bluuebunny/crossref_metadata_2025 huggingface dataset:
P261 Burden of bowel urgency across specific treatment groups among Ulcerative Colitis patients – real world global study analyses
Authors: Atreya R , Redondo I , Hill J , Streit P , Hartz S , Knight H , Barlow S , Hennessy F , Hunter T
Published: January 2022

Background

Bowel urgency, the sudden and immediate need to have a bowel movement, is a common symptom in ulcerative colitis (UC) and is associated with higher disease activity, decreased work productivity and markedly reduced quality of life1. This study explored differences in disease burden among UC patients with bowel urgency based on their treatment pathway.

Methods

Data were extracted from the Adelphi Disease Specific Programme for UC, a point-in-time survey of gastroenterologists (GIs) and patients from Jan 2020-Mar 2021 in Germany, France, Spain, Italy, UK and US. GIs provided patient demographics, clinical characteristics and treatment history. The same patients were invited to complete the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), EQ-5D and Work Productivity and Activity Impairment (WPAI) questionnaire. Three patient subgroups were identified: never received targeted therapy (biologics and JAK inhibitors) (TT-naïve), receiving first TT currently (1L TT) and receiving TT with prior TT use (TT-exp). Within these groups, patients currently experiencing day- or nighttime bowel urgency, reported by physicians, with current treatment duration >3 months, were included. ANOVA, chi-squared and Kruskal-Wallis tests were used to compare the groups.

Results

Of the UC patients in the TT-naïve (n=595), 1L TT (n=851) and TT-exp (n=321) groups, 23%, 17% and 26% experienced bowel urgency, respectively. Of those with bowel urgency, TT-naïve patients were younger with lower BMI and the lowest proportion of never smokers vs. the 1L TT and TT-exp groups (Table 1). 70–80% of patients across the three groups remained in non-remission based on the derived Mayo score, while 19% of the TT-naïve group were flaring vs. 18% 1L TT and 32% TT-exp patients (p=0.0324). Steroid use was highest in the TT-naïve group (43%) vs. 10% 1L TT and 17% TT-exp (p<0.0001). 1L TT had the highest number of visits to healthcare professionals in the last 12 months. The patient reported outcome measures indicated substantial and similar quality of life impairment across all patients with bowel urgency (Table 2). The only significant difference was across impairment while working (31% TT-naïve, 17% 1L TT, 28% TT-exp; p=0.0232).

Conclusion

This study confirmed that a substantial proportion of patients across all three groups still experience bowel urgency despite receiving treatment. Since bowel urgency is known to negatively impact patients’ quality of life, there is a therapeutic need to address this symptom.

Reference

1. Ha, C, et al. Rectal Urgency Among Ulcerative Colitis and Crohn’s Disease Patients: Analyses from a Global Survey. Poster presented at: Digestive Disease Week; 2021 May 21–23; Online event.
P269 Spaciotemporal machine learning analysis of complete small bowel capsule endoscopy videos for prediction of outcomes in Crohn’s disease
Authors: Kellerman R , Bleiweiss A , Samuel S , Barzilay O , Margalit Yehuda R , Zimlichman E , Eliakim R , Ben-Horin S , Klang E , Kopylov U
Published: January 2022

Background

Capsule endoscopy (CE) is a prime modality for diagnosis and monitoring of Crohn’s disease (CD). However utilization of CE for monitoring of CE is hampered by prolonged reading time and interobserver variability. Machine learning (ML) techniques such as convolutional neural networks (CNN) are capable of accurate detection and grading of inflammatory findings on isolated images from CE in CD patients, with accuracy above 95%. However, ML-based analysis of complete CE films have not yet been reported; moreover, the predictive utility of ML of CE in CD for disease outcomes has not been examined so far.

Methods

The study cohort included treatment-naïve CD patients that have performed CE (SBIII, Medtronic) within 6 months of diagnosis of CD and had a minimal follow-up of 6 months. Complete small bowel videos (first duodenal to first cecal image) were extracted using the RAPID reader software, V9.0. Prior to extraction, CE videos were scored using the Lewis score (LS). Clinical, endoscopic and laboratory data were extracted from the electronic medical records. All patients were classified as per start of biological therapy during follow-up. Machine learning analysis was performed by Intel Inc. using TimeSformer computer vision algorithm developed by Facebook. Timesformer algorithm utilizes spaciotemporal

Results

The patient cohort included 103 patients (54 (52%) female, median age- 25 years, interquartile ratio (IQR) 21–40). The median duration of follow-up was 941 (363–1644) days. The median LS was 450 (IQR-225–900). Biological therapy was initiated by 41(39.8%) of the patients (adalimumab -20 (48.7%), infliximab-14 (34,1%), vedolizumab- 7 (17%) patients, respectively). TimeSformer algorithm achieved training and testing accuracy of 91% and 79% respectively, with area under the curve (AUC) of 0.79 for prediction of the need for biologic therapy. In comparison, the AUC for LS was 0.69. The required time for analysis per complete video was 440ms on a single GPU.

Conclusion

Spaciotemporal analysis of complete small bowel CE videos of newly diagnosed CD patients achieved accurate prediction of the need for biological therapy. The accuracy was superior to that of human reader index. Following future validation, this approach will allow for fast and accurate personalization of treatment decisions in CD.
P286 Sustained improvement in health-related quality of life outcomes in patients with Ulcerative Colitis with long-term tofacitinib treatment in the open-label extension study, OCTAVE Open
Authors: Biedermann L , Dubinsky M C , Vermeire S , Fellmann M , Gardiner S , Hur P , Mundayat R , Panés J , Rubin D T
Published: January 2022

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Tofacitinib induction and maintenance therapy has previously been shown to improve health-related quality of life (HRQoL) outcomes. Here, we present HRQoL data from patients (pts) with UC who received tofacitinib 5 or 10 mg twice daily (BID) in the Phase 3 open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612), up to Month (M)72.

Methods

Proportions of pts with an Inflammatory Bowel Disease Questionnaire (IBDQ) total score ≥170, and EuroQol-5D (EQ-5D) and Short Form-36 Health Survey (SF-36) scores were analysed up to M72 in 4 subpopulations in the OLE study: ‘maintenance remitters’ completed OCTAVE Sustain in remission and received tofacitinib 5 mg BID in the OLE study; in contrast, ‘maintenance treatment failures’ (induction responders who experienced treatment failure), ‘maintenance non-remitters’ and ‘induction non-responders (IndNR)’ received tofacitinib 10 mg BID in the OLE study (Figure 1). Data were analysed for each subpopulation overall and stratified by prior tumour necrosis factor inhibitor (TNFi) failure, prior immunosuppressant failure and baseline corticosteroid use.

Results

Baseline demographics and clinical characteristics for each subpopulation are shown in Table 1. Among the 163 maintenance remitters, HRQoL outcomes were maintained up to M72: 80.0% of pts had an IBDQ total score ≥170 (Figure 1); changes from baseline in EQ-5D scores up to M72 and SF-36 scores up to M33 were minimal (eg M72 EQ-5D utility score -0.07 [standard deviation 0.10]; M33 SF-36 physical functioning score -1.3 [8.3]). Among pts continuing long-term tofacitinib treatment, improvement in IBDQ total score was maintained/achieved by M2 (first post-baseline assessment), and was stable up to M72, with maintenance treatment failures and IndNR subpopulations experiencing the largest improvements from baseline (Figure 1). Similar trends were observed for improvement in EQ-5D and SF-36 scores. Improvements in HRQoL outcomes were independent of prior TNFi failure, prior immunosuppressant failure or baseline corticosteroid use, eg in maintenance remitters with prior TNFi failure, 90.9% of pts had IBDQ total score ≥170 at M60 vs 88.9% of pts without prior TNFi failure.

Conclusion

Sustained beneficial effects in HRQoL were observed among pts continuing long-term tofacitinib treatment in OCTAVE Open. In maintenance remitters, improvements in all HRQoL outcomes were maintained with tofacitinib therapy. In pts who entered the OLE study not in remission and received tofacitinib 10 mg BID, HRQoL improvements were observed within the first 2 months, and were maintained up to M72, regardless of treatment history including prior TNFi failure.
P298 Pregnancy in Crohn’s and Colitis - Observations, Levels and Outcomes Extension (PICCOLO-X) Study: Biological therapy reduces faecal calprotectin and the need for corticosteroids in pregnant women with Inflammatory Bowel Disease
Authors: Prentice R , Wright E , Flanagan E , Goldberg R , Prideaux I , Ross A , Burns M , Bell S
Published: January 2022

Background

Active Inflammatory Bowel Disease (IBD) in pregnancy is associated with adverse obstetric and neonatal outcomes. PICCOLO-X is an ongoing prospective cohort study of pregnant women with IBD, aiming to describe rates of biochemically active IBD in the current therapeutic landscape, and associations with adverse outcomes.

Methods

Participants were evaluated preconception, in each trimester and postpartum with clinical and biochemical data collected. Univariate and multivariate logistic regression was performed to identify the relative risk (RR) of adverse outcomes by relevant exposures. Fischer’s exact test was used to compare group medians.

Results

164 completed pregnancies were included, with 62% exposed to biologic therapy and 56% having Crohn’s Disease (Table 1).

Clinically active disease (PGA ≥1) was reported in 23.9% in trimester 1 (T1), 18.8% in trimester 2 (T2) and 17.5% in trimester 3 (T3), and was less common in biologic exposed patients (Table 2 & 3).

The median faecal calprotectin (FC) was <50μg/g in all trimesters, and was lower in those receiving biologics (24.9 vs 86μg/g T1 p=0.02, 26.25 vs 46μg/g T2 p=0.02, 30 vs 58μg/g T3 p=0.04) (Table 3). Adverse pregnancy outcome rates were equivalent to the normal population (Table 2). Corticosteroid (CCS) exposure in T2 was associated with an increased risk of preterm delivery (PTD) on multivariate analysis (RR 8.12, 95%CI 1.23–53.72, p=0.03). T1 FC ≥250μg/g (RR 2.41 95% CI 0.5–4.31, p=0.01), clinically active disease in T3 (RR 4.7, 95% CI 1.02–26.61, p<0.01) & T3 FC 100–250 (RR 6.8 95% CI 1.71–26.0, p<0.01), but not T3 FC ≥250μg/g (RR 1.6, 95% CI 0.41–8.25, p=0.6) were associated with an increased risk of PTD on univariate analysis (Table 4).

Biologic exposure was associated with a reduced need for CCS; no participants on a biologic had CCS in T1, with RR 0.14 (95% CI 0.03–0.66, p=0.01) in T2 and 0.11 (95% CI 0.02–0.46, p=0.003) in T3. On multivariate analysis, FC >100μg/g in T2 was associated with an increased risk of emergency caesarean section (RR 1.65, 95% CI 0.47–2.82, p<0.01), whilst FC >100μg/g in T2 (RR 1.65 95% CI 0.4–2.91 p=0.01) and T3 (RR 2.47,95% CI 1.36–8.82, p<0.01) were associated with an increased risk of neonatal intensive care unit admission.

Conclusion

PICCOLO X describes low rates of biochemical and clinical active disease in pregnant women with IBD as compared to historical cohorts, possibly due to the cohort’s high rate of biologic use. Pregnancy outcomes were favourable overall. Clinical and biochemical inflammation and CCS exposure were associated with an elevated risk of adverse pregnancy outcomes. Biologic therapy reduces FC and the need for steroids.
P331 Composite outcomes in Crohn’s disease: a systematic review and meta-analysis of observational studies
Authors: Estevinho M M , Sottomayor C , Alves C , Santago M , Ministro P , Lago P , Correia L , Gonçalves R , Carvalho D , Portela F , Dias C C , Dignass A , Danese S , Peyrin-Biroulet L , Magro F
Published: January 2022

Background

Observational studies are essential to analyse outcome reporting in inflammatory bowel disease. However, such studies are usually heterogeneous. Therefore, the development of core outcome sets to be included in future observational studies is of major importance. Composite and aggregate outcomes (in which an event is classified by the presence of any one or by the combination of every individual variable under assessment, respectively) allow maximizing the statistical power of observational studies. A systematic review and meta-analysis were performed to assess composite and aggregate outcomes in observational studies for Crohn’s disease (CD) and to evaluate whether the number and type of variables affect the frequency of the outcome.

Methods

Three online databases (PubMed, Scopus and Web of Science) were searched to identify observational studies that enrolled CD patients and evaluated a composite or aggregate outcome. The proportion of patients achieving the outcome was determined and a random-effects meta-analysis was performed to evaluate how the frequency of each outcome varied according to the reporting of predefined variables.

Results

From the, 10.257 identified records, 46 were included in the systematic review and, 38 in the meta-analysis. The median frequency of composite and aggregate outcomes was, 0.445 [95% confidence interval (CI), 0.389–0.501] and, 0.140 [95% CI, 0.000-, 0.211], respectively. When comparing composite outcomes by the number of included variables, the frequency was, 0.271 [95% CI, 0.000-, 0.405] and, 0.698 [95% CI, 0.651–0.746], for one and six variables, respectively. The frequency of the composite outcome varied according to the set of variables being reported. Specific pairs of predefined variables had a significant effect on the frequency of composite outcomes.

Conclusion

Composite outcomes with an increasing number of variables and those including the variables “surgery” and “steroids” presented higher frequencies. Moreover, specific variables and pairs of variables had a clear effect on the frequency of composite outcomes. Taking this information into account, future efforts must be made to standardize CD outcome reporting, a yet unmet need.
P343 Changing the coUrse of cRohn’s disease with an Early use of adalimumab: The CURE study from the GETAID
Authors: Peyrin-Biroulet L , Bouhnik Y , Laharie D , Elgharabawy Y
Published: January 2022

Background

Crohn’s disease (CD) is a disabling and destructive disease. Early intervention associated with tight monitoring appear to the best way to achieve deep remission and to prevent disease progression. Whether anti-TNF therapy can be interrupted in patients with early CD who have undergone a period of prolonged deep remission is unknown. The primary objective was to evaluate the sustained deep remission rate one year after discontinuation of a, 12-month course of adalimumab in adult patients with early CD who achieved deep remission at, 12 months and who were already in clinical remission and biomarker remission at, 6 months.

Methods

We carried out a multicentre prospective GETAID cohort study. All patients were naïve to biologics. The primary study endpoint was the percentage of patients with sustained deep remission at, 2 years after a, 12-month course of adalimumab in patients who achieved deep remission without therapeutic intervention (i.e. no surgery, no clinical flare-up, no introduction of CD-related treatment, no need for adalimumab optimization) AND who were already in clinical remission (CDAI <, 150) and biomarker remission (CRP <, 5 mg/L and fecal calprotectin <, 250) at, 6 months.

The time to first relapse in patients who achieved deep remission after, 12-month therapy was also evaluated.

Results

A total of, 201 subjects were included between March, 2015 and March, 2019. The median disease duration was, 4 months.

Overall, 56/183 (30.6%) of patients achieved deep remission at one year. From those who achieved deep remission, not lost to follow-up (n=8) and without protocol violation (n=2), 20/46 (43.48%) maintained their deep remission for one year after their treatment discontinuation (month, 24 of the study). Probabibility of relapse-free survival following adalimumab discontinuation in patients achieving deep remission at, 12 months was, 44.8% (Figure).

Conclusion

Three out of, 10 patients with early CD and naïve to biologics achieved deep remission at one year with adalimumab. Among these patients, about half of them maintained deep remission at, 2 years. The identification of factors associated with treatment success will allow identifying CD patients who can stop anti-TNF therapy after achieving deep remission.
P367 Quality of life in patients with Inflammatory Bowel Disease
Authors: Salem J , Ghandour F , Halabi M T , Douaihy T , Matta J , Bedran K , Farhat S
Published: January 2022

Background

Inflammatory bowel disease (IBD) has a lengthy natural history with significant symptomatic impacts. Crohn’s disease (CD) and Ulcerative colitis (UC) both have a major impact on patient Health Related Quality of Life (HRQoL). This study aims to evaluate the postulated negative effect of IBD on HRQoL in the Lebanese population.

Methods

Cross sectional data was collected from a group of, 55 Lebanese patients with IBD (43 with CD and, 12 with UC). Demographic and disease-related data were recorded. Health Related Quality of Life was assessed by disease-specific and generic questionnaires, Inflammatory Bowel Disease Questionnaire (IBDQ) and Short Form Health Survey (SF-36), respectively. Disease activity was assessed based on Harvey-Bradshaw Index (HBI) and the Colitis Activity Index (CAI) for CD and UC patients, respectively.

Results

IBD resulted in sub-optimal scores in both IBDQ-32 and SF-36, especially in UC patients (mean IBDQ-32 of, 174.8 [UC]vs, 208.8 [CD]; P<0.01 and mean SF-36 of, 111.4 [UC] vs, 130.3[CD]; P<0.05) and in patients classified in the increased disease activity group “Severe symptoms” (P<0.01 for both questionnaires). In addition, only IBDQ-32 scores were significantly decreased for patients classified in the long disease duration group “>60 months” (P<0.05). Last but not least, treatment modality had a significant relation to HRQoL for all studied treatment subtypes.

Conclusion

Health Related Quality of Life in Lebanese patients is negatively impacted by IBD, but relatively to a lesser degree than what has been previously reported from other countries using IBDQ questionnaire as an assessment tool. More specifically, patients with UC, longer disease duration and higher disease activity have an increased negative impact on HRQoL. Treatment modality had significant relation to HRQoL, but larger scale studies are still needed to reach more reliable conclusions.
P401 Tofacitinib tissue exposure correlates with endoscopic outcome
Authors: Verstockt B , Alsoud D , van Oostrom J , Smith J , Stylli J , Singh S , van Gennep S , Rahimian P , Sabino J , Ferrante M , Singh S , D’Haens G , Vermeire S
Published: January 2022

Background

Small molecules are being added to the treatment armamentarium of ulcerative colitis (UC). In contrast to monoclonal antibodies, very little is known about their pharmacokinetic-pharmacodynamic profile. We therefore assessed pharmacokinetic-pharmacodynamic changes in Tofacitinib (TFC) treated UC patients, with a focus on STAT3 phosphorylation, as it has been proposed as a marker of efficacy.

Methods

Thirty UC patients initiating TFC therapy, 10mg BID were prospectively monitored (Table, 1). At week, 8, patients could de-escalate to, 5mg BID or maintain, 10mg BID depending on their response. Endoscopic assessment and sampling (colonic tissue and serum) was performed at baseline and, 8–16 weeks after TFC initiation. Endoscopic improvement was defined as Mayo endoscopic subscore, 0–1. TFC was extracted from tissue using acetonitrile, dried down and quantitated using mass spectrometry. Both total as well as phosphorylated STAT3 were measured in lysed tissue using specific antibodies with an ultrasensitive luminescent oxygen channelling assay.

Results

TFC tissue and serum concentrations correlated significantly (r=0.92, p<0.001), though were significantly higher in tissue (median, 520.19ng/g vs, 17.35ng/mL, p<0.001). In contrast to TFC serum exposure (p=0.26), TFC tissue exposure at the end of induction was associated with endoscopic improvement by week, 16 (p=0.04) (Figure, 1). In TFC responders (n=14), TFC tissue exposure exceeded the concentration required to block, 90% of the target (IC90) reported in literature (median tissue exposure, 1,055.00ng/g; IC90, 823ng/g). TFC tissue exposure in non-responders (n=16) was lower, but clearly exceeded the IC50. Although IL-6 was not significantly downregulated after TFC induction, a significant decrease in the ratio of mucosal IL-6 driven phosphorylated STAT3 over total STAT3 (pSTAT3/STAT3) was observed in responders (p=0.05), but not in non-responders (p=0.88). The pSTAT3/STAT3 ratio also correlated significantly with faecal calprotectin (r=0.35, p=0.05), but only weakly with the Mayo endoscopic sub score (r=0.22, p=0.13). Baseline mucosal pSTAT3/STAT3 did not differ significantly between future responders and non-responders.

Tofacitinib tissue (A) and serum (B) exposure at the end of high dose induction in relation to the achievement of endoscopic improvement at week, 16, defined by a Mayo endoscopic sub-score of, 0–1.

Conclusion

We could demonstrate for the first time a mucosal exposure-response relationship with TFC in UC patients. Additionally, pSTAT3/STAT3 ratio was identified as potential molecular marker to track response directly linked to the mode-of-action of TFC. Whether an increased local dose of TFC could result in better efficacy without compromising safety should be further explored.
P411 Stable pharmacokinetics and biochemical markers of inflammatory bowel disease activity: Results from a real-world adalimumab biosimilar switching program
Authors: Moore A C , Russell D , Dart R , Dias S , Ghuman S , Petri B , Sharma E , Ray S , Anderson S , Mawdsley J , Irving P M , Samaan M A
Published: January 2022

Background

Biosimilars have delivered significant cost savings, increasing access to biologics for many patients. While numerous studies have demonstrated no difference in efficacy between originators and biosimilars, the impact of switching between originator and biosimilar adalimumab on drug levels and disease activity in real world cohorts remains largely unknown.

Methods

We conducted a retrospective observational cohort study of, 392 patients with IBD (347 (89%) CD, 45 (11%) UC) who had switched from Humira to the biosimilar, Idacio, between February - November, 2021. Therapeutic drug monitoring was carried out using a commercially available, drug sensitive ELISA (LISA TRACKER, Theradiag). Therefore, antidrug antibodies could only be detected in the setting of low or absent serum drug concentrations. Drug level data was parametric and analysed by paired student t test and Pearson correlation coefficient. CRP data was analysed by Wilcoxon test. Data was analysed using GraphPad Prism.

Results

The baseline characteristics of the study participants are presented in the table., 96 patients had paired adalimumab drug levels before and after the switch. There was no difference between median adalimumab drug levels before and after the switch (9.5 vs, 9.2 ug/mL, p=0.67). Furthermore, drug levels were positively correlated before and after switching demonstrating similar levels at both time points for most patients (correlation co-efficient, 0.47, p <, 0.0001) (Figure, 1). Prior to switching, no patients had detectable antidrug antibodies. Following switch, one patient (1%) developed high-titre antidrug antibodies and undetectable drug levels. Prior to switch their levels were, 14, without detectable antidrug antibodies

CRP levels were available for, 163 patients before and after the switch, with no difference in median CRP at either time point (1 vs, 1mg/L p=0.60).

33 (8%) patients experienced injection site pain with Idacio and therefore, switched back to Humira. The annual cost saving to the UK National Health Service for patients on weekly and every other week switched to Idacio is £5096 and £2548, respectively

Conclusion

Our study demonstrates stable pharmacokinetics and biochemical disease activity amongst a significant cohort of patients switching from originator to biosimilar adalimumab as part of a real-world switching program. However, a small proportion of patients did not tolerate Idacio due to injection site pain. There are clear financial benefits in carrying out non-medical, biosimilar switching programs but further work is needed to evaluate the effect on clinical and endoscopic disease activity in a real-world setting.
P416 Addition of oral antibiotics to mechanical bowel preparation significantly improves anastomotic healing after ileocolic resection for Crohn’s disease
Authors: Poredska K , Kunovský L , Marek F , Kala Z , Ivanecká D , Iesalnieks I
Published: January 2022

Background

Addition of oral antibiotics (OA) to mechanical bowel preparation (MBP) is thought to reduce postoperative morbidity compared to MBP alone. However, data supporting this concept in Crohn’s disease patients undergoing ileocolic resection do not exist.

Methods

Starting, 2016, all ileocolic resections were performed after preoperative MBP combined with OA consisting of two separate dosages of Metronidazole/Neomycine or Metronidazol/Paramomycine. These patients were compared to previous controls undergoing ileocolic resection after mere MBP (1992–2005). Between, 2005 and, 2016, surgeries were performed without preoperative MBP. Patients undergoing an ileocolic resection without construction of anastomosis (i.e., two staged resection) and patients not receiving MBP were excluded from the study. „Anastomotic complications“ were defined as anastomotic leakage, presence of abscess or peritonitis in direct proximity to anastomosis.

Results

312 patients underwent ileocolic resections with construction of an anastomosis:, 159 after MBP only and, 153 after preoperative MBP+OA. Patients in MBP+OA group were older (39 y. vs., 35 y., p=0.001), had penetrating disease less frequently (50% vs., 69%, p=0.001), were on biologicals more frequently (31% vs., 1%, p<0.001), on steroids less frequently (12% vs., 59%, p<0.001), underwent laparoscopic surgery more often (80% vs., 15%, p<0.001), and received preoperative parenteral nutrition more often (16% vs., 7%, p=0.033). Patients receiving OA were not able to complete MBP more often (19% vs., 9%, p=0.009). By the multivariate analysis, addition of OA to MBP was associated with a significant reduction of anastomotic complication rate (3% vs., 11%, Hazard ratio, 0.24, p=0.036). Weight loss and steroids were associated with an increased anastomotic morbidity.

Conclusion

Oral antibiotics added to MBP further improve the anastomotic healing in Crohn’s disease patients undergoing ileocolic resection, although the study has demonstrated an apparent time bias. Further research is needed to clarify whether OA without MBP are as protective as MBP+OA.
P449 Autologous fat graft injection for the treatment of perianal fistulas in Crohn’s disease: A systematic review and single-arm meta-analysis
Authors: De Gregorio M , Tiang T , Lee T , Stellingwerf M E , Basnayake C , Kamm M A , Niewiadomski O , Schulberg J D , Wright E K , Connell W , Thompson A J , D’Souza co-lead senior author B , Ding N S
Published: January 2022

Background

Perianal fistulas are a debilitating complication of Crohn’s disease. Long-term fistula healing rates remain poor with a need for effective novel therapies. Autologous fat graft injections are hypothesised to promote healing through the regenerative effects of mesenchymal stem cells; however, its efficacy remains unclear. We herein evaluated the efficacy of autologous fat graft injections for the treatment of Crohn’s perianal fistulas in a systematic review and meta-analysis.

Methods

A systematic review using the PRISMA Statement guidelines was performed. Database searches of MEDLINE, Embase, and PubMed, and grey literature searches were completed from January 1st, 2001, to August 2nd, 2021. Included publications evaluated fat graft injections for the treatment of Crohn’s perianal fistulas. Excluded studies assessed injection of in vitro expanded mesenchymal stem cells or anovaginal fistulas. Primary outcomes included rates of clinical healing, which was defined as the presence of non-draining fistula tract external openings, and closure, which was defined as complete closure of fistula tract external openings. The secondary outcome was pooled clinical healing or closure, assessed in a random effects meta-analysis across identified studies, excluding case reports.

Results

A total of 1,258 publications were identified, with 891 articles assessed for eligibility and 107 deemed relevant for paper review. Six studies met inclusion criteria for qualitative analysis, comprising four single-arm intervention trials and two case reports. A total of 51 patients received autologous fat graft injections for treatment of Crohn’s perianal fistulas, with follow-up ranging from 3 to 12 months. Variable techniques and filtration kits were used to acquire and process the harvested fat, with further differences in tract preparation, graft volume, and adjunctive surgical techniques. Two studies evaluated clinical healing (n = 20) which was achieved in 20% and 60% at 3 and 12 months, respectively. Four studies evaluated clinical closure (n = 31) which was achieved in 100%, 83%, and 100% at 3, 6, and 12 months, respectively. Clinical healing or closure was achieved in 74% in the pooled meta-analysis (95% confidence interval: 0.57, 0.85), with moderate heterogeneity between studies (I2 Statistic: 59%; Cochran’s Q test: P-value < 0.05). See Figure 1.

Conclusion

Autologous fat graft injections for the treatment of Crohn’s perianal fistulas shows promising results as a novel therapy in this systematic review and meta-analysis. Limited efficacy data showed clinical healing or closure as early as 3 months, with 74% achieving clinical success up to 12 months. Further assessment in controlled matched studies is needed.
P495 Perianal fistula closure in patients receiving ustekinumab: Results from the SEAVUE and STARDUST trials
Authors: Peyrin-Biroulet L , Panaccione R , Gasink C , Hoops T , Izanec J L , Ma T , Nazar M , Bravata I , Lahaye M , Irving P M , Loftus E V , Danese S , Sands B E
Published: January 2022

Background

Perianal fistulas are common and cause significant quality of life impairment in patients (pts) with Crohn’s disease (CD). In previous phase 2/3 studies, ustekinumab (UST) showed some evidence of efficacy on fistula resolution, with no clear dose-response relationship. Additional studies are needed to evaluate the role of UST in perianal fistula treatment. Here, we report fistula data from two recent studies of UST in CD, SEAVUE and STARDUST.

Methods

In SEAVUE, biologic-naïve pts with moderate-to-severe CD were randomized to receive blinded UST (⁓6mg/kg IV at baseline then 90mg SC q8w) or adalimumab (ADA; 160/80mg SC at baseline/W2, then 40mg SC q2w). In STARDUST, biologic-naïve and biologic-failure pts with moderate-to-severe CD received open-label UST ⁓6mg/kg IV at baseline and UST 90mg SC at W8. At W16, pts were randomized to maintenance treatment under standard of care (90mg SC q12w or q8w) or treat-to-target (90mg SC q12w or q8w with potential adjustment to q4w) regimens. In both trials, the number of open and draining perianal fistulas was evaluated at baseline and the end of maintenance (SEAVUE W52, STARDUST W48). Fistula resolution was defined as closure of all fistulas. Pts with missing data at W52/W48 were considered to not have been in fistula resolution. In SEAVUE, pts who had a prohibited CD-related surgery, discontinued for lack of efficacy or an adverse event of worsening CD, or had prohibited concomitant medication changes before W52 were considered not to be in fistula resolution.

Results

In SEAVUE, 7 of 13 pts (53.8%) with active perianal fistulas at baseline in the UST group had complete fistula resolution at W52, and 6 of 16 patients (37.5%) in the ADA group had fistula resolution. In STARDUST, 9 of 19 pts (47.4%) with active perianal fistulas at baseline had complete fistula resolution at W48. Of the 9 pts in fistula resolution, 2 were receiving q12w at W48, 6 were receiving q8w, and 1 was receiving q4w. Of the 10 pts without fistula resolution, 2 were receiving q12w at W48, 3 were receiving q8w, 1 was receiving q4w and 4 discontinued before W48. In both studies, among pts with evaluable samples for pharmacokinetic analysis, fistula closure at W52/48 was not associated with higher serum drug concentrations at either the early time point of W16 or at the end of maintenance (Figure). This result was consistent for UST in both studies as well as ADA in SEAVUE.

Conclusion

Of pts with perianal fistulas at baseline in SEAVUE and STARDUST who received UST (32 pts in total), half were in fistula resolution after ~1 year of maintenance treatment. No relationship was observed between fistula resolution and serum drug concentrations, but no definite conclusions can be drawn given the relatively small sample size.
P510 Comparative efficacy of biologic therapies for inducing response and remission in fistulizing Crohn’s disease; Systematic Review and Network Meta-analysis
Authors: Shehab M , Alrashed F , Heron V , Restellini S , Bessissow T
Published: January 2022

Background

The management of patients with fistulising Crohn’s disease (CD) is challenging. Several biologics have been used for the treatment of fistulising CD over the last two decades. We aimed to compare the efficacy of biologic therapies in inducing response and remission in fistulising Crohn’s disease.

Methods

Systematic searches were made of MEDLINE, EMBASE, Scopus, Cochrane Central databases for randomized controlled trials (RCTs) to November 2021 that assessed the efficacy of infliximab, adalimumab, certolizumab, vedolizumab, or ustekinumab against placebo or an active agent for induction of response or remission in adult Crohn’s patients with fistulising disease. Primary outcome was proportion of patients with fistula response or remission as defined by each RCT. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% confidence interval (CI).

Results

Ten studies were included in the analysis. Main analysis showed that there was no statistical difference in inducting remission between infliximab, adalimumab, certolizumab, vedolizumab and ustekinumab. Anti-TNFs were superior to placebo in inducing response [OR= 0.51 (95% CI 0.35; 0.750] and remission [OR= 0.36 (95% CI 0.22; 0.58)]. Infliximab was superior to placebo in inducing response [OR= 0.36 (95% CI 0.17; 0.75)] and remission [OR=0.17 (95% CI 0.03; 0.87)]. Ustekinumab was superior to placebo in inducing response [OR=0.48 (95% CI 0.26; 0.860] but not remission [OR=0.50 (95% CI 0.13; 1.93)]. Vedolizumab was not superior to placebo in inducting remission [OR=0.32 (95% CI 0.04; 2.29)]. Certolizumab was not superior to placebo in inducting response [OR=0.78 (95% CI 0.40; 1.55)] or remission [OR= 0.78 (95% CI 0.40; 1.55)]. Infliximab was superior to adalimumab in inducting response [OR=0.24 (95% CI 0.06; 0.99)] but not remission [OR=0.31 (95% CI 0.04; 2.27)].

Conclusion

In patients with fistulising Crohn’s disease, anti-TNFs are effective in inducing response and remission. Infliximab was superior to adalimumab in inducing response but not remission. No difference among various biologics was observed for inducing remission. These data highlight the need for dedicated studies to assess the efficacy of biologics in fistulising Crohn’s disease.
P513 Treatment persistence in bio-naive patients with long-standing Crohn’s disease treated with first-line biologics: real-life data from a Croatian tertiary center
Authors: Biscanin A , Tomasic V , Babic F , Dorosulic Z , Kralj D , Cacic P , Ogresta D , Hrabar D
Published: January 2022

Background

All available biologics have demonstrated efficacy and safety as first-line treatment options for bio-naive Crohn’s disease (CD) patients. Real-world data about persistence with biologic treatment in patients with CD are lacking. The aim of this study was to assess and to identify potential factors affecting treatment persistence with index biologic medication in our tertiary center.

Methods

A single-center, noninterventional, retrospective chart review study (January 2015-October 2020) was performed on real-life data of adult bio-naïve CD patients who were treated with infliximab, adalimumab, vedolizumab or ustekinumab for >12 months duration of drug exposure. Treatment persistence was assessed using Kaplan-Meier analysis for a 36 month period and t-test for independent samples was used to identify predictors of long-term biologic persistence rates.

Results

Out of 84 patients (51.7% female; median age 33) included in the study 38.4% were smokers, 34.5% had history of intestinal resection and 25.6% had extraintestinal manifestations of CD. At the start of the biologic-induction regime 35.7% of patients were treated with corticosteroids and 43.4% with concomitant immunomodulator (81.8 % azathioprine, 18.2 % methotrexate). The median of CD duration was 47 months and the mean duration of treatment persistence was 29 months. After 36 months of treatment duration, the persistence rates for ustekinumab, adalimumab and infliximab were 61.9%, 56% and 48.1% respectively. Vedolizumab results were omitted from final analysis due to the small number of patients treated with the drug (N=3). Factor associated with higher persistence was body mass index (BMI) > 25 kg/m2 at the time of biologic therapy induction (p=0.05). Concomitant therapy with immunomodulator numerically significantly prolongs the therapy persistence (33.6 vs. 24.5 months). No other patient or disease-related factors (including disease duration) were found to be associated with treatment persistence for studied biologics.

Conclusion

These real-world data suggest that infliximab, adalimumab and ustekinumab are effective and efficient therapeutic options for bio-naive patients with moderate to severe long-standing Crohn′s disease. Concomitant immunomodulatory therapy and BMI >25 kg/m2 at the time of therapy induction were factors associated with higher biologic treatment persistence in those patients.
P530 Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn’s disease - a systematic review with meta-analysis
Authors: Attauabi M , Madsen G R , Bendtsen F , Seidelin J B , Burisch J
Published: January 2022

Background

Several studies have indicated a reduced efficacy of vedolizumab among patients with ulcerative colitis (UC) and Crohn’s disease (CD) previously exposed to biological therapies. The purpose of this study was to determine the efficacy and safety of vedolizumab among bio-naïve patients with UC or CD as compared with bio-exposed patients.

Methods

The systematic review and meta-analysis were conducted according to Cochrane’s recommendations. PubMed, EMBASE, and The Cochrane Library databases were searched from database inception till December 2020 for studies that reported any efficacy or safety outcome among bio-naïve patients with UC or CD receiving vedolizumab. Meta-analyses were performed using a random-effects model based on the inverse-variance method. The methodological quality of was assessed in line with National Institute for Health and Care Excellence (NICE) guidelines.

Results

The systematic search identified 79 eligible studies, including a total of 2,830 and 2,381 bio-naïve patients with UC and CD, respectively, compared with 7,392 and 10,511 bio-exposed patients, respectively. The mean NOS score was 6.0 and 6.1 in UC and CD, respectively. Meta-analysis showed that bio-naïve patients with UC more frequently achieved clinical remission at week 14 (risk ratio (RR)=1.27 [95% confidence interval (CI) 1.00, 1.62]) and week 52 (RR=1.25 [95% CI 1.11, 1.42]) compared to bio-exposed patients. Similar results were found in terms of steroid-free clinical remission at week 52 (RR= 1.36 [95% CI 1.06, 1.76]). Likewise, bio-naïve patients with CD were more likely to achieve clinical remission at week 52 (RR= 1.23 [95% CI 1.05, 1.43]), while clinical remission at week 14 and steroid-free clinical remission could not be assessed in a meta-analysis. A similar pattern was observed regarding the achievement of endoscopic remission at week 52 in UC (RR= 1.48 [95% CI 1.28, 1.72]) but not in CD (RR=1.48 [95% CI 0.82, 2.65]) (Tables 1–2).

Finally, bio-naïve UC patients did not experience any difference in rates of adverse events as compared with bio-exposed patients (UC: RR= 0.96 [95% CI 0.70, 1.31]) but experienced significantly less serious adverse events (RR= 0.47 [95% CI 0.26, 0.82]). In line with this, patients with CD experienced fewer adverse events (RR= 0.73 [95% 0.64, 0.83]) and serious adverse events (RR= 0.54 [95% CI 0.34, 0.85]).

Conclusion

This meta-analysis suggests that the reduction of efficacy of vedolizumab following exposure to other biologicals is statistically and clinically significant. Our findings add to the body of evidence regarding tailoring of biological therapies for patients with UC and CD.
P532 Proactive therapeutic drug monitoring improves clinical outcomes in patients with inadequate post-induction infliximab trough levels
Authors: Botto I , Coelho Rodrigues I , Serrazina J , Fernandes S , Bernardo S , Gonçalves A R , Moura Santos P , Valente A , Correia L , Tato Marinho R
Published: January 2022

Background

A large body of evidence demonstrates a significant correlation between week 14 infliximab trough levels (IFXTL) and several clinical outcomes. In patients with low IFXTL at week 14, proactive therapeutic drug monitoring (TDM) may potentially improve clinical results.

Methods

Retrospective study including 181 patients (63.5% with Crohn’s disease) under proactive TDM. IFXTL were measured at week 14 and every 2 infusions using a drug sensitive assay (Theradiag®, Lisa Tracker) with treatment proactively escalated to an IFXTL 5–10 ug/ml. We compared the clinical outcomes between patients with low (<5 ug/ml) and adequate IFXTL at week 14, in respect to clinical remission, fecal calprotectin (Fc) remission, C-reactive protein (CRP) remission, hospitalization, treatment discontinuation, and surgery up to 1 year of follow-up.

Results

Ninety-one patients (50.3%) had low IFXTL at week 14. These patients presented lower rates of clinical remission (69.2% vs 82.2%, P=0.031), Fc remission (41.9% vs 73.4%, P<0.001), and CRP remission (60.7% vs 72.7%, P= 0.061) at week 14 of treatment. Likewise, worse outcomes were also shown by the end of the study, with lower rates of clinical remission (64.8% vs 87.8%, P<0.001), and Fc remission (58.9% vs 77.9%, P=0.005), and higher rates of hospitalization (17.6% vs 6.7%, P=0.021), surgery (5.5% vs 0%, P=0.030), treatment discontinuation (36.3% vs 17.8%, P=0.004), and any unfavorable outcome (42.9% vs 21.1%, P=0.001). Following proactive treatment escalation, fifty-nine patients (64.8%) were successful in increasing IFXTL ≥5 ug/ml within subsequent infusions. These patients presented higher rates of clinical remission (79.7% vs 37.5%, P<0.001), and lower rates of treatment discontinuation (20.3% vs 65.6%, P<0.001), surgery (1.7% vs 12.5, P=0.05), and any unfavorable outcome (28.8% vs 68.8%, P<0.001), with a non-significant trend for higher rates of Fc remission (63.8% vs 50%, P=0.147). These patients also presented similar outcomes compared to patients with adequate week 14 IFXTL in respect to clinical remission (P=0.134), Fc remission (P=0.049), hospitalization (P=0.131), surgery (P=0.396), treatment discontinuation (P=0.426), and any unfavorable outcome (P=0.189).

Conclusion

IFXTL significantly influence early and long-term treatment outcomes. In patients with inadequate IFXTL at week 14, proactive TDM was associated with improved clinical outcomes.
P537 Steroid use in patients with immune checkpoint inhibitor colitis
Authors: Crothers-Stomps L , Mohsen W , Kakkadasam Ramaswamy P , Mason R , Dzienis M , Edwards J
Published: January 2022

Background

Immune checkpoint inhibitors (ICIs) encompass drugs targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), inhibitors of programmed cell death receptor-1 (PD-1), and inhibitors of programmed cell death ligand 1 (PD-L1) used for the treatment of cancer. Gastrointestinal side effects associated with ICI therapy are among the most common complications. This study aims to review steroid use in patients admitted with ICI colitis.

Methods

This was a retrospective review of patients in a tertiary center who received ICIs between January 2018 and December 2020 who required admission for the development of ICI colitis. Demographic data, previous and ongoing therapy, laboratory parameters, medical therapy and endoscopic findings were reviewed.

Results

Of the 545 patients who received ICIs, 4% (22) required admission with ICI colitis. Of those who developed ICI colitis 31.8% (7) were receiving combination ipilimumab and nivolumab, 31.8% (7) were receiving pembrolizumab, 27.3% (6) were receiving nivolumab, 4.5% (1) were receiving cemiplimab and 4.5% (1) were receiving ipilimumab.

The median age was 64.5 years (52–75) with the median CTCAE severity score of colitis being 3 (2–3) and the median CTCAE diarrhoea score being 3 (3). On admission, the median stool frequency was 6 (5–8), with median symptom duration of 7 (4–13) days, and median hospital stay of 3 (3–6) days. Laboratory markers were monitored during admission (Table 1).

72% (16) of patients were commenced on intravenous corticosteroid therapy whilst an inpatient, with 95% (21) being discharged on oral prednisolone. Median duration on oral steroid was 22 (8–35) weeks. 36% (8) had oral prednisolone ongoing at the end of the review period. 27% (6) died whilst still on a weaning prednisolone regimen.

Conclusion

Despite improvement of symptoms during hospital admission with corticosteroid therapy, the majority of patients admitted for ICI colitis required prolonged treatment with corticosteroids.