bluuebunny/crossref_metadata_2025_split huggingface dataset:
P461 COVID-19 outcomes in patients receiving anti-TNF treatments: A systematic review and meta-analysis
Authors: Kokkotis G , Kitsou K , Xynogalas I , Spoulou V , Magiorkinis G , Poulakou G , Syrigos K , Bamias G 
Published: January 2022

Abstract

Background
Accumulating evidence suggests a beneficial effect of tumor necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however, is not validated by all studies. We aimed to perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients.

Methods
A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September-2021 were included. Pooled effect measures were calculated using a random-effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta-analysis were described qualitatively.

Results
In total, 84 studies were included in the systematic review, and 31 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases had a lower probability of hospitalisation (25 studies, pooled OR=0.34, 95%CI:0.30–0.38, I2=0) and severe disease defined as intensive care unit admission or death (eight studies, pooled OR=0.38, 95%CI: 0.27–0.55, I2=0). After adjustment for validated predictors of adverse disease outcomes, patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases preserved a lower probability of hospitalisation (eight studies, pooled OR=0.53, 95%CI:0.42–0.67, I2=0) and severe disease (two studies, pooled OR=0.63, 95%CI: 0.41–0.96, I2=0). No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5,994,958 participants, pooled Risk Ratio=0.97, 95%CI: 0.68–1.39, I2=20) adjusted for age, sex and comorbidities.

Conclusion
TNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.
P472 Changes in colectomy for Ulcerative Colitis during the last two decades: an in-depth retrospective analysis
Authors: Le Cosquer G , Capirchio L , Rivière P , de Suray N , Poullenot F , De Vroey B , Berger A , Denis M A , Zerbib F , Bachmann R , Remue C , Celerier B , Leonard D , Denost Q , Kartheuser A , Laharie D , Dewit O 
Published: January 2022

Abstract

Background
The management of ulcerative colitis (UC) has been improved due to progresses in medical and surgical practices during the past twenty years. Yet the impact of new therapies on the evolution of the three colectomy’s indications in UC (severe acute colitis, refractory ulcerative colitis and (pre-)neoplastic complication) is still not well established. The aim of this study was to compare the evolution of the surgical indications within the last two decades.

Methods
This was an observational retrospective study carried out in two tertiary hospitals. All patients with UC who underwent total or segmental colectomy between 2001 and 2020 were included, without age restriction. Two periods were compared: 2001–2010 and 2011–2020. Endpoints were to compare the colectomy indications, patients’ characteristics, surgical procedures, and rates of postoperative complication between the two cohorts.

Results
Among the 286 patients included (57% were men; median age of 40 years; 60.5% of extensive and 35.7% of distal colitis), 87 (30.4%) underwent colectomy in 2001–2010 and 199 patients (69.6%) in 2011–2020. Patients’ characteristics were similar between the two periods, including duration of UC and the severity according to the global Mayo score. Colectomy rate for refractory UC significantly decreased over time (n=119) (50.6% vs. 37.7%; p=0.042), while it increased for acute severe colitis (n=116) (36.8% vs. 42.2%; p=0.390) and (pre-)neoplastic indication (n=51) (12.6% vs. 20.1%; p=0.130) (Figure 1).
Regarding surgery, there was an increased use of laparoscopic colectomy (47.7% vs. 81.4%; p&lt;0.001) during the latter period and the median length of stay in hospital after surgery has decreased from 13 to 10 days (p=0,098). There were less early (12.6% vs. 5.5%; p=0.038) and late severe complications (1.6% vs. 0.8%; p&lt; 0.001) and less surgical revisions (38.6% vs. 19.5%; p&lt;0.001) without change on 30-day mortality rate (2.3% vs. 1%; p=0.391). The rate of extraintestinal postoperative infections (especially urinary, pulmonary and catheters infections) increased during the second period (27% vs; 45.7%; p=0.018).
As expected, the mean number of past biotherapies was higher during the second period (1.2 versus 0.6; p&lt;0.001), as well as the rate of pre-operative exposition to TNFα antagonists (68.4% vs. 50.6%; p=0.016).

Conclusion
The rate of surgery for refractory colitis has significantly decreased while the rate of colectomy for cancer and acute severe colitis has risen during the last twenty years. In the same time, surgical technics have changed with more laparoscopic surgeries associated with a reduction of postoperative morbidity despite the larger use of biotherapies.
P474 Prevalence of fecal incontinence and clinical characteristics of IBD patients in remission and treated with biologics – experience from a tertiary referral center
Authors: Jelakovic M , Turk N , Brinar M , Barisic A , Grgic D , Cukovic-Cavka S , Krznaric Z 
Published: January 2022

Abstract

Background
Fecal incontinence (FI) is a debilitating disorder highly prevalent in inflammatory bowel disease (IBD) patients with reports in literature ranging from 20–80%. There is limited data on FI prevalence in IBD patients who are in remission, treated with biologics and their clinical characteristics.

Methods
In this cross-sectional observational study we have included IBD patients in remission, treated with biologics. Demographics and medical data were collected from electronic medical charts while patients were screened for FI using the St. Mark’s incontinence score (SMIS). Significant FI was characterized as SMIS ³6. Descriptive statistical analysis was used.

Results
We included 57 patients (24 female/33 male) in clinical remission treated with biologics, median age 41 years (18–70), 23 patients had ulcerative colitis (UC) and 34 had Crohn’s disease (CD). Median disease duration was 8 years (1–31). Significant FI was identified in 41 patient (71.9%) out of which 87.8% were in biochemical and 34.1% in endoscopical remission. FI was more prevalent among CD patients (76.4%) compared to UC (65.2%), but the difference did not reach statistical significance. FI was not significantly correlated to gender, type or number of biologics but there was significant positive correlation with disease duration (r=0.3139; p&lt;0.05), especially for patients with disease duration longer than 5 years who had significantly higher mean SMIS score (9.1±4.6 vs 5.2±2.6; t-2.86; p&lt;0.05). Furthermore, patients older than 50 years of age also had significantly higher average SMIS scores compared to younger patients (10.6±4.6 vs 7.6±4.3;t-2.09;p&lt;0.05)

Conclusion
FI is highly prevalent in IBD patients treated with biologics, even in those who have reached endoscopical remission. Clinicians should be aware of this disorder and use available screening tools especially in older patients with longer disease duration in order to further improve quality of life of these patients.
P476 Disease recurrence patterns in patients undergoing bowel resections for Crohn’s disease
Authors: Ahmed M , Chacko J , Zimerly S , Patel A 
Published: January 2022

Abstract

Background
Despite numerous advances in the medical management of IBD, it is estimated that 70–90% of patients with Crohn’s disease require surgical intervention with a significant proportion requiring repeat surgery. There is evidence to suggest that biologic agents may reduce the incidence of disease recurrence and may delay progression to further surgery. We aim to compare disease progression in biologic-naïve patients with patients on established biologic therapy

Methods
A retrospective single-centre UK study including patients who underwent primary Ileo-caecal resections for Crohn’s disease between 01/01/2014 to 31/12/2019. Patients were classified according to the Montreal classification. Electronic case records used to obtain patient data. Disease recurrence was defined as active disease on radiological imaging or endoscopic visualisation up until 01/11/2021. Prophylactic treatment included medical therapy initiated postoperatively prior to disease recurrence.

Results
In total, 88 patients, with a median follow-up of 54 months (IQR: 1–104 months), were included (Table 1). Of these, 69 patients had been started on medical therapy prior to surgery and 21 had Biologic treatment. Nearly half of the patients (36/88) underwent emergency resections (Table 2).
Postoperative prophylaxis was given to 28 patients (31.8%), of which 8 were given Biologics. Patients who were smokers were more likely to be offered post-operative prophylaxis (55.56% vs 22.9%). 58 patients (65.9%) developed disease recurrence and 9 patients (15.5%) required further resections. Use of biologic therapy preoperatively was associated with an increased risk of requiring further resections (20.8% vs 6.8% with alternative agents; OR: 3.684, p-value: 0.030). Biologics were continued postoperatively in 5/21 patients and none of these required further resections. Discontinuation of biologics postoperatively was associated with a higher risk of recurrence (68.75%) and further bowel resection (25%). Prophylactic use of biologics had an overall net preventive effect on disease recurrence compared to alternative agents (62.5% vs 89%; OR: 0.417).

Conclusion
Preoperative biologic therapy can be a marker of more severe disease at presentation and may indicate need for repeat resection. In addition, patients on biologic therapy preoperatively have significantly worse outcomes if this is discontinued in the postoperative period.
P477 Rectal bleeding and stool frequency improvement with tofacitinib retreatment in patients with Ulcerative Colitis after treatment interruption: Results from OCTAVE Open
Authors: Allegretti J R , Gecse K B , Chiorean M V , Argollo M , Guo X , Lawendy N , Su C , Mundayat R , Paulissen J , Salese L , Irving P M 
Published: January 2022

Abstract

Background
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Patients may require retreatment following treatment interruption for reasons such as adverse events or pregnancy.1 In the tofacitinib UC clinical programme, patients who responded to tofacitinib 10 mg BID during induction, and experienced treatment failure whilst receiving placebo during maintenance (OCTAVE Sustain) and subsequently received tofacitinib 10 mg BID in the open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612), comprised the retreatment subpopulation. The efficacy and safety of tofacitinib in the retreatment subpopulation have previously been reported.1 Here, we evaluated patient-reported outcomes to assess rectal bleeding and stool frequency improvement in the retreatment subpopulation in OCTAVE Open.

Methods
The following efficacy endpoints based on the Mayo subscores were analysed in the overall retreatment subpopulation and by prior tumour necrosis factor inhibitor (TNFi) failure status: rectal bleeding improvement (≥1 point decrease in rectal bleeding subscore [RBS] from OLE study baseline), and stool frequency improvement (≥1 point decrease in stool frequency subscore [SFS] from OLE study baseline), up to Month (M)6 in the OLE study (full analysis set, non-responder imputation). Changes from baseline in partial Mayo score (PMS), RBS and SFS at M1, by M2 clinical response status, were also analysed (as observed).

Results
In OCTAVE Open, 101 patients were included in the retreatment subpopulation, of which 46 (45.5%) had prior TNFi failure. Overall, at M1 and M6 of OCTAVE Open, 83.2% and 76.2% of patients had rectal bleeding improvement, respectively (Figure 1). Corresponding values for stool frequency improvement were 70.3% and 75.2%. At most time points, rates of rectal bleeding and stool frequency improvements were similar in patients with and without prior TNFi failure. Mean decrease from baseline in PMS, RBS and SFS at M1 was similar in patients with and without a clinical response at M2 (Figure 2).

Conclusion
In this post hoc analysis, in patients with UC who had loss of response after 8–52 weeks of treatment interruption, retreatment with tofacitinib 10 mg BID resulted in rectal bleeding and stool frequency improvement in the majority of patients by M1, which was maintained to M6, regardless of prior TNFi failure status.

Reference
1. Panés J et al. J Crohns Colitis 2021. Epub ahead of print.
P478 The role of proactive measurement of adalimumab trough levels and antibodies to adalimumab in Greek patients with Inflammatory Bowel Disease
Authors: Orfanoudaki E , Gazouli M , Theodoraki E , Foteinogiannopoulou K , Andreou N P , Koutroubakis I E 
Published: January 2022

Abstract

Background
Therapeutic drug monitoring (TDM) of adalimumab trough levels (ADA-TLs) and antibodies to adalimumab (ADA-Abs) in patients with inflammatory bowel disease (IBD) is usually performed in a reactive setting when the disease flares. There is not enough evidence in favor of proactive TDM in these patients.

