bluuebunny/crossref_metadata_2025_split huggingface dataset:
P283 Infliximab re-challenge: could it be an option in refractory IBD patients?
Authors: Truyens M , Pijoan Comas E , Glorieus E , Geldof J , Lobatón Ortega T 
Published: January 2022

Abstract

Background
Infliximab (IFX) is effective in treatment of inflammatory bowel disease (IBD). However, primary non-response and secondary loss-of-response rates go up to 30–40% and intolerance may occur leading to treatment switch. Unfortunately, even with increased availability of new molecules, some patients remain refractory to all currently available medical options. This study assesses the effect of IFX re-challenge in a real-life cohort of highly refractory IBD patients.

Methods
A retrospective observational study was set up to analyse the effect of IFX rechallenge in IBD patients previously treated with IFX and found refractory to other biologics. Cases between August 2018 and June 2021 with at least one year of follow-up (FU) were analysed. Clinical, biological (CRP and faecal calprotectin [FC]) and endoscopic response was evaluated, as well as adverse events (AE).

Results
Ten patients with refractory IBD were included (9 Crohn’s disease [CD], 1 ulcerative colitis [UC]). Details on previous treatment before IFX re-challenge are shown in Table 1.
All patients had active disease at the start of IFX re-challenge. Median baseline CRP was 12.6mg/L [4.9–24.1] and FC 396mg/kg [64–2786.8]. IFX was started in combination with systemic steroids, immunosuppressants and ustekinumab in 50%, 70% and 10% of patients, respectively. Baseline endoscopy showed severe active disease in 7/8 patients.
Clinical and endoscopic response rates are shown in Table 2. Biological response is shown in Figure 1. After 1 year FU, all (7/7) required intensified dosing (4-weekly), in 3/7 corticosteroid free clinical remission was reached. IFX re-challenge was discontinued after the second administration in 2/10, due to a severe allergic reaction despite premedication with antihistamines and corticosteroids (1 anaphylactic shock admitted to intensive care unit, fully recovered). IFX was continued in 8/10.
Other AE (not in all cases considered to be related to IFX) included: disease flare-up requiring hospitalization (3/10), liver test abnormalities (1/10), new perianal abcedation (1/10), subobstruction (1/10), C. difficile infection (1/10), EBV infection (1/10) and Addison crisis (1/10).

Conclusion
IFX re-challenge was efficient in inducing clinical and endoscopic response in this highly refractory IBD population. However, there is a non-negligible risk of AE including infusion reaction.
P287 The knowledge and skills needed to perform intestinal ultrasound – An international Delphi consensus survey
Authors: Madsen G R , Wilkens R , Boysen T , Burisch J , Bryant R , Carter D , Gecse K , Maaser C , Maconi G , Novak K , Palmela C , Nayahangan L J , Tolsgaard M G 
Published: January 2022

Abstract

Background
Intestinal Ultrasound (IUS) is a non-invasive modality for monitoring disease activity in inflammatory bowel diseases (IBD). IUS training currently lacks well-defined standards and international consensus on IUS competency criteria. Hence, the aim of this study was to achieve international consensus on what competencies should be expected from a newly certified IUS practitioner.

Methods
A three-round iterative Delphi process was conducted among 54 IUS experts from across 17 countries. Round 1 was a brainstorming phase with an open-ended question to identify the knowledge and skills that the experts believed a newly certified IUS practitioner should have. The experts’ suggestions were summarised and organised into statements by a Steering Committee. Round 2 allowed the experts to provide comments and to rate the statements on a five-point Likert scale by level of agreement, i.e., how much they agreed or disagreed that a newly certified IUS practitioner should have a specific knowledge or skill. Statements were revised based on the comments and ratings from the experts. In round 3, the experts re-rated the revised statements. Statements achieving the pre-defined consensus-criterion (at least 70% agreement) were included in the final list of consensus statements.

Results
858 items were suggested by the experts in first round. Based on the suggested items, 55 statements were summarised and organised into three categories; knowledge, technical skills and interpretation skills. After the second round, two statements were merged and one statement was excluded, leaving 53 revised statements. After the third and final Delphi round, a total of 41 statements were included in the final list of consensus statements.

