bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma
Authors: Vos E L , Carr R A , Hsu M , Nakauchi M , Nobel T , Russo A , Barbetta A , Tan K S , Tang L , Ilson D , Ku G Y , Wu A J , Janjigian Y Y , Yoon S S , Bains M S , Jones D R , Coit D , Molena D , Strong V E
Published: May 2021

Background

Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively.

Methods

Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher’s exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray’s test.

Results

Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy.

Conclusion

In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.
DOP09 Mirikizumab-induced transcriptome changes in patient biopsies at Week 12 are maintained through Week 52 in patients with Ulcerative Colitis
Authors: Johnson T , Steere B , Zhang P , Zang Y , Higgs R , Gottlieb K , Reinisch W , Panés J , Krishnan G
Published: May 2021

Background

Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomised clinical trial in patients with moderate-to-severe ulcerative colitis (UC; NCT02589665). After 12 weeks (W) of treatment, miri was shown to down-regulate several transcripts correlated with increased UC disease activity as well as anti-TNF resistance. Here we show W52 gene expression analysis from the induction responder cohort at W12 for both miri and PBO treated patient biopsy samples to identify sustained changes in gene expression.

Methods

Miri-treated patients who achieved clinical response (decrease in 9-point Mayo subscore [rectal bleeding, stool frequency, endoscopy] of ≥2 points and ≥35% from baseline [BL] with either a decrease of RB subscore of ≥1 or an RB subscore of 0 or 1) or better at W12 were re-randomised to miri 200 mg administered subcutaneously (SQ) every 4 weeks or every 12 weeks through W52. Patients given placebo (PBO) in induction who achieved clinical response continued on PBO in the maintenance period. Colonic biopsies were obtained at W0, 12, and 52 from the most affected area at least 30 cm from the anal verge (miri N=31, PBO N=7). Transcript changes at W12 from BL in the PBO and miri arms were clustered into differentially expressed genes (DEGs) using the Bayesian Limma R-package. Among these DEGs, similarly expressed genes (SEGs) were identified as those which maintained their W12 expression level through W52.

Results

Analysis of transcript changes in W12 responders who continued to maintenance identified a profile of DEG-SEGs in responders (Fig 1A). Of these genes, 63 (70.8%) were present only in miri responders, 5 (5.6%) were present only in PBO responders, and 21 (23.6%) were present in both groups (Fig 1B, C). The magnitude of transcript changes was greater at W12, and more consistent through W52, in the group of miri responders compared to PBO responders (Fig 2). A separate cluster of DEG-SEGs correlated with to disease activity indeces (Robarts Histopathology Index [RHI], modified Mayo; both r>0.5) were shown to be sustained in the miri treated patients but not in the placebo patients.

Conclusion

In this limited sample of W12 PBO and miri responders, miri responders showed broader, larger, and more sustained magnitude of changes at W52 compared to PBO responders. The qualitative description of transcripts suggests a distinct molecular healing pathway associated with miri treatment, as compared to the spontaneous healing that occurred in PBO responders. A cluster of transcripts that correlated with disease activity indices was identified, demonstrating consistency across molecular, endoscopic and clinical indices of healing in UC.
DOP12 Validation of a modified simple ultrasound activity Score for children with Crohn’s Disease
Authors: Ma H , Isaac D M , Petrova A , Almeida P , Parsons D , Kuc A , Carroll M W , Wine E , Huynh H
Published: May 2021

Background

Transabdominal bowel ultrasound (TABUS) is an ideal tool to assess the bowel wall thickness (BWT) of children with Crohn’s disease (CD) due to its minimal invasiveness. Recently the Simple Ultrasound Activity Score for CD (SUS-CD) was developed and validated in adults using the Simple Endoscopic Score for CD (SES-CD). Our aim was to determine how the SUS-CD performed in children at diagnosis in comparison to endoscopy.

Methods

Pediatric patients (0–18 years old) with suspected inflammatory bowel disease (IBD) were prospectively enrolled through the Edmonton Pediatric IBD Clinic in Alberta, Canada. Patients underwent a baseline TABUS to visualize the intestine (excluding rectum, which is difficult to see with TABUS), blood work and endoscopy. The weighted pediatric CD activity index (wPCDAI) assessed disease activity, and SES-CD assessed endoscopic disease. Modified SUS-CD (excluding rectal sub score) was calculated using BWT scores (0=<3mm, 1=3–4.9mm, 2=5–7.9mm, 3=>8mm) and colour doppler scores (0=no or 1 vessel, 1=2–5 vessels, 2=>5 vessels per cm2) for each segment (terminal ileum, right colon, transverse colon, left colon) and compared to SES-CD. Modified SUS-CD was correlated to wPCDAI score, C-reactive protein (CRP) and fecal calprotectin (FCP). Using SPSS, anova and Chi square were used to assess for an association between TABUS parameters and wPCDAI. Spearman’s rank (rho) and Pearson’s correlation (r) were used to assess for a correlation between modified SUS-CD with SES-CD, wPCDAI, CRP and FCP.

Results

40 patients recruited, 35 had CD (mean age 12.6(2.85)) and 5 were normal and scanned for suspected IBD (mean age 12.2(3.75)). Median wPCDAI and SES-CD scores for CD patients were 61(IQR 35.6–77.5) and 15(IQR 7.5–21) respectively. Fat proliferation was associated with severe CD based on wPCDAI (p<0.05). The modified SUS-CD score correlated well with the modified SES-CD score (rho=0.79,r=0.76,p<0.001,R2 linear=0.465). When the BWT threshold was lowered by 0.5mm for each BWT category, correlation improved (rho=0.80,r=0.82,p<0.001,R2 Linear=0.541). Using a similar lower threshold for BWT, a receiver operating characteristic curve analysis revealed an area under the curve of 0.87 and 0.90 for detecting mild endoscopic activity and moderate endoscopic activity, respectively. There was a significant correlation between SUS-CD and wPCDAI score (r=0.56,p<0.01), CRP (r=0.55,p<0.01) and FCP (r=0.56,p<0.01).

Conclusion

Fat proliferation was associated with more severe CD. The modified SUS-CD correlated well with modified SES-CD score, wPCDAI, CRP and FCP. Correlation improved when BWT threshold in each category was dropped by 0.5mm. These data support the use of TABUS as an effective adjunct to the assessment of pediatric CD.
DOP60 Simplified rules to identify bio-naïve patients with Crohn’s Disease with higher likelihood of clinical remission when initiating vedolizumab versus anti-TNFα therapies: Analysis of EVOLVE study data
Authors: Mantzaris G , Yarur A , Wang S , Adsul S , Kamble P , Luo M , Guerin A , Billmyer E , Nguyen H , Bressler B
Published: May 2021

Background

Previously, we identified subsets of biologic-naïve patients (pts) with Crohn’s disease (CD) from the EVOLVE study who had higher rates of clinical remission (CR) [Fig 1] when initiating vedolizumab (VDZ) vs anti-TNFα treatment, using prediction models based on multiple baseline characteristics.1,2 To aid use in practice, we investigated whether these subsets could be identified using simpler rules based on fewer baseline characteristics.

Methods

Using data from EVOLVE, we used recursive partitioning and regression tree (RPART) classification to predict membership in the previously identified higher CR subsets for VDZ. The RPART algorithm repeatedly splits data, based on baseline predictors (demographics, prior treatments, clinical characteristics at treatment initiation, Charlson comorbidity index, prior extraintestinal manifestations [EIMs], and prior healthcare resource use). At each split, the predictor and its value as chosen by the algorithm to split the data were those that maximized the number of pts classified correctly. Simplified rules were developed from the resulting RPART decision trees. Analyses of the treatment effect of VDZ vs anti-TNFα were conducted in the subsets of pts identified by each rule.

Results

Pts with data on CR and candidate predictors were included (VDZ [n=195]; anti-TNFα [n=245]). Three simplified rules (A, B, & C) were identified (Table 1). Pt characteristics included in the rules (exacerbation ongoing at treatment initiation, no emergency department/emergency room (ED/ER) visits prior to treatment initiation, no fistulae at most recent assessment prior to treatment initiation, pre-initiation disease behaviour) were among the main predictors of CR in VDZ pts identified previously. Pts identified by Rule A comprised 32% of the EVOLVE population, and were those who 1) had an exacerbation ongoing at index, 2) did not have ED/ER visits prior to initiation and 3) had pre-initiation disease behaviour classified as other than stricturing with/without perianal disease. Among these pts, median time to CR for VDZ and anti-TNFα pts were 6.7 and 18.1 months, respectively (unadjusted log-rank p<0.001), and the adjusted hazard ratio (HR) of CR for VDZ vs anti-TNFα was 2.9 (95% CI: 1.7, 5.0). Rules B & C identified larger subsets in which VDZ vs anti-TNFα treatment differences were smaller but still statistically significant.

Conclusion

Simple rules were developed to identify biologic-naïve, CD pts in whom VDZ initiation appeared to have a larger effect on CR relative to anti-TNFα initiation. Validation of these rules in other data sources is important to confirm these findings; if validated, these simplified rules can inform targeting of treatment and optimization of outcomes for pts with CD treated with VDZ.
DOP73 Antibiotic use differentially affects the risk of antidrug antibody formation during anti-TNFα therapy in Inflammatory Bowel Disease
Authors: Gorelik Y , Freilich S , Gerassy-Vainberg S , Blatt A , Pressman S , Focht G , Friss C , Loewenberg Weisband Y , Greenfeld S , Kariv R , Ledderman N , Iris D , Kashi Y , Turner D , Chowers Y
Published: May 2021

Background

Anti-drug antibodies (ADA) to anti-TNF therapy drive loss of response to treatment. Links between intestinal microbial composition and response to anti-TNF therapy were demonstrated, and antibiotic use during anti-TNF therapy reduced the risk of ADA formation. Here, we aimed to assess the possible implications of specific antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD) patients.

Methods

We performed a retrospective analysis of data from three health maintenance organizations, covering 89% of the Israeli population. All patients with IBD and available ADA levels were included. Survival analysis using Kaplan-Meier and multivariate Cox proportional hazards regression with drug use as time varying covariates methods were used to assess the association between specific antibiotic use and ADA development. C57BL and germ free mice were treated with respective antibiotics followed by immunization with infliximab. ADA were assessed after 14 days.

Results

We analyzed 1,946 patients treated with anti-TNF. Positive ADAs were detected in 363 patients (18.6%). Age, gender and concomitant use of immunomodulators where comparable in patients who eventually developed ADAs or not. However, infliximab and not adalimumab therapy, previous anti-TNF therapy and higher baseline C-reactive protein levels were significantly associated with ADA development in univariate analysis. Kaplan-Meier curves of prior antibiotic use demonstrated significant hazard of ADA development in patients who used cephalosporins or penicillins with beta-lactamase inhibitors (BLI) and reduced risk with prior use of fluoroquinolones, macrolides or metronidazole (Figure 1) with early risk divergence for most classes. Multivariable Cox proportional hazards model adjusted for multiple factors associated with ADA development was overall consistent with Kaplan-Meier estimates (Figure 2). In mice exposed to infliximab, increased ADA production by cefuroxime treatment and a non-significant reduction following azithromycin treatment was noticed (Figure 3). Germ free mice produced no ADA.

Figure 1: Kaplan-Meier curves of cumulative risk of ADA development for prior use of specific antibiotics. P value for the log rank test is presented in each plot.

Figure 2: Multivariable-adjusted HR with 95% CI of ADA for use of various antibiotic classes during anti-TNF therapy.

Figure 3: Mean ADA levels in mice treated with anti-TNF and prior cefuroxime, azithromycin, or no antibiotic

Conclusion

ADA production is microbial dependent. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillins with BLI, or possibly reduced by treatment with fluoroquinolones or macrolides.
DOP78 The differential diagnosis and clinicopathological spectrum of Inflammatory Bowel Disease: An interesting and informative ECCO topical review
Authors: Feakins R M , Torres J , Borralho-Nunes P , Burisch J , Cúrdia Gonçalves T , De Ridder L , Driessen A , Lobatón T , Menchén L , Mookhoek A , Noor N , Svrcek M , Villanacci V , Zidar N , Tripathi M
Published: May 2021

Background

A wide variety of intestinal and non-intestinal diseases can resemble chronic idiopathic inflammatory bowel disease (IBD) clinically and/or pathologically. The aim of the current Topical Review was to explore the differential diagnosis of IBD and to discuss clinical, histomorphological features and ancillary techniques that help distinguish between IBD and its mimics.

Methods

An open ECCO call led to the selection of 12 participants who formed three working groups (WG) to study the mimics of IBD. WG 1 comprised gastroenterologists, who explored mainly the clinical features. WG 2 consisted of histopathologists, who focused on macroscopic and microscopic pathological aspects. WG 3 was a mixed group of pathologists and clinicians who studied the value of additional investigative techniques such as imaging, serology and molecular markers. A systematic literature search allowed exploration of these topics and the identification of the most helpful and relevant distinguishing features. The process led to the development of Current Practice Position (CPP) statements and supporting text. Consensus meetings with voting by all participants facilitated modification and finalisation of CPP statements.

Results

The project highlighted several points. Firstly, there is a wide and sometimes overwhelming variety of potential mimics of new and established IBD, both in adults and in children.

Secondly, some mimics are more important clinically and others pathologically, meaning that the emphasis on the mimics of IBD is different for clinicians and pathologists. Thirdly, close attention to all clinical features, pathological findings and other evidence optimises accuracy. Finally, newer techniques sometimes have a role, e.g., in distinguishing monogenic IBD-like disorders from IBD in young children, and the value of many novel techniques is as yet uncertain. A practical message is that constant awareness by clinicians and pathologists of the possibility of mimics is particularly important.

Conclusion

Discussions between pathologists and clinicians were particularly useful during this process and were a reminder of the importance of clinicopathological correlation. There is a wide variety of mimics of IBD, including infections, diverticular disease, drug effect, radiation damage, immune disorders, vascular disorders and diversion proctocolitis. An important, relatively new, and sometimes very close mimic of IBD is immune checkpoint inhibitor colitis. In turn, reliable distinction between IBD and other entities requires a multidisciplinary approach with a full clinical history (including duration of disease), and with appropriate investigations that may include endoscopy, pathology, imaging, microbiological tests, serology, and newer molecular tests.
DOP87 Disease clearance as a new therapeutic target in patients with Ulcerative Colitis: A multicenter retrospective cohort study
Authors: D’Amico F , Fiorino G , Massarini E , Solitano V , Guillo L , Allocca M , Furfaro F , Zilli A , Bonovas S , Peyrin-Biroulet L , Danese S
Published: May 2021

Background

Symptom control and endoscopic endoscopic healing have been the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC. We aimed to evaluate the impact of disease clearance on long-term outcomes in patients with UC.

Methods

A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between January 2014 and February 2021. All consecutive adult patients with confirmed UC undergoing colonoscopy with biopsies and available histological reports and clinical data within one month of colonoscopy were eligible for inclusion. Disease clearance was defined as clinical (partial Mayo score ≤2 with no subscore >1), endoscopic (endoscopic Mayo score= 0), and histological (Nancy index= 0) remission of disease. The first available endoscopic procedure was considered as baseline. Disease clearance was measured at baseline and during follow-up by comparing the occurrence of negative disease outcomes in patients who achieved or not disease clearance.

Results

A total of 302 patients were included (46.4% female). Disease clearance was detected in 42 patients (13.9%) at baseline. Median follow-up was 32.2 ± 20.2 months. No patient achieving disease clearance underwent surgery during follow-up compared with 22 subjects in the non-disease clearance group (0.0% vs 8.5%, p=0.1). Similarly, a lower hospitalization rate was detected in patients with disease clearance at baseline compared with the control group (7.1% vs 25.4%, p=0.01). Interestingly, 51/302 patients (16.9%) achieved both endoscopic and histologic remission. This subgroup experienced a significantly lower rate of hospitalization (7.8% vs 25.9%, p=0.008) and surgery (0.0% vs 8.8%, p=0.05) compared with patients with endoscopic and/or histologic disease activity. The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk for surgery (p=0.04) and hospitalization (hazard ratio (HR)= 0.49, 95% confidence interval (CI) 0.08–2.29, p=0.009) (Figures 1–2).

Conclusion

Disease clearance is a new outcome that simultaneously takes into account remission of symptoms, endoscopy and histology. Patients with disease clearance are at significant lower risk for hospitalization and surgery and could be the ultimate therapeutic target for full disease control.
P124 Gastroenteropancreatic Neuroendocrine Neoplasms in patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series
Authors: Festa S , Zerboni G , Derikx L , Ribaldone D G , Dragoni G , Buskens C J , Nieveen van Dijkum E , Pugliese D , Panzuto F , Krela-Kaźmierczak I , Reiss H , Shitrit A B G , Chaparro M , Gisbert J P , Kopylov U , Teich N , Vainer E , Nagtegaal I , Hoentjen F , Garcia M J , Filip R , Foteinogiannopoulou K , Koutroubakis I , Argollo M , van Wanrooij R , Laja H , Truyens M , Lobaton Ortega T , Molnar T , Savarino E , Aratari A , Papi C , Goren I
Published: May 2021

Background

Neuroendocrine Neoplasms (NENs) are a heterogeneous group of tumours deriving from the diffuse endocrine system. NENs may occur almost everywhere in the body but are most common in the gastrointestinal tract, the pancreas, and the lungs, with gastroenteropancreatic (GEP) tumours representing 70% of all NENs. GEP-NENs have rarely been reported in association with inflammatory bowel diseases (IBDs) but no definitive relationship between these tumours and IBD has been established

Methods

This was an ECCO COllaborative Network For Exceptionally Rare case reports project (ECCO-CONFER). We included cases of GEP-NENs diagnosed in patients with IBD that met the diagnostic criteria for NEN according to the European Neuroendocrine Tumour Society. Data were retrospectively collected in a standardized case report form and analysed for event association with patient’s and IBD-related factors

Results

GEP-NEN was diagnosed in 100 patients with IBD [61% female, 55% Crohn’s disease, median age 48 years (IQR 37–59)]. Overall the most common location was the appendix (39/100) followed by the colon (22/100). Complete IBD-related data was available for 50 individuals with a median follow-up of 30.5 months (IQR 11.2–70) following NEN diagnosis. At the last follow-up data, 47/50 patients were alive. Three deaths occurred, of which 2 were related to NEN. Median duration of IBD at NEN diagnosis was 84 months (IQR 10–151), and in 18% of cases NEN and IBD were diagnosed concomitantly. 20/50 of NENs were at stage I (T1N0M0) and 28/50 graded G1 (ki 67 ≤2 %) at diagnosis.

Incidental diagnosis of NEN either during follow-up or during surgery as well as receiving diagnosis of NEN concomitantly with IBD was significantly associated with an earlier NEN stage (p< 0.01 and p<0.02, respectively). Exposure to immunomodulatory and/or biologic therapy was not associated with advanced NEN stage or grade. Interestingly, primary GEP-NEN sites significantly correlated to the segment affected by IBD (62% vs 38% p = 0.02)

Conclusion

In the largest case series to date, prognosis of patients with concomitant GEP-NEN and IBD seems favorable. Incidental NEN diagnosis correlates with an earlier NEN stage and IBD-related therapies are independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis
P145 Inflammatory Bowel Disease patients requiring surgery can be treated in referral centres regardless of the COVID-19 status of the hospital: results of a multicentric European study during the first COVID-19 outbreak (COVIBD-Surg)
Authors: Rottoli M , Pellino G , Tanzanu M , Baldi C , Frontali A , Carvello M , Foppa C , Kontovounisios C , Tekkis P , Colombo F , Sancho-Muriel J , Matteo F , Danelli P , Celentano V , Spinelli A , Panis Y , Sampietro G , Poggioli G
Published: May 2021

Background

Little is known regarding the outcomes of inflammatory bowel disease (IBD) patients who required surgery during the outbreak of Coronavirus disease 19 (COVID-19). This study aimed to compare outcomes of IBD patients undergoing surgery in COVID-19-treatment and COVID-19-free hospitals.

Methods

Retrospective study involving patients undergoing IBD surgery in seven centres (six COVID-19-treatment hubs and one COVID-free hospital) across 5 European countries during the period of highest reduction of elective activity due to the first peak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Predictive variables of the risk of moderate-to-severe postoperative complications were analysed using logistic regression analysis. Considering the large number of regressors and the risk of over-fitting due to the small number of events, the least absolute shrinkage and selection operator (LASSO) method was used.

