bluuebunny/crossref_metadata_2025 huggingface dataset:
P475 Profiling the use of Complementary Alternative Medicines among IBD patients
Authors: Sudhakar P , Stiers R , Dycker E D , Geens P , Paps A , Lambrechts T , Keersmaekers B , Sabino J , Ferrante M , Vermeire S , Verstockt B
Published: January 2022

Background

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease of the gut, characterized by multiple symptoms of which some cannot be successfully managed by existing conventional therapies. The use of complementary alternative medicines (CAMs) and CAM services among patients with chronic disorders including IBD has increased globally over the past several years (Rawsthorne Gut 2012; Weizman APT 2012). The main aims of this study were (a) to profile the use of CAMs and CAM services in a cohort of IBD patients being treated at a Belgian IBD referral center and (b) to identify the clinical and demographic factors associated with the use of CAMs.

Methods

An anonymized and customized Dutch version of the international questionnaire to measure the use of complementary and alternative medicine (I-CAM-Q – Quandt J Altern Complement Med 2009) was provided over an 8-week period spanning September and October 2021) to all IBD patients visiting the IBD outpatient clinic and infusion unit. Pearson’s Chi-square test was used to identify the relationships between clinical and demographic variables (age, gender, educational status) and CAM usage.

Results

From among the 410 IBD (144 UC, 253 CD) patients who responded to the survey, 173 (42.2%) were using CAMs or had used CAMs. A vast majority (79.8%) of the CAM using IBD patients reported the use of nature-based therapies (aloe vera, green tea, curcumin, cannabis, vitamin/mineral supplements and probiotics), a fifth of which was accounted for by Cannabis and its derivatives. This was followed by mind-body therapies (42.1%) (mindfulness, yoga, acupuncture, hypnotherapy, meditation). Two-thirds of patients (66.7%) mentioned to use CAMs for IBD-related symptoms. 125/173 of the CAM using IBD patients attributed the use of CAMs to their know-how about the potential of CAMs in ameliorating symptoms (32%), low efficacy or presence of adverse effects of conventional therapies (29.6%), minimize disease burden (28.8%) and avoiding surgery (7.2%). A vast majority (93.9%) of the CAM using IBD patients who responded to the query stated that consultation with their gastroenterologist would be beneficial to ascertain possible interference with their ongoing conventional therapy.

Conclusion

A significant proportion of IBD patients use CAMs to manage the complicated and often systemic symptoms of IBD. The most frequently used CAMs included nature-based therapies such followed by mind-body medicine. Given that CAMs are not officially regulated as medicinal therapies, their impact on conventional therapies is not entirely clear and should be further studied. Multi-center surveys profiling the use of CAMs in IBD patients as well as other chronic disorders are warranted.
P485 Apolipoprotein C3 is Downregulated in Patients with Inflammatory Bowel Disease
Authors: Hernandez Camba A , Carrillo Palau M , Ramos L , Alonso I , Vela M , Hernández A , Arranz L , Hernández N , Hernández-Guerra M , Ferráz I
Published: January 2022

Background

Inflammatory bowel disease (IBD) has been associated with an abnormal lipid profile. Apolipoprotein C3 (ApoC3) is a key molecule of triglycerides metabolism that is known to be related to inflammation and cardiovascular (CV) disease. In the present study, we aim to study if ApoC3 serum levels differ between patients with IBD and controls, and if the hypothetical disturbance of ApoC3 can be explained by IBD characteristics.

Methods

Cross-sectional study that included 405 individuals, 197 patients with IBD and 208 age- and sex-matched controls. ApoC3 and standard lipid profiles were assessed in patients and controls. A multivariable analysis was performed to analyze whether ApoC3 serum levels were altered in IBD and to study their relationship to IBD characteristics.

Results

After fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with IBD showed significant lower serum levels of ApoC3 (beta coef. -1.6 [95%CI -2.5- -0.7] mg/dl, p=0.001). Despite this, inflammatory markers, disease phenotypes or disease activity of IBD were not found to be responsible for this downregulation.

Conclusion

Apolipoprotein C3 is downregulated in patients with IBD.
P500 The use of budesonide results in lower risk for infections compared to systemic glucocorticoids
Authors: Pallmer K , Timeus S , Laoun R
Published: January 2022

Background

We analysed the occurrence of infections with individuals treated with either budenoside (locally acting) or systemically available glucocorticoids (GC); prednisolone, prednisone and methylprednisolone. The risk of infection was divided according to the origin; viruses, bacteria, fungi and parasites and we assessed which virus and bacterium caused the most side-effects between locally and systemically acting GC.

