bluuebunny/crossref_metadata_2025_split huggingface dataset:
P510 Comparative efficacy of biologic therapies for inducing response and remission in fistulizing Crohn’s disease; Systematic Review and Network Meta-analysis
Authors: Shehab M , Alrashed F , Heron V , Restellini S , Bessissow T 
Published: January 2022

Abstract

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

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

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

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

Abstract

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

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

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

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

Abstract

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

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

Results
The systematic search identified 79 eligible studies, including a total of 2,830 and 2,381 bio-naïve patients with UC and CD, respectively, compared with 7,392 and 10,511 bio-exposed patients, respectively. The mean NOS score was 6.0 and 6.1 in UC and CD, respectively. Meta-analysis showed that bio-naïve patients with UC more frequently achieved clinical remission at week 14 (risk ratio (RR)=1.27 [95% confidence interval (CI) 1.00, 1.62]) and week 52 (RR=1.25 [95% CI 1.11, 1.42]) compared to bio-exposed patients. Similar results were found in terms of steroid-free clinical remission at week 52 (RR= 1.36 [95% CI 1.06, 1.76]). Likewise, bio-naïve patients with CD were more likely to achieve clinical remission at week 52 (RR= 1.23 [95% CI 1.05, 1.43]), while clinical remission at week 14 and steroid-free clinical remission could not be assessed in a meta-analysis. A similar pattern was observed regarding the achievement of endoscopic remission at week 52 in UC (RR= 1.48 [95% CI 1.28, 1.72]) but not in CD (RR=1.48 [95% CI 0.82, 2.65]) (Tables 1–2).
Finally, bio-naïve UC patients did not experience any difference in rates of adverse events as compared with bio-exposed patients (UC: RR= 0.96 [95% CI 0.70, 1.31]) but experienced significantly less serious adverse events (RR= 0.47 [95% CI 0.26, 0.82]). In line with this, patients with CD experienced fewer adverse events (RR= 0.73 [95% 0.64, 0.83]) and serious adverse events (RR= 0.54 [95% CI 0.34, 0.85]).

Conclusion

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

Abstract

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

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

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

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

Abstract

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

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

Results
Of the 545 patients who received ICIs, 4% (22) required admission with ICI colitis. Of those who developed ICI colitis 31.8% (7) were receiving combination ipilimumab and nivolumab, 31.8% (7) were receiving pembrolizumab, 27.3% (6) were receiving nivolumab, 4.5% (1) were receiving cemiplimab and 4.5% (1) were receiving ipilimumab.
The median age was 64.5 years (52–75) with the median CTCAE severity score of colitis being 3 (2–3) and the median CTCAE diarrhoea score being 3 (3). On admission, the median stool frequency was 6 (5–8), with median symptom duration of 7 (4–13) days, and median hospital stay of 3 (3–6) days. Laboratory markers were monitored during admission (Table 1).
72% (16) of patients were commenced on intravenous corticosteroid therapy whilst an inpatient, with 95% (21) being discharged on oral prednisolone. Median duration on oral steroid was 22 (8–35) weeks. 36% (8) had oral prednisolone ongoing at the end of the review period. 27% (6) died whilst still on a weaning prednisolone regimen.

Conclusion
Despite improvement of symptoms during hospital admission with corticosteroid therapy, the majority of patients admitted for ICI colitis required prolonged treatment with corticosteroids.
P565 COVID-19 vaccination satisfaction and hesitancy in patients with inflammatory bowel disease: “inside referral center” survey
Authors: Todeschini A , Contaldo A , Ierardi E , Di Leo A , Principi M 
Published: January 2022

Abstract

Background
Covid-19 infection is an exceptional pandemic that has involved millions of people worldwide with dramatic humane, social and economic concerns. Since December 2020, two mRNA and one inactivated vaccines were approved for people administration. The vaccinal access calendar was scheduled according with risk degree of infection and complications. In some regional setting patients with inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) were considered fragile and therefore had a priority approach to vaccine administration compared to the general population. The purpose of this work was to measure the satisfaction and the concerns of a cohort of IBD patients who were administered the anti-Sars CoV-2 vaccine “inside reference center” by their dedicated nursing staff.

Methods
Anti-SARS-CoV-2 vaccine (PfitzerÆ) in two shots were administrated to 346 IBD patients. Afterwards completed vaccination, all patients were given a questionnaire consisting of 4 items focused on the level of satisfaction and the impact of the pandemic on their illness.

Results
346 patients, 168 CD and 178 UC, 147 female and 199 male, 249 in biologicals and 97 in immunomodulatory therapy, regularly followed up in an IBD unit, were enrolled. All patients received two shots of SARS-CoV-2 vaccine by their IBD nursing staff. Upon close of the vaccination course, a questionnaire was dispensed. The pandemic did not affect IBD at all in 37.5% and a lot in 9.2% of participants. The majority (95%) of patients welcomed the possibility of getting vaccinated; only 7% feared the vaccine’s influence on the course of the IBD. The main concerns were the possibility of adverse effects (33%) and the failure to achieve immunity (17%), few for the type of vaccine (3%) and the need for a further booster (6%). Almost all patients (99%) felt safer to have vaccinated at their IBD reference center.

Conclusion
In this cohort of IBD patients, SARS-CoV-2 vaccination “inside reference center” has shown broad compliance and a high degree of confidence. Most did not report that the pandemic affected regular IBD management.
P570 Prevalence and risk factors for intestinal resection in patients with Crohn’s disease in a Greek referral center
Authors: Orfanoudaki E , Foteinogiannopoulou K , Theodoraki E , Drygiannakis I , Romanos I , Koutroubakis I E 
Published: January 2022

Abstract

Background
Nearly half of patients with Crohn’s disease (CD) require any kind of surgical resection within 10 years after diagnosis and about one third of them need an additional second intervention within the next decade. We aimed to investigate the prevalence and risk factors for intestinal resection in Greek patients with CD.

Methods
Consecutive CD patients with complete follow up data, recorded prospectively in a registry of a tertiary university hospital from 2011–2021, were studied retrospectively. All patients with a history of at least one bowel resection for luminal disease were enrolled. Surgeries for perianal disease, fistulae or other complications were excluded. At the same time, the role of potential risk factors for surgical intervention was analyzed.

Results
Out of a total of 372 CD patients recorded in the database, 85 patients (23%) with a history of 96 surgical resections were identified. Sixty one percent were male, with a mean (±SD) age of 48.5 (±15.3) years, median (IQR) age at disease diagnosis 25.5 (21–37) years, 39% smokers, L1 49%, L2 11%, L3 40%, B2 57% and B3 37%.
Median (IQR) time from diagnosis to first surgical resection was 58 (8.3–120.8) months, while in 17% the diagnosis was made with the surgery. Half of the patients (52%) were operated due to no response to treatment, presenting with ileus or stricture formation, whereas other causes for operation were perforation ± abscess (24%) and dysplasia (4%) [20% cause not specified in files]. Fifty three percent were naïve to biologic treatment prior to surgery and needed resection sooner that those experienced to biologics [median (IQR) time from diagnosis to surgery 12 (0–72) vs 88 (46–172) months, p&lt;0.0001]. A second surgery became necessary in 11 patients (13%) due to disease recurrence after a mean (±SD) time of 152 (±117) months after the first, whereas only one needed a third one.
In the univariate analysis bowel resection was associated with younger age at diagnosis (p&lt;0.0001), shorted disease duration (p&lt;0.0001), structural and fistulizing phenotype (p&lt;0.001) and smoking (p=0.0017). All associations remained significant also in the multivariate analysis (Table 1).

Conclusion
One out of four patients in our cohort needed bowel resection for their luminal CD with younger age at diagnosis, shorter disease duration, structuring/fistulizing phenotype and smoking being identified as possible risk factors.
P571 The Nordic diet as a tool to improve the activity of disease and psycho-emotional wellbeing in patients with mild and moderate Ulcerative Colitis – the pilot study
Authors: Birka I , Girgensone G , Anspuka L , Šantare D 
Published: January 2022

Abstract

Background
The Nordic diet (ND) has been associated with reduced inflammatory markers and improved anxiety and stress symptoms. Our aim was to evaluate the effect of the ND on the activity of ulcerative colitis (UC), symptoms of anxiety, depression, and fatigue.

Methods
Patients (N=12) with mild and moderate UC were included (excluding severe UC, UC proctitis, infections). The activity of UC was evaluated with partial Mayo score (pMS) and fecal calprotectin (FC), psycho-emotional wellbeing – using hospital anxiety and depression scale (HADS) and inflammatory bowel disease – fatigue (IBD-F) questionnaire. The patients were evaluated at 3 consecutive visits at week 0, 6 and 10. During the first visit, the patients were consulted by a nutritionist to adjust their diets, received written recommendations and were able to contact the nutritionist later. At every visit HADS, IBD-F scores, and BMI, pMS and FC were registered. The ND score was calculated as described by Bjørnarå et al., 2015. Patients were considered compliant if the ND score increased by at least 2 points and unhealthy snacks were absent or almost excluded. Related samples Wilcoxon signed rank test and independent samples Kruskal-Wallis test were used to assess statistical significance. The ND score was described as low (0–3), medium (4–5) or high (6–10).

Results
The characteristics of all patients are summarised in Table 1. One patient had mild exacerbation of UC during the study managed with increased dose of mesalamine. Changes of the ND score (Fig.1) differed significantly in visit 2 (p=0.01).
After exclusion of non-compliant patients, the data of 8 patients was analysed. The pMS, FC, HADS, IBD-F (level and impact) did not show significant changes at visit 2. BMI was significantly reduced at visit 2 (p=0.018), median at visit 1 was 28.55 (IQR: 24.16 – 32), visit 2 - 27.65 (23.2 – 30.16) kg/m2.
We also found lower FC levels in patients with high ND score, but the difference was not statistically significant (Fig. 2). No significant differences were found regarding the psycho-emotional wellbeing but the impact of fatigue on everyday life was higher in low ND score group (Fig. 3).

Conclusion
We were not able to show improved FC nor psycho-emotional symptoms after 6 weeks of the ND. The adherence decreased after visit 2, therefore another consultation with the nutritionist could be beneficial to improve the understanding and motivation of the patients. Compliance with the ND reduced BMI and high adherence might be associated with lower FC levels. Further studies with larger patient groups would improve reliability of the results. This pilot study is part of the project financed by BIOCODEX MICROBIOTA FOUNDATION 2020.
P573 The safety profile of upadacitinib maintenance therapy in ulcerative colitis in the Phase 3 U-ACHIEVE study is consistent with that in approved indications
Authors: Colombel J F , Panaccione R , Nakase H , Burmester G , Cohen S B , Mease P , Guttman-Yassky E , Liu J , Zhou W , Ilo D , Higgins P 
Published: January 2022

Abstract

Background
The oral, small-molecule, selective and reversible Janus kinase inhibitor upadacitinib (UPA) is approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), moderate-to-severe atopic dermatitis (AD) and ankylosing spondylitis, and is under investigation in ulcerative colitis (UC). This assessment reviewed adverse event (AE) data for UPA maintenance therapy in UC in the context of the known long-term safety profile of UPA in its approved indications.

Methods
Safety data were collated from patients with UC who responded to 8 weeks’ induction treatment with UPA 45 mg once daily (QD) and were enrolled in U-ACHIEVE to receive maintenance treatment (UPA 15 mg, 30 mg QD or placebo) for ≤52 weeks. Treatment-emergent AEs (TEAEs) were defined as AEs with an onset on or after the first dose, and ≤30 days after the last dose, of study drug. Safety data were also collected from two AD (15 and 30 mg doses), six RA (15 mg dose in all, 30 mg dose in four) and two PsA (15 and 30 mg doses) Phase 3 trials. Exposure-adjusted event rates were calculated for TEAEs and AEs of special interest (AESIs).

Results
Data were available for 746 patients with UC who received 8 weeks’ induction with UPA 45 mg and were randomised to maintenance treatment as follows: placebo, n=245; UPA 15 mg, n=250; UPA 30 mg, n=251. Rates of any AEs, serious AEs, severe AEs and AEs leading to treatment discontinuation were lower with both UPA doses versus placebo (Table 1). No deaths occurred. Rates of the above AE categories in patients with UC who received maintenance treatment with UPA 15 or 30 mg were within the ranges previously reported in AD, RA and PsA, apart from neutropenia (Table 1). AESI rates in UC were generally similar with UPA and placebo, except for higher rates of herpes zoster, creatine phosphokinase elevation, hepatic disorder, and venous thromboembolism (VTE), but lower rates of anaemia, with UPA (Table 2). Non-melanoma skin cancer was reported only with UPA 30 mg. One adjudicated major cardiovascular event was reported in each of the placebo and UPA 30 mg arms. VTE only occurred with UPA treatment (two events per arm). Based on the limited number of patients exposed, and apart from a higher VTE rate, AESI rates in the UC maintenance study were generally similar to those reported in patients receiving long-term treatment with UPA 15 or 30 mg QD in AD, RA or PsA.

Conclusion
The safety profile of UPA maintenance treatment in UC is consistent with that in its approved indications. Although VTE rates were higher in UC, background VTE risk is known to be increased in UC versus AD, RA and PsA. This review identified no new important safety risks.