Results

Of the 91 patients (59 males, 64.8%) with Crohn’s disease (54, 59.3%) or ulcerative colitis (37, 40.7%), 66 (72.5%) had surgery in a COVID-19-treatment hospital, while 25 (27.5%) were treated in the COVID-19-free centre. A higher proportion of COVID-19-treatment patients required urgent surgery (48.4% vs 24%, p=0.035), did not discontinue the biologic therapy (15.1% vs. 0%, p=0.039), underwent surgery without a SARS-CoV-2 test (19.7% vs. 0%, p=0.0033), and were admitted to intensive care postoperatively (10.6% vs. 0%, p=0.032). Three patients (4.6%) of the COVID-19-treatment group had a SARS-CoV-2 infection during the hospital course.

Use of steroids at surgery (Odds ratio [OR]=4.10, 95% CI 1.14–15.3, p=0.03), presence of comorbidities (OR=3.33, 95% CI 1.08–11, p=0.035), and Crohn’s disease (vs. ulcerative colitis, OR=3.82, 95% CI 1.14–15.4, p=0.028) were associated with risk of moderate-to-severe postoperative complications. The admission to a COVID-19-treatment hospital was not associated with higher risks of complications (OR 2.06, 95% CI 0.54–10.4, p=0.30)

Conclusion

Although a SARS-CoV-2 infection in the postoperative period represented a concrete risk in IBD patients undergoing surgery in COVID-19-treatment hospitals, the study showed that IBD patients can undergo surgery regardless of the COVID-19-status of the referral centre. The study also showed the lack of standardized practice for IBD patients requiring surgery during the COVID-19 outbreak.
P154 Faecal calprotectin and patient reported disease control of IBD: results from the baseline dataset of the PREdiCCt study
Authors: Siakavellas S , Derikx L , Derr L , Williams L , Plevris N , Jenkinson P , Lucaciu L , Constantine-Cooke N , Covil K , Murdoch L , Jones G R , Lees C
Published: May 2021

Background

There is an established disconnect between intestinal inflammation and symptoms in patients with IBD. Faecal calprotectin (FCAL) is an excellent surrogate for mucosal healing and we have good data to support treat to target approaches based on FCAL. However, there is relatively little data analysing how well FCAL correlates with a fuller breakdown of a patient’s symptoms. We were interested to explore the impact of ongoing intestinal inflammation as measured by FCAL in patients reported to be in clinical remission.

Methods

The PREdiCCt study (https://www.predicct.co.uk) is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 48 UK sites and followed for 2 years. 1946 (74%) patients completed the baseline questionnaires. We present here the results of the baseline questionnaire analysis of IBD symptoms (IBD Control questionnaire). Eight of the question items generate a summary score (IBDControl-8) ranging from 0 (worst control) to 16 (best control). This questionnaire also includes a visual analogue scale (VAS) for disease control ranging from 0 (worst control) to 100 (best control). These data were matched to a contemporaneous FCAL measurements, taken at study entry.

Results

IBD Control-8 results are available in 1,919 patients [male=840, CD=985 UC/IBDU=934, age 45.8±15.5 (mean±SD in years)]). Median FCAL values were 46 mcg/g (IQR 20–150) for the overall cohort, 50 mcg/g (IQR 20–156) for CD and 39 mcg/g (IQR 20–143) for UC. UC patients reported better disease control compared to CD patients (p<0.001, for both IBDControl-8 and VAS). CD patients with previous surgery (p=0.031 for IBDControl-8) and perianal disease (p=0.015 and p=0.035, for IBDControl-8 and VAS respectively) reported worse disease control than the rest of the CD patients. Better disease control was reported in males versus female patients (p<0.001 and p=0.003 for IBDControl-8 and VAS respectively).

There was a negative correlation between baseline FCAL values and (p<0.001). Patients who reported waking up at night due to their disease had higher FCAL values at baseline [median 60 mcg/g (IQR 20–162) vs 43 mcg/g (IQR 20–144), p=0.013] with the correlation being more prominent in UC (p=0.002). Patients who reported the need to change their treatment had higher FCAL values at baseline [85 mcg/g (IQR 24–336) vs 43 mcg/g (IQR 20–139), mcg/g, median (IQR), p=0.032].

Conclusion

This is the first detailed symptom examination of clinical versus deep remission. We show how residual gut inflammation in patients in clinical remission affects meaningful patient reported outcomes measures including waking at night. UC and male patients reported better disease control compared to CD and female patients.
P305 Effectiveness and Safety of Vedolizumab in Biologic-Naïve Patients: Real-World Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)
Authors: Macaluso F , Fries W , Renna S , Viola A , Muscianisi M , Cappello M , Guida L , Siringo S , Camilleri S , Garufi S , Privitera A C , Belluardo N , Giangreco E , Bertolami C , Vassallo R , Rizzuto G , Orlando R , Ventimiglia M , Orlando A
Published: May 2021

Background

Biologic-naïve patients treated with Vedolizumab (VDZ) are largely underrepresented in real-world cohorts. We performed a multicentre, observational, cohort study on the effectiveness and safety of VDZ as treatment for Crohn’s disease (CD) and ulcerative colitis (UC) among biologic-naïve subjects.

Methods

Data of consecutive biologic-naïve patients with CD and UC treated with VDZ from July 2016 to December 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The primary outcome was the clinical response at 14 and 52 weeks evaluated with Harvey Bradshaw Index in CD and partial Mayo score in UC.

Results

172 consecutive patients (CD: n=88; UC: n=84; median age 66.0 years) were included, with a median follow-up of 58.8 weeks. After 14 weeks, a clinical response was reported in 68.2% of patients with CD and 67.9% of patients with UC treated with VDZ, including 45.5% patients in the CD group and 46.4% patients in the UC group who achieved steroid-free remission. After 52 weeks, a clinical response was reported in 77.4% of CD and in 73.8% of UC patients treated with VDZ, including 59.7% patients in the CD group and 60.7% patients in the UC group who achieved steroid-free remission. All differences between CD and UC were not statistically significant. Cox survival analysis showed no significant difference in the probability of treatment discontinuation between CD and UC patients (log-rank p=0.73).

Conclusion

This large, real-world, multicenter study demonstrated the effectiveness and safety of VDZ as a first-line biologic, showing high rates of clinical response and steroid-free remission at both induction and maintenance.
P322 Hepatitis B reactivation under biologic therapy in patients with HBsAg negative phase of chronic HBV infection
Authors: Ergenç I , Kani H T , Karabacak M , Cömert Özer E , Mehdiyev S , Jafarov F , Abacar K Y , Kutluğ Ağaçkıran S , Seven Sevik G , Alibaz Öner F , İnanç N , Atagündüz M P , Gençosmanoğlu D S , Özen Alahdab Y , Ergun T , Direskeneli R H , Atuğ Ö
Published: May 2021

Background

Biologic agents are widely used in immune mediated inflammatory diseases (IMID). The risk and consequences of hepatitis B reactivation in hepatitis B surface antigen (HBsAg) negative phase of hepatitis B virus (HBV) exposed patients is not clear. We aim to investigate the reactivation rate in biologic exposed patients within surface antigen negative phase of HBV infection.

Methods

We identified patients followed up at gastroenterology, rheumatology and dermatology out-patient clinics with a diagnosis of IMID from clinical charts. Patients exposed to biologic agents with a negative HBsAg and positive Anti-HBc IgG were included. Primary outcome was HBV reactivation, which was defined as reverse seroconversion of HBsAg.

Results

We screened 8266 IMID patients and 2484 of them were exposed to biologic agents. A total of 221 patients were included in the study. The mean age was 54.08 ± 11.69 years and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1 – 6). The mean biologic agent exposure time was 55 (range: 2 – 179) months. One hundred and fifty-two (68.8%) patients were using concomitant immunomodulatory agents and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of HBsAg positivity was observed in the whole cohort. Antiviral prophylaxis for hepatitis B was given to 48 (21.7%) patients with entecavir, tenofovir or lamivudine. HBV-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients had HBV-DNA reactivation with a negative HBsAg during exposure to the biologic agent.

Conclusion

Though only 21.7% of our patients used prophylaxis, we found only two reactivations (1%) and no HBsAg seroconversion in our cohort. Our results suggest a re-assessment of antiviral prophylaxis for anti-HBc Ag (+) patients exposed to biologic agents. Current guidelines would be updated in the light of future studies.
P323 Efficacy and safety of tofacitinib treatment for one year in Japanese patients with Ulcerative Colitis in a specialized Inflammatory Bowel Disease center
Authors: Kojima K , Yokoyama K , Kaku K , Takashima Y , Sato T , Kawai M , Kamikozuru K , Takagawa T , Yokoyama Y , Watanabe K
Published: May 2021

Background

Few reports of the real-world efficacy and safety of tofacitinib (TFB) in Asians are available, and potential predictors of the response to therapy are unclear. We investigated the efficacy and safety profiles of TFB treatment for one year in patients with active Ulcerative Colitis (UC) in our specialized Inflammatory Bowel Disease center.

Methods

This study included 111 patients who received TFB between May 2018 and February 2020. We assessed disease activity using the partial Mayo Score (pMS). Clinical remission was defined as pMS ≤2, with no subscore >1 and a rectal bleeding subscore of 0. Clinical response was defined as a decrease in pMS of ≥2 points from baseline with an accompanying decrease in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1 point.

Results

Mean patient age was 35 years (interquartile range [IQR]: 28-47), 60 (59.4%) were men, and mean disease duration was 4.8 years (IQR:1.5-10). The pMS was 6 (IQR:4-7) and C-reactive protein was 0.30 mg/dl (IQR: 0.1-1.0). At baseline, 63 (62.4%) patients received an anti-TNFα agent, 11 (10.9%) received vedolizumab, and 7 (6.9%) received both. Clinical response and clinical remission were, respectively, 66.3% (67/101) and 50.5% (51/101) at week 8, and 47.1% (40/85) and 43.5% (37/85) at week 48. The cumulative remission rate was 61.7% at 1 year and 51.7% at 2 years, and tended to be better in the ≥2 anti-TNFα agents failure group than in the 1 anti-TNFα agent failure and bio-naïve groups (P=0.10). Cumulative colectomy-free survival was 91.9% at 1 year and 89.1% at 2 years. Cumulative drug-free survival in the non-remission group at week 8 was 30.9% at 1 year and 30.9% at 2 years, significantly lower than in the remission-achieving group at week 8 (P<0.01). Baseline pMS was significantly lower in responders vs non-responders at week 8 (odds ratio, 0.61; 95% confidence interval, 0.45-0.82). Relapse occurred in 45.7% of patients after tapering TFB, and 85.7% of patients with re-increased TFB responded by week 4. Herpes zoster occurred in 6 unvaccinated patients (46±16 years old). There were no specific features regarding age, TFB dosage, duration of administration, or lymphocyte count in these patients. No thrombotic adverse events occurred, even though 54.1% patients continued treatment with 10 mg twice daily at week 48.

