bluuebunny/crossref_metadata_2025 huggingface dataset:
P288 Recurrence rates of advanced neoplasia after endoscopic or surgical resection in Inflammatory Bowel Disease patients: a retrospective cohort study
Authors: Derks M , te Groen M , Peters C P , Dijkstra G , de Vries A C , Römkens T E , Horjus C S , de Boer N K , Nagtegaal I D , Derikx L A , Hoentjen F
Published: January 2022

Background

Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (AN) including high grade dysplasia (HGD) and colorectal cancer (CRC). Historically, a (sub)total colectomy was recommended in these patients, but alternatively, endoscopic resection or partial colectomy can be considered as well. We aimed (1) to identify factors associated with AN treatment choice and (2) to assess AN recurrence rates following different treatment modalities.

Methods

In this retrospective multi-center cohort study we used the Dutch nationwide histopathology registry (PALGA) to identify ulcerative colitis (UC), Crohn’s disease (CD) and IBD-unclassified patients diagnosed with colonic AN between 1991 and 2020 in seven hospitals in the Netherlands. Exclusion criteria were familial CRC or AN prior to IBD diagnosis. Data regarding the first (index) AN, treatment and endoscopic and surgical follow-up were collected. Recurrence was defined as colorectal AN (independent of colonic location) detected after treatment of index AN. Multinomial logistic regression and cox regression analysis were used to assess in respective associations with treatment choice and recurrence free survival.

Results

We included 189 patients with index AN (n=81 HGD, n=108 CRC) with a median follow up of 27 months (IQR 7–69 months). (Sub)total colectomy was performed in 79 patients (41.8%; n=33 HGD, n=46 CRC), whereas 55 patients (29.1%; n=12 HGD, n=43 CRC) had a partial colectomy. Endoscopic resection was performed in 38 patients (20.1%; n=35 HGD, n=3 CRC), of which EMR/ESD n=12 (6.3%). Seventeen lesions (8.9%; n=1 HGD, n=16 CRC) were not removed, due to comorbidity or metastatic disease. CRC, primary sclerosing cholangitis (PSC), extensive disease and younger age at time of index AN were associated with (sub)total colectomy (Table 1). Twenty-one patients (12.2%) developed recurrence AN (n=12 HGD, n=9 CRC), after a median of 24 months (IQR 14–48; figure 1). Endoscopic resection was associated with recurrence (adjusted hazard ratio 4.0, confidence interval [1.3–12.2], p=0.02), as 14/21 patients (66.7%) with recurrence were initially (for index AN) treated with endoscopic resection. In addition, 3 patients (14.3%) were treated with partial colectomy and 4 (19.0%) with (sub)total colectomy. In 11/21 patients (52.4%) recurrence was treated with surgical resection.

Conclusion

Factors associated with AN treatment with (sub)total colectomy were CRC, PSC, extensive disease and younger age. After AN treatment, 1 out of 10 IBD patients developed recurrence of AN, mainly after endoscopic resection. This underlines the importance of stringent endoscopic surveillance following treatment of AN, especially after endoscopic resection with residual colon in place.
P300 Very early onset Inflammatory Bowel Diseases: Review of the Genoa-Messina joint clinical experience. Therapeutic approach: Part II
Authors: Gramaglia S M C , Cucinotta U , Dipasquale V , Serena A , Gandullia P , Romano C
Published: January 2022

Background

Pediatric inflammatory bowel diseases (pIBD) have specific phenotypes compared to Inflammatory Bowel Diseases (IBD) in adults. The Very Early Onset-IBD (VEO-IBD) is considered a diagnosis of IBD in children before age, 6 years old with, 15% of prevalence.

Methods

The objective of this study was to compare the clinical and endoscopic features of VEO-IBD compared to pediatric IBD (diagnosis >, 6 years old) also in terms of natural history and response to treatment.

The VEO patients followed at the IBD-Centers of Messina and Gaslini were enrolled retrospectively. We compared the results of this population with what is reported in the literature in terms of therapeutic approach and surgery. Percentage comparison of data was performed.

Results

74 VEO-IBD patients were enrolled. At the onset of the disease, during induction therapy, we found, 15–21% of VEO-IBDs are corticoresistant, remission was with Infliximab (table 1). During disease follow-up of at least, 5 years from onset: CD, 47,4% and CU, 61,1% of VEO-IBDs remain in therapeutic maintenance with, 1st line drugs (Mesalazine and Azathioprine; table 2). This result highlights how the VEO-IBDs also maintain clinical, histological and endoscopic remission even with, 1st line drugs, the only exception being the monogenic forms that may also require HSC transplantation.

The surgical approach, according to our data, is far superior to that reported in the literature, although there are several conflicting studies in this regard. Patients undergoing major surgery (colectomy, ileostomy, ileorectoanastomosis, J pouch) are CD, 36.8% and CU, 18.5%, if we also consider minor surgery (perianal surgery; CD, 36.8%) the percentage of patients with Crohn’s disease undergoing surgery increases to, 52.6%. These numbers are far above what is reported in the literature:, 14–15% after, 5 years from diagnosis. It is likely that this result is due to the high numbers of procedures performed at Gaslini Institute, National Center for these diseases.

A monogenic form of VEO-IBD was found in, 5.4% frequently linked to immunedeficiency, 2 cases (2,7%) required allogeneic HSC transplantation (XIAP, WAS) with complete recovery from disease.

Conclusion

VEO-IBDs represent a challenge for the pediatric gastroenterologist. Therapy is no different in terms of response from pediatric inflammatory bowel diseases, with the exception of monogenic forms who may need HSC transplant. Many VEO IBDs maintain remission with, 1st line drugs. Further studies will be needed to define the best therapeutic and diagnostic approach for these diseases.
P302 Malignancy surveillance in patients with primary sclerosing cholangitis and Inflammatory Bowel Disease – keeping up with international guidelines? A Norwegian cohort study
Authors: Tønjum T K , Anisdahl K , Folseraas T , Midgard H , Høivik M L
Published: January 2022

Background

Primary sclerosing cholangitis (PSC), especially PSC in inflammatory bowel disease (PSC-IBD), increases risk of developing several types of cancers, including cholangiocarcinoma (CCA), gall bladder cancer and colorectal cancer (CRC) – highlighting the need for frequent and thorough screening employing several diagnostic modalities, in these patients. We aimed to assess whether current international guidelines for malignancy surveillance were followed for the PSC-IBD population at the Department of Gastroenterology (DoG) at Oslo University Hospital (OUH).

Methods

Data from health records of patients at DoG OUH containing the term ‘PSC’ was screened for IBD and PSC diagnoses, disease activity and severity, as well as follow-up of PSC disease progression and surveillance of PSC-associated malignancies. All data was collected in the last quarter of, 2020 and registered in the local IBD registry.

Results

Clinical characteristics [Table 1] and surgical intervention for PSC-IBD [Table 2] are displayed below. In the last year, magnetic resonance cholangiopancreatography (MRCP) was performed in, 16 patients (26%), while, 47 (78%) had an abdominal ultrasound (US). Colonoscopy or other lower endoscopy was performed within the last year in a total of, 42 patients (69%). In those who had not undergone colectomy, 33/40 (83%) underwent colonoscopy in the last year, while, 31/40 (78%) had biopsies taken.

Conclusion

Abdominal US and colonoscopy with biopsies should be performed annually in all PSC-IBD patients1,2, meaning, on average, about one fifth of PSC-IBD patients at OUH may be at risk of unnecessary and preventable affliction. Also, there is a void of guidelines regarding CRC screening in colectomised patients. Evidence for screening for CCA with MRCP remains unclear3, but when performed may indicate severe economic impact on public health systems.

References

1. Chapman MH et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut., 2019;68(8):1356–78.

2. Aabakken L et al. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. Endoscopy., 2017;49(6):588–608.

3. Schramm C, Eaton J, Ringe KI, Venkatesh S, Yamamura J. Recommendations on the use of magnetic resonance imaging in PSC - A position statement from the International PSC Study Group. Hepatology., 2017;66(5):1675–88.
P304 Intensified versus conventional infliximab induction in acute severe steroid-refractory Ulcerative Colitis
Authors: Pedro J , Coelho Rodrigues I , Botto I , Fernandes S , Bernardo S , Gonçalves A R , Moura Santos P , Valente A , Correia L , Tato Marinho R
Published: January 2022

Background

Infliximab is effective as salvage therapy in severe steroid-refractory Ulcerate Colitis. However, up to one third of patients do not respond to this treatment and require surgery. There is still insufficient evidence regarding the benefits of intensified infliximab induction regimens in this setting.

Methods

Retrospective study including, 51 patients meeting the Truelove and Witts criteria for severe acute Ulcerative Colitis with refractoriness to intravenous steroids requiring infliximab rescue therapy. We compared patients under conventional infliximab induction therapy (n=29) with patients performing an intensified infliximab induction regimen (n=22), defined as a higher dose/shorter interval of treatment during induction.

Results

There was no difference in respect to median age [IQR] (32.0 [27.0–43.0] vs, 42.0 [29.0–58.0], p=0.116), and male gender (69.0 % vs, 63.6%, p=, 0.458) between patients with conventional or intensified infliximab. Compared to patients with conventional induction, patients under optimized infliximab presented reduced admission to intermediary/intensive care unit (4.5% vs, 31.0%, p=, 0.019), and surgery (13.6% vs, 41.4%, p=, 0.031). There were no differences in deaths (3.4% vs, 9.1%, p=0.396), readmission rates (17.2% vs, 28.6%, p=, 0.270), and median duration [IQR] of hospitalization (19.0 [10.5–31.0] vs, 12.0 [8.0–15.5], p=0.094) between patients with conventional or intensified regimens. In a multivariate analysis, the use of an intensified infliximab induction regimen was associated with a lower risk of surgery (OR, 0.224, 95%CI [0.054–0.929], p=, 0.039).

Conclusion

In this small cohort, there was some suggestions that intensified infliximab induction may improve treatment outcomes in acute severe steroid refractory Ulcerative Colitis.
P308 Quadruple oral antibiotic treatment in refractory Paediatric Inflammatory Bowel Disease – incidence and analysis of responders from a, 10 year cohort
Authors: Meredith J J , Armstrong K , Russell R K , Henderson P , Wilson D C
Published: January 2022

Background

Recent, albeit limited, studies indicate that combination oral antibiotic therapy may be an efficacious, immunosuppressive-free, alternative strategy to achieve remission in a subset of medically refractory IBD patients. We sought to identify incidence data and provide cohort analysis of any refractory IBD patients who subsequently responded to combination oral antibiotic therapy from a large paediatric inflammatory bowel disease [PIBD] centre.

Methods

We identified a regional cohort of prospectively acquired incident cases of paediatric inflammatory bowel disease (CD, UC and IBD-U) diagnosed <16 years of age in South-East Scotland over a, 10-year period (2009–2018) and conducted a retrospective review identifying all cases with treatment refractory disease who subsequently achieved remission with a quadruple oral antibiotic regimen (vancomycin/doxycycline/metronidazole/amoxicillin) as salvage therapy. We characterised demographic data, IBD disease type, classification, severity, duration, as well as prior treatment efficacy and duration. There was a minimum of, 2 years of follow data available.

Results

In total, 4 cases of successful treatment with a quadruple oral antibiotic regimen in refractory patients were identified from our, 10-year PIBD registry that included, 222 new cases of PIBD (cumulative incidence, 1.8%). Treatment was attempted in, 9 refractory patients over the period. All responders were male, median age at diagnosis, 13.1yrs (0.5, 11.3, 14.8, 15.7yrs), median disease duration was, 1.3yrs. All responders had chronically active moderate-severe disease., 3 had ulcerative colitis (Paris classification E4), the remainder had Crohn’s disease (Montreal classification B1, L3/4). All responders had disease refractory to a least, 2 biological therapies that were co-administered with either thiopurines or methotrexate., 3 of the, 4 had failed at least one steroid induction course., 3 of the, 4 maintained clinical remission at the minimum, 2 year follow up on regular oral vancomycin therapy.

Conclusion

A subset of patients with PIBD that is highly refractory to conventional therapeutics, including to steroids and multiple biologics, may achieve remission with a quadruple combination oral antibiotic regimen. Those with active colitic phenotypes at intervention were more likely to respond and longer-term disease remission may be maintained with regular oral vancomycin.
P311 Depression and anxiety are associated with poor clinical outcomes in Inflammatory Bowel Disease: A Nationwide Population-Based Study in South Korea
Authors: Kim S , Seungwoo L , Kyungdo H , Hyun Jung L , Jong Pil I , Joo Sung K
Published: January 2022

Background

The increase in prevalence of depression and anxiety disorder in Inflammatory Bowel Disease (IBD) is demonstrated from previous studies, but it is uncertain whether the patients with depression and anxiety are at higher risk of poor outcomes of IBD. Therefore we aimed to determine the impact of depression and anxiety on clinical outcomes in patients with IBD.

Methods

We conducted a nationwide, population-based retrospective cohort study using the Korean national health insurance claims data between, 2010 and, 2017. Patients with Crohn’s Disease and Ulcerative Colitis were targeted through the registration program for rare/intractable diseases, and patients with depression and anxiety were also identified by the International Classification of Disease, tenth revision (ICD-10) code. The primary outcome of this study is the poor IBD-related outcomes and we defined the poor IBD-related outcomes as IBD-related emergency room visits, hospitalization, and surgery in this study.

Results

A total of, 36,379 IBD patients (10,754 Crohn’s disease (CD) and, 25,625 ulcerative colitis (UC)) were enrolled in this study between, 2010 and, 2017 and among them, 4,335 (11.9%) had depression/anxiety. Multivariate analysis showed that CD patients with depression/anxiety were at an increased risk of ER visits (HR, 1.858, 95% CI, 1.5–2.301) and hospitalization (HR, 1.727, 95% CI, 1.315–2.269). UC patients with depression/anxiety were also at increased risk for ER visits (HR, 1.339, 95% CI, 1.084–1.654) and hospitalization (HR, 1.367, 95% CI, 1.059–1.764). While the risk of surgery in patients with depression/anxiety was not different from those without depression/anxiety in both CD and UC.

Conclusion

Depression and anxiety disorder was associated with a higher risk for poor clinical outcomes in patients with IBD. The results of this study suggest that psychologic co-morbidities such as depression and anxiety might improve the clinical course of IBD
P315 High symptom burden and impact on health-related quality of life in patients with Crohn’s perianal fistulas: results from a global burden of illness study
Authors: Karki C , Sharpe E , Hantsbarger G , Lee K , Perovic M , Raven L , Sajak-Szczerba M , Silber A , Yoon A , Tozer P
Published: January 2022

Background

Perianal fistulas (PAF) are a common complication in Crohn’s disease (CD) and can be associated with an increased burden of illness. A global study was conducted to assess the burden of illness in patients with Crohn’s perianal fistulas (CPF) compared with patients with CD without PAF (non-PAF CD). Here we present patient symptom burden and impact on HRQoL.

Methods

This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as having non-PAF CD (cohort, 1) or CPF without PAF-related surgery (cohort, 2) or CPF with PAF-related surgery (cohort, 3). Customised questions and validated general and disease-specific patient-reported outcome data were collected via a, 45-min IRB/EC-approved web-enabled questionnaire. Symptom burden and impact on HRQoL were evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ, scores, 1–7 [low–optimum] with, 2-week recall period) in all cohorts and Quality of Life in Patients with Anal Fistula (QoLAF, scores, 14–70 [low–high impact]) in cohorts, 2 and, 3. Data were analysed using descriptive statistics.

Results

Of, 929 patients recruited (cohort, 1, n=620; cohort, 2, n=174; cohort, 3, n=135), 58–69% were male and, 55–67% were aged, 21–40 years across all cohorts. Cohorts, 2 and, 3 experienced a significantly higher frequency of CD-related complications than cohort, 1 (mean [standard deviation, SD]:, 9.4 [4.5] and, 11.1 [5.2] vs, 6.0 [4.1], respectively; both p <0.05, Table, 1) and had a higher number of CD-related surgeries (other than PAF-related surgeries) in the past, 12 months (mean [SD]:, 1.8 [1.1], p =0.109 and, 2.2 [1.3], p <0.0001 vs, 1.5 [0.9], respectively). In patients with CPF, a smaller proportion in cohort, 2 had active PAF vs cohort, 3 (136 [78%] vs, 119 [88%], respectively; p =0.022) and a smaller proportion had experience with post-treatment PAF recurrence/persistence in cohort, 2 vs cohort, 3 (84 [48%] vs, 80 [59%], respectively; p =0.055). Overall SIBDQ scores were significantly lower (worse) in cohorts, 2 and, 3 than in cohort, 1 (3.8 and, 3.7 vs, 4.1 respectively; both p <0.001). In patients with CPF, total QoLAF scores were comparable between cohorts, 2 and, 3 (41 and, 42, respectively), although patients in cohort, 3 had a significantly higher (worse) score in the physical impact domain compared with cohort, 2 (21 vs, 19, respectively; p <0.05).

