bluuebunny/crossref_metadata_2025_split huggingface dataset:
A140 INTEROBSERVER RELIABILITY OF THE PARIS CLASSIFICATION FOR SUPERFICIAL GASTROINTESTINAL TRACT NEOPLASMS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Gupta S , Seleq S , Gimpaya N , Khan R , Scaffidi M , Grover S 
Published: February 2022

Abstract

Background
The Paris classification is an international classification system that characterizes the morphology of superficial gastrointestinal tract neoplasms. Given its ability to predict the risk of submucosal invasion, this tool plays an important role in the preliminary endoscopic assessment of early gastrointestinal neoplastic lesions. Despite its international prevalence, there are no pooled reliability analyses to assess agreement amongst endoscopists using this classification system.

Aims
To systematically review and meta-analyze the interobserver reliability (IOR) of the Paris classification system.

Methods
We conducted a systematic review and meta-analysis according to the PRISMA recommendations. A comprehensive literature query was conducted on biomedical databases through December 2020. Studies were included if they quantitively evaluated the IOR of the Paris classification with at least 5 endoscopists participating in the study cohort. Two authors independently screened studies and abstracted data using an a priori designed data collection form. We pooled the results of studies which provided IOR with kappa statistics and confidence intervals using DerSimonian and Laird random effects models. Risk of bias was independently assessed by two study authors using the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) tool.

Results
From an initial 1541 studies, 5 were included in the qualitative review and 3 reported data that allowed for a quantitative analysis of the primary outcome, representing a total of 28 endoscopists. All three of these studies were high quality. The IOR for the Paris classification amongst all endoscopists was 0.541 (95% CI, 0.466–0.617). There was no significant improvement (p=0.551) in the IOR of the Paris classification system following an educational training intervention (pre-education pooled kappa, 0.498; 95% CI, 0.429–0.567 compared to post-education pooled kappa, 0.530; 95% CI, 0.451–0.608).

Conclusions
Interobserver reliability of the Paris classification is moderate with no significant improvement following educational intervention.

Funding Agencies
None
A145 EFFICACY AND SAFETY OF UPADACITINIB MAINTENANCE THERAPY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM A RANDOMIZED PHASE 3 STUDY
Authors: Panaccione R , Danese S , Zhouwen W , Pangan A , Hébuterne X , Nakase H , D’Haens G , Panes J , Lindsay J , Higgins P , Loftus E , Sandborn W , Xie W , Sanchez gonzalez Y , Liu J , Weinreich M , Vermeire S 
Published: February 2022

Abstract

Background
Upadacitinib (UPA), an oral selective and reversible JAK inhibitor, demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 induction trials.

Aims
Evaluate safety and efficacy of 52 weeks of UPA 15 mg QD (UPA15) and 30mg QD (UPA30) compared to placebo in patients achieving clinical response following UPA 45 mg treatment in the induction trials.

Methods
The primary analysis (n=451) evaluated efficacy and safety of UPA15 and UPA30 compared to PBO as maintenance therapy. The primary endpoint was clinical remission via adapted Mayo score at wk 52. Ranked secondary endpoints included endoscopic improvement, maintenance of clinical remission, corticosteroid-free clinical remission, maintenance of endoscopic improvement, endoscopic remission, maintenance of clinical response and Histologic-endoscopic mucosal improvement (HEMI).

Results
Baseline characteristics were similar between all treatment groups. Both UPA15 and UPA30 met the primary endpoint, and all secondary endpoints. Significantly greater percentages of patients receiving UPA15 and UPA30 vs. PBO achieved clinical remission (42.3% and 51.7%, vs. 12.1%), endoscopic improvement (48.7% and 61.6%, vs. 14.5%), maintenance of clinical remission (59.2% and 69.7%, vs. 22.2%), corticosteroid-free clinical remission (57.1% and 68.0%, vs. 22.2%), maintenance of endoscopic improvement (61.6% and 69.5%, vs. 18.9%), endoscopic remission, (24.2% and 25.9%, vs. 5.6%) and HEMI (34.8% and 49.3%, vs. 11.8%) (p&lt;0.001 for all endpoints). UPA15 and UPA30 were both well-tolerated and no new safety signals were observed. Rates for serious adverse events (AEs) and AEs leading to treatment discontinuation were similar between UPA15 and UPA30 groups and lower compared to the PBO group. Most common AEs were nasopharyngitis and creatine phosphokinase elevation among UPA groups and UC exacerbation within the PBO group (30.2%). Herpes zoster was only reported in UPA groups (3.9%-4.1%). Similar rates of malignancy excluding NMSC were seen within all groups (0.7%-1.3%). MACE were only reported among patients receiving PBO (0.7%), while VTE were only found with UPA30 (1.3%).

Conclusions
In patients responding to UPA induction therapy, both UPA15 and UPA30 were safe and effective as maintenance treatment at 52 wk for all primary and secondary endpoints. Patients receiving UPA30 responded approximately 10% better for most endpoints compared to those receiving UPA15. Both doses were well-tolerated, with no new safety signals observed.

Funding Agencies
AbbVie
A147 SIMILAR OUTCOMES IN PATIENTS SWITCHED TO INFLIXIMAB BIOSIMILARS COMPARED TO THOSE REMAINING ON REMICADE IN A BRITISH COLUMBIA INFLAMMATORY BOWEL DISEASE PRACTICE
Authors: Painchaud M , Singh S , Penner R M 
Published: February 2022

Abstract

Background
In 2019 the Canadian province of British Columbia (BC) launched an initiative to switch inflammatory bowel disease (IBD) patients on the infliximab originator, Remicade, to biosimilars Inflectra or Renflexis. Evidence shows that such switches can be made without compromising efficacy or safety of treatment.

Aims
We examined results in a large IBD practice, with the hypothesis that patients required to switch to a biosimilar would have similar remission rates to those who remained on Remicade.

Methods
A total of 113 patients were included in this retrospective chart study. 80 of these were switched to biosimilars and were compared with 33 who remained on Remicade based on availability of private or compassionate coverage. Individual patient timelines were created, the start set as when the mandated switch was discussed. Data was collected retrospectively for 6 months. Outcomes included remission status, occurrence of flares, adverse events, hospitalizations, and necessity of dosage or drug change.

Results
Pre-switch, 49 of the 113 patients were in complete remission on Remicade (43.4%). 27% of the Remicade patients and 28.8% of the biosimilar patients remained in complete remission throughout follow up (p=0.87). Of the patients who began the study in complete remission, similar numbers of patients in the Remicade and biosimilar groups experienced flares (11.1% vs 27.5%; p=0.3); adverse events (33.3% vs 25%; p=0.61) and hospitalizations (0% vs 5.0%; p=0.49) respectively. 6.1% of patients beginning the trial in complete remission required a change in medication after the switch, all of which were in the biosimilar group (0% vs 7.5%; p=0.39). Among all 113 patients in the study, there was a numerical difference between the Remicade group and biosimilar group of patients who required a change in medication to another biologic. While clinically important, this was not statistically significant (0% vs 8.8%; p=0.08). Other clinical outcomes were similar between Remicade and biosimilar patients in the full group of 113 patients.

Conclusions
IBD patients remaining on Remicade or switching to biosimilars demonstrated similar patient outcomes after a 6-month period.

Funding Agencies
None
A149 REAL WORLD OUTCOMES OF NON-MEDICAL SWITCHING OF INFLIXIMAB BIOSIMILAR IN BRITISH COLUMBIA FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE (IBD)
Authors: Reid J , Rosenfeld G , Galorport C 
Published: February 2022

Abstract

Background
A mandated non-medical switch to the infliximab biosimilars was launched in British Columbia in 2019. British Columbia was the first province in Canada to mandate the switch from the originator infliximab (RemicadeTM) to one of the 2 approved biosimilars (InflectraTM or RenflexisTM). There is limited data for mandatory non-medical switching in IBD as was undertaken in BC.

Aims
This study aimed to obtain real-world evidence evaluating the clinical outcomes of nonmedical switch from Remicade to the infliximab biosimilars.

Methods
This is a retrospective observational study from the IBD Centre of BC (a tertiary care referral centre in Vancouver, BC). Patients on infliximab at the time of the mandated switch were identified through search of the electronic medical record. The primary outcome was drug continuation at 12 months post switch. Secondary outcomes included flare of disease, adverse events, and number of doctor visits within the first 12 months post switch. A comparison group included patients maintained on originator infliximab.

