bluuebunny/crossref_metadata_2025_split huggingface dataset:
P597 The changing landscape of paediatric Inflammatory Bowel Disease medication in Australia 2015-2021, A population-based study
Authors: Gawade G , Massuger W , Giles E 
Published: January 2024

Abstract

Background
There have been significant advancements in the pharmaceutical management of paediatric inflammatory bowel disease (IBD) with cost and clinical implications. The real-world shifts in prescribing habits in Australia have yet to be characterised. As part of the National Inflammatory Bowel Disease Paediatric Quality of Care project, this study sought to examine patterns of IBD-related medication use in the Australian paediatric population from 2015 to 2021.

Methods
We used Services Australia Pharmaceutical Benefits Scheme 10% data to identify prescriptions for paediatric IBD patients from 1/1/2015 to 31/12/2021. In Australia, select prescribers must specify an authorised indication for the government subsidy of authority-required medications (i.e. aminosalicylates (5-ASAs) and biologics), enabling patients to be tagged with Crohn’s disease (CD) or ulcerative colitis (UC). To be included in the analysis, patients must have received at least one prescription of an authority-required medication and be aged between 0 and 17 years at the time of dispensing their first IBD-related medication. Trends over time were assessed for significance with the chi-squared test for trend.

Results
The data identified 2940 UC patients (mean age 14.09 ± 3.15) and 2840 CD patients (mean age 14.20 ± 2.67) across 2015-2021. In 2015, 54.90% of IBD patients were dispensed at least one prescription of corticosteroids (CCSs). Trends showed CCS use to fall dramatically to only 29.27% of patients in 2021 (p &lt; 0.0001). Among CD patients on azathioprine (AZA) treatment, there was a disproportionate decrease in male usage, with the male CD patients on AZA falling from 47% (n=277) in 2015 to 38% (n=167) in 2021 (p &lt; 0.0001). Simultaneously, CD patients on methotrexate rose from 11% (n=130) to 28% (n=330) (p &lt; 0.0001). Biologic use rose continually among both CD and UC patients. CD patients on infliximab (IFX) rose from 34% (n=420) in 2015 to 59% (n=670) in 2021 (p &lt; 0.0001), whilst UC patients on IFX increased from 5% (n=70) to 24% (n=220) over the same time (p &lt; 0.0001). Despite rising patient numbers, the total estimated government expenditure on IFX for CD decreased by over 50% from AUD 7.1 million in 2015 to AUD 3.4 million in 2021.

Conclusion
This study quantifies the temporal trends in prescribing habits for paediatric IBD in Australia, observing a shift towards increasingly biologic-centred therapy. Despite increasing IFX use in CD, government expenditure decreased, suggesting that escalated medication use in paediatric IBD care does not necessarily lead to increased costs over time.
P621 Safety and effectiveness of vedolizumab and ustekinumab in inflammatory bowel disease patients after liver transplantation for primary sclerosing cholangitis: results from an ECCO-confer case series
Authors: Holvoet T , Verstockt B , Lenfant M , Julsgaard M , Drobne D , Thakor A , Gordon H , Molnar T , Savarino E V , Ribaldone D G , Miheller P , Vieujean S , Candel I , Menchen L , Bettenworth D , Eder P , Issachar A , Lobaton T 
Published: January 2024

Abstract

Background
Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting.

Methods
A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation.

Results
In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10).
Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table).

Conclusion
In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.
P622 Network meta-analysis comparing efficacy between biologics and conventional therapies to prevent endoscopic postoperative recurrence in patients with Crohn's disease
Authors: Hupé M , Pereira B , Mathieu N , Buisson A 
Published: January 2024

Abstract

Background
As no direct comparison between IBD drugs to prevent endoscopic postoperative recurrence (POR) In Crohn’s disease (CD) are available, hierarchizing these therapeutic options remains challenging.
The objective of this network meta-analysis was to compare the effectiveness of treatments to prevent endoscopic POR of CD.

Methods
We performed a systematic review and network meta-analysis of comparative studies conducted in adults, evaluating a treatment to prevent endoscopic POR after ileocecal resection. The selection of studies was made according to PRISMA guidelines. The primary endpoint was endoscopic POR at 6 months defined as Rutgeerts score ≥ i2.
The network meta-analysis was carried out according to a random effects model. The results are presented as odds ratio (OR) with 95% confidence interval, adjusted for risk factors of POR. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ². The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results
Twenty studies were included in this network meta-analysis, including a total of 2414 patients. Overall heterogeneity was moderate (τ²=0.34). After adjustment for POR risk factors, ustekinumab (OR = 0.23 [0.07-0.70]), vedolizumab (OR = 0.17 [0.05 -0.59]), infliximab (OR = (0.18 [0.36-0.88]) and adalimumab (OR = 0.17 [0.07-0.42]) were superior to placebo to prevent endoscopic POR, contrary to 5-ASA (OR = 0.79 [0.42 -1.48]) and thiopurines (RR = 0.52 [0.22-1.24]) (Table 1).
Ustekinumab (OR = 0.29 [0.08-0.99]), vedolizumab (OR = 0.22 [0.06-0.85]), infliximab (OR = (0.23 [0.09-0.54]) and adalimumab (OR = 0.22 [0.08-0.59]) were more effective than 5-ASA in preventing endoscopic POR. Adalimumab (OR = 0.33 [0.15-0.74]) and infliximab (OR = 0.34 [0.13-0.87]) were also more effective than thiopurines. We observed no difference in efficacy between the 4 biologics (infliximab, adalimumab, ustekinumab and vedolizumab) (Table 1).
The SUCRA ranking identified adalimumab (SUCRA=0.81), infliximab (SUCRA=0.80), vedolizumab (SUCRA=0.79) and ustekinumab (SUCRA=0.72) as the most effective treatments. The likelihood that thiopurines (SUCRA=0.41), 5-ASA (SUCRA=0.24), placebo (SUCRA = 0.16) and antibiotics (SUCRA=0.08) was the best option is very low.

Conclusion
This network meta-analysis confirms the efficacy of anti-TNF agents, vedolizumab and ustekinumab in preventing endoscopic CD POR without any difference between them. When prophylactic therapy is necessary, biologics appear as the best therapeutic option to prevent of endoscopic POR. Due to lower efficacy, the use of 5-ASA and thiopurines should be limited in this situation.
P688 Comparative Effectiveness of Ustekinumab Versus Vedolizumab in Treating Crohn’s Disease After Failure of Anti-TNF Agents: Real-World Evidence
Authors: Alamer A , Al Lehaibi L , Alomar M , Aldhuwayan F , Alshouish S , Al-Ali A , Almudhry Z , Almulhim A , Althagafi A , Aldosari S , Alameel T 
Published: January 2024

Abstract

Background
Despite effective anti-TNF agents in treating Crohn’s disease (CD), some recipients experience primary or secondary non-responses, requiring alternative options. Ustekinumab and vedolizumab have not been compared in randomized controlled trials (RCTs) among CD population. Thus, we used real-world data to compare ustekinumab and vedolizumab at 12 weeks after failure of TNF inhibitors.

Methods
A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia. Patients with CD who had not responded to anti-TNF agents and had never been exposed to vedolizumab and/or ustekinumab were included. Children ≤ 18 years of age, naïve CD patients, CD patients using only anti-TNF agents, and patients who lost follow up were excluded. Primary endpoints were clinical improvements, which were measured by Harvey-Bradshaw Index scores at 12 weeks, and clinical remission, which was measured as an ordinal outcome. Remission clinically, biochemically, and endoscopically; clinical response; cumulative steroid dose; and corticosteroid-free days were secondary endpoints. Using probabilistic Bayesian models and proportional odds models, we analyzed outcomes, and the posterior distribution was used to calculate the probability of treatment effectiveness. A national institutional review board approved the study.

Results
Five hundred forty-six patients received biological agents for inflammatory bowel disease, of whom 101 received biological agents for CD; 71 patients received ustekinumab, and 30 patients received vedolizumab. The baseline characteristics were similar except for perianal disease, which was frequently reported in ustekinumab arm (P = 0.006). Most of the patients were male (54.5%), with a median age of 32 (IQR: 26.0-38.0). Most patients (51.5%) had stricturing disease in the Ileocolonic site (70.3%). For ustekinumab, the median HBI score was 5 (IQR: 3.0 -8.0) whereas for vedolizumab, it was 5 (IQR: 4.0 -7.0). In table 1, a Bayesian multivariable proportional odds model revealed a 40% reduction in median HBI scores at 12 weeks favoring ustekinumab, with an aOR of 0.60 (95% CI: 0.25 to 1.31) and a probability of effectiveness of 75% for ustekinumab. At 12 weeks, the ordinal outcome scale was 39% lower for ustekinumab arm, with an aOR of 0.61 (95% CI: 0.26 to 1.35) and a probability of effectiveness of 73% for ustekinumab arm. Secondary endpoints showed favorable results for ustekinumab reaching up to a 90% probability of effectiveness.

Conclusion
Among CD patients who failed anti-TNF therapies, ustekinumab was more effective than vedolizumab. To validate these results and determine these treatments’ relative efficacy in managing CD, further investigations, including prospective studies and RCTs, are essential.
P692 An IBD nurse-led educational programme on safety and efficacy of adjuvated recombinant zoster vaccine can improve vaccine uptake in IBD patients on immunosuppressive treatment
Authors: Zaetta D , Roncen E , Franco M , Riguccio G , Santarossa A , Buda A , De Bona M 
Published: January 2024

Abstract

Background
Herpes Zoster (HZ) represents one of the most frequent opportunistic infections in IBD patients under immunosoppressive treatment and can be prevented by vaccination. Adjuvated recombinant zoster vaccine (RZV) is the first HZ vaccine approved for immunocompromised persons. IBD patients are less likely to receive appropriate vaccinations compared to the general population. IBD nurses operate as the primary point of contact for patients and this unique position provides a suitable opportunity to positively impact patient care and encourage vaccination. We aimed to improve RZV vaccination rates by a nurse-led education intervention within an on-site RZV vaccination programme.

Methods
IBD patients on immunosuppressive therapies were actively recruited by phone contact, mail and during outpatient clinic or infusion centre attendance. Prior immunization to VZV was collected from medical records. Patients were randomly assigned to receive either standard explanation on the importance of HZ vaccination by the IBD attending physician (group P) or additional education by an IBD nurse (group N). Patients in group N were referred to an IBD nurse for an individual 15 minutes nurse–patient interview. During the interview, disease activity and current treatment, previous immunization to VZV and history of HZ were reviewed; the importance, benefits and safety of HZ vaccination with RZV were discussed with the patient. Patients were then referred to dedicated on-site vaccination clinics where vaccine administration was provided by the IBD nurses running the infusion centre. Reasons for vaccine refusal was also recorded.

Results
From February to April 2022, 164 (80%) out of 205 eligible patients were enrolled (median age 48.5 years, 54.1% male; 48.7% UC, 51.3% CD); 65 patients (39.6%) were randomized to group P and 99 patients (60.4%) to group N. Six months after randomization, 112 (68.2%) had received at least 1 RZV vaccine dose whereas vaccination was completed in 110 patients (67%). Vaccination rate was significantly higher in the nurse-led education intervention group compared to standard clinical care (group N 75.7% vs group P 56.9%,p&lt;0.05). Most common reasons for vaccine hesitancy were concerns about side effects (40.9%), fear of vaccine aggravating the disease (14.7%), considering themselves not at risk (13.3%) and objection to the administration of vaccine (10.1%).

Conclusion
Vaccination recommendations should be responsibility of the IBD patient care team and efforts should be made to reduce vaccine hesitancy. We showed that a simple nurse-led educational intervention on vaccine safety and efficacy was able to improve RVZ vaccination rates in IBD patients on immunosuppressive treatment.
P739 Translating Pharmacokinetic and Efficacy Outcomes of NLRX1 Agonist NX-13: Contrasting a Pig Model and a Human Phase 1b Clinical Trial in Ulcerative Colitis
Authors: Siegmund B , Verstockt B , Dubinsky M , Mosig R , Cataldi F , Danese S , Yarur A 
Published: January 2024

Abstract

Background
In rodent models of ulcerative colitis (UC), NX-13 (as an orally active, gut selective NLRX1 agonist) improves disease activity through a novel bimodal mechanism. Subsequently, a pig DSS colitis experiment was performed to generate pharmacokinetic (PK) and mechanistic insights, given pigs can be dosed with tablets and their gastrointestinal physiology, microbiome, and immune system is markedly more similar to humans than rodents are. We here describe the efficacy and PK of NX-13 tablets in pigs compared to phase 1 clinical trials.

Methods
NX-13 immediate release (IR) tablets were used in pig studies and human clinical trials with plasma samples collected at hourly intervals. Stool samples were collected at ~24hrs after last dose. NX-13 phase 1 clinical trials were double blind, randomized and placebo-controlled studies testing multiple IR doses in healthy subjects (1a) or subjects with active UC (1b) 1,2. NX-13 concentrations were determined by LC-MS/MS and linear regression to standard curve.

Results
In pigs, oral NX-13 treatment dampened colitis development with differences as early as day 2, becoming significant at days 4-6 (Fig. 1A). Consistent results were observed in the human Phase 1b trial, including fast rectal bleeding improvement as early as week 2 (Fig. 1B) and endoscopic improvement at week 4. Nonetheless, the NX-13 PK characteristics differed between pigs and humans. Firstly, NX-13’s low level of systemic exposure peaked 1 hour after dosing in the human studies, whereas Tmax in pigs was 7 hours at comparable doses. Secondly, the portion of NX-13 retained in the stool is greater in pigs (250-1000 times greater than plasma levels), compared to humans (150-400 times greater) although both stool and plasma concentrations were greater in pigs (Fig. 1C). This suggests NX-13 is not gut-restricted in humans, but rather gut-selective with low systemic absorption. Interestingly, the stool:plasma ratio was numerically lower in patients with UC compared to normal healthy volunteers (Figure 1C), implying epithelial barrier integrity may affect absorption. Despite these differences in PK characteristics, we see similarly fast onset of action signals in the pig model and the human phase Ib trial, suggesting that sufficient target engagement is achieved locally in both species.

Conclusion
NX-13, a novel NLRX1 agonist, has a low percentage of drug absorbed systemically in both pigs and humans, although there are species specific differences in absorption patterns. The hypothesis of a gut-selective compound with low systemic absorption and PK characteristics of NX-13 will be analyzed in the ongoing NEXUS phase 2 study in patients with moderate to severe UC.
1 Leber et al. UEG J (9) Supp.
2 Peyrin-Biroulet, et al. JCC (17) Supp.
P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohort
Authors: Banerjee R , Pal P , Mekala D , Raghunathan N , Joshi V , Akki Y , Patel R , Godbole S , Valluri S , Nagasuri P , Haridas A 
Published: January 2024

Abstract

Background
Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India.

Methods
Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse.

Results
Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%).
Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A).
Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse.

Conclusion
60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.
P833 Burden of steroid use in patients with moderate ulcerative colitis in Europe and the United States
Authors: Shah S , Knight H , O’Neill G , Lukanova R , Davé K , Rosen M 
Published: January 2024

Abstract

Background
Steroids are an effective short-term therapy option for induction of remission of ulcerative colitis (UC). However, long-term and frequent steroid use is common in clinical practice despite the risks of complications and adverse events.1 We aimed to describe disease burden in moderate UC patients (pts) based on their steroid use history.

Methods
Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their pts in France, Germany, Italy, Spain, the UK and US from Jan 2020–Mar 2021. GIs reported patient demographics, clinical characteristics, treatments and healthcare resource utilization (HCRU). Pts reported quality of life (QoL) via the EQ-5D, short inflammatory bowel disease questionnaire (SIBDQ), and work productivity and activity impairment (WPAI) questionnaire. Pts had received 5-ASA or immunomodulator with no biologic or Janus kinase inhibitor in the 90 days following treatment initiation, had a history of physician-assessed moderate disease severity or a Mayo endoscopic subscore of 2, and no history of colectomy. Pts were categorized as: no steroids (NS; never received steroids), short term/intermittent (ST/I; currently receiving intermittent steroids or received steroids within the last two years for &lt;90 days), or long term/escalated (LT/E; received steroids for ≥90 days within the last two years or had undergone steroid dose escalation within their current course). Analyses were descriptive.

Results
Overall, 217NS, 88 ST/I and 172 LT/E pts were analysed (Table 1). Median (interquartile range) total steroid use duration was 4.1 (1.6–22.3) months for ST/I and 14.9 (5.8–36.7) months for LT/E. NS (24.4%), ST/I (25.0%) and LT/E (26.2%) pts experienced abdominal pain; 0.5%, 4.6% and 5.2% had severe/extremely severe pain, respectively. Non-bloody diarrhoea was reported by 16.6%, 14.8%, 20.9% of pts, respectively. In the last 12 months, mean (standard deviation; SD) number of health care visits for NS, ST/I and LT/E was 6.1 (6.2), 7.3 (4.8), 8.0 (7.1); mean (SD) number of tests was 20.8 (17.2), 23.3 (15.7), 25.2 (18.2), respectively. NS, ST/I and LT/E patients reported mean EQ-5D scores (0.85, 0.81, 0.79), SIBDQ total scores (54.6, 49.7, 48.3) and overall work impairment (19.4, 23.1, 27.7). Key comorbidities experienced by ST/I and LT/E were hypertension, depression and diabetes (Figure 1).

Conclusion
Patients with long-term or escalated steroid use had high symptom burden, frequent comorbidities, high HCRU, and poor QoL. This highlights the need for alternative treatment approaches for moderate UC patients to avoid long-term steroid use.
1. Cross R.K. Inflamm Bowel Dis. 2017;23(10):1689–1701