bluuebunny/crossref_metadata_2025_split huggingface dataset:
P531 Stringent screening strategy significantly reduces reactivation rate of Tuberculosis in Patients with Inflammatory Bowel Disease on anti-TNF therapy in a TB endemic region
Authors: Kumar P , Vuyyuru S K , Kante B , Sahu P , Goyal S , Madhu D , Jain S , Ranjan M K , Mundhra S , Golla R , Singh M , Virmani S , Gupta A , Yadav N , Kalaivani M , Sharma R , Das P , Makharia G , Kedia S , Ahuja V 
Published: January 2022

Abstract

Background
Anti-tumour necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB) reactivation despite LTB screening, especially in TB endemic regions. We evaluated the effect of stringent screening strategy and latent tuberculosis (LTB) prophylaxis on TB reactivation.

Methods
We performed an ambispective comparison between patients who were started on anti-TNF therapy after January 2019 (Cohort A) and between Jan 2005-Dec 2018 (Cohort B). Cohort A patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy.

Results
One hundred seventy-one patients (63-Ulcerative colitis/108-Crohn’s disease; mean age diagnosis-28.5±13.4 years; 60% males; median follow-up duration after anti-TNF:33months [interquartile range, 23–57 months]) were included. Among 112 in Cohort B 22(19.6%) had LTB and 19(17%) developed TB. In comparison, 26(44%) had LTB and only 1(1.7%) developed TB in Cohort A (p&lt;0.01). On survival analysis, patients in Cohort B had a higher probability of TB reactivation compared to Cohort A at 5 years of follow up, HR-14.39 (95% CI,1.88- 109.81[p=0.010]) after adjusting for gender, age at anti-TNF therapy initiation, concomitant immunosuppression, the total number of anti-TNF doses and therapy escalation.

*Log rank p value=0.006
Figure 1: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who were started on anti- TNF therapy till January 2019 (Cohort B) and those who were started on anti-TNF after January 2019 (Cohort A).

*Log rank p value=0.02
Figure 2: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who had incomplete latent TB screening and those with complete TB screening.

Conclusion
The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.
P539 COVID-19 is Associated with Long-term Elevated Fecal Calprotectin Levels in Patients with Crohn’s Disease but not in Ulcerative Colitis
Authors: Shafrir A , Benson A A , Zinger A , Shauli Aharonov M , Katz L H 
Published: January 2022

Abstract

Background
Data regarding the long-term effects of COVID-19 on patients with Inflammatory bowel disease is scarce. Fecal calprotectin (FC) correlates with IBD clinical and endoscopic activity. We compared fecal calprotectin levels between patients with COVID-19 to a control group tested negative to SARS-CoV-2.

Methods
We gathered data from a large health medical organization in Israel of insured individuals who underwent a SARS-COV-2 PCR test from March 1, 2020, to December 31, 2020. Among patients with IBD, data regarding fecal calprotectin taken 30–365 days before SARS-CoV-2 testing was gathered. We compared fecal calprotectin levels taken at least 30 days following COVID-19 infection to those who tested negative.

Results
1924 Crohn’s disease (CD) patients and 949 Ulcerative Colitis (UC) patients were tested for SARS-CoV-2. 322 (16.7%) were tested positive in the CD group and 114 (13.7%) in the UC group.
Pre-COVID-19 calprotectin levels did not show statistically significant differences between patients who ended up testing positive for SARS-CoV-2 and those who tested negative in CD (377 ±759.08 vs. 451.84±869, p-value = 0.4) and in UC (466.93±766.69 vs. 617.91 ±1243.99 p-value=0.37). Post-COVID-19 fecal calprotectin was higher among patients with CD who were tested positive than those who tested negative for SARS-CoV-2 (617.42±832.68 vs. 355.94±1207.46, p value=0.04). In a multivariate linear regression controlling for age, gender, BMI, smoking status, and pre-COVID-19 fecal calprotectin, SARS-CoV-2 positivity was associated with higher fecal calprotectin levels (p value=0.03). In contrast, there was no statistically significant change in fecal calprotectin levels among patients with UC and SARS-CoV-2 positivity (547.2±1089 vs.458.32± 689 p value=0.9). In a 2:1 propensity score-matched cohort (n=264), calprotectin levels were higher among patients with CD who suffered from COVID-19 compared to controls (657.64 vs. 384.94 p-value = 0.03)

Conclusion
Patients with CD who had COVID-19 have higher FC levels compared to similar CD patients who did not have COVID-19. This finding was not found in patients with UC.
P558 Should we introduce early a new biological agent in patients with Inflammatory Bowel Disease after anti-TNF discontinuation due to severe anti-TNF-induced skin lesions? A multicenter cohort study
Authors: Cottron C , Treton X , Altwegg R , Reenaers C , Amiot A , Fumery M , Vuitton L , Peyrin-Biroulet L , Bouguen G , Dewit O , Nancey S , Caillo L , Roblin X , Beylot-Barry M , Rivière P , Laharie D 
Published: January 2022

Abstract

Background
Data to manage patients with Inflammatory Bowel Disease (IBD) after anti-TNF discontinuation due to severe induced skin lesions are scarce. Our study aimed to assess dermatological and IBD outcomes after discontinuation of an anti-TNF agent related to skin side effects.

Methods
We conducted a multicenter retrospective study including consecutive IBD patients who discontinued anti-TNF due to induced skin lesions. Objectives were to determine factors associated with remission of induced skin lesions and with IBD relapse in patients with inactive disease at inclusion, particularly the impact of early introduction of a new biological agent within three months of anti-TNF discontinuation.

Results
Among the 181 patients (134 women, 160 Crohn’s disease) included in the 13 participating centers, 99 (55%) started a new biological agent within the first three months that was mainly ustekinumab in 75% of them. Remission of induced skin lesions occurred in 110 (62%) patients with a median [interquartile range (IQR)] interval of 8.0 (6.8–11.0) months since anti-TNF discontinuation. Scalp location was independently associated with a reduced risk of remission of induced skin lesions [HR 0.64 (95%CI 0.43- 0.94), p=0.02] while early biological therapy was independently associated with a higher probability of remission of skin lesions [HR 1.64 (95%CI 1.1–2.5), p=0.02]. Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 (51%) patients with a median (IQR) interval of 26.0(23.0–39.1) months. Survival rates without IBD relapse at 1 year were 85.8% (95%CI 77.5–94.9) in the early introduction group and 59.3% (95%CI 48.9–71.9) in the other group (p&lt;0.01).

Conclusion
Early introduction of a new biological is associated with higher probability of healing of anti-TNF-induced skin lesions and significantly reduces risk of IBD relapse.
P562 A Phase 1 Study Evaluating the Effect of Coadministration of Etrasimod on the Pharmacokinetics and Pharmacodynamics of a Monophasic Oral Contraceptive in Healthy Female Volunteers
Authors: Lee C , Tang Y , Villa-Caballero L , Liu K , Randle A , Grundy J 
Published: January 2022

Abstract

Background
Etrasimod (ETR) is a once-daily (QD), oral, selective sphingosine 1-phosphate receptor modulator in clinical development for immune-mediated inflammatory disorders including inflammatory bowel disease (IBD) and atopic dermatitis. At diagnosis, ~50% of patients with IBD are &lt;35 years old. Oral contraceptives (OC) are the most common birth control among women in the US. It’s important to ensure an IBD therapy does not impact the pharmacokinetic (PK)/pharmacodynamic (PD) performance of the OC. This study evaluated the effect of coadministration of ETR on the PK/PD performance of a monophasic OC.

Methods
This open-label Phase 1 study enrolled 21 premenopausal healthy female adults (18–40 years). On Days 1–21 of Period 1 (Days 1–28), participants received OC containing 30mcg ethinylestradiol (EE) and 50mcg levonorgestrel (LVG). On Day 23, participants initiated ETR 2mg QD such that steady-state concentrations were achieved by Day 28 and thereafter. On Days 29–49 of Period 2 (Days 29–50), the OC was coadministered with ETR 2mg QD. Samples for measuring the pharmacologically active components of the OC (EE and LVG) were collected over 24 hours on Days 21 and 49. Log-transformed primary PK parameters were calculated and compared using analysis of variance with treatment as fixed effect and participant as random effect. PD markers (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone) were measured at baseline (Days 1 and 29) and throughout Periods 1 and 2. Largest ovarian follicle size measured by transvaginal ultrasound (TVUS), sex hormone–binding globulin (SHBG) levels, and Hoogland score were measured on Days 1 (before OC dosing), 11, 29 (before OC+ETR dosing), and 39. Safety and tolerability were also evaluated.

Results
Only minor-to-mild increases in EE and LVG Cmax,ss and AUCtau,ss exposure measures were observed when the OC was coadministered with ETR vs when the OC was administered alone (Table). These changes were not considered clinically relevant. Markers of ovarian activity (FSH, LH, estradiol, progesterone, SHBG, TVUS/Hoogland score) demonstrated no clinically relevant impact of coadministration of ETR on the PD performance of the OC. All treatments were generally well tolerated. Most treatment-emergent adverse events (AEs) were mild or moderate; 2 participants had severe AEs. No abnormalities in laboratory parameters, vital signs, or 12-lead electrocardiogram assessments were noted.

Conclusion
The PK/PD performance of the monophasic OC was not altered to a clinically relevant extent; thus contraceptive efficacy was maintained during coadministration with ETR. ETR and the monophasic OC, administered alone or in combination, were generally well tolerated.
P569 Fecal Microbiome Transplantation for Recurrent C. difficile Colitis: Treatment Efficacy, Short and Long-term Follow-up Results from Consecutive Case Series
Authors: Urbonas T , Ianiro G , Gedgaudas R , Sabanas P , Urba M , Kiudelis V , Kiudelis G , Petkevicius V , Vitkauskiene A , Cammarota G , Gasbarrini A , Kupcinskas J 
Published: January 2022

Abstract

Background
Many studies have shown a high effectiveness of fecal microbiota transplantation (FMT) in treatment of recurrent or refractory Clostridioides difficile infection (CDI). Nevertheless, data on long term outcomes and complications after FMT are still lacking. We aimed to evaluate the efficacy, the peri- procedural safety profile and the long-term efficacy and safety of FMT for recurrent CDI during a median follow up period of 24 months.

Methods
Our study included 60 consecutive patients that were treated from 2015 to 2019 for recurrent CDI. In all patients FMT was performed through the nasoenteric tube placed during upper GI endoscopy. Fresh donor feces were used for FMT from unrelated donors. Pre-FMT preparation included CDI treatment with oral vancomycin 500 mg q.i.d. for at least five days and proton pump inhibitor (PPI) administration before FMT. Follow up data included information about recurrent CDI episodes, early and late complications, health status at 3, 12 and 24 months after FMT.

Results
FMT was performed for 60 patients (median age 72.5 years) with recurrent CDI. Clinical improvement after the first FMT procedure was observed in 48 patients (80%). Ten of 12 initially non-responding patients had a clinical resolution after a second FMT leading to an increased overall cure rate of 96.7 %. The remaining two patients needed a third FMT with a final overall cure rate of 100%. Nine of 60 patients were under immunosuppressive therapy. Six immunosuppressed patients were in the group of initial responders and the remaining three in the initially non-responder group. We observed a very low rate of adverse events in the short and long-term after FMT. During the first eight weeks after the FMT procedure, the death of three patients occurred, but they were not related to the FMT procedure. Patients were followed up for a median of 20 months, with the range from 12 to 55 months. During the follow-up period no long-term serious adverse events (SAE) were documented.

Conclusion
Our study confirms excellent efficacy rates of FMT in the treatment of recurrent CDI. In addition, this study shows that it is possible to avoid short term SAE when FMT is administered via a nasoenteric tube by following a very stringent peri-procedural patient follow-up protocol. Our study also demonstrates good safety with a low rate of long-term adverse events after FMT.
P586 Surgical recurrence in Crohn’s Disease: Can we prevent it?
Authors: Botto I , Serrazina J , Coelho Rodrigues I , Fernandes S , Bernardo S , Gonçalves A R , Moura Santos P , Valente A , Correia L , Tato Marinho R 
Published: January 2022

Abstract

Background
Crohn’s Disease (CD) is a chronic inflammatory disease primarily affecting the bowel. In the pre-biological era, approximately 40–50% of patients would undergo surgery within the first 2 decades after diagnosis, with a risk of postoperative recurrence up to 50% at 10 years. Although post-operative prophylaxis is recommended to prevent clinical and endoscopic recurrence, little is known about the factors associated with surgical recurrence.

Methods
Single-center, retrospective study including 992 patients with CD. Demographic and clinical data were retrieved from patients’ medical charts. Patients with 1 or more surgeries were selected for analysis, excluding perianal disease surgeries. Thiopurines and biologics were considered as prophylaxis for surgical recurrence only if initiated within the first year after surgery. A logistic regression analysis was performed to evaluate potential predictors of surgery recurrence.

Results
Three hundred and nine patients (31.1%) required at least one surgery during follow-up. Two hundred and twenty-four patients (72.5%) underwent a single surgery and 85 (27.5%) required two or more interventions. Patients with surgical recurrence were younger [31 (23–36) vs 34 years (24–44), p=0.009], and had lower rates of prophylaxis with thiopurines (23.5% vs 37.5%, p=0.013), and anti-tumor necrosis factor (TNF) agents (8.2% vs 22.3%, p=0.002) compared with patients without surgical recurrence. Multivariate analysis identified stricturing and penetrating phenotype as risk factor for surgical recurrence (OR 2.292 95%CI [1.500–3.502], p&lt;0.001]). Likewise, older age (OR 0.949 95%CI [0.94–0.996], p=0.034), and prophylaxis with anti-TNFs (OR 0.309 95% [0.126–0.754], p=0.01) were protective factors against surgical recurrence. Twenty-five patients (29.4%) developed a second surgical recurrence. Patients with more than one surgical recurrence had lower utilization of thiopurines (16% vs 45%, p=0.009) and anti-TNFs (0% vs 26.7%, p=0.002).

Conclusion
Our findings suggest that postoperative prophylaxis with immunosuppressants, especially anti-TNFs, significantly reduces the risk of surgical recurrence. Postoperative prophylaxis should be implemented in high-risk patients, especially younger patients and those with a non-inflammatory phenotype.
P594 Vedolizumab dose intensification does not always improve treatment persistence
Authors: Hilley P , Peterson A R , Wong D , Hine K , Srinivasan A , Choy M C , De Cruz P 
Published: January 2022

Abstract

Background
Vedolizumab is effective in inducing and maintaining remission in patients with both Crohn’s Disease (CD) and ulcerative colitis (UC). Recent data has demonstrated that there is superior persistence with vedolizumab compared to anti-TNF biologics. However, the efficacy of dose intensified vedolizumab remains uncertain. We aimed to assess whether vedolizumab dose intensification resulted in a meaningful improvement in treatment persistence and to determine whether there were any clinical, biochemical or endoscopic parameters that were associated with a response to dose intensification.

Methods
A retrospective analysis of all patients with CD or UC that had received dose intensified vedolizumab every 4 weeks, was undertaken at an Australian tertiary, metropolitan IBD service between the 1st of July 2015 and 15th of November 2021. Electronic medical records were reviewed to retrospectively calculate the partial Mayo score (pMS) for UC and Harvey-Bradshaw Index (HBI) for CD, as well as document the C-Reactive Protein (CRP), Faecal Calprotectin (FC) and endoscopic disease assessment. Data were obtained at commencement of vedolizumab, time of dose escalation, as well as at 6 and 12 months post escalation. The primary outcome was treatment persistence at 6 months post escalation.

Results
A total of 33 patients required dose intensification to address primary non-response or secondary loss of response. Median time to escalation was 9 months (IQR 3–14). 11/33 (33%) remained on escalated dosing at the end of the study period. 4/11 (36%) were escalated prior to, and 7/11(32%) after week 14. Escalated therapy was continued for a median of 5 months (IQR 3–12).
Treatment persistence was 45% at 6 months, and 24% at 12 months. In patients who had vedolizumab ceased at 6 months post escalation, there was a rate of clinical activity of 93%, biochemical activity of 93% and endoscopic activity of 100%. For those maintained on vedolizumab at 6 months post intensification the rates were 50% for both clinical and biochemical activity. No clinical/biochemical/endoscopic parameters were associated with response and no statistically significant difference was noted in disease activity following escalation.

Conclusion
There was a low rate of treatment persistence for patients undergoing vedolizumab dose intensification. Rates of disease activity at the time of cessation for patients who discontinued vedolizumab were high. Dose intensification of vedolizumab may not capture response nor translate into treatment persistence. Further prospective studies examining vedolizumab levels and dose intensification are warranted but these data suggest a low threshold for switching to alternative agents if response cannot be captured within 6 months of dose escalation.
P602 Tofacitinib treatment prevents post-operative recurrence of Crohn’s Disease modeled by ileocecal resection in HLA-B27 transgenic rats
Authors: Blondeaux A , Speca S , Valibouze C , Lambin T , Dubuquoy C , Titecat M , Genoscreen L , Neut C , Genin M , Zerbib P , Foligne B , Desreumaux P 
Published: January 2022

Abstract

Background
Post-operative recurrence (POR) after ileocecal resection (ICR) affects most of Crohn’s disease (CD) patients. Immunomodulatory treatments have not proven efficiency in preventing POR except for anti-TNFα biologic agents. We evaluate the efficacy of the JAK inhibitor Tofacitinib to prevent POR after ICR in HLA-B27 transgenic rat model (TgB27).

Methods
Thirty-three rats (strain F344, 29 TgB27, 4 control non Tg (nTg) rats) were operated on an ICR at the 12th week (W12) of life and were sacrificed at W18. Tofacitinib (15 mg/kg, n=17) or placebo (n=16) were daily administered by oral gavage at W10 until W18. Anastomotic recurrence were blindly analyzed using macroscopic (from 0 to 4) and histologic (from 0 to 6) scores. Luminal microbiome was analyzed by shotgun metagenomic sequencing (Hiseq Illumina) in 9/33 rats before (W9) and after Tofacitinib treatment or placebo (W12 and W18). STAT3 phosphorylation was quantified in ileal samples by western blotting. Data were expressed by median with IQR. Comparisons were performed using not parametric two tailed Mann-Whitney analysis for unmatched data and Wilcoxon matched-pairs test for matched data. Two tailed χ2 test was used for contingency analysis. Spearman rank correlation was used for microbiota analysis.

Results
8/14 TgB27 rats receiving placebo (57%) showed signs of POR (macroscopic score ≥ 2) which were significantly prevented in 2/15 TgB27 rats (13%) treated with Tofacitinib (p= 0.013). nTg animals did not show macroscopic signs of POR. Macroscopic lesions were located 2 cm around the anastomosis in the TgB27 placebo group and consisted in ulcerations with a score of 2 (1–2.25). 11/15 TgB27 rats (73%) treated with Tofacitinib did not show macroscopic lesions and their score were significantly improved (0 (0–1), p= 0,0006). Histologic scores were significantly higher in TgB27 placebo group vs TgB27 Tofacitinib-treated rats (3 (2–4) vs 2 (1–3), p=0.036). Tofacitinib did not impact on alpha diversity and the relative abundance of bacterial taxa either before and after surgery. In contrast, surgery led to a significant 47% decrease of alpha diversity (p=0.0008) and loss of specific taxa in both TgB27 and nTg animals. No correlation was found between individual lesion scores and alpha diversity indexes. Ileal pSTAT3/STAT3 ratios were decreased by 80% in TgB27 rats treated with Tofacitinib (n=4) compared to placebo group (n=4) (0.3 ± 0,16 vs 1.58 ± 0,3, p=0,028).

Conclusion
We develop a reliable model of ICR in TgB27 rats mimicking the POR of CD. Tofacitinib prevents the macroscopic and histologic POR after ICR, without major modifications of the microbioma.
Acknowledgments: Charity Foundation DigestScience and Pfizer SAS
P604 Infection Risk in Elderly Patients with Inflammatory Bowel Disease under anti-TNF, ustekinumab or vedolizumab biologic therapies: A Prospective Multicenter observational One-Year follow-up comparative study
Authors: Bozon A , Serrero M , Caillo L , Gilletta C , Benezech A , Nancey S , Combes R , Danan G , Akouete S , Pages L , Bourgaux J F , Boivineau L , Meszaros M , Altwegg R 
Published: January 2022

Abstract

Background
The emergence of biologics has significantly improved the course of inflammatory bowel diseases (IBD) despite a potential higher risk of infections. Use of biologics in the elderly population remains a challenge since elderly patients are at higher risk of infection. Anti-tumor necrosis factor (anti-TNF), vedolizumab and ustekinumab are all potentially susceptible to increase the risk of infection. We conducted a one-year, prospective, multicenter, observational study comparing the respective infectious risk under anti-TNF, vedolizumab or ustekinumab in elderly patients with IBD.

Methods
All IBD patients over 65 years, from six medical centers and receiving anti-TNF (first group), vedolizumab or ustekinumab (second group, defined as new biologics) treatment were included. The primary endpoint was the prevalence of at least one infection during follow-up. The cumulative risk of severe infection requiring hospitalization was recorded.

Results
The study included 207 consecutive patients, 113 under anti-TNF and 94 patients under vedolizumab or ustekinumab (median age 71 years, 112 with Crohn’s disease and 95 with ulcerative colitis). There was no difference concerning combination therapy, steroids use and the Charlson index between the two groups. The prevalence of infections was similar in patients under anti-TNF (29%) and in those under vedolizumab and ustekinumab (28%) (p=0.81). There was no difference in terms of type of infection, infection-related hospitalization (7% vs 6.4%), antibiotic prescription and treatment efficacy between the two groups. In patients over 75 years of age (n=50), the prevalence of infections was comparable in both groups.

Conclusion
Around 30 % of elderly patients with IBD under biologics experienced at least one infection during the one-year study period. The risk does not differ between patients treated with anti-TNF and those under vedolizumab or ustekinumab.