PS discontinuation rates even when using a conservative analysis approach. Future research will be required to determine individual predictive factors of PS discontinuation.
P433 Sex-based differences in response to tumor necrosis factor inhibitor induction therapy for ulcerative colitis: a pooled analysis of individual patient-level clinical trials data
Authors: Agrawal M , Petralia F , Tepler A , Durbin L , Reinisch W , Colombel J F , Shah S
Published: May 2021

Background

There are increasing data on sex-based differences in IBD epidemiology, phenotype and outcomes. The purpose of this study was to characterize sex-based differences in response to tumor necrosis factor inhibitor (TNFi) therapies in patients with ulcerative colitis (UC).

Methods

We conducted a pooled analysis of individual-level data from randomized clinical trials (RCTs) on induction therapy with infliximab and golimumab, accessed through the Yale University Open Data Access platform. We analyzed patients in the treatment and placebo arms separately. Using multivariable logistic regression modeling, we compared the primary outcome of clinical remission, and secondary outcomes of clinical response and mucosal healing, according to clinical trial definitions, between male and female patients with UC at week 6 (golimumab) or week 8 (infliximab) of induction therapy. Effect estimates were expressed as adjusted odds ratios (aOR) and 95% confidence intervals (CI).

Results

We included 1639 patients (696, 42.5% were women, Table) from two trials using infliximab (ACT-1 and 2) and one trial using golimumab (PURSUIT). Male patients were older than female patients in the treatment arm of the overall cohort [mean age (standard deviation) 31.31 (16.53) years and 29.34 (15.19) years, respectively). All other baseline characteristics, such as sex, race, Mayo score at screening, and concomitant systemic corticosteroid and immunomodulator use were comparable. Compared to female patients, male patients were significantly less likely to achieve clinical remission in both treatment and placebo arms (aOR 0.55, 95% CI 0.31, 0.97 and 0.34, 95% CI 0.15, 0.82, respectively, Figure). Compared to female patients, male patients were significantly less likely to achieve mucosal healing and clinical response in the treatment arm (aOR 0.47, 95% CI 0.27, 0.83 and 0.51, 95% CI 0.29, 0.90, respectively), but there was no significant difference in these secondary outcomes by sex in the placebo arm.

Conclusion

Based on this analysis of pooled data from RCTs, we demonstrate that clinical remission, response and mucosal healing with TNFi induction therapies are less likely in male patients compared to female patients with UC. Clinical remission is also less likely in male patients on placebo. These finding may lead to further research on sex-based differences in treatment outcomes, including mechanistic studies.
P529 Adalimumab persistence and its biosimilar in inflammatory bowel disease: experience in a tertiary centre
Authors: Fernandez Cano M C , Sánchez-Capilla A D , Martín-Rodríguez M M , Cabello-Tapia M J , Redondo-Cerezo E
Published: May 2021

Background

Adalimumab biosimilars experience in real practice is still limited. Some changes in efficacy, safety, adherence or tolerance in comparison with the original could lead to a cessation of this drug. We propose the use of persistence as a reliable parameter to report the absence of drug withdrawal. To date, there are no studies specifically about the persistence of these biosimilars compared to the original and this project aimed to analyze it, in addition to advance concerning safety.

Methods

We performed a retrospective study with 104 patients from our hospital, consecutively selected between 2018–20. Data were obtained from the digital medical record. The primary outcome measure was persistence during 1 year, represented in Kaplan-Meier analysis. We gathered secondary endpoints such as the treatment-emergent adverse events (TEAE), clinical efficacy, serum biomarkers such as protein-C-reactive (CRP) and faecal calprotectin (FC). Were considered mild TEAE which did not require its withdrawal and we were considered severe those which led to discontinuing the drug, needed hospital admission or specialized care.

Clinical response was considered according to Harvey–Bradshaw Index (HBI) (decrease ≥3 below the baseline) or Partial Mayo Index (PMS)( ≤ 2 points below baseline). We considered p < 0.05 as statistical significance.

Results

Our sample included 104 patients divided into 3 groups: 50 received biosimilar (A), 29 original (B), and 25 started with biosimilar but previously had received original (were “denominated mixed group”)(C). The persistence of group A was higher (p =0.04) while concerning adverse reactions, no differences were obtained about mild and there were differences in severe ones (p = 0.009). Group C obtained higher severe TEAE. The inflammatory biomarkers were reduced in a similar proportion in the 3 groups, and 43% had a clinical response to Adalimumab at week 20 without differences between them.

Conclusion

According to our study, patients who received exclusive biosimilar presented a higher persistence. Regarding safety, biosimilars are safe with a similar profile in comparison to the reference drug in most clinical settings. However, based on our data, the switch within the same active principle (from original to biosimilar) could generate interferences in the clinical results and could cause the appearance of TEAEs that would suppose drug withdrawal. These aspects are related to the nocebo effect, and our advice is to avoid this strategy to minimize these negative effects of therapy switch. Further research is needed to improve the knowledge about adalimumab biosimilars with longer follow-up and with larger cohorts including multicentric researches.