Methods

In this analysis, infection reported outcomes with GC drugs reported to FAERS (USA) were extracted and compared to approximately 25’000 drugs in the database. Odds ratio (OR) and 95% confidence interval (CI) for the association of infections between budesonide and systemic GC. The data were classified into virus, bacteria, fungi, parasites and non-defined infections. The number of reported side-effects were ranked from highest to lowest, the 20 most reported viral and bacterial infection were assessed, respectively. All related terms for one species were combined e.g. “SARS-CoV-2” and “Coronavirus”.

Results

The database contained 20’363 reports for budesonide, 35’452 for methylprednisolone, 60’516 for prednisolone and 102’982 for prednisone. Of these, a total of 4’465 concerned infection related AEs associated with the budesonide and 93’020 for systemic steroids. Bacteria and virus associated side-effects seemed to be more pronounced with the use of systemic GCs, while for fungal infections the risk was less prominent. Interestingly, budesonide users reported less parasite infections compared to systemically GC treated patients (Fig. 1). The highest number of infections of viruses and bacteria were analysed (generic terms such as “Viral infection” were excluded).The most frequent reported viral infections were Herpes Viruses followed by Influenza, Hepatitis B Virus and SARS-CoV-2. Budesonide treated individuals have a lower risk for virus infections, except for influenza, Adenovirus and Respiratory Synctial Virus (Fig. 2); there was a reduced risk for all bacterial infections in budesonide treated patients, compared to systemic GC. The most reported bacterial infections were Mycobacterium Tuberculosis, Escheria Coli and Clostridium Difficile (Fig. 3).

Conclusion

This unbiased analysis revealed that the use of budesonide was associated with a lower risk of infections of viruses, bacteria and parasites compared to systemic GC. In order to reduce the risk of infections, especially during the COVID-19 pandemic, inflammatory bowel disease patients should, where possible, switch from systemic GC to budesonide.
P504 Prospective analysis of micronutrient status and disease course in Inflammatory Bowel Disease
Authors: Brownson E , Saunders J , Gerasimidis K , Karafoulidou Z , Seenan J P , Macdonald J
Published: January 2022

Background

Biochemical deficiencies of iron, B12, vitamin D, vitamin K, folic acid, selenium and zinc are common in patients with Inflammatory Bowel Disease (IBD) and some micronutrient deficiencies have been associated with adverse disease outcomes. This study describes the micronutrient status of a cohort of patients on biologic therapy for IBD and explores the relationship with disease activity.

Methods

Adult patients with IBD on biologic therapy attending the nurse specialist clinic had 16 serum micronutrients measured alongside routine biochemical screening for disease activity. 12 months of follow up data was collected using electronic patient records. Faecal calprotectin (FCP), albumin and CRP were measured at baseline - patients in whom these biomarkers were within normal range (i.e CRP <10mg/L, albumin >35g/L and FCP <250µg/g) were defined as being in biochemical remission. Disease relapse at follow-up was defined as escalation of maintenance therapy, use of corticosteroid, hospital admission or surgery.

Relationships between micronutrient status and time to disease relapse were explored.

Results

216 patients (42% female, median age 42, IQR: 30–57) were included. 128 patients had Crohn’s disease (CD). 97 patients were in biochemical remission at enrolment.

12.9% of the total cohort were zinc (Zn) deficient and 6.5% were selenium (Se) deficient. Deficiencies of folate, vitamin C, vitamin B12, vitamin B6 and vitamin D were also prevalent within the cohort.

Se deficiency was associated with high CRP (p=.001), low albumin (p=.022), and raised FCP (p=.002) at baseline. Zn deficiency was associated with high CRP (p<.001) and low albumin (p<.001). During the 12 month follow up period, 22/216 patients suffered a disease relapse.

Patients with low Zn or low Se levels at baseline were significantly more likely to relapse (p=.007 and p=.019 respectively). In subtype analysis, patients with CD and Zn deficiency were significantly more likely to relapse (p=.003) but this was not the case for UC patients. Patients with UC and Se deficiency were significantly more likely to relapse (p=.001) whereas those with CD were not.

Conclusion

Zn and Se biochemical deficiencies are common in our cohort of IBD patients on biologic therapy and are predictive of subsequent disease relapse. Whether these signals are causal or a secondary effect of disease activity needs to be explored in future intervention studies.
P508 The impact of disease duration and early biologic treatment on transmural healing in Crohn’s disease
Authors: Revés J , Freire G , Sousa P , Primitivo A , Nascimento C , Morão B , Abreu N , Palmela C , Glória L , Torres J
Published: January 2022

Background

Although transmural healing (TH) has not yet been considered a formal target in CD, it is considered a desired goal, as it seems to be associated with better outcomes. Early biologic treatment has been shown to lead to higher clinical remission and increased endoscopic healing. However, to date, there is no information on the impact of disease duration on TH. We aimed to assess the efficacy of early biologic treatment on the achievement of TH.