Results
A total of 235 patients were evaluated; 175 patients in the biosimilar switch group, and 60 patients in the control group. Baseline characteristics of the groups were similar. Discontinuation of infliximab occurred in 22 patients (17 in biosimilar switch group and 5 in the control group. There was no difference in the rate of discontinuation of infliximab between the biosimilar group (9.7%) and the originator molecule group (8.3%); chi squared (1, N=235) = 0.1004, p = .75. The most common reason for discontinuation was flare of disease in 6 patients in the biosimilar group and 4 patients in the control group. An additional 4 patients in the biosimilar group and 3 patients in the control group had a flare of symptoms but were maintained on therapy with an escalation of dosage or course of corticosteroids. Two patients had active disease at the time of switch and discontinued therapy. Adverse events accounted for discontinuation in 5 patients on biosimilar and 1 in the control group. These included joint pain, epigastric symptoms, drug intolerance, drug induced lupus, and drug induced pulmonary nodules in the biosimilar group, and drug induced vasculitis in the control group. Two patients in the biosimilar group discontinued due to antibody formation. Two patients in the biosimilar group discontinued therapy due to preference.

Conclusions
In this small subset of the BC IBD population undergoing a non-medical biosimilar switch of infliximab, there was no difference in the discontinuation rate between the biosimilars or the originator infliximab molecule. These findings are consistent with the existing real-world evidence.

Funding Agencies
None
A150 ASSOCIATION BETWEEN SERUM USTEKINUMAB CONCENTRATIONS AND ENDOSCOPIC DISEASE ACTIVITY IN CROHN’S DISEASE
Authors: Yanofsky R , Abduallah Y , Golovics P , Lakatos P L , Bitton A , Wild G , Afif W , Bessissow T 
Published: February 2022

Abstract

Background
Therapeutic drug monitoring, the measurement of serum biologic concentrations and immunogenicity, has become an important method in guiding the management of biologic therapy in patients with Crohn’s disease (CD). Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an approved therapy for patients with CD. However, few studies have explored the relationship between serum ustekinumab drug levels and outcomes in CD. Thus, the utility of serum ustekinumab drug levels in the management of CD remains unknown.

Aims
The primary objective of the study was to evaluate the association between serum ustekinumab drug levels and endoscopic remission (ER) in CD. Secondary outcomes included evaluating the association between serum ustekinumab drug levels and clinical (CR), biochemical, and histological remission (HR).

Methods
Adult patients with CD maintained on ustekinumab were prospectively recruited at the time of routine colonoscopy from 2018 to 2021 at the Montreal University Health Centre, Montreal, Quebec. Clinical and demographic information was obtained from chart and patient review. CD symptom severity was assessed by the Harvey-Bradshaw Index (HBI), with clinical remission defined as an HBI score less than 5. Blood samples were drawn for measurement of serum ustekinumab drug level and C-reactive protein. Stool samples for fecal calprotectin were also collected. Elevated C-reactive protein and fecal calprotectin were defined as a value greater than 5 mg/L and 200 ug/g, respectively. Endoscopic remission was evaluated by the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), with ER defined by an SES-CD score less than 3. If biopsies were taken, histological outcomes were recorded. HR was defined as inactive colitis.

Results
53 patients were included in the study, of which 22 (41.5%) were in ER. Median [interquartile range] ustekinumab drug levels were not associated with ER (ER = 5.4 mg/L [2.6–9.4 mg/L], no ER = 4.3 mg/L [2.3–9.4 mg/L]; P=0.843). There was also no association between quartiles of ustekinumab drug levels and ER (P=0.772). In addition, there was no association observed between median ustekinumab drug level and CR (CR = 4.7 mg/L [2.7–8.3 mg/L], no CR = 3.8 mg/L [2.1–9.6 mg/L]; P=0.993) or HR (HR = 6.4 mg/L [3.5–9.5 mg/L], no HR = 3.7 mg/L [2.2–8.0 mg/L]); P=0.168). There was no association observed between median ustekinumab drug level and C-reactive protein or fecal calprotectin as well (P=0.158 and 0.923, respectively).

