bluuebunny/crossref_metadata_2025 huggingface dataset:
P422 How achievable are the STRIDE-II treatment targets in real-world practise and do they affect outcome?
Authors: Routledge E , Meade S , Sharma E , Zeki S , Ray S , Anderson S , Sanderson J , Mawdsley J , Samaan M
Published: January 2022

Background

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative provides recommendations on treatment targets for patients with Crohn’s disease (CD). The Simple Endoscopic Score for CD (SES-CD) is a validated endoscopic score and STRIDE-II recommends its use in clinical practice. We aimed to assess whether the STRIDE-II endoscopic endpoints are achievable and whether the degree of mucosal healing (MH) affects long term outcomes.

Methods

This is a retrospective observational study from, 2015–2020. We included patients with CD who had a baseline and follow-up SES-CD score after biologic therapy initiation. Data was collected via electronic records. The primary outcome was treatment failure, defined as the need for: i) change of biological therapy ii) corticosteroid use iii) CD-related hospitalisation or iv) surgery. We compared rates of treatment failure with the degree of MH achieved. Patients were followed up until treatment failure or study end (Aug, 2021). Statistics were performed using GraphPad v9.1.0 Software.

Results

50 patients were included (Fig, 1). Table, 1 shows the baseline characteristics. The median time to interval colonoscopy was, 16.3 (11.2–21.3) months. The proportion of patients achieving STRIDE-II end-points were: SES-CD (28, 56%), absence of ulcers (25, 50%) and endoscopic response [50% reduction in SES-CD] (31, 62%). Combined remission (SES-CD and Harvey Bradshaw Index [HBI] <5) occurred in, 25 cases (50%). Treatment failure occurred in, 13 (26%) patients: biologic switch (7/50, 14%), corticosteroids use (2/50, 4%), CD-related admission (5, 10%), or surgery (6, 12%). Median time to treatment failure was, 19 months.

Fig, 2 shows the cumulative risk of treatment failure according to the achievement, or otherwise, of STRIDE-II endoscopic targets. Additionally, we show outcomes for combined endoscopic and clinical remission (HBI<5). Failure to achieve SES-CD or a, 50% improvement in SES-CD were the strongest predictors for treatment failure.

Conclusion

In real-world clinical practice, calculating SES-CD scores at serial endoscopies is feasible and STRIDE-II targets are achievable in a reasonable proportion of patients (50%). Furthermore, achieving these targets has favourable long-term, clinically relevant outcomes.
P429 Mesalazine has no place in the treatment of Crohn’s disease. Really?
Authors: Mantzaris MD- PhD- AGAF- FEBG- MACG G , Archavlis E , Christidou A , Viazis N , Karampekos G
Published: January 2022

Background

According to international guidelines mesalazine may have no place in the treatment of Crohn’s disease (CD). However, real-world studies have shown a defined, 5-ASA-dependent group of patients with CD whereas a large proportion of CD patients in the community is still being treated with mesalazine. We aimed at studying the clinical, biomarker and endoscopic characteristics and the course of disease in a selective group of patients on maintenance treatment with mesalazine since the diagnosis of CD.

Methods

This is a prospective, single-center study. Patients followed in IBD clinic were included in a, 15-yearlong observational study starting in the, 1st year after confirmed diagnosis of CD provided that they were in deep remission defined as clinical remission (Harvey-Bradshaw Index, HBI, <5, with normal biomarkers [C-reacting protein (CRP) <0.6 mg/dl and/or Faecal Calprotectin (FC) <150 μg/g faecal tissue] and complete or near complete mucosal healing (<10 or <5 focal micro-aphthous or aphthous ulcers, respectively) assessed by ileocolonoscopy and/or capsule endoscopy. Patients with normal HBI but persistent elevations of CRP and/or FC at baseline were excluded. Patients were followed prospectively every, 3–6 months with HBI score, FBC, LFTs, CRP and/or FC; ileocolonoscopy or CE were performed every, 2–3 years unless they had a flare of CD. Patients who during follow up developed a flare (HBI>4) associated with persistently abnormal CRP and FC and deterioration of the endoscopic findings vs baseline were considered as treatment failures.

Results

Patient demographic, clinical, biomarker and endoscopic data at baseline and during the course of CD is shown in Table, 1. Ileocolonoscopy findings remained persistently unchanged in all but, 2 patients who developed a flare and needed escalation of treatment after, 2 and, 3 years, respectively. CE was performed at two different times during follow up in, 8 patients with L1 phenotype and did not show any change in the number of detected lesions. Overall, 35 of, 55 patients had a voluntary drug holiday for, 4–6 months resulting in a rise of HBI to, 6–8 and mild elevations of FC (200–300 μg/g) but not of CRP; however, clinical symptoms were relieved and HBI and FC returned to normal following re-initiation of mesalazine indicating, 5-ASA dependence. None of the patients reported disease complications or treatment-related adverse events

Conclusion

There is a distinct group of non-smoking patients with mild CD (on clinical, biomarker, and endoscopy grounds) at diagnosis who are in deep remission at the end of the, 1st year following treatment with mesalazine. These patients maintain a, 5-ASA-dependent deep remission as long as they are compliant with treatment.
P434 The PROPER study: interim analysis of a Pan-European real-world study of SB5 adalimumab biosimilar after transition from reference adalimumab in patients with Crohn’s disease
Authors: Dignass A U , Gisbert J P , Bossa F , Freudensprung U , Addison J
Published: January 2022

Background

SB5, a biosimilar to reference adalimumab (ADL), received EU marketing authorisation in August, 2017, based on pre-clinical and clinical phase I and III studies that demonstrated bioequivalence and comparable efficacy, safety and immunogenicity profiles to ADL. The real-world study ‘PROPER’ is designed to provide insights into outcomes of the transition from reference to SB5 outside the controlