bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &lt;, 150) and biomarker remission (CRP &lt;, 5 mg/L and fecal calprotectin &lt;, 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

Abstract

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&lt;0.01 and mean SF-36 of, 111.4 [UC] vs, 130.3[CD]; P&lt;0.05) and in patients classified in the increased disease activity group “Severe symptoms” (P&lt;0.01 for both questionnaires). In addition, only IBDQ-32 scores were significantly decreased for patients classified in the long disease duration group “&gt;60 months” (P&lt;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

Abstract

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&lt;0.001), though were significantly higher in tissue (median, 520.19ng/g vs, 17.35ng/mL, p&lt;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

Abstract

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 &lt;, 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

Abstract

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&lt;0.001), on steroids less frequently (12% vs., 59%, p&lt;0.001), underwent laparoscopic surgery more often (80% vs., 15%, p&lt;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

Abstract

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 &lt; 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

Abstract

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.