Conclusions
There was no association observed between serum ustekinumab drug levels and endoscopic remission. Further studies are required to validate our findings.

Funding Agencies
None
A151 RISK FACTORS FOR VENOUS THROMBOEMBOLISM AFTER HOSPITAL DISCHARGE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Gozdzik M , Unninayar D , Sarker A , Chin Koon Siw K , McCurdy J 
Published: February 2022

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic inflammatory condition which is independently associated with venous thromboembolism (VTE). Although the absolute risk of VTE is greatest during hospitalization, the risk remains elevated in the early post-discharge period. The risk factors for VTE during this vulnerable period remain unknown.

Aims
We performed a systematic review and meta-analysis to determine risk factors for VTE in the post discharge period among adult patients with IBD.

Methods
We performed a systematic search of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception through April 29, 2021 for publications that reported risk factors for VTE during the post-discharge period among patients with IBD. Study eligibility was assessed independently in duplicate without age or language restriction. We defined the post-discharge period as within 6 months of discharge. Pooled summary estimates of adjusted hazard/odds ratios, when available, were calculated for individual risk factors using random effects model with 95% confidence intervals. The analysis was performed when a minimum of three studies were available for a given risk factor. Heterogeneity was assessed using I2 statistic. Study quality was assessed using an adapted version of the National Institute of Health criteria.

Results
We identified 10 studies from a total of 4339 abstracts that met our inclusion criteria: 8 population-based studies, 1 multicenter observational study and 1 single center observational study. Risk factors for post-discharge VTE were assessed at 6 weeks in 1 study, 1 month in 5 studies, 3 months in 2 studies, and 6 months in 2 studies. The variables assessed in our meta-analysis are reported in Table 1. Exposure to corticosteroid (odds ratio [OR], 1.77; 95% CI, 1.53–2.06) but not biologics (OR, 1.21; 95% CI 0.80–1.82) was associated with an increased risk of VTE. Furthermore, greater length of stay (OR 1.49; 95% CI, 1.01–2.20), ulcerative colitis (OR 1.41; 95% CI, 1.19–1.66), history of malignancy (OR 1.35; 95% CI, 1.12–1.62), and surgery during admission (OR 1.26; 95% CI, 1.12–1.42) but not female sex (OR 0.98; 95% CI, 0.88–1.10) or surgery type (OR 1.09; 95% CI, 0.75–1.57) were associated with increased risk of VTE after discharge. Overall, the study quality was rated as fair.

Conclusions
In our meta-analysis, which consisted of moderate quality of evidence, we identified multiple risk factors associated with VTE in the post-discharge period. This work will help inform which factors should be considered for developing point of care clinical predictive models to help guide when extended VTE prophylaxis is required.

Funding Agencies
None
A155 ASEPTIC ABSCESS SYNDROME IN INFLAMMATORY BOWEL DISEASE: A CASE REPORT
Authors: Tam L , Akhtar D , Salh B 
Published: February 2022

Abstract

Background
Aseptic abscess syndrome (AAS) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD) and it is characterized by the formation of sterile collections of neutrophils in various organs. Misdiagnosis frequently leads to unnecessary surgical procedures and prolonged courses of antibiotics. There are only 61 reportable cases of AAS in the international literature and 2 cases in Canada. This case and the associated literature review highlight the diagnostic considerations, treatment options and disease course of this rare disease.

Aims
To describe a case of AAS in IBD.

Methods
Case report and review of the literature.

Results
A 24-year-old male with a history of ulcerative pancolitis (UC) initially presented with a 3-week history of malaise, abdominal pain, and fevers with a computed tomography (CT) scan showing multiple splenic abscesses. Over the next year, he had multiple readmissions for recurrent sepsis from culture negative multi-focal abscesses. Serial CT scans revealed new abscesses in the liver, scrotum, and lungs with interval progression in size. Unsuccessful attempts to isolate a culprit organism which included serological markers and cultures from blood, bronchial washings, aspirate from abscesses, and surgical tissue. All samples demonstrated frank pus with suppurative granulomatous inflammation. The patient was trialed on various courses of antibiotics without improvement. Therefore, a decision was made to treat for AAS given his IBD history. Antibiotics were discontinued and prednisone was initiated with rapid improvement in symptoms and biochemistry. In the three years following, he was transitioned to a combination of infliximab and azathioprine. He had rapid resolution of his abscesses on serial CT scans following steroid and anti-TNF therapy. Currently, he is no longer on steroids and his CRP has normalized with no recurrence of his symptoms.