Conclusion
We established an international consensus on the knowledge and skills that should be expected from a newly certified IUS practitioner. The inception of these consensus statements is the first step in the process of developing training standards. Educators can utilize these consensus statements to guide them in designing training programs and in evaluating the competencies of trainees before they engage in independent practice.
P319 Incorporating HLADQA1*05 in pre-biologic screening in IBD patients initiating biologic therapies
Authors: Aleman Gonzalez H , Ramachandran S , Whitehead E , Pattinson A , Stamp K , Turnbull J , Myers S , Talbot A , Sebastian S 
Published: January 2022

Abstract

Background
The PANTS study reported high risk of immunogenicity and loss of response in anti Tumor Necrosis Factor (anti-TNFs) treated Crohn’s disease (CD) patients carrying HLADQA1*05 allele. The proposed biomarker stratified trial to evaluate the usefulness of HLA testing prior to initiation of anti-TNFs is not yet available. We aimed to evaluate the use of HLADQA1*05 as part of pre-biologic screening in IBD patients initiating biologics on MDT decision on drug choice and disease outcomes

Methods
We prospectively included all IBD patients who had HLADQA1*05 tested prior to initiation of biologics over a period of, 12 months. Patients with definitive indication for one class of drug or drug strategy (perianal fistula, acute severe colitis, contraindications to infliximab, co-existent EIMs) were excluded. Primary outcome was treatment persistence at, 6 and, 12 months. Secondary outcomes were steroid free remission at, 6 and, 12 months, use concomitant immunosuppression and proportion needing dose escalation.

Results
Seventy-six patients were included in analysis (UC=, 32, CD=43, IBD-U =1). HLADQA1*05 was positive in, 46.7% of patients. The therapy class choice was as recorded in figure 1. Concomitant immunosuppression was used in, 44% of the whole cohort and in, 100% of HLADQA1*05 positive patients started on anti-TNF agents. Primary non-response was recorded in, 8 patients and secondary loss of response in, 3 patients. Among patients started on anti-TNFs, anti-drug antibodies were detected in, 10 (15.6%) patients with, 7 out of, 10 positive for HLADQA1*05. However, only, 3 (4.6%) had undetectable drug levels in the presence of antibody and all three were HLADQA1*05 positive. Two patients had reactions during induction therapy both were HLADQA1*05 positive and were on combination therapy with Infliximab. Therapy persistence with initial drug strategy and steroid free remission at, 6 months was recorded in, 77.1% and, 78% respectively. There was no significant difference in drug persistence rates at, 6 months and, 12 months in patients with HLADQA1*05 variant or those with variant absent (Figure, 2). Steroid free remission at, 6 and, 12 months was also similar irrespective of the variant status (Figure 3)

Conclusion
Choice of therapy incorporating HLADQA1*05 status may allow anti-TNF monotherapy and tailoring of therapy in IBD patients. A randomised stratified biomarker trial is required to determine the utility of pre-treatment testing.
P356 Czech experience with treatment of Crohn′s disease perianal fistulas by allogenic mesenchymal stem cell
Authors: Serclova Z , Lengálová M , Zusková P , Tremerová A , Drvostepova L 
Published: January 2022

Abstract

Background
Perianal complex fistulas in Crohn′s disease (CD) are difficult to treat by both surgical and conservative methods. Administration of allogenic, adipose-derived mesenchymal stem cells (darvadstrocel) was studied in a prospective randomised trial (PRS) with a success rate of more than, 50%. The aim of our study was prospectively evaluate results of commercial treatment of perianal fistulas in CD patients by darvadstrocel in Czech Republic.

Methods
We prospectively followed, 42 consecutive patients treated commercially by darvadstrocel since August, 2019 till August, 2021. Perianal CD activity index (PDAI) was recorded for all patients as well as well as AGA clinical fistula assesment. Complete healing was considered as: no secretion from the external opening, no infiltration perianally, no pain; treatment failure: clear perianal secretion, painful infiltration and / or the need for surgery; partial response: anamnestic mild secretion from one external opening, infiltration around the fistula without pain and without the need for surgical intervention.

Results
42 prospectively monitored patients (17M /, 25F), average age, 42 years (range;, 21–70 years) underwent darvastrodstrocel treatment in, 2 Czech mesenchymal stem cell therapy centers (39 pp in NH Hospital, 3 in ISCARE center). Patients suffered from intestinal CD for an average of, 15.6 years (3–34 years), perianal CD for, 8.9 years (2–23 years) and underwent an average of, 7.5(3–24) minor perianal surgeries before the treatment., 38% (16) of patients had anorectal stenosis at the time of the treatment. Patients were treated on average, 25 months (6–84) by stable immunosuppressive and/or biologic therapy. Locally, it was complex fistulas, mostly high trans-sphincteric with, 1–3 external openings (EO) (78.6%;, 33 pp had, 1 EO) and with, 1–2 internal openings (IO) (14.3%;, 6 pp had, 2 IO). Patients were monitored for an average of, 10.5 months (range;, 4–26 months). Complete healing occurred in, 76% patients (32), partial response in, 11.9% (5pp) and treatment failure was in, 5 patients (11.9%). PDAI before MSC surgery was on average, 9.7 (3–13), 3 months after surgery, 3.2 (0–13) and, 6 months after surgery, 2.6 (0–13) in patients who have healed or healed partially.

Conclusion
The treatment was more successful in real life than in PRS, which may be due to the relatively short follow-up period. Another reason for better outcome could be proper selection of patients with long term stable conservative treatment, which demonstrates stable CD. In our conditions, this treatment is similarly effective as eradication of the fistula using AF, but it can also be used in difficult conditions such as anorectal stenosis or chronic changes in the rectal mucosa.
P363 Are clinical decision support tools for vedolizumab and ustekinumab in biologic naïve patients with Crohn’s disease drug-specific?
Authors: Kim J E , Won H , Kim Y H , Kim E R , Hong S N , Chang D K , Won Hojeong 
Published: January 2022

Abstract

Background
Clinical decision support tools (CDST) were developed to predict drug response with introduction of various biologics to Crohn’s disease (CD) treatment. This study aimed to determine whether CDST’s for vedolizumab (V-CDST) and ustekinumab (U-CDST) could be used as prognostic markers or drug-specific markers to predict response.

Methods
A hypothetical scenario was created with, 872 CD patients who used first biologic at Samsung Medical Center between, 1995 and, 2020. V-CDST & U-CDST were calculated with clinical and laboratory data just before the first biologic was started. Cumulative Link Mixed Model (CLMM) test, weighted Kappa and plot, and Spearman’s correlation statistical techniques were used to check the degree of agreement and difference between the two tools.

Results
Twenty-five percent of biologic naïve CD patients could be categorized to different probability group using V-CDST and U-CDST. The difference between the two tools was significant [Two-sample Paired Ordinal Test with Cumulative Link Mixed Model (CLMM), p value &lt;, 0.001)]. Concordance between the two tools with a total of, 654 people (75% of all patients) was evaluated to have the same probability (weighted Kappa:, 0.47, 95% CI:, 0.41–0.52).

Conclusion
V-CDST and U-CDST are similar and different. V-CDST and U-CDST are useful for choosing vedolizumab or ustekinumab in, 25% of biologic-naïve CD patients in our hypothetical scenario.
P368 Safety issues of azathioprine in patients with inflammatory bowel disease: clinical experience from a referral center
Authors: Fousekis F , Kourtis G , Saridi M , Albani E , Katsanos K , Christodoulou D 
Published: January 2022

Abstract

Background
Despite the development new agents for inflammatory bowel disease (IBD) therapy, azathioprine (AZA) is widely used as both as monotherapy and as combination therapy for induction and maintenance of remission both Crohn’s disease (CD) and ulcerative colitis (UC). Aim of this study is to investigate the long-term safety of AZA, to document the prevalence of adverse events of AZA in patients with IBD.

Methods
In this retrospective study, we included, 222 patients with IBD, who were monitored at University hospital of Ioannina from, 2003 to, 2019. The diagnosis of IBD was made based on endoscopic and histologic findings after ileocolonoscopy with biopsies. Inclusion criteria of study were diagnosis of IBD and regular follow-up intervals at least every six month after start of AZA administration.

Results
The average age of patients was, 46.9 years (Std. Dev., 17,9) at start of AZA administration., 65.6% of IBD patients (146/222) had CD and, 34.4% had UC (76/222). The mean duration of AZA administration was, 51 months (range:, 0–135 months). The most frequent location of CD was ileocolonic (38.4%, 56/146), while the most patients with UC had left sided colitis (54%, 41/76). Furthermore, the main indication for AZA treatment was the maintenance of remission both in UC and CD. The most common dose of AZA was, 100mg/day (range:, 50-200mg). The most common adverse events were gastrointestinal symptoms (8.6%, 18/222), leucopenia (2.7%, 6/222), hepatotoxicity (5.4%, 12/222) and pancreatitis (1.8%, 4/222). Two patients were diagnosed with basal cell cancer. Infections were recorded in, 19 patients (8.6%) of whom, 6 needed hospitalization.

Conclusion
According to this retrospective observational study, approximately one-third of IBD patients receiving AZA presented clinical significant adverse event during follow-up. Azathioprine withdrawal or dose reduction was needed in, 47 (21%) patients.
P374 Front loading infliximab dosing regimen improves outcomes in Crohn’s Disease perianal fistulas
Authors: Lloyd A , Wilkinson A , Aleman Gonzalez H , Ramachandran S , Whitehead E , Pattinson A , Stamp K , Turnbull J , Talbot A , Sebastian S 
Published: January 2022

Abstract

Background
Higher infliximab maintenance trough levels are found to be associated with higher perianal fistula healing rates in Crohn’s Disease. The relevance of accelerated front loading dosing in perianal fistula has not been determined. This study aimed to establish whether front loading with a higher dose infliximab regime at induction is associated with better fistula outcomes.

Methods
Crohn’s Disease patients with perianal fistulas treated with infliximab in a tertiary referral centre IBD unit were included. Patients were categorised as standard or front loading based on induction dose infliximab of, 5mg/kg or, 10mg/kg. The target for infliximab maintenance trough levels was &gt;10mcg/mL. The primary outcome was the need for reintervention (defined as repeat abscess drainage, seton re-insertion, diverting stoma or proctectomy) at, 12 months post initiation of treatment. Secondary outcomes were the proportion of patients having clinical healing, radiologic healing and combined clinical and radiologic healing. Drug levels post induction and post first maintenance were evaluated. The proportion of patients needing dose escalation or de-escalation were also assessed. Chi-squared or Fisher exact tests were used to compare categorical variables and Kaplan-Meier survival curves were plotted for re-intervention free survival.

Results
Seventy-nine patients were included in analysis (Males: Females, 36:43, median age with fistula = 31). Seventeen (22%) of patients received a front loading dose of, 10mg/kg while sixty-two (79%) patients received the standard dose of, 5mg/kg among whom, 70% had dose escalation. Need for reintervention was significantly lower in patients who received a front loading dosing schedule compared to the standard dose (2/17 (12%) vs, 26/62 (42%), p=0.02) (Figure, 1). Higher clinical fistula healing rates were observed with front-loading dosing (82% vs, 45%, p=0.008). Radiologic healing in those who had follow up Magnetic Resonance Imaging (MRI) was not significant between both groups (8/17 (47%) vs, 20/62 (32%), p=0.133). Target therapeutic infliximab levels at maintenance was achieved in, 14/17 (82% of the patients receiving front loading dosing, while this was achieved in only, 2 of the, 43 (5%) tested patients with standard dosing. Reintervention requirement rates were higher in those patients with suboptimal maintenance levels (17/44 (39%) vs, 2/16 (12.5%), p=0.01). The Kaplan-Meier curves confirm that the front loading dosing regimen does prevent the need for reintervention (p=0.03) (Figure 2).
Figure1:

Figure 2:

Conclusion
Front loading with higher infliximab dose achieves better fistula healing and reduce the need for reinterventions in Crohn`s disease with perianal fistula.
P390 Efficacy and safety of mesenchymal stem cell therapy with darvadstrocel for complex perianal fistulizing Crohn′s disease: multicentric experience in the Basque Country and Navarre
Authors: Elorza A , Arzallus T , Izagirre A , Vicuña M , Rodriguez C , Cabriada J L , Rodriguez-Lago I 
Published: January 2022

Abstract

Background
Perianal fistulizing Crohn′s disease has a negative impact on patients′quality of life and despite advances in medical and surgical treatment, high rates of recurrence are still reported. Mesenchymal stem cell therapy has recently been authorized for the treatment of complex perianal fistulas in adult patients with Crohn’s disease, and it may be an effective and safe alternative. The aim of this study was to evaluate the results of efficacy, defined as combined clinical and radiological remission, and safety after administration of darvadstrocel.

Methods
A retrospective and observational analysis of patients with complex perianal disease treated with darvadstrocel at three centers in Spain were included. The inclusion criteria and the surgical technique followed the specifications from the Ministry of Health and Consumption. Follow-up visits were performed at, 6 and, 12 months after the treatment and evaluated by clinical disease activity and pelvis magnetic resonance.

Results
From November, 2020 to July, 2021, 13 patients (mean age, 39 years, IQR, 30–48, 69% males) were treated with mesenchymal stem cell therapy. The most common type of fistulas were transsphinteric (77%), high intersphinteric (15%) and the suprasphinteric (15%), the latter associated with other types of fistulas. All patients received concomitant anti-TNF (61%), ustekinumab (31%) or vedolizumab (8%). Eight patients (62%) have reached the, 6-month follow-up, five (62%) of them have had combined response, one patient (13%) had radiologic response and two (25%) showed disease progression (Figure, 1). Among those patients with &lt;6 months follow-up, four (80%) of them have shown clinical response. Most of the patients (77%) had no adverse events related to therapy. One patient had rectal bleeding and two patients developed a new fistula or abscess, with no need for reintervention in any of them.

Conclusion
The initial experience with mesenchymal stem cell therapy show promising results in terms of effectiveness and safety in the short term in complex perianal disease. A longer follow-up period is still needed to confirm these promising data.
P397 Can upskilling pharmacy technicians support a robust and cost-effective Inflammatory Bowel Disease patient review process? A single-centre prospective study
Authors: Rees F , Packham A , St Clair Jones A , Smith M 
Published: January 2022

Abstract

Background
Immunomodulators are key to the management of Inflammatory bowel disease (IBD). To ensure safety and efficacy, UK guidance recommend immunomodulator review.
At University Hospitals Sussex (UHS), reviews are completed by a multi-disciplinary team (MDT), with specialised IBD pharmacists and nurses leading on autonomous blood monitoring and symptom review (figure 1).
This workload puts considerable strain on the UHS IBD team. Upskilling and task shifting is recognised as legitimate strategy for service enhancement, care access, cost effectiveness and sustainability plus ensures team flexibility, boosted morale and career progression.
The UHS IBD team includes a highly motivated pharmacy technician (PT). In the UK, PT are registered non-prescribing healthcare professionals, but training does not include autonomous blood monitoring and symptom review.

Methods
To ensure competency of autonomous blood monitoring and symptom review, a training package was developed and was approved by UHS Medicines Governance Group.
Once accredited, PT prospectively recorded blood monitoring and symptom review activity over, 10-weeks (figure 2 and, 3) and referrals completed (figure 4).

Results
The training package was completed in, 10 weeks.
Over, 10 weeks, PT completed, 699 distinct monitoring activities, with, 57 (8%) needing referral to the specialised pharmacist.
The highest proportion of workload was observed in the IBD infusion clinic (314, 45%), followed by thiopurine monitoring (250, 36%) and then ‘others’ (135, 19%). ‘Others’ were essential IBD activities including faecal calprotectin levels (FCPL), pre-initiation tests (e.g. thiopurine methyltransferase levels (TPMT), viral screening, t-spots) and medication levels to optimise therapy.
All referrals to the specialised pharmacist were appropriate as needed action by a prescribing professional.
In addition, PT contributed substantially to data collection for virtual biologic clinic (VBIC) reviews;, 32 patients.
Feedback has been overwhelmingly positive from all effected stakeholders (PT, IBD pharmacy and nursing team and gastroenterologists).

Conclusion
Identifying appropriate tasks and upskilling the IBD PT has enabled a more cost-effective and efficient use of IBD workflow, care standardisation, team robustness and staff morale.
Approved training and support are required to enable upskilling and continued service safety and we recommend that skills are recognised locally and nationally.