Conclusion

TFB was more effective in low-activity UC patients and its efficacy was not affected by previous treatment with anti-TNF agents. Most patients in the remission groups at week 8 could continue TFB for one year without severe adverse events, although careful monitoring for herpes zoster is necessary. The risk of thrombotic adverse events might be lower in Japanese UC patients.
P335 Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: A KASID multicenter cohort study
Authors: Oh K , Hong S N , Kim E S , Na S Y , Kang S B , Koh S J , Bang K B , Jung S A , Kim K O , Choi C H , Ye B D
Published: May 2021

Background

Tofacitinib is a small molecule which inhibits janus kinase and has been shown to be effective for patients with active ulcerative colitis (UC). We investigated the real-life therapeutic effectiveness and safety of tofacitinib treatment for Korean patient with UC.

Methods

We retrospectively analyzed the data of patients with UC who received tofacitinib treatment at 10 hospitals in Korea. The primary outcome was clinical remission at week 16 which was defined as a partial Mayo score ≤2 with a combined rectal bleeding subscore and stool frequency subscore ≤1. The secondary outcome was endoscopic remission (Mayo endoscopic subscore ≤1) at week 16. Adverse events including herpes zoster and deep vein thrombosis were also evaluated.

Results

Between January 2018 and November 2020, a total of 123 patients with UC received tofacitinib treatment (Table 1). Clinical effectiveness was evaluated for those who had completed or stopped the tofacitinib therapy by week 16, week 24 and week 52, respectively (Figure 1). Clinical remission and response rates at week 16 were 65.3% and 73.7%, respectively (Figure 2A). Ninety-one out of 123 patients (74.0%) were followed up to week 52. Their clinical remission and response rates at week 52 were 49.5% and 58.2%, respectively (Figure 2A). Among 117 patients with baseline Mayo endoscopic subscore ≥2, endoscopic remission rate at week 16 was 55.6% (Figure 2C). Any adverse events occurred in 15 patients (12.2%) and serious adverse events occurred in 9 patients (7.3%). Herpes zoster occurred in 4 patients (3.3%) and one patient (0.8%) suffered from deep vein thrombosis (Table 2).

Conclusion

Tofacitinib was effective with an acceptable safety profile for Korean patients with UC in the real world.
P342 Correlation of the first lateral flow-based Point of Care test to quantify infliximab and anti-infliximab antibodies in a finger prick sample with the reference ELISA technique
Authors: Ruiz-Argüello M B , Pascual J , Del Río L , Urigoitia A , Balo Farto C , Fernández C , Mera A , De Toro J , Nagore D , Ametzazurra A
Published: May 2021

Background

The goal of this study was to validate the use of capillary blood in a real point-of-care (POC) setting for patients under infliximab treatment by using Promonitor Quick lateral flow (LF) tests. Results were compared to the Promonitor ELISA reference technique in serum samples used by centralised laboratories.

Methods

A prospective, observational study was designed to evaluate the performance of a rapid LF test (Promonitor Quick IFX, Progenika, Spain). 160 infliximab treated rheumatology consecutive patients (400 samples) were recruited in two hospitals in Galicia, Spain. Prior to the infusion, a finger prick sample was obtained and analysed. Anti-infliximab antibodies were also determined with Promonitor Quick ANTI-IFX1-4. Results were read with the automated portable PQreader instrument. Additionally, a serum sample was collected for subsequent comparative analysis with either LF or ELISA tests.

Qualitative (positive (PPA) and negative (NPA) agreements) and quantitative (Pearson correlation and bias) performance of the LF test was compared to ELISA, as well as between different specimens following CLSI EP09-A3.

Results

Overall agreement between Promonitor Quick IFX finger prick and ELISA test was 91% (88% PPA; 100% NPA). The quantitative comparison showed a good correlation (Pearson correlation coefficient: 0.85 and observed bias: 25%) (Table 1).

Similar results were also observed when serum was used with either the LF or the ELISA tests (98% overall agreement, 0.91 correlation coefficient; 6% bias) (Table 1).

Overall agreements for visual and automated (PQreader) interpretations with Promonitor Quick ANTI-IFX were 99% and 100% for finger prick and serum specimens, respectively (Table 2).

Conclusion

Promonitor Quick can be used to reliably quantify infliximab in capillary blood samples and results are comparable to those obtained with the reference ELISA technique. The use of the rapid POC test with finger prick will allow clinicians to monitor their patients in a fully decentralized mode to aid in the decision making process. PQreader is a sensitive portable equipment to report drug as well as antibody levels in the patient samples.

References
P343 Maintenance of deep remission in Crohn’s disease after switching from anti–TNF to ustekinumab
Authors: Mantzaris G , Vraka M , Beka H , Georgiadi T , Albani F , Veretanos C , Mountaki K , Trikola A , Archavlis E , Christidou A , Manolakis A , Viazis N , Karampekos G , Philippidis G , Hatzievangelinou C , Tsatsa A , Georgiadou A , Panagopoulou S
Published: May 2021

Background

Anti-TNF agents, infliximab (IFX) and adalimumab (ADL) are first line treatment for moderate-to-severe Crohn’s disease (CD) and for preventing post-operative recurrence of CD (CD-POR) following right hemicolectomy (RH). However, a considerable proportion of patients develop allergic reactions and/or paradoxical inflammation to anti-TNFs necessitating switching to out of class biologic despite deep remission. We aimed to assess whether ustekinumab (UST), an IL12/IL23 inhibitor, can maintain deep remission in these patients.

Methods

This prospective, single centre study enrolled CD patients with B1 phenotype or on POR preventive therapy who were in prolonged deep remission when became intolerable of anti-TNFs. Deep remission was defined as clinical (HBI<4), biomarker (normal CRP and faecal calprotectin [FC<150μg/dl]), and endoscopic remission (SES-CD≤2 or Rutgeerts’ score [RS]≤1). Patients received UST (6mg/kg iv followed by 90mg sc q8 weeks) and were followed every 2 months with HBI score calculation and routine laboratory tests. Ileocolonoscopy was performed at 1y after UST initiation and the SES-CD or the RS were calculated. Absence of deep remission was defined as clinical (HBI>5), or biomarker relapse or endoscopic recurrence (SES-CD>2 or RS≥2, respectively).

Results

Twenty five patients (15 males), median age(range) 42(20-65)y were included. Seven patients had undergone RH, 6 had colitis and 12 had ileitis or ileocolitis; 13 patients had received ADL, 8 IFX and 4 both. Patients were in deep remission for 3.8 (2-10)y [median (range)]. Reasons for switching were severe psoriasis/proriasiform lesions (11), persistent arthralgias (10), infusion/injection reactions (2), anti-TNF-induced lupus erythematosus (2), sweet syndrome (1), and vasculitis (1). Two patients had more than one paradoxical inflammation. At baseline the median (range) CRP was 0.21mg/dl (0.10-0.40), FC 52μg/g (20-114). Trough levels for anti-TNFs in 15/25 patients were normal without antibodies. At 1-year post-switching endoscopic CD-POR was seen in 3/7 patients (RS≥2b) associated with biomarker relapse in 2 and clinical relapse in 1 patient. Of 18 patients with B1 phenotype deep remission was maintained in 15: two patients with infusion reactions to IFX relapsed and 1 patient developed endoscopic lesions in view of normal CRP but abnormal FC (SES-CD 6, 5 and 3, respectively). Paradoxical inflammation resolved in all 23 patients but de novo arthralgias developed in 2 patients. Thus, one year after switching to UST, 19/25 CD patients maintained deep remission.

Conclusion

UST seems to be a reliable therapeutic alternative for anti-TNF-dependent patients who have who cannot tolerate anti-TNFs.
P347 Vedolizumab as first line biologic therapy in elderly patients with contraindications against anti-TNF therapy - A real-world nationwide cohort of patients with inflammatory bowel diseases
Authors: Attauabi M , Höglund C , Fassov J , Pedersen K B , Bansholm Hansen H , Wildt S , Dam Jensen M , Neumann A , Lind C , Albæk Jacobsen H , Popa A M , Kjeldsen J , Pedersen N , Molazahi A , Haderselv K , Aalykke C , Knudsen T , Cebula W , Munkholm P , Bendtsen F , Seidelin J B , Johan B
Published: May 2021

Background

Data regarding the efficacy and safety of vedolizumab as the first line of biologic therapy for elderly patients with ulcerative colitis (UC) and Crohn’s disease (CD) or patients with contraindications against anti-tumor necrosis factor antagonists (anti-TNFs) are scarce. Therefore, we aimed to investigate the short and long-term efficacy and safety of vedolizumab in patients with bio-naïve UC and CD stratified according to age.

Methods

A Danish nationwide cohort study was conducted between November 2014 and November 2019, including all bio-naïve patients receiving vedolizumab. The primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission defined as clinical remission at week 14 through week 52. Elderly patients were defined as patients aged 60 years or older at initiation of vedolizumab.

Results

The study included 56 patients (UC: 31 (55.4%), CD: 25 (44.6%)) with 15 (60.0%) and nine (47.4%) elderly patients with UC and CD, respectively. Elderly patients with UC and CD experienced higher rates of early response, remission, and steroid-free clinical remission, which, however, did not reach statistical significance (Figures 1 and 2). However, elderly patients with CD had similar long-term response as compared with younger patients.

In the overall study population, lack of remission at week 52 was associated with female gender (p=0.01) in UC and ileal CD (p=0.03). Discontinuation due to primary non-response occurred in 20.0% and 5.3%, while rates of secondary loss of response were 12.0% and 5.3% after 26 weeks and 52 weeks, respectively.

Only one UC patient, who developed a serious infection, experienced a serious adverse event during treatment with vedolizumab. However, mild adverse events were experienced by 35.5% and 8.0% of patients with UC and CD, respectively. As shown in Table 1, elderly patients experienced adverse events similar to the corresponding younger patients.

Conclusion

Vedolizumab is effective for induction of short and long-term sustained clinical remission in bio-naïve elderly and younger UC and CD patients with contraindications to anti-TNFs.