Conclusions
AAS has often been associated with IBD, particularly Crohn’s disease and more rarely in UC. Case series have shown that AAS is not strongly associated with IBD activity as only 55% of cases have concomitant IBD flare and abscess formation. The syndrome continues to pose a diagnostic conundrum among specialists as there is no established diagnostic criteria and thus AAS remains a diagnosis of exclusion. This has led many patients to suffer from AAS for prolonged periods and receive unnecessary investigations and treatments. Steroids remain the gold standard for initial induction of remission. However, the ideal regimen for maintenance therapy is still evolving and case reports have described the effects of immunotherapy and biologics on AAS. AAS has a substantial impact on quality of life and is very responsive to therapy; this case report reminds the clinician that AAS should be considered in patients with IBD presenting with multifocal abscesses unresponsive to antimicrobials.

Serial CT scan (coronal view) of abdomen demonstrating multiple hepatic abscesses (blue arrows)

Funding Agencies
None
A157 DEFINITIONS OF MEDITERRANEAN DIET INCONSISTENTLY ASSOCIATE WITH MARKERS OF GUT BARRIER FUNCTION OR SUBCLINICAL INFLAMMATION IN A POPULATION-BASED COHORT
Authors: Neustaeter A , Timpano J , Lee S , Xue M , Leibovitzh H , Madsen K , Meddings J , Espin-Garcia O , Goethel A , Griffiths A , Moayyedi P , Steinhart H , Panaccione R , Huynh H Q , Jacobson K , Aumais G , Mack D R , Bernstein C N , Marshall J , Xu W , Turpin W , Croitoru K 
Published: February 2022

Abstract

Background
The Mediterranean Diet (MD) is proposed to reduce the risk of Crohn’s disease (CD) onset in cohort studies, with inconsistent results. This inconsistency may be due to heterogeneity in defining MD scores. Additionally, relationships between MD compliance and intestinal permeability or sub-clinical inflammation are not defined.

Aims
We examined correlations between different MD scores, and determined associations between MD compliance and intestinal permeability or subclinical inflammation in a cohort of first degree relatives of CD patients.

Methods
We used food frequency questionnaire data from 2,112 subjects of the Crohn’s Colitis Canada- Genes, Environment, Microbial (CCC-GEM) project. We obtained 12 MD definitions from the literature and calculated daily percent compliance, we further compared MD scores via pairwise correlations (Kendall’s Tau). We measured intestinal permeability via urinary fractional excretion ratio of lactulose to mannitol (LMR) (LMR≥0.03 defined abnormal), and subclinical inflammation via fecal calprotectin (FCP) measured with BÜHLMANN fCAL® ELISA (FCP≥250 defined abnormal). We fit multivariable regression models between MD compliance and abnormal LMR and FCP, respectively. Two-sided p&lt;0.05 defined significance.

Results
There was large variation in cross-correlations among MD scores, from nil (t=0.0, p=0.54) to highly significant (t=0.97, p&lt;2.2e-16). Associations of MD compliance and abnormal LMR or FCP were in both directions of effect, largely non-significant. Of the 12 MD scores, none associated with abnormal LMR, while 4 associated with abnormal FCP-Odds Ratios =1.22, 1.23, 1.24, and 1.30; p=0.02, 0.02, 0.01, and 0.009, and 95% Confidence Intervals = [1.03,1.45], [1.04,1.45], [1.05,1.47], and [1.07,1.59] respectively. No diet remained significant after correcting for multiple testing.

Conclusions
Currently MD definitions vary widely. Despite discrepancies, we expected consistent directions of effect for MD compliance on LMR or FCP. The largely non-significant associations between MDs suggest limitations in definition, interpretation, and relation to biological outcomes.
Submitted on behalf of the CCC-GEM consortium.

Funding Agencies
CIHRCrohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III;The Leona M. and Harry B. Helmsley Charitable Trust; Justine Timpano is a recipient of a fellowship award from Mount Sinai Hospital; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases