bluuebunny/crossref_metadata_2025 huggingface dataset:
P562 Safety and persistence oh the first JAK inhibitor Tofacitinib in patients with ulcerative colitis
Authors: González Chávez J , Santos Fagundo A , Ceballos Santos D , Calzado Gómez G , González Pérez Y , Morales León V , Otazo Pérez S M , Hernandez Camba A
Published: January 2024

Background

A drug safety warning was published in 2021 about the risks associated with tofacitinib, which were found in the Oral-Surveillance study. The European Medicines Agency (EMA) and the Spanish Agency for Medicines and Medical Products (AEMPS) have recommended, due to this warning, some precautions in the prescriptions: It should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with cardiovascular or malignancy risk factors unless there are no suitable treatment alternatives. The aim fo this study was to assess the safety and treatment persistence of tofacitinib in clinical practice in three Spanish third-level hospitals.

Methods

Retrospective observational multicenter study of patients with Ulcerative Colitis (UC) treated with tofacitinib from January 2019 to October 2023. Sex, age, line of treatment, persistence, adverse events, discontinuations and risk factors associated with the warning were evaluated. Information was collected from the hospital’s information systems.

Results

A total of 56 patients, 53% women, mean age 55 (18-72) years old. Tofacitinib was the first line treatment in 2% of the patients after loss of response to the conventional treatment, second line for 57%, third line for 30% and fourth line for 11% after biological drugs (infliximab, adalimumab, vedolizumab and ustekinumab). 52% of patients needed maintenance with the higher doses (10mg dose) after induction due to the lack of response with the 5 mg dose, with an average of 52 weeks. The mean persistence was 18 months (1-56), with 19,6% discontinuations due to primary failure and secondary failure. It must be noted that one patient, who received tofacitinib for three years, underwent appendicular neoplasia and finally died due to liver metastases. There was not discontinuation due to other adverse events, which were: 3,6% herpes zoster, 46,4% increased total cholesterol level >200 mg/dl (compared with the initial measurement), of which 19% received statins.There were 27 (48%) patients with risk factors associated with the safety warning: 37% cardiovascular risk, 3,7% older than 65 years, 11,1% previous malignancy, 18,5% current or past smokers and 29,6% had several of these risks.

Conclusion

In this multicenter real-world treatment-refractory UC population cohort, tofacitinib was well tolerated in the long term, even in the patients with risk factors related to the warning.
P588 Evolution and management of inflammatory joint pathology with non-anti-TNF therapies in inflammatory bowel disease
Authors: Gonzalez Diaz I , Suarez Ferrer C , Plasencia Rodriguez C , Gutierrez M , Rueda Garcia J L , Martin-Arranz E , Poza Cordon J , Sanchez-Azofra M , Amor Costa C , Amiama Roig C , Martin-Arranz M D
Published: January 2024

Background

The role of ustekinumab (UST) and vedolizumab (VDZ) in articular extra-intestinal manifestations of IBD remains unclear and most existing studies are retrospective. The aim of this study is to analyze the incidence of new onset or worsening of a preexisting IBD-associated arthropathy in patients treated with UST and VDZ.

Methods

An observational prospective study in a tertiary care University hospital was conducted. IBD patients undergoing treatment with VDZ or UST with previous spondyloarthritis (SpA) or new onset arthropathy were included. Articular manifestations were evaluated by a rheumathologist within 72 hours. IBD and rheumatological related variables were assessed at baseline and after 6 months, including demographics, clinical, biochemical, endoscopic and ultrasound data.

Results

201 patients were on treatment with UST and VDZ. Of these, 80 were referred to rheumatology for previous SpA or symptoms onset. 56 (70%) with VDZ and 24 (30%) with UST. 24 (30%) of them were classified as SpA: 22 (92%) had a previous diagnosis and 2 (8%) debuted during treatment with VDZ or UST. The remaining 56 (70%) were diagnosed with other rheumatological pathologies. Type of arthritis was: peripheral arthritis, 11 (46.4%); axial, 7 (29%) and mixed, 6 (25%).

Most patients had received 1 or 2 biological therapies (73%), 90% of them were anti-TNF experienced. 48% of patients received UST or VDZ in monotherapy, without disease-modifying antirheumatic drugs (DMARDs).

The most frequent type of arthritis in patients with previous SpA was peripheral (50% peripheral only and 18% mixed). Joint activity remained stable or even improved in these patients. Only 2 (9%) had axial disease flare-up, one with UST and one with VDZ. Both patients had moderate intestinal activity (C-reactive protein; CRP > 2.5 mg/dl and faecal calprotectin; FC > 600 ug/g). Treatment was not discontinued in any case.SpA debuted in 2 patients with mixed arthritis on treatment with VDZ. Both patients also had poor IBD control (CRP > 3.5 mg/dl and CF > 600 ug/g). A change of biologic therapy was performed in addition to adjusting treatment with concomitant DMARDs.

Conclusion

In our experience, treatment with UST and VDZ did not worsen joint pathology in patients with SpA. Most of them remained stable or improved. Patients with joint flare-ups also had poor control of bowel activity, which could be the main cause of worsening SpA.
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

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 < 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 < 0.0001). Simultaneously, CD patients on methotrexate rose from 11% (n=130) to 28% (n=330) (p < 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 < 0.0001), whilst UC patients on IFX increased from 5% (n=70) to 24% (n=220) over the same time (p < 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

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

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

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

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<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

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

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

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 <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
P854 Tofacitinib demonstrates preliminary efficacy in induction of remission in chronic pouchitis
Authors: Khoo E , Amiss A , Ding J N , Bryant R , Mohsen W , Connor S , Leung R , Croft A , Lynch K , Sparrow M , De Cruz P , An Y K , Holtmann G , Begun J
Published: January 2024

Background

Pouchitis is common following total proctocolectomy for ulcerative colitis (UC) and ileal pouch-anal anastomosis (IPAA) and generally responds to antibiotics. However, up to 20% of patients develop either antibiotic-dependent or antibiotic-refractory pouchitis, collectively referred to as chronic pouchitis.

Methods

We report our preliminary induction results from a multi-center open label induction with randomized withdrawal trial to assess the efficacy of tofacitinib in chronic pouchitis. All eligible participants received 10mg tofacitinib twice daily for 8 weeks, with an additional 8 weeks of therapy given to patients with an inadequate initial clinical response. The primary endpoint was clinical response (a reduction of clinical PDAI≥2) at week 8. Secondary endpoints included endoscopic response (a reduction of endoscopic PDAI≥2), mPDAI remission (modified pouchitis disease activity index (mPDAI)≤ 4 and a reduction of mPDAI≥2), mPDAI response (a reduction of mPDAI≥2) and improvement in health-related quality of life (HRQoL) using the short inflammatory bowel disease questionnaire (SIBDQ). Serum cytokine levels was analyzed using LEGENDplex human inflammation panel 1. Univariate analysis was performed to identify clinical and biochemical predictors of response to tofacitinib.

Results

A total of 33 patients with chronic pouchitis (Table 1) were included in the preliminary analysis. The clinical and endoscopic response rates at week 8 were 55% and 58% respectively, with a median improvement of 1 (p<0.05) and 3 (p<0.05) respectively (Figure 1). The mPDAI remission rate was 49% at week 8 with an mPDAI response rate of 73%. Endoscopic responders exhibited significant improvements in endoscopic oedema, granularity, friability, and mucous exudate (p<0.05). There was significant improvement in HRQoL, with the median SIBDQ score increasing from 35 at baseline to 54 at week 8 (p<0.05). Eleven patients received a further 8 weeks of therapy with a clinical response rate of 36%, yielding an overall response rate including extended induction of 67%. Univariate analysis did not reveal significant differences in baseline characteristics, clinical, or biochemical markers between responders and non-responders. However, a history of corticosteroid use (p=0.08) and high baseline levels of faecal calprotectin (p=0.15) demonstrated a non-significant association with treatment response. Elevated baseline serum levels of IL-1b, IFN-a and IL-33 were associated with a treatment response at week 8 (p<0.05).

Conclusion

Tofacitinib demonstrated preliminary efficacy in inducing both clinical and endoscopic response in patients with chronic pouchitis who have undergone IPAA for UC.
P856 Influential factors on the clinical and radiological closure of resistant perianal fistula treated with stoma
Authors: Candan S , Bakkaloglu O K , Bayar M , Eskazan T , Hatemi I , Erzin Y , Celik A F
Published: January 2024

Background

Perianal fistula (PaF) is a debilitating and difficult to treat form of Crohn's disease. Although biological (anti-TNF) treatments are almost always used, long term fistula closure rates are far from being satisfactory. Radiological closure, which should be the treatment goal, is even much rarer. Stoma is one of the last steps in the treatment of resistant fistula. In our study, we examined the patients who underwent stoma, in our series, due to resistant PaF and the factors associated with radiological closure.

Methods

Crohn's disease cohort was retrospectively evaluated for patients with resistant perianal fistula (history of poor response to anti-TNF) who underwent stoma. Demographic, treatment, and clinical characteristics of the patients were evaluated in terms of radiological closure (complete resolution of the fistula tract, disappearance of T2 hyperintensity and absence of contrast enhancement on MRI) of the PaF.

Results

There were 47 patients (11%) who underwent stoma due to perianal fistula among 423 Crohn's disease patients with PaF. The median age in the patient group (at the time of stoma) was 34 years and 47% of the patients were male. Radiological fistula closure was achieved in 42% of the patients and clinical remission (>3 months) was achieved in 66%. Table -1 summarizes the comparison of demographic, clinical and treatment parameters of the study group and patients with and without radiological closure. Radiologic closure and non-closure groups were similar regarding pre-stoma- and during stoma treatment status. Being a never smoker was associated with poor radiological closure and could be an indicator of treatment resistance while ex-smoker status had a favorable outcome. Both recurrent antibiotic treatment (>2/year) need for clinical fistula closure and history of seton replacement were associated with radiological unresponsiveness. During stoma, the early partial radiological response - achieved in the 3rd month of perianal MRI fistulography -was strongly associated with later radiological closure in the follow up. In Kaplan-Meir analysis; anatomically branching fistula had the poorest response, but the number of fistula did not have any influence, mucosal remission was associated with earlier and better radiological response, pre-stoma reccurent antibiotic need was associated with worse outcome Figure 1.

Conclusion

Radiological closure of PaF can be achieved with stoma in nearly half of the patients under already combined conventional treatment. History of seton replacement, recurrent antibiotic need and being never smoker are the indicators of resistance to radiological closure. Third month radiological response – is an important and early sign of radiological complete fistula closure.
P885 Pharmacokinetics, pharmacodynamics, and immunogenicity of biosimilar infliximab in pediatric patients with inflammatory bowel disease
Authors: Dipasquale V , Alibrandi A , Pellegrino S , Ramistella V , Romano C
Published: January 2024

Background

The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly understood. We examined some factors predicting IFX-BioS trough levels (TLs) in children.

Methods

Children with Crohn's disease (CD) and ulcerative colitis (UC) with an indication to start IFX-BioS in our center were prospectively included (January 2021-June 2022). TLs were measured with an in vitro lateral flow immunoassay (therapeutic range:3-7 microg/mL) at the 4th and 6th infusions and correlated with several covariates.

Results

A total of 110 TLs in 55 children (34 UC and 21 CD) were included. The mean TLs were 8.8±7.6 microg/mL and 9.8±6.7 microg/mL at the 4th and 6th infusions, respectively. The multivariate linear regression model at the 4th infusion found a positive correlation between TLs and age at diagnosis (B: 1.950, 95% CI: [0.019, 3.882], p=0.048) and IFX-BioS dose/kg (B: 1.962, 95% CI: [0.238, 3.687], p=0.029), and a negative correlation with clinical scores (B: -0.401, 95% CI: [-0.738, -0.064], p=0.023). At the 6th infusion, female gender (B: 6.887, 95 CI: [0.861, 12.913], p=0.029), hemoglobin (B: 1.853, 95% CI: [0.501, 3.204], p=0.011), and IFX-BioS dose/kg (B: 1.792, 95% CI: [0.979, 2.605], p<0.001) were found to be positively correlated to TLs. Clinical remission was achieved in 71% (4th infusion) and 67.2% (6th infusion) of patients. Logistic regression analysis revealed no significant association between combined clinical and biochemical remission and TLs at the 4th (OR: 0.010, 95% CI: [0.928; 11.099], p=0.819) or 6th (OR: 0.017, 95% CI: [0.924; 1.119], p=0.732) infusion, corrected for IFX-BioS dose/kg and interval between infusions.

Conclusion

We discovered some predictors IFX-BioS TLs in IBD children. Understanding the IFX-BioS pharmacokinetics and pharmacodynamics could allow physicians to identify which patients are at higher risk of poor outcomes and adjust treatment accordingly.
P889 Facilitating equitable IBD care trust-wide: a need for treatment targets in IBD?
Authors: Hentges M , Ibarra A , Onyl Ronquillo F , Gnanasampanthan S , O’Shea I , Utulu S , Vlachou F , Gordon H , Jawad N
Published: January 2024

Background

Timely biological therapy in IBD is associated with reduced disease progression, especially in CD (Berg et al 2019). However, there are no clear UK standards detailing the timescale in which IBD care should be delivered. We evaluated the time between initial consideration of therapy and first dose in a district general hospital and tertiary referral centre in Barts Health NHS Trust.

Methods

Details of patients receiving biologics for IBD at Newham (NUH) and Royal London Hospital (RLH) (between 2018 – 2022) were obtained from infusion clinics; electronic records were reviewed for 50 recent referrals. The following information was collected: demographics, phenotype, drug, first documentation of consideration of biologic, completion of funding application, onset of therapy.

Results

Demographics:

NUH: Age (median(IQR)) = 43.5(30.3 – 50.56) Gender (F:M) = 26:24, CD:UC = 34:16, Biologic: infliximab:vedolizumab:ustekinumab:adalimumab: 29:5:11:5, First biologic: n=34

RLH: Age (median(IQR)) = 31.6 (24.6 – 41.1) Gender (F:M) = 27:23 CD:UC = 23:27, Biologic: infliximab:vedolizumab:ustekinumab:adalimumab: 34:12:3:1, First biologic: n=25

There was substantially longer time between initial consideration of therapy and first dose delivered at NUH 94.5 days (44 – 174) compared with RLH 35.5 days (23.75 –69) (p<0.01). However, time from completion of funding application to first dose did not differ significantly between sites (43.5 days (30.3 – 50.6) vs 31.6 (24.6 – 41.1), p=0.42). In patients receiving first biologic, there was a trend towards a longer time since diagnosis at NUH (3.2 years (1.0 – 9.1) vs 1.7 years (0.5 – 4.3), p=0.08).

Conclusion

Patients treated in a tertiary referral centre started biologics sooner after consideration, and earlier in disease course. This does not appear due to availability of infusion services, but due to time to complete initial investigations and finalise escalation. This may reflect differences in service set-up; in particular, NUH manages IBD care with a single IBD nurse, and fewer options for fast-track clinic follow up. A clear UK IBD standards framework identifying recommended time frames for establishing biologics is indicated, to ensure equity in care across tertiary and DGH settings.
P912 A Real-World Evidence Study of Dose Escalation and associated costs of advanced therapies for Ulcerative Colitis in France and United Kingdom
Authors: Treuer T , Richards M , Mert C , Dhesi E , Silva L , Tan Y , Hoque S
Published: January 2024

Background

Dose escalation to optimize advanced therapies is common practice in ulcerative colitis (UC) to avoid intra-class or inter-class drug switching and maintain clinical response. Dose escalation also has impact on healthcare resource utilization (HRU) and costs. However, there are limited data available on real-life dose-escalation. Study aim was to understand real-world dose escalation/de-escalation UC advanced therapy drugs patterns in two European countries (France, United Kingdom [UK]).

Methods

This retrospective study analysed data from the THIN®/CEGEDIM database to identify adult patients with moderate-to-severe UC who were naïve to advanced UC therapies or had not received any of the UC advanced therapy drugs of interest (adalimumab [ADA], golimumab [GOL], infliximab [INF], tofacitinib [TOF], ustekinumab [UST], or vedolizumab [VED]) for at least 12 months prior first prescription (and/or dispensation for France) between January 2017 and February 2022. A dose increase of ≥20% during the maintenance period compared to lowest Summary of Product Characteristics recommended dose was considered dose escalation. Proportions of patients with dose escalation after maintenance date were estimated using Kaplan-Meier (KM) survival analyses. Clinical response (defined as absence of: UC-related hospitalization or colectomy, treatment switch or addition of another UC advanced drug, systemic/rectal corticosteroids exposure), and direct (consultations, hospitalisations, diagnostic tests, UC drugs, complementary therapy) and indirect costs related to UC by treatment cohort were also analysed.

Results

1663 patients fulfilled the selection criteria, of whom 619 had information on dose patterns. Overall, 89% of patients (range 33% [INF] to 100% [GOL, TOF, and UST]) had dose escalation within the first 24 months after start of maintenance, with a median % dose increase ranging from +15% [VED] to +198% [GOL] (Table). Median (95% CI) time to first dose escalation was 2.1 (1.8-2.4) months (range 0.7 [UST] to 4.6 [VED]). Clinical response ranged from 56.3% (ADA) to 77.0% (INF). Direct annual HRU costs related to UC ranged from 3,085 (INF) to 16,527 (UST) EUR in France and from 1,857 (INF) to 4,104 (VED) GBP in the UK. Mean direct HRU costs in France were 25% higher in escalated patients compared to de-escalated patients (range: +4.2% GOL to +61.9% UST).

Conclusion

Dose escalation of advanced therapies for UC is a common strategy to avoid treatment-switching. Despite dose escalations and their cost to the system, a proportion of patients fail to achieve clinical response, highlighting the need for more efficacious and durable treatments for patients with moderate-to-severe UC.
P914 Immunogenecity of Hepatitis B Vaccination in Patients with Ulcerative Colitis on Infliximab Monotherapy : A Prospective Comparative Study
Authors: Shehab M , Alfadhli A
Published: January 2024

Background

Hepatitis B virus (HBV) infection has been associated with chronic hepatitis and cirrhosis. Patients with inflammatory bowel disease (IBD) maybe at higher risk of HBV infection, especially those on biologic therapies. There is limited data on the effectiveness of HBV vaccination in patients with IBD receiving different types of IBD medications. This study intends to compare the effectiveness of HBV vaccine in patients with ulcerative colitis (UC) on Infliximab (IFX) compared to those on 5-aminosalicylic acid (5-ASA).

Methods

Patients with UC aged between 18-85 years were prospectively enrolled in the study. The patients were divided into two groups: group 1 ( patients with UC on 5-ASA) and group 2 (patients with UC on IFX). HBV vaccination was administered (20 mcg) following the standard regimen, and Hepatitis B serum antibody (HbsAb) titres were assessed three months after the final dose. The response to HBV vaccines was categorized as 'adequate' immune response (≥10 IU/L) and 'effective' immune response (≥100 IU/L).

Results

In our final analysis of 118 patients with UC, 54.2% were male, and 52.5% had extensive disease. HBsAb titer levels were significantly higher in the 5ASA group (126.7 ± 37.5) compared to the IFX group (55.5 ± 29.4). Stratifying HBsAb levels into two categories (≥10-99 IU/L and ≥100 IU/L) revealed a significantly greater proportion of subjects in the 5-ASA group with levels ≥100 IU/L (76.7%) compared to the IFX group (12.1%). Conversely, the IFX group showed a higher percentage of subjects with levels between 10-99 IU/L (87.9%) relative to the 5-ASA group (23.3%). Logistic regression analysis demonstrated that patients with UC receiving 5-ASA were 23.94 times more likely to exhibit HBsAb levels ≥100 compared to those on IFX (OR 23.94, 95% CI 8.89-64.49).

Conclusion

Immune response to hepatitis B vaccination in patient with ulcerative colitis on infliximab is attenuated compared to those on 5-ASA. Therefore emphasizing the importance of HBV vaccination for patients with IBD before starting anti-TNF therapy, especially infliximab, and advocating for screening is imperative in high risk countries.
P925 Predicted inflammatory status and Inflammatory Bowel Disease among Korean adults: a Multicentre case-control study
Authors: Kim D H , Okekunle A P , Kang J , Kim H S , Kim S H , Jung M K , Park J H , Na S Y , Lee J E , Lim Y J , Chun H
Published: January 2024

Background

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a complex disease attributable to an anomalous immune response to intestinal microbiome antigenic stimulation, but there are limited studies on the overall implication of diet and lifestyle factors in the development of IBD, particularly among East Asian. This study assessed the association of pro-inflammatory predicted high sensitivity C-reactive protein (hs-CRP) scores (derived from diet and lifestyle factors) with IBD among Korean adults.

Methods

From July 2017 to September 2023, 912 subjects who underwent gastrointestinal endoscopy at eight tertiary medical centres and completed a food frequency questionnaire were used in this study. The study included subjects with IBD and matched them in a 1:1 ratio (using propensity score matching) with normal control; subjects without colonic inflammation or cancer. Pro-inflammatory predicted hs-CRP score was derived from sociodemographic, lifestyle, and dietary information and multivariable-adjusted conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of IBD by tertile distribution of predicted hs-CRP scores (adjusting for age, sex alcohol intake, smoking, education, physical activity and energy-adjusted dietary energy intakes) at a two-sided P<0.05.

Results

Overall, 127 patients with IBD and 127 healthy controls were included in the study after propensity score matching. Of 127 IBD cases, 59 (46.5%) presented with CD and 51 (40.2%) were females. The prevalence of alcohol use was higher in the healthy control group compared to IBD patients (70.1% vs. 48.0%, p < 0.05), while a BMI ≥ 23 was more common in IBD patients (58.3% vs. 35.4%, p < 0.05). Smoking, age, sex, physical activity, and energy intake differed insignificantly between the two groups. Overall, the median (interquartile range) of the predicted hs-CRP was -2.6 (-3.0, -2.2), and multivariable-adjusted ORs and 95% CIs for IBD by tertiles of the predicted hs-CRP score were 1.00, 1.00 (0.44, 2.25), 8.67 (2.24, 33.51; P trend = 0.004) in males and females combined. When the association was stratified by IBD subtype, the association remained for UC but not CD.

Conclusion

Pro-inflammatory predicted hs-CRP score (derived from diet and lifestyle characteristics) was associated with higher odds of IBD, particularly among IBD cases presenting with UC. Promoting lifestyle modification to avoid pro might be promising for the primary prevention of IBD.