Conclusion

In this large global study, we observed that patients with CPF had incrementally higher symptom burden, owing to both CD and PAF, compared with patients with non-PAF CD. For patients with CPF, there was no difference in HRQoL irrespective of whether they had received PAF-related surgery or not.
P321 Mucosal Healing and Clinical remission after Treatment with Adalimumab in Small Intestinal Crohn’s Disease (SIMCHA study): final results from a prospective, open-label, single-arm study
Authors: Wetwittayakhlang P , Golovics P , Hahn G , Bessissow T , Afif W , Wild G , Bitton A , Lakatos PhD P L
Published: January 2022

Background

Endoscopic mucosal healing is a key treatment target in inflammatory bowel disease (IBD). The aim of this study was to investigate small bowel (SB) mucosal healing using video capsule endoscopy (VCE) in patients with Crohn’s disease (CD) following, 24 weeks of adalimumab therapy.

Methods

In this prospective study, moderate to severe SB involvement CD patients were enrolled, defined by a Lewis score on VCE at diagnosis >, 790 in at least one tertile. All patients were treated with adalimumab monotherapy at the standard dosing for CD for, 24 weeks prior to undertaking the follow-up second VCE. The primary outcome was the endoscopic healing defined as a Lewis score (LS) <, 350, whereas partial response was defined as a >, 50% decrease from baseline in LS. Secondary outcomes included the remission in the clinical symptoms (Harvey Bradshaw Index, HBI <, 4) and biomarkers (fecal calprotectin, FC <, 200 ug/g, and c-reactive protein, CRP <, 5 mg/l).

Results

A total of, 59 CD patients were screened at McGill University Health Centre between November, 2011 and October, 2021;, 15 patients were met the eligibility criteria and were enrolled. The median age at inclusion was, 46 years (IQR, 28–51), 8 patients (53.3%) had ankylosing spondylitis. The most frequent locations of CD on VCE findings were the proximal-mid ileum (93.3%) and jejunum (73.3%). Primary outcome; complete endoscopic healing was observed in, 8 patients (53.3%, p=0.002, OR for remission = 2.14, 95%CI:, 1.25–3.68), and partial response in an additional, 5 patients (33.3%) after, 24 weeks. The median total Lewis score was decreased significantly compared to the baseline (1,912 vs., 337, p=0.0005). Secondary outcomes; the HBI at baseline was elevated (>, 4) in, 11 patients. Post-treatment HBI was consistent with clinical remission in all cases (11/15 vs., 0/15, p <0.0001 OR clinical remission = 0.27,95%CI:0.12–0.62). Nine patients who had baseline CRP elevation had achieved normal CRP after treatment, and the median CRP was significantly decreased from, 7.3 mg/L (1.8 -18.0) to, 1.6 mg/L (IQR, 1.0 –, 3.2), p=0.025. However, there were no significant changes in FC pre-and post-treatment. In addition, baseline VCE demonstrated ulcerated SB strictures in, 3 patients, 2 had non-ulcerated strictures on the second VCE. No capsule retention or other adverse events were observed.

Conclusion

Adalimumab led to significant improvement of small intestinal endoscopic healing in Crohn’s disease, with, 53% achieving complete healing.
P335 Utility of Intestinal Ultrasound in Monitoring Disease Activity in Ulcerative Colitis Patients Treated with Biologics
Authors: Tomašić V , Kralj D , Bišćanin A , Ćaćić P , Ogresta D , Dorosulić Z , Hrabar D
Published: January 2022

Background

Given the invasive nature and high cost of frequent and repeated endoscopies needed to monitor UC, search for non-invasive diagnostic alternative is warranted. Intestinal ultrasound is a cost-effective, well-tolerated, non-invasive and readily available „point-of-care“ tool for the management of patients with Crohn’s disease. The role and widespread use of IUS for UC is still limited. We aimed to evaluate association between UC disease activity assessed by IUS on one hand and standard clinical, biochemical, and endoscopic parameters on the other one.

Methods

A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (FC), endoscopic (Mayo Endoscopic Subscore - MES), and IUS parameters (bowel wall thickness - BWT and colonic wall hyperemia assessed by colour Doppler imaging - CDS) were assessed before initiating biologics. Normal distribution was assessed using Shapiro-Wilk tests. Spearman correlation coefficients were calculated and ROC analysis was carried out.

Results

Total of, 44 patients (50% females, mean age, 37.4 ±, 14.05 years) with predominantly extensive UC (75%) were analysed. Positive correlation was observed between combination of BWT and level of CDS with SFS (rs = 0.68, p <, 0.01, N = 33) as well as with RBS (rs = 0.44, p <, 0.01, N = 34). Moreover FC values were in positive correlation with BWT (rs = 0.54, p <, 0.01, N = 36), levels of CDS (rs = 0.66, p <, 0.01, N = 33) and combination of BWT coupled with level of CDS (rs = 0.7, p <, 0.01, N = 33). In case of clinical active UC (SFS, 2/3 + RBS, 2/3 + FC >150 mg/g) correlation coefficient between FC level and BWT coupled with level of CDS rises to rs = 0.72, p <, 0.01, N = 30. Positive correlation of CDS with MES (rs = 0.65, p <, 0.01, N = 16) as well as between combination of BWT + level of CDS with MES (rs = 0.6, p <, 0.02, N = 16) was observed. Interestingly, positive correlation between BWT and MES didn′t reach statistical significance (rs = 0.42, p = 0.1, N = 16). The area under the curve (AUC) for the FC values and disease activity (defined as SFS, 2/3 + RBS, 2/3 + BWT >4 mm + presence of CDS) was, 0.96 (SE:, 0.03;, 95% CI, 0.89–0.99, p<0.01). FC values >134 mg/g were associated with active disease (sensitivity, 89.3%, specificity, 87.5%).

Conclusion

Results of this study show a good correlation between IUS and clinical, biochemical and endoscopic parameters of UC disease severity. IUS as a monitoring tool can be helpful in estimation of UC disease activity and can guide daily management of patients treated with biologics.
P337 Therapeutic drug monitoring: standardization of Promonitor Quick IFX and Promonitor Quick ADL point of care tests with WHO International Standards for the quantification of infliximab and adalimumab in whole blood and serum
Authors: Ametzazurra A , Pascual J , Del Rio L , Urigoitia A , Nagore D , Ruiz-Argüello M B
Published: January 2022

Background

Promonitor Quick IFX and Promonitor Quick ADL are rapid point of care lateral flow tests (LFT) based on a sandwich immunoassay for the quantification of infliximab (IFX) and adalimumab (ADL), respectively, in human whole blood (finger prick or venous) or serum. These tests are to be used as an aid in Therapeutic Drug Monitoring (TDM) of inflammatory bowel disease (IBD) and rheumatic patients under anti-TNFα therapy. The international standards (IS) developed by World Health Organization (WHO) for IFX and ADL allow harmonization and comparability among different assays. The aim of this study, was to show that Promonitor Quick IFX and Promonitor Quick ADL can measure either reference or biosimilar drugs, as well as to evaluate the agreement of Promonitor Quick IFX and Promonitor Quick ADL tests and the WHO IS.

Methods

Clinical and Laboratory Standards Institute EP10-A3 guidelines were followed to estimate the bias of Promonitor Quick assays when used to quantify IFX or ADL in samples containing the reference drugs, biosimilars or the WHO IS. Briefly, whole blood was spiked with four known concentrations of IFX or ADL, including current clinical decision levels. Ten replicates were measured of each level along two days.

Promonitor Quick IFX was evaluated using the reference drug, SB2 and CT-P13 biosimilars, and the WHO IS (NIBSC, 16/170).

Promonitor Quick ADL was evaluated using the reference drug, ABP501 and SB5 biosimilars, and the WHO IS (NIBSC, 17/236).

Results were obtained in combination with the automated portable reader PQreader.

Results

Bias was estimated by comparing the observed concentration of drug spiked whole blood samples. Each biosimilar was compared to the reference at the different drug levels tested. Results showed that Promonitor Quick IFX (Table, 1) and Promonitor Quick ADL (Table, 2) are able to measure equivalently any molecule.

The accuracy or closeness of the agreement between the result provided by Promonitor Quick IFX and Promonitor Quick ADL and the true value of the measurand was assessed by measuring the IS developed by the WHO (Tables, 1 & 2).

Similar results were obtained when serum matrix was used.

Conclusion

Promonitor Quick IFX and Promonitor Quick ADL allow monitoring of patients treated with IFX and ADL, respectively, with just a finger prick sample. Both tests can quantify reference and biosimilar drugs with equivalent results. Moreover, comparable results were obtained with the WHO IS, and thus, demonstrate that Promonitor Quick tests are suited to accurately determine drug levels at the clinical decision points in both whole blood and serum, proving to be an effective and valuable tool in TDM and immediate decision making in the doctor office or hospitals.
P341 Pharmacokinetics and exposure-response analyses of upadacitinib in patients with moderate to severe ulcerative colitis – Analyses of induction and maintenance clinical trials
Authors: Ponce-Bobadilla A V , Stodtmann S , Eckert D , Zhou W , Liu W , Mohamed M E
Published: January 2022

Background

Upadacitinib (UPA), an oral selective and reversible JAK1 inhibitor, showed favorable efficacy and safety profile in Phase, 2b and, 3 studies in subjects with moderate to severe ulcerative colitis (UC). Population pharmacokinetics and exposure-response analyses were performed to characterize the relationships between UPA plasma exposures and key efficacy and safety endpoints using data from these studies.

Methods

The pharmacokinetics (PK), efficacy, and safety of UPA for induction and maintenance treatment in UC were evaluated in a Phase, 2b induction, two replicate Phase, 3 induction, and a Phase, 3 maintenance clinical trials. UPA PK was characterized using data from, 978 UC patients. UPA exposure-response relationships for key efficacy and safety endpoints at the end of induction and maintenance periods were characterized using data from, 1,234 and, 449 UC patients, respectively. Quartile plots and logistic regression models were used to evaluate the exposure-response relationships across UPA doses of, 7.5 mg to, 45 mg once daily (QD) for induction and, 15 mg to, 30 mg QD for maintenance.

Results

UPA PK in UC patients was consistent with other patient populations and between the induction and maintenance periods. The percentage of subjects achieving clinical and endoscopic efficacy endpoints at the end of the induction increased with increasing UPA average plasma concentration (Cavg), and became mostly flat at Cavg values approximately equivalent to the, 45 mg QD (Figure, 1). For maintenance treatment, there was a trend for increasing the percentage of subjects achieving clinical remission, steroid-free remission, endoscopic improvement, and histo-endoscopic mucosal improvement within the range of UPA plasma exposures evaluated. Exposures associated with UPA, 30 mg QD were estimated to provide a, 8% to, 10% increase in the percentage of subjects achieving these endpoints compared to, 15 mg QD (Figure, 2). There was no trend for exposure-response relationships within the range of evaluated UPA exposures for any of the evaluated safety endpoints (>2 g/dL decrease in hemoglobin and >2 g/dL decrease in hemoglobin and < lower limit for normal, hemoglobin <, 8 g/dL, lymphopenia ≥ Grade, 3, neutropenia ≥ Grade, 3, Herpes Zoster infection, serious infections, and pneumonia) at the end of induction or maintenance periods.

Conclusion

UPA plasma exposures associated with the, 45 mg QD induction dose maximized efficacy for clinical and endoscopic endpoints at Week, 8. Plasma exposures associated with UPA, 30 mg maintenance dose provide additional incremental benefit compared to, 15 mg QD. No trends were observed for increase in the evaluated safety events with increasing UPA plasma exposures at the end of induction or maintenance periods.
P346 Chronic pouch failure rates after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis
Authors: Reijntjes M , de Jong D , Bocharewicz E , Elise W , Duijvestein M , Bemelman W
Published: January 2022

Background

During restorative (completion) proctectomy and Ileal pouch-anal anastomosis (IPAA), rectal dissection can be performed in either the total meso-rectal excision (TME) plane with anterolateral exception, or as a full close rectal dissection (CRD). CRD showed lower postoperative morbidity and better short-term quality of life (QOL) when compared to TME. We aimed to compare the incidence of chronic pouch failure (PF) in patients undergoing TME or CRD during proctectomy followed by IPAA for inflammatory bowel diseases (IBD).

Methods

This mono-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC from January, 2002 to October, 2017 in a tertiary IBD referral centre. Outcomes of this study were chronic pouch failure (PF) rates and PF-free survival between patients who underwent CRD and TME. Chronic PF was defined as a pouch-related complication occurring <, 3 months after IPAA surgery requiring pouch-redo surgery, -excision or definitive ileostomy without excision. PF-free survival was defined as months between date of functional pouch and date of surgical PF. Multivariable cox- regression was used to determine whether CRD as dissection type had impact on PF-free survival, when compared to TME. (Chronic) anastomotic ileal pouch-anal leakage and fistula were also included in analyses as confounding factors, which is in line with available literature1.

Results

Out of, 293 patients that underwent pouch surgery, 123 (42.0%) had a proctectomy in the CRD plane, and, 170 (58.0%) in the TME plane. As the median operation year for CRD was, 9 years later (2006 vs, 2015), a significantly shorter postoperative follow-up for CRD patients was reported (74 vs, 172 months, p<0.01). PF occurred in, 27 (9.2%) patients, of which six (4.9%) underwent CRD and, 21 (12.4%) underwent TME (p=0.03). Both the mean PF-free survival in months (162 vs, 195, p=0.31) and PF-free survival rate after, 36 months (98.1% vs, 92.1%) were comparable among patients who underwent CRD and TME (Figure, 1, p=0.31). CRD was not associated with developing chronic PF (Odds ratio = 0.96, CI, 95%:, 0.35–2.61) after multivariable cox-regression analysis.

Figure, 1. PF-free survival curve for patients who underwent CRD (red) and TME (blue)

Conclusion

In the current study, we did not observe a significant difference in chronic PF after either CRD or TME. Although data on long-term functional outcomes and QOL are necessary to draw final conclusions, results of this study suggest that long-term outcomes of CRD were comparable to outcomes after TME. As an earlier study concluded CRD is beneficial when it comes to postoperative morbidity and short-term QOL, surgeons should consider performing close rectal dissection during IPAA surgery for IBD.
P352 Ustekinumab is associated with superior treatment persistence compared to vedolizumab in Crohn’s disease patients who failed to anti-TNF therapy: results from a Hungarian cohort study
Authors: Bacsur P , Resál T , Miheller P , Szamosi T , Schäfer E , Sarlós P , Iliás Á , Szántó K J , Rutka M , Bálint A , Fábián A , Bor R , Zoltán S , Matuz M , Molnár T , Farkas K
Published: January 2022

Background

Anti-tumor necrosis factor alpha treatments are effective and safe as first line therapy, however, their long-term efficacy is limited by primary (PNR) and secondary non-response (LOR) resulting in treatment discontinuation in approximately, 40–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapy could be good alternative in patient with anti-TNF failure, however, no direct comparison has been made. This study aimed to assess treatment persistence and long-term efficacy of VDZ and UST as second- and third line biological therapies in Crohn’s disease (CD) patients refractory to anti-TNF therapy.

Methods

In this multicentre study, CD patients on VDZ or UST maintenance therapy were enrolled. We analysed data of medical history retrospectively in case of both agents. Demographic and clinical data at baseline and one-year were obtained. Clinical (CDAI<150) and biochemical (CRP<10) activities and steroid-free remission were assessed while concomitant medications, hospitalisations and surgeries were recorded during the follow-up. We performed Kaplan–Meier analyses of persistence on treatment including age, CRP, CDAI at baseline, localisation, disease duration, treatment level as possible predictors.

Results

200 UST and, 96 VDZ-treated patients were included in the study. After exclusion of confounders, 162 UST and, 77 VDZ-treated patients were completed the follow-up. Mean age was, 41,1 (±16,5) and, 37,9 (±11,3) years at both agents at baseline. Steroid-free clinical and biochemical remission rates did not differ between VDZ and UST groups at one year (73% vs, 73% and, 67% vs., 51%). Kaplan-Meyer analysis revealed superiority of UST during follow up (86,5% vs., 62,9%, p<0,0001). At both agents, second-line therapy was superior to third line in drug persistence (p=0,019,Exp(B)=, 0,314). None of the further examined parameters predicted treatment outcome. Therapies were terminated due to PNR in, 14 (18%) vs., 8 (5%) cases, while LOR appeared at, 13 (17%) vs., 12 (7,4%) cases at VDZ and UST treatment. One patient discontinued UST therapy due to adverse drug reaction at w20. Other drug-associated adverse reactions didn’t occur during the follow-up. During the follow-up surgery was indicated in, 6 and, 4 cases on VDZ, and, 8 and, 1 cases on UST treatment due to activity and perianal disease (8 and, 5%;, 5 and, 1%, p=0,39, p=0,04).

Conclusion

We confirmed that VDZ and UST are effective and safe alternatives to CD patients who have failed to anti-TNF therapy. UST has a superiority in drug persistence compared to VDZ. Second compared to third line of sequential therapy results in better outcome in drug persistence in case of both agents, however, head-to-head comparison of both agents are needed to verify our data.
P357 Monitoring of Thiopurines and Methotrexate in Inflammatory Bowel Disease: Are we Monitoring Too Frequently? A Cross Sectional Study
Authors: Liao Y W , Oh S , Wright A , Evans C , Duff C , Farmer A , Fryer A
Published: January 2022

Background

The use of immunosuppressive medications such as thiopurines and methotrexate (MET) are commonly employed in inflammatory bowel disease (IBD) to control symptoms and maintain remission. The British Society of Gastroenterology recommends three monthly full blood count (FBC) and liver function tests (LFT) to monitor for myelotoxicity and hepatotoxicity after being established on therapy. However, the quality of evidence for this is low.

Due to the high burden of blood tests and patients becoming increasingly apprehensive to attend hospital or their general practice surgery in the midst of a pandemic, we aimed to investigate (1) the feasibility to adhere to these recommendations and (2) the frequency of abnormal blood test when recommendations are adhered.

Methods

We performed a, 12-month cross sectional study from July, 2017 to July, 2018 of patients established on azathioprine (AZA), 6-mercaptopurine (6-MP), or MET. The timeline was split into four windows of three months each. A patient was removed from the study if they reached any one of these six end points: no FBC or LFT checked within a window, new abnormal LFT, white cell count (WCC) less than, 3.5, change in medication, change in dosage, and medication stopped.

Results

As of, 2019, 4327 patients were under the care of our specialist IBD team with, 1081 on active therapy. We identified, 205 patients who were established on these agents (AZA = 156, 6-MP = 41, MET = 8) within the determined study period. A total number of, 96 patients reached an end point during this period.

For our first objective, a patient was deemed to have been monitored if FBC and LFT was checked at least once during a window., 26% (54/212) of patients were removed from the study as they did not fulfil this criteria.

Of the remaining, 41 patients who reached an end point, 14 were due to a new abnormal LFT result (AZA = 8, 6-MP = 6, MET = 0) and, 5 due to a WCC less than, 3.5 (AZA = 4, 6-MP = 1, MET =0). Excluding non-adherent patients, our study revealed only, 12% (19/158) of patients had to discontinue therapy due to an abnormal blood test.

Conclusion

Achieving an adherence of, 74% was possible with a team of dedicated IBD specialist nurses and doctors in a tertiary centre. Whilst there is still much room for improvement, this may be difficult to replicate in smaller centres with more limited resources.

Despite the small sample size, our finding of only, 12% of abnormal blood test is consistent with similar studies done by Fournier et.al in, 2010 and Chaparro et.al in, 2013. This would certainly pose the question if we can consider monitoring less frequently.
P393 Efficacy and Safety of Induction Therapy With Calcineurin Inhibitors in Combination With Ustekinumab for acute severe colitis
Authors: Veyrard P , Pellet G , Laharie D , Nachury M , Juillerat P , Altwegg R , Nancey S , Fumery M , Allez M , Tran minh M L , Roblin X
Published: January 2022

Background

Ulcerative colitis is a chronic inflammatory bowel disease., 20% of patients will experienced acute severe colitis during their life. In acute severe colitis, when IV steroids failed, two strategies can be used with equivalent efficacy: Ciclosporin and Infliximab. Recently, Pellet et al reported the interest of association ciclosporin – vedolizumab. Regarding results from Varsity trial, more patients are treated before a CAG with vedolizumab. Recently, UNIFI trial showed the interest of ustekinumab in UC patients. So, it should be interesting to analyze the interest of the association Ciclosporin -Ustekinumab in case of acute severe ulcerative colitis. In this study, we retrospectively evaluated the clinical response and the rate of colectomy when we used anticalcineurin and Ustekinumab in acute severe colitis refractory to IV steroids.

Methods

All patients with acute severe colitis who failed to IV steroid and who were treated with calcineurin inhibitor and Ustekinumab, can be included. They were treated with a, 6mg/kg infusion and then a, 90mg subcutaneous injection every, 8 weeks. Eight referral French center and a Switzerland referral center were involved in this study. The primary endpoint was clinical response at, 6 months. We also evaluated the rate of colectomy and survival without Ustekinumab discontinuation. We reported also adverse events in this cohort.

Results

Eleven patients were included., 82% were women, with a median age of, 32.2 years (range, 25.5–36.5 y). The median disease duration was, 8.2 years (range, 3–9.5 y). Ten patients failed to Infliximab and, 9 to Vedolizumab. At inclusion, median Lichtiger score, Mayo score and CRP were respectively, 13,4 [IC95, 12.5–14.5], 10.6 [IC95, 10–11.5] et de, 24.5 mg/L [IC95, 4.5–35.7mg/l]. The mean Endoscopic Mayo score was, 2.6 +/-0.7. The median time between beginning of Calcineurin inhibitor and Ustekinumab was, 22 days (minimum, 6d, maximum, 128d). Median follow-up was, 11 months. None of the patients underwent colectomy at, 6 months. The mean full Mayo score was significantly lower during the follow-up (10.6 at baseline and, 1.0 at, 6 months; p = 0.005). The mean CRP level was significantly reduced (from, 24.5 mg / L [CI95, 4.5–35.7] to, 2.6 mg / L [2–3.1], p = 0.02). Only one patient stopped ustekinumab at the end of follow-up. Two patients required treatment optimization. Tolerance to treatment was well with only one case of alopecia described without withdrawal of treatment.

Conclusion

In this retrospective study including patients hospitalized for IV Steroid-resistant acute severe colitis, the sequence of treatment with induction anti-calcineurin with ustekinumab therapy appears to be effective and well tolerated. These results need to be confirmed on a larger number of patients.
P396 COVID-19 pandemic-related endoscopy delays did not translate to deleterious outcomes for patients with Inflammatory Bowel Disease: A retrospective cohort study
Authors: Chambers J , Gurpreet M , Maria M , Reena K , Aze Suzanne W
Published: January 2022

Background

Inflammatory Bowel Disease (IBD) patients require frequent endoscopies for disease assessment and confirmation of remission, making it a crucial component in their management. It is unknown if measures put in place to reduce the spread of the virus SARS-CoV-2, including the delay of non-urgent IBD patient endoscopy, resulted in more deleterious outcomes for patients with IBD. Therefore, we aimed to determine if delays in endoscopy during the COVID-19 pandemic were associated with an increased risk of adverse IBD outcomes (emergency room, ER presentation, hospitalization, surgery or escalation of drug therapy).

Methods

A retrospective cohort study was performed in IBD patients receiving outpatient endoscopies between March and August, 2019 (pre-COVID-19 pandemic) and, 2020 (during the COVID-19 pandemic) at two tertiary care centers affiliated with Western University, London, Canada. Data pertaining to endoscopy timing, IBD drug prescription, ER attendance, hospitalization, and surgery were collected.

Results

A total of, 1160 endoscopies (2019, n=718;, 2020, n=442) occurred across, 1083 patients (2019, n=669;, 2020, n=414). More endoscopies were delayed in, 2020 than, 2019 (26.7% vs., 9.7% respectively, p<0.0001) and for longer, 56 days (IQR=63) in, 2020 vs., 30 days (IQR=42) in, 2019. No differences were seen in the baseline demographic characteristics based on cohort year or occurrence of endoscopy delay. Also, rurality, sex, IBD type, and age were not associated with a delay in endoscopy. It was found that endoscopy delay was not associated with an increased risk of an adverse IBD outcome (composite outcome of emergency room presentation, ER presentation, hospitalization, surgery or escalation of drug therapy) (RR, 1.23, p=0.20).

Conclusion

A greater proportion of delays in endoscopy were observed during the COVID-19 pandemic; however, delays in general were not associated with more adverse IBD outcomes, and were found to be associated with less deleterious IBD outcomes. This may reflect the accurate and preferential triage of more severe IBD patients to endoscopic assessments.
P399 C-Reactive Protein Values After Surgery for Inflammatory Bowel Disease: Is It Still A Good Marker For Intra-Abdominal Complication? A Retrospective Cohort Study of, 347 procedures
Authors: Gaspard B , Alexandre C , Thibault V , Lauren O , Clotilde D , Najim C , Yann P , Lefevre J
Published: January 2022

Background

C-reactive protein (CRP) is a useful predictive test to early detect abdominal complication after colorectal surgery. Inflammatory bowel disease (IBD) is responsible of chronic inflammation and abnormal basal CRP that could influence the interest of its management after abdominal surgery.

The aim of this study was to evaluate CRP as an indicator of postoperative complication in a specific IBD population.

Methods

Retrospective study of patients undergoing ileocolic resection or ileal pouch-anal anastomosis for IBD between, 2012 and 2019.

Intra-abdominal complication was defined as any intra-abdominal event, infectious or otherwise, occurring during the immediate postoperative period.

The early postoperative period was defined as post-operative days (POD), 1 and, 2 and late postoperative period as POD, 3 and 4.

Results

Ileocolic resection represented, 242 patients and ileal pouch-anal anastomosis, 105 patients.

Intra-abdominal complications occured in, 18.1% of patients (ICR=40, 16.5% and IPAA=23, 21.9%).

Pre-operative CRP (48 hours before surgery) was available for, 96 patients (29.8%). Among them, 64 had an abnormal CRP value (median:, 13±45.4). No relation was found between a preoperative abnormal CRP value and post-operative intra-abdominal complications.

CRP was significantly higher at an early (105.2±56.0 vs, 128.1±69.8; p=0.008) and late stage (112.9±72.8 vs, 185.3±111.5; p <, 0.0001) for patients having an intra-abdominal complication.

The best sensitivity and specificity values were obtained at POD, 3–4 with a CRP cut-off of, 75 with an area under the curve of, 0.71. The ability to rule out an intra-abdominal complication with a CRP Value <75 mg/L was good with, at POD, 1–2 NPV=86.4% and PPV=19.9% and, at POD, 3 an NPV=90.3% and PPV=22.2%.

A BMI >25kg/m2 (p=0.04) and an open surgical approach (p=0.009) were associated with higher CRP levels in the first POD.

In multivariate analysis, pre-operative steroid use (p=0.03), CRP at POD, 3 >, 100mg/L (p=0.002) and a rise between CRP values more than, 50 mg/L (p=0.005) or, 100 mg/L (p <, 0.0001) at, 48 hours were significantly associated with intra-abdominal complication. A CRP at POD, 1 <75mg/L was associated with a lower rate of intra-abdominal complication (p=0.01).

A score using these, 4 independent factors was created and showed significant differences in intra-abdominal complication, anastomotic leakage and readmission rate.

Conclusion

CRP is a useful predictive marker to detect abdominal complication after surgery in IBD population. Measurement of CRP can help to reduce hospitalization stay and orientate towards complementary examinations.