Methods

Unicentre retrospective cohort study comparing patients who started early and late biologic therapy (defined as ≤ 12 months vs > 12 months from diagnosis). We included patients with CD who were receiving biologic therapy, and had a baseline computed tomography enterography (CTE) or magnetic resonance enterography (MRE) before the initiation of a biologic (median 2.5, IQR 0–50 months), and a follow-up CTE/MRE performed 12 ± 6 months after therapy initiation. Endoscopic healing was defined as a SES-CD score <3. Three experienced radiologists blinded to the therapeutic group reviewed every CTE and MRE and assessed several pre-defined parameters of cross-sectional inflammation. TH was defined as the absence of active inflammation, extra-enteric signs, and CD-related complications (strictures, fistulas or abscesses). The effect of early biologic treatment on transmural healing was analysed using logistic regression.

Results

60 patients were included (51.7% males), with a median age at diagnosis of 24.5 years old (IQR 17.5–32.5). Most patients had ileocolonic disease (58.3%) and non-stricturing non-penetrating phenotype (60%). Twenty-eight patients (46.7%) started biologic therapy within the first 12 months of diagnosis. There were no significant differences in baseline clinical features or baseline radiologic assessment between the groups, except for the extension of the most affected segment, which was higher in the group of late biologic therapy (197 vs 129.5mm, p=0.05) (Table 1). Patients on early biologic treatment achieved endoscopic healing more frequently than those on late biologic treatment (65.4% vs 23.3%, p=0.002). Early biologic treatment was also associated with increased transmural healing (OR 4.1, 95% CI 1.2–13.6, p=0.02). In a multivariate model including baseline characteristics of the disease, only the use of biologics within the first 12 months and the absence of ileocolonic disease were significant predictors of the achievement of transmural healing (Figure 1).

Conclusion

Early biologic treatment seems to be independently associated with higher transmural healing rates, further adding to the relevance of early intervention in CD. Our findings are limited by the small sample size and short follow-up.
P522 Upadacitinib Promotes Histologic and Endoscopic Mucosal Healing: Results from the Upadacitinib Ulcerative Colitis Phase 3 Program
Authors: Peyrin-Biroulet L , Siegel C , Tanida S , Bossuyt P , Torres E , Dubinsky M , Baert F , Zhou W , Klaff J , Berg S , Laroux F S , Sanchez Gonzalez Y , Yao X , Zhou Q , Reinisch W
Published: January 2022

Background

Upadacitinib (UPA), an oral selective and reversible JAK inhibitor, demonstrated significantly greater efficacy compared to placebo (PBO) as treatment for moderate to severe ulcerative colitis (UC), in phase 3 induction (U-ACHIEVE and U-ACCOMPLISH) and maintenance (U-ACHIEVE Maintenance) studies. We evaluated UPA efficacy on histologic outcomes with or without endoscopy in this phase 3 program. The STRIDE II initiative identified histological healing as a treatment target signaling the importance of histologic endpoint inclusion in clinical trials and practice.

Methods

The UC phase 3 program were multicenter, double-blind PBO-controlled trials. Induction studies enrolled adult patients with moderate to severe active UC (defined as Adapted Mayo Score of 5–9 points and a centrally reviewed endoscopy subscore of 2–3), with randomization 2:1, UPA 45mg (UPA45) once daily (QD) or PBO. Patients eligible for U-ACHIEVE Maintenance primary analysis (N=451) were clinical responders (per Adapted Mayo score) to 8-weeks (wks) of induction treatment with UPA45. U-ACHIEVE Maintenance patients were randomized 1:1:1 UPA 15mg QD (UPA15): UPA 30mg QD (UPA30): PBO for 52 wks. Endpoints were assessed at wk 8 and/or 52: histological improvement, histologic remission, histologic endoscopic mucosal improvement (HEMI), and mucosal healing (a more stringent endpoint defined as endoscopic score=0 and Geboes score<2.0). For endpoint definitions, see Tables 1 and 2.

Results

Baseline characteristics were similar at wk 0 of induction or maintenance studies. In U-ACHIEVE Induction, patients treated with UPA45 demonstrated a significant increase in histologic improvement (55.0% vs 22.5%), HEMI (30.0% vs 6.6%), and mucosal healing (10.7% vs 1.3%); compared to PBO-treated patients (p< 0.001 for all endpoints, Table1). In U-ACCOMPLISH, patients treated with UPA45 experienced superior efficacy in histologic improvement (62.2% vs 24.5%), HEMI (36.7% vs 5.8%), and mucosal healing (13.5% vs 1.7%) compared to PBO-treated patients (p<0.001 for all endpoints). Significantly higher percentages of patients that received UPA15 and UPA30 (42.8% and 56.9%) at wk 52 demonstrated increased histological improvement compared to PBO-treated patients (20.6%; p<0.001). In addition, patients treated with UPA15 and UPA30 demonstrated superior HEMI (UPA15 34.8%; UPA30 49.3%; PBO 11.8%, p<0.001) and mucosal healing rates (UPA15 17.6%; UPA30 19.0%; PBO 4.7%; p<0.001 for both endpoints).

Conclusion

UPA induction and maintenance treatment achieved superior efficacy compared to PBO for all histologic and endoscopic assessments including mucosal healing. [Clinicaltrials.gov, U-ACHIEVE Induction and Maintenance (NCT02819635) and U-ACCOMPLISH (NCT03653026)]
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

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<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

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

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<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

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 <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

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

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<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

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

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

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.
P621 Secure Electronic Document Signing Uptake in Biologic Prescribing for Immune Mediate Diseases
Authors: Sharma S , Jones J , Stewart M
Published: January 2022

Background

The COVID-19 pandemic drastically impacted workflows in gastroenterology practice. Physicians managing immune-mediated diseases (IMDs) must complete special authorization (SA) and prescription renewal (Rx) forms for patients on biologic therapy. This adds significant administrative burden potentially leading to delays in therapy initiation and care continuity. Historically, document completion has largely been paper-based, with forms faxed between patient support programs (PSPs) and physician offices. The use of secure electronic document signing (SEDS) platforms during the pandemic has allowed physicians to receive and complete documents digitally. The aim of the project was to evaluate the impact of SEDS-based biologic documentation on clinical practice in order to 1) Determine if the use of SEDS platforms increased timeliness of document returns compared to traditional workflows 2) Assess whether SEDS usage is acceptable and sustainable and 3) Assess MD satisfaction with SEDS platforms.

Methods

This was a retrospective audit of SEDS and paper-based biologic document workflows from a single PSP (Abbvie Care). Outcomes of interest were the number of documents completed monthly using SEDS, new monthly users, and the number of active monthly users between April 1, 2020-March 31, 2021. Time (days) to SEDS completion (vs. paper process) was determined by reviewing timepoint data for SA and Rx documents from May 2019-January 2020 (‘pre- SEDS’) and for SEDS documents from May 2020-January 2021(‘SEDS’). The return time (RT) was defined as the time between date sent to a physician’s office by the PSP to the date returned to the PSP. Documents in the pre-SEDS cohort with a RT exceeding 30 days were excluded.

Results

In total, 5573 SA and Rx documents were completed by 383 physicians using the SEDS platform from April 2020-March 2021. A mean of 14.6 (sd 21.8) documents were signed per physician. The number of monthly electronic documents processed increased from 104 in April 2020 to 800 in March 2021. Active monthly users increased from 24 in April 2020 to 213 in March 2021 (31 new users monthly). A total of 19,387 paper documents were processed during the ‘pre-SEDS’ period and 3,317 electronic documents processed in the ‘SEDS’ period. The mean RT in the ‘pre-SEDS’ period was 8.03 days (sd 8.2) and the ‘SEDS’ period was 1.11 days (sd 2.6).

Conclusion

This data demonstrates acceptability, appropriateness, and improved processing efficiency of an SEDS platform improving timeliness of patient care. Next steps in this research include surveying physicians to understand the work-flow impact of SEDS, functionality, long-term sustainability, satisfaction and impacts on disease related outcomes.
P626 Anti-TNF monotherapy is associated with an adverse clinical outcome in female Inflammatory Bowel Disease patients who stop Anti-TNF treatment during the third trimester of pregnancy
Authors: Lastiri E , Herrera-De Guise C , Casellas F , Mayorga L , Robles V , Cespedes E , Perez Z , Oller E , Borruel-Sainz N
Published: January 2022

Background

Anti-TNF drugs are safe during pregnancy in inflammatory bowel disease (IBD), but they cross the placenta most actively in the third trimester, and some guidelines still recommend stopping them during this period. There few data that examines the impact of anti-TNF discontinuation on the clinical course of IBD, so we aimed to explore the clinical outcomes of IBD pregnant patients who stopped anti-TNF at the third trimester.

Methods

We performed a retrospective, longitudinal study on female IBD patients receiving anti-TNF agents at our IBD clinic. We included IBD pregnant patients who discontinued the anti-TNF in the third trimester of pregnancy, and we matched these cases in a 1:1 ratio with non-pregnant female IBD patients by age, type of IBD, type of anti-TNF, duration of treatment, location, and behavior of IBD. Demographic and clinical variables were collected from 18 months before anti-TNF discontinuation and 12 months after discontinuation, and when available endoscopic indices (SES CD and UC). We determined whether subjects presented any adverse clinical outcome during the follow-up defined as development of disease flare, corticosteroid use, hospital admission, need for surgery, biologic dose escalation, or switch.

Results

We included 34 pregnant patients and 34 controls. Patients who stopped anti-TNF more frequently presented an adverse clinical outcome during the follow-up year when compared to the control group (47.1% vs. 23.5% p = 0.04) and flare activity (35, 3 vs. 11.8%, p = 0.02). We found no differences in escalation or biologic switch, hospital admission, or surgery between the subjects. We also found an association between the development of an adverse clinical outcome and anti-TNF monotherapy (p=0.009) and a higher SESCD in the previous year (p=0.017). In the multivariate analysis, anti-TNF monotherapy was the only independent factor for developing an adverse clinical outcome up to 1 year after anti-TNF discontinuation (OR: 3.47, CI 95%: 1.16–10.4, p=0.026).

Conclusion

In our cohort of female IBD patients on anti-TNF, monotherapy was independently associated with an adverse clinical outcome in the following year after anti-TNF discontinuation.
P640 Incidence, prevalence, disease phenotype and maximal therapeutic step in Crohn’s disease patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem county cohort
Authors: Lakatos L , Gonczi L , Golovics P , Pandur T , David G , Erdelyi Z , Szita I , Lakatos P L
Published: January 2022

Background

The number of epidemiological population-based studies are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to analyze the incidence and disease phenotype at diagnosis, and the maximal therapeutic step distributions during follow-up in a prospective population-based database from Veszprem Province, including incident Crohn’s disease (CD) patients diagnosed between January 1, 2007 and December 31, 2018.

Methods

Data of 421 incident CD patients were analyzed (male/female: 237/184; median age at diagnosis: 29 years(y) [IQR: 21–42]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The source of age- and gender-specific demographic data was derived from the national population census in 2011.

Results

Adjusted mean incidence rate was 9.94(CI95%: 9.0–10.9)/105 person-years in this 12 year period[males:11.5(CI95%:10.2–13.2)/105; females:8.4(CI95%:7.3–9.7)/105]. Prevalence rate was 191.18(CI95%:177.0–205.7)/105 persons in 2011 and 236.78(CI95%:220.8–252.8) in 2015. For detailed annual incidence rates and age-specific mean incidence rates see Figure1 and 2. Peak onset age in CD was 20–29 years of age. Diagnostic delay from symptom onset was ≥1year in 26.6%, and ≥3 years in 10% of the patients. Disease location was ileal(L1) in 29.7%, colonic(L2) in 24.5%, and ileo-colonic(L3) in 45.8% at diagnosis. Upper gastrointestinal manifestation or perianal disease were present in 7.6% and 13.5%. Disease behavior at diagnosis was luminal(B1) in 62.5%, stenosing(B2) in 17.6%, penetrating(B3) in 16.4%, and B2+B3 in 3.6%. Patients with ileocolonic disease were younger (29.2y,SD:14.6) at diagnosis compared to patients with ileal(35.7y,SD:15.5;p<0.001) or colonic disease(37.7y;SD:18.1;p<0.001). Extraintestinal manifestations were as follows: hepatic5.0%(PSC 1.9%), arthritis13.8%, ocular1.7%, cutan4.3%. Active smokers at diagnosis were 35.4%. Distribution of maximal therapeutic steps during the course of follow-up (8.53y,SD: 3.3) were 5-ASA in 15.7%, systemic corticosteroids in 14.3%, immunosuppressive therapy in 42.5%; anti-TNF biologic therapy in 23.3% and other biologic therapy in 2.9%.

Conclusion

The incidence of CD in this 12 year period was high, comparable to high-incidence areas in Western European countries, and comparable to previous data from the Veszprem cohort, while prevalence rates continue to rise.(Lakatos 2011, IBD). Ileocolonic location and penetrating disease behavior were somewhat higher compared to previous population-based data from Western Europe.(Burisch 2018, JCC).