Methods
We aimed to evaluate the role of proactive measurement of ADA-TLs and ADA-Abs in IBD patients under treatment with adalimumab. Consecutive IBD patients on maintenance treatment with ADA, were included. ADA-TLs and Abs were measured using ELISA (Immunoguide, Aybayteche, Turkey) on serum samples drawn before ADA administration. At the same time serum biomarkers [Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells (WBC), hemoglobin (Hgb), platelets (PLT)] as well as home-based fecal calprotectin (FC) ±3 months from blood sampling were assessed. After the measurements patients were followed and treatment changes made were recorded.

Results
A total of 52 patients receiving ADA maintenance therapy [48 CD, 4 UC, 31 males, mean age (±SD) 42.1±12.6 years, 8 on combination therapy with immunomodulators (IMMs), 23 under intensified dose (either 40mg/w or 80mg/2w)] were included. Median (IQR) time since ADA initiation was 31 (17.5–38.5) months and median value (IQR) of serum ADA-TLs was 8.24 μg/ml (3.32–10.02). Five out 52 (9.6%) were positive for ATIs (&gt;3 AU/ml). Patients with positive Abs had median (IQR) ADA-TLs 0.41 μg/ml (0.10–0.71) statistically lower compared to those with negative Abs [8.86μg/ml (5.6–10.0) (p=0.0004)]. The correlations of ADA-TLs with disease characteristics, treatment and biomarkers in IBD patients are presented in Table 1. Elevated CRP was negatively associated with ADA-TLs. No other significant correlations were observed except a trend towards significance for body mass index (BMI) and ADA treatment duration (both p=0.09). After a median (IQR) follow up of 15 (11.5–16) months treatment optimization became necessary in 4 patients (8%) [adalimumab dose intensification in 2, change to a clinical trial medication in 1 and 1 underwent surgery] who initially had significantly lower ADA-TLs than the rest patients [median (IQR) ADA-TLs 0.51μg/ml (0.26-5.09-10.04) vs 8.62 (4.48–10.04); p=0.0362].

Conclusion
Proactive measurement of ADA-TLs and Abs in patients under maintenance treatment with adalimumab may be worth using along with other parameters in the management of IBD patients. Additional long term research in larger populations focused on the optimal use of proactive TDM is needed.
P491 Efficacy and safety outcomes of long-term treatment with filgotinib 200 mg among patients with Ulcerative Colitis: An interim analysis of SELECTIONLTE
Authors: Feagan Senior Scientific Officer B G , Matsuoka K , Rogler G , Faes M , Oortwijn A , de Haas A , Rudolph C , Patel H , Peyrin-Biroulet L 
Published: January 2022

Abstract

Background
Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor in development as an ulcerative colitis (UC) therapy. In the phase 2b/3 SELECTION trial, FIL 200 mg (FIL200) was well tolerated and effective in inducing and maintaining clinical remission vs placebo (PBO) in patients with UC.1 We assessed the efficacy and safety of continued FIL200 therapy in the SELECTION long-term extension (LTE) study.

Methods
The SELECTION programme comprised SELECTION (NCT02914522)1 and an ongoing LTE study, SELECTIONLTE (NCT02914535). Adults with moderately to severely active UC received induction (IND) FIL200 or FIL100 or PBO for 11 weeks in SELECTION. Patients in clinical remission or Mayo Clinic Score (MCS) response at week 10 (responders) could enter the 47-week Maintenance (MNT) Study. Patients who completed the SELECTION IND and MNT studies (completers), IND non-responders and patients with disease worsening during MNT could enter SELECTIONLTE. This interim analysis assessed the efficacy of open-label FIL200 among completers and non-responders in SELECTIONLTE up to LTE weeks 48 and 96, respectively. Partial MCS (pMCS) and achievement of the minimal clinically important difference (MCID) in total health-related quality of life (HRQoL) IBDQ score (≥16-point increase vs baseline) were assessed over time. Exposure-adjusted incidence rates per 100 patient-years of exposure (PYE) of treatment-emergent adverse events (TEAEs) and TEAEs of interest were assessed in patients treated with open-label FIL200 in the LTE.

Results
These analyses included 147 completers and 372 non-responders (IND FIL200, n=160; IND FIL100, n=212). Data were available for 136 completers at LTE week 48 and for 97 IND FIL200 and 139 IND FIL100 non-responders at LTE week 96. Among completers, the mean pMCS reductions observed in SELECTION were maintained up to LTE week 48 (Figure 1). Among IND FIL200 and FIL100 non-responders, mean pMCS decreased from LTE baseline to week 96 (Figure 2). The proportion of patients achieving the MCID in total IBDQ score increased over time among completers (IND week 10, 90.4%; LTE week 48, 96.1%) and IND FIL200 non-responders (LTE week 48, 60.6%; LTE week 96, 66.7%) (Table 1). Safety events among patients treated with open-label FIL200 in the LTE study (total PYE, 970.9) to the date analysed are reported in Table 2.

Conclusion
FIL200 was effective in maintaining long-term improvements in UC symptoms and HRQoL among patients who completed SELECTION. Among non-responders, initiating open-label FIL200 in the LTE study led to improvements in UC symptoms and HRQoL that were sustained over time. Safety events were as expected in the LTE study based on initial data.

Reference
1. Feagan BF et al. Lancet 2021;397:2372–84.
P512 Vedolizumab is effective in the prevention and treatment of postoperative recurrence in patients with Crohn′s disease
Authors: Kadleckova B , Podmanicky D , Lipovska A , Zelinkova Z 
Published: January 2022

Abstract

Background
Vedolizumab (VDZ), an anti-integrin monoclonal antibody has demonstrated its efficacy in inducing and maintaining response in patients with luminal Crohn`s disease (CD). Postoperative recurrence (POR) affects over half of the patients with CD and currently, majority of these patients undergo surgery due to primary or secondary failure of anti-tumor necrosis factor (antiTNF) biologics. Thus, data on efficacy of other agents in this setting are needed. Considering the slow onset of action of VDZ together with its favorable safety profile in older and co-morbid patients, VDZ would represent a good candidate for preventing and treating POR but the data on its efficacy in this specific clinical situation are scarce. Therefore, the aim of this study was to evaluate the efficacy of VDZ in preventing and treating of Crohn`s disease postoperative recurrence.

Methods
In this retrospective single-center cohort study, we included all patients with CD treated with VDZ between May 2015 and August 2020. Patients who started with VDZ immediately postoperatively or continued from the pre-operative period (prevention of POR) or patients who started VDZ because of clinical or endoscopic POR (treatment of POR) with a minimal follow-up of one year were eligible for further analysis. The effect of VDZ was determined by Harvey-Bradshaw Index ≤ 4 in case of prevention of POR, or as any decrease of 3 or more points in case of treatment of POR. Endoscopic response was evaluated by Rutgeerts` score as any decrease of the score. All patients underwent the colonoscopy at 6 months postoperatively and further follow-up colonoscopy one year after treatment adjustment.

Results
In the defined period, a total of 54 patients with Crohn`s disease were treated with VDZ. Of these 54 patients, sixteen (11 women; median age 57 years, range 25–75) receive VDZ for prevention (6) or treatment (10) of postoperative recurrence. Six patients received first-line VDZ due to high risk profile for systemic biologics (age and/or co-morbidities), the remaining ten patients all had previously failed at least one anti-tumor necrosis factor biologic agent.
During the median follow-up of 24 months (range 12 to 70), thirteen patients (81%) had clinical response or achieved remission, eleven (69%) had endoscopic response. Three patients with no response had to change the treatment to another biologic. Out thirteen responders, seven (54%) necessitated intensification of dosing regimen to every 4 or 6 weeks in order to achieve clinical and/or endoscopic response.

Conclusion
Vedolizumab is effective in preventing and treating of Crohn`s disease postoperative recurrence in a difficult-to-treat population of patients.