bluuebunny/crossref_metadata_2025 huggingface dataset:
P265 Open approach for ileocolic resection in Crohn’s disease in the era of minimally invasive surgery: indications and perioperative outcomes in a referral centre
Authors: Calini G , Abdalla S , Abd El Aziz M A , Benammi S , Merchea A , Behm K T , Mathis K L , Larson D W
Published: January 2022

Background

Minimally invasive surgery (MIS) is the first-line approach for ileocolic resection in patients with Crohn’s disease (CD) and it is safe and feasible even in complex cases. However, an open approach is still required, but indications to open ileocolic resection for CD are not well described.

Methods

All consecutive adult patients with CD who underwent elective ileocolic resection in the Departments of Colon and Rectal Surgery at Mayo Clinic Rochester, Minnesota and Jacksonville, Florida between September 2014 and March 2021 were included and divided into “open” and “MIS” groups. Open approach was defined as upfront laparotomy, MIS included laparoscopic and robotic approaches, and conversion was defined as incision made earlier than planned. Indications to open approach were retrospectively reviewed by two authors, and any incongruity was resolved. Analogous indications were also assessed in the MIS group, as appropriate. Indications, baseline, perioperative characteristics, and short-term postoperative outcomes were compared between open and MIS.

Results

Among 319 ileocolic resections for CD, 45 (14.1%) were open and 274 (85.9%) MIS. Indications for open approach were severe disease, adhesions at previous surgery, history of abdominal sepsis, multifocal and extensive disease, abdominal wall involvement, concomitant open procedures, small bowel dilatation, and anaesthesiologic contraindications (Table 1). In addition, two or more of the above indications were present in 40 patients (89%) in the open group, while only in 6 patients (2%) in the MIS group (p<0.001). Compared to MIS patients, patients undergoing open ileocolic resection were older, with longer CD duration, more previous surgery and preoperative intra-abdominal abscess drainage (Table 2). Nine patients were converted in the MIS group (3.3%). Intraoperatively, open group had more adhesiolysis ≥45 min, more intraoperative complications, more blood loss, more primary stoma, less anastomosis, and longer operative time (Table 3). Postoperatively, they had more overall postoperative complications, ileus, surgical site infections, dehydration, vascular thromboembolism, higher severity by Clavien-Dindo classification, and longer length of stay (Table 4).

Conclusion

Overall rate of open approach ileocolic resection for CD was 14 % during a 7-years period in a referral centre. Open approach was the only operation performed in cases of abdominal wall involvement, concomitant open procedures, and anaesthesiologic contraindication. In addition, the presence of at least two indications,predicting high technical complexity, may be considered as a no-go for the MIS approach in ileocolic resections for CD.
P267 Milan Ultrasound Criteria are accurate in assessing endoscopic remission and treatment response in patients with ulcerative colitis
Authors: Allocca M , Dell’Avalle C , Radice S , Furfaro F , Zilli A , D’Amico F , Peyrin-Biroulet L , Fiorino G , Danese S
Published: January 2022

Background

We assessed the accuracy and the responsiveness to change of Milan Ultrasound Criteria (MUC) in patients with ulcerative colitis (UC), using colonoscopy as the reference standard.

Methods

We performed a prospective observational study of 49 patients with active UC. All patients underwent bowel ultrasound and colonoscopy at baseline and at reassessment, at week 48, after treatment with biologics (29 patients were treated with infliximab, 14 with vedolizumab, four with adalimumab, two with ustekinumab). Furthermore, patients underwent bowel US also at week 12 and 24. Disease activity was quantified using Mayo endoscopic subscore and MUC. The primary analysis was to determine the accuracy of MUC in identification of endoscopic remission defined as a Mayo endoscopic subscore < 2. Additional analyses established the accuracy of MUC in determining change in lesion severity. Logistic regression was used to examine the relationship between the absence or presence (0/1) of endoscopic remission at reassessment as the dependent variable and possible predictors at week 12 as the independent variables. The model was performed using the stepwise backward method.

Results

Eighteen patients (37%) got endoscopic remission at reassessment. In Table 1 are summarized endoscopic and ultrasound outcomes achieved at reassessment according to the different treatments. MUC < 6.2 determined endoscopic remission with 83% sensitivity, 84% specificity, 84% accuracy, 75% PVP and 90% PVN (Table 2). MUC was sensitive to change in ulcerative colitis [Guyatt’s responsiveness index: 1.73; standardised effect size ratio: 2.0]. MUC changed significantly from baseline to reassessment [8.72 (7.78−9.14) vs 7.60 (4.71−8.53), p < 0.0001], with the largest drop at week 12 [8.72 (7.82−9.19) vs 7.46 (5.80−7.98), p < 0.0001] (Figure 1). A change of -2 in MUC overtime predicted endoscopic remission at reassessment (AUC 0.806, 95% CI 0.667–0.904; sensitivity 89%, specificity 77%). At multivariable analysis only MUC < 6.2 at week 12 was statistically significantly associated with endoscopic remission at reassessment (Table 3).

Conclusion

MUC accurately detects endoscopic remission. MUC is a highly responsive, reliable tool for assessing treatment response in patients with ulcerative colitis.
P271 Fecal calprotectin at diagnosis is associated with oral steroid use first year of Inflammatory Bowel Disease
Authors: Strande V , Småstuen M C , Huppertz-Hauss G , Perminow G , Henriksen M , Bengtson M B , Høie O , Ricanek P , Opheim R , Cetinkaya R B , Torp R , Vatn S , Aabrekk T B , Detlie T E , Hovde Ø , Høivik M L , Kristensen V A
Published: January 2022

Background

Fecal (f-) calprotectin is demonstrated to predict forthcoming flares in Inflammatory Bowel Disease (IBD). Predictive value in newly diagnosed IBD is scarcely studied. The aim of this study was to investigate if high or low f-calprotectin at time of diagnosis of IBD was associated with need of steroids during first year of disease in a population-based inception cohort study (IBSEN III).

Methods

Newly diagnosed IBD patients >18 years, enrolled from the South-Eastern Health Region of Norway in the period of 2017–2019, were studied. Age, gender, smoking status, CRP and level of f-calprotectin were registered at diagnosis. At one-year follow-up, oral and intravenous (IV) steroid use during first year of disease were registered. Associations between high levels of f-calprotectin (≥ 500 mg/kg) at diagnosis and steroid use were tested using logistic regression analyses. A p-value of 0.05 was considered statistically significant.

Results

At baseline, 352 adult patients with Crohn’s disease (CD) and 702 patients with ulcerative colitis (UC) provided samples for f-calpotectin and were included in this study. Steroid use (both IV and oral) was associated with higher levels of f-calprotectin. When adjusted for CRP, age, gender and smoking status, the association remained statistically significant for oral steroid use (CD: OR=2.21, 95%CI [1.25; 3.93], p=0.007. UC: OR=1.87, 95%CI [1.26;2.78], p=0.002), however not for IV steroid use.

Conclusion

High level of f-calprotectin at time of diagnosis is associated with oral steroid use during the first year of disease for patients with IBD.
P277 Assessment of fatigue as a patient-reported outcome: Correlation with baseline disease activity and therapy response in Inflammatory Bowel Disease
Authors: Tran F , Schrinner F , Nikolaus S , Kümpers J , Sievers L K , Lessing A , Lintner J , Lessing M , Rosenstiel P , Aden K , Franke A , Schreiber S
Published: January 2022

Background

Currently available disease activity indices for IBD (e.g., CDAI and Mayo score) focus on symptoms directly related to intestinal function, while other relevant health consequences of disease activity including quality of life, neuropsychiatric symptoms like depression, and social functionality, are not captured. With better therapies more stringent definitions of patient health have come into focus. One of the most common patient reported outcomes (PROs) in IBD is fatigue, which can be unrelated to endoscopic disease activity. We have shown earlier a strong degradation of tryptophan in active IBD (Nikolaus et al, 2017, Gastroenterology) and low tryptophan levels have been linked in various chronic disease to high fatigue levels. Here, we aim to study the relationship of fatigue with disease activity in the context of therapy response to a biological treatment.

Methods

Patients with Crohn’s disease and ulcerative colitis with high disease activity (Mayo score ≥ 6, CDAI ≥ 220) and planned new therapy with a biologic agent were included into a prospective observational protocol. After informed consent, clinical disease activity, inflammatory biomarkers, tryptophan levels in serum and fatigue levels were assessed longitudinally at week 0, 2, 6 and 14 after start of induction therapy. Complete assessments including week 14 were available for 38 patients for this interim analysis of the ingoing study. For fatigue assessment we used the validated German version of the fatigue subscale of the FACIT-F questionnaire. Patients were stratified into therapy responder (clinical remission (CR), reduction of partal Mayo score (pMayo) > 50%, CDAI < 150), non-responders (reduction of Mayo <30%, CDAI reduction <70) and partial responders at week 14.

Results

In the cross-sectional analysis of all patients (n = 76), the fatigue score strongly (inversely) correlated with pMayo and CDAI and correlated positively with tryptophan levels in serum. In receiver operating characteristic (ROC) analysis, FACIT-F score were able distinguish active vs. non-active disease (p < 0.0001, AUC = 0.7619) with specificity of 0.7103 and sensitivity of 0.7160. We did not observe significant differences in fatigue scores between males and females. In the longitudinal analysis, fatigue score only improved in the CR group (n = 25, median FACIT score 30 at baseline vs. 44 at week 14, p = 0.0221), and was significantly higher in CR vs. non-responder (n = 16, median FACIT score 44 vs. 31.5, p = 0.007).

Conclusion

Fatigue is strongly related but not completely overlapping with disease activity. Fatigue will be evaluated as a a patient-oriented indicator for therapeutic response. This observation will be extended by increasing the cohort size and independent validation.
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

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

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

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

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

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 <, 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

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

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 >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

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 <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

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.
P413 Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b2 vaccines in the immunosuppressed (RESCUE)
Authors: Tran A P , Tassone D , Nossent J C , Ding N S
Published: January 2022

Background

Immunocompromised patients are inherently vulnerable to severe outcomes to vaccine preventable infections compared to the general population. This study aims to investigate the impact of immunosuppression on response to the ChAdOx1nCov-19 and BNT162b2 vaccines to better inform vaccination efforts in this cohort.

Methods

A three-armed randomised controlled trial was performed. Patients with autoimmune disorders on immunosuppressive therapies and healthy controls were recruited from two sites. Participants receiving immunosuppression were randomly assigned to either withhold or continue treatment contemporaneous to vaccine administration. Serum SARS-Cov2 immunoglobulin assays were performed at baseline and, 4-weeks following first and second vaccine doses. Between group comparisons were performed to examine differences in vaccine seroconversion and immunogenicity.

Results

A total of, 253 participants of median age, 55 years (IQR:, 45.5–64) including, 193 patients receiving immunosuppression and, 60 healthy controls were studied. Immunosuppressed patients were randomly allocated to continue (n=105) or withhold (n=88) treatment. Of those receiving immunosuppression, 27.08%, 40.63% and, 32.29% of patients were exposed to cDMARDs, bDMARDs and tsDMARDs respectively while rates of BNT162b (Pfizer) vaccination were, 52.33%, 60.67% and, 48.33% among the continue, withhold, and control groups respectively. Post-first dose vaccination seroconversion rates were highest among healthy controls (90%) and patients who temporarily withheld immunosuppressants (76.32%) compared to patients continuing treatment (48.24%) p=0.000. Post-second dose vaccination seroconversion rates were, 100% in both the control and withhold groups and, 86.75% in the continuation (p=0.001). Mean quantitative serum SARS-CoV-2 IgG titres were, 8.58 U/ml, 5.11 U/ml and, 3.29 U/ml (p=0.0001) between the controls, withhold and continue groups respectively following first vaccination. While post-second vaccination mean serum IgG titres were, 96.31 U/ml, 91.86 U/ml, and, 49.73 U/ml (p=0.0066) between these groups.

Conclusion

COVID-19 vaccine response in terms of seroconversion and the level of antibody production was highest among healthy controls compared with patients with autoimmune diseases receiving immunosuppression. Temporary cessation of immunosuppressant therapy, contemporaneous to COVID19 vaccination appears to improve vaccine response in this cohort.
P418 Development and validation of a digital health platform (IBD NutriCare) for telenutrition in patients with Inflammatory bowel disease
Authors: Gupta A , Singh N , Madan D , Farooqui M , Singh N , Singh M , Virmani S , Verma M , Bajaj A , Markandey M , Kante B , Vuyyuru S K , Kumar P , Sahu P , Makharia G , Kedia S , Ahuja V
Published: January 2022

Background

Introduction-Telenutrition with digital health platforms is the future step towards improving patient care in patients with inflammatory bowel disease(IBD). Additionally, it offers an advantage of conducting multicenter longitudinal dietary intervention studies. Aim-To develop and validate a digital health platform for patients with IBD to provide nutrition care and record longitudinal diet data on a large-scale basis.

Methods

Methods-The development of the digital health platform was done from October, 2019 -June, 2021 by gastroenterologists and dieticians. For validation, patients with IBD at All India Institute of Medical Sciences, New Delhi recorded, 7 days diet in the App. 24-hours diet recall for, 3 days at random during the same week was also done. Energy, protein, carbohydrate, fat, fiber, cereals, fruits, vegetables, grain, legumes, milk products were compared between two methods.

Results

Results-An Android and iOS-based digital health platform, ‘IBDNutriCare’ was developed in English and, 7 Indian languages. This user-friendly interface can be downloaded by the patients free of cost from Google store and App store. This platform provides a recording of diet variables based on, 600 Indian food recipes, patient parameters like subjective global assessment, medications, and clinical activity scores. It also provides a graphical representation of nutrient analysis, with web applications generating comprehensive reports to enable large-scale data analysis. Forty-nine patients with IBD were enrolled in a validation study comparing ‘IBDNutricare’ based analysis with dietary recall method. The mean intake of all food groups and macronutrients was comparable between the two methods. There was a significant interclass correlation [excellent for macronutrients and all food groups except vegetables (moderate, 0.79] and Bland-Altman plot analysis showed good agreement between the two methods.

Conclusion

Conclusion- This study developed and validated a digital health platform for telenutrition in patients with IBD. This app helps in real-time tracking of dietary details and recording the data on a large scale.
P420 Long term efficacy of ustekinumab in Crohn’s disease patients after vedolizumab failure
Authors: Melotti L , Dussias N K , Belluzzi A , Salice M , Calabrese C , Rizzello F , Gionchetti P
Published: January 2022

Background

Ustekinumab (UST) and vedolizumab (VDZ) are approved biologic therapies for moderate-to-severe Crohn’s disease (CD). Data regarding their comparative efficacy in patients previously treated with anti-TNF agents are available. However, data is lacking regarding their long-term effectiveness after failure of a second or third-line biologic treatment. Our aim is to evaluate ustekinumab efficacy after swapping from vedolizumab therapy for primary or secondary failure.

Methods

We conducted a single-centre, retrospective study in CD patients treated with UST as third line biologic therapy who swapped from VDZ therapy upon failure between January, 2019 and October, 2021. We assessed clinical (HBI), laboratoristic (CRP), endoscopic (SES-CD) activity and use of steroids at the beginning of ustekinumab therapy and after, 12 months of treatment. We also collected data regarding previous biologic treatments. Clinical remission was defined as HBI <, 5, while clinical response was defined as a reduction of at least three points of HBI from baseline and/or the suspension of steroids.

Results

Of, 43 patients treated with UST after VDZ failure, 26 had a minimum follow up of, 12 months and were included in the study. All patients had previously been treated with antiTNF agents. After, 12 months, 4 patients have suspended treatment for failure; among patients still on treatment, clinical remission was evident in, 63% (n = 14) of cases, 13 of them were also in laboratoristic remission. Endoscopy at, 12 months was available in, 11/14 patients in clinical remission; of these, 6 (55%) were in endoscopic remission. In patients who did not achieve clinical remission, 18% (n = 4) obtained clinical response. The last, 18% (n = 4) of patients persisted on therapy.

Conclusion

Ustekinumab seems to be a viable and effective therapeutic option in patients with failure to multiple prior biologic therapies, obtaining deep remission after, 12 months of treatment in a large proportion of patients.
P425 Rates of tuberculosis infection in Crohn’s Disease patients before and during anti-tumor necrosis factor therapy
Authors: Georgieva PhD A C , Atanassova A , Mirchev M
Published: January 2022

Background

In the last, 20 years, IBD treatment has made great progress with the implementation of biological drugs. Although the use of anti-tumor necrosis factor-alpha (anti-TNF-α) agents is highly effective in achieving and maintaining remission, 1, anti-TNF-α agents are associated with a, 5-fold increased risk of reactivation of various opportunistic infections, including TBI, 2,3.

Our study aims to determine the incidence of TBI (active tuberculosis (ATBI) and latent tuberculosis (LTBI)) among patients with Crohn’s disease (CD) receiving anti-TNF-α therapy.

Methods

For the period between June, 2010 to December, 2019, we performed a retrospective analysis of a total of, 109 CD patients, screened before the start of biological treatment. Anti-TNF-α therapy was initiated by, 97 patients, 74 of whom were retested for TBI during follow-up. All patients were BCG vaccinated.

Results

Before starting biological treatment, we etablished LTBI in, 11/109 (10.1%):, 8/11 (72.7%) patients were TST (+) alone, 2/11 (18.2%) were IGRA (+) and TST (-), 1/11 (9.1%) were both IGRA and TST (+). Chest x-ray abnormalities were not detected in all, 11 patients.

After prophylaxis with isoniazid (INH), 300 mg / daily for, 9 months, 9/11 (83.3%) patients with LTBI reached treatment with an anti-TNF α agent. Of this group, 7/9 (77.8%) patients were retested for TBI:, 6/7 (85,7%) were TST and IGRA were (-), and one (14,3%) developed active pulmonary tuberculosis. Two patients were lost to follow up.

In the follow-up of patients under anti-TNF-α therapy, 74/97 (76.3%) patients were retested for TBI, with median duration of anti-TNF-a therapy was, 24 (IQR, 6–90) months.

A total of, 16/74 (21.6%) patients were newly diagnosed with LTBI:, 5/16 (31.3%) had TST conversion alone, 8/16 (50.0%) were TST(+) and IGRA (-), 1/16, 6.3%) were both TST and IGRA (+), 1/16 (6.3%) had IGRA conversion alone, 1/16 (6.3%) were TST (-) and IGRA (+).

ATBI developed in, 3/74 (4.1%) patients, one of them on the background of chemoprophylaxis with INH for LTBI. Median duration after the first dose of biologic therapy to detection of TBI was, 12 (IQR, 6–60) months.

Conclusion

This study instruct the clinician to be specifically vigilant when initiating anti-TNF-α therapy in IBD patients, because reactivation of TBI is a life-threatening complication in immunosuppressed patients.
P436 Efficacy and safety of biosimilars of anti-TNF-a in paediatric-onset Inflammatory Bowel Disease: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)
Authors: Dipasquale V , Pellegrino S , Cucinotta U , Citrano M , Graziano F , Cappello M , Busacca A , Orlando A , Accomando S , Romano C
Published: January 2022

Background

Few data regarding the use of biosimilars of anti-tumour necrosis factor-a (TNF-a) in children with Inflammatory Bowel Disease (IBD) have been reported. We aimed to assess the efficacy and the safety of biosimilars of infliximab (IFX) and adalimumab (ADA) in paediatric-onset IBD.

Methods

This was a multicentre, observational, retrospective study performed among the cohort of the Sicilian Network for the Inflammatory Bowel Disease (SN-IBD) and including all patients with paediatric-onset IBD treated with the biosimilars of IFX or ADA. Demographic and clinical data were collected from medical records. PUCAI and PCDAI scores at the time of IFX start, after, 14 and, 54 weeks were recorded. The primary outcome was the rate of clinical remission at weeks, 14 and, 54. Secondary outcomes included treatment duration and incidence of adverse events.

Results

They were included, 128 patients, of whom, 87 on IFX biosimilar (group, 1) and, 41 on ADA biosimilar (group, 2) (Table 1).

Table, 1.Baseline characteristics of patients

At week, 14, UC patients on IFX biosimilar had a median PUCAI score of, 10 (IQR, 5.0–22.5), while CD patients a median PCDAI score of, 5 (IQR, 5.00–10.8). Overall, the remission rate on IFX biosimilar at week, 14 was, 61.5%, and it was significantly associated with positive family history [OR, 13.18 (2.44–245.65, p=0.015)], older age at starting biosimilar [OR, 1.19 (1.02–1.41, p=0.038)], and diagnosis of CD (in comparison to UC) [OR, 3.45 (1.35–9.23, p=0.011)]. At week, 54, both UC and CD patients on IFX biosimilar had a median clinical score of, 5. The remission rate was, 69.1%, and no significant association with any variable was found. Patients on ADA showed a remission rate of, 75% at, 14 weeks, and of, 70% at, 54 weeks, both associated with shorter disease duration [OR, 0.67 (0.45–0.93, p=0.025) and OR, 0.55 (0.28–0.86, p=0.026), respectively]. At, 54 weeks, patients on IFX showed a >90% failure-free survival (Figure, 1), which was inversely associated with the presence of extraintestinal manifestations (HR, 5.12, p=0.014) and non-naive patients (HR, 3.81, p=0.025). Patients on ADA biosimilar had >83% failure-free survival at, 12 months (Figure, 2), associated with shorter disease duration (HR, 1.41, p=0.043). About safety, a total of, 13 adverse events were registered, 9 in group, 1 (incidence of, 6.13/100 PY) and, 4 in group, 2 (incidence of, 12.23/100 PY). Most (n=7) were acute infusion reactions.

Figure, 1.Failure-free survival on IFX biosimilar

Figure, 2.Failure-free survival on ADA biosimilars

Conclusion

This is one of the largest cohorts of paediatric-onset IBD on biosimilars, and confirmed these drugs are effective and safe in this group of patients, with high percentage of failure-free survival at, 1 year and low incidence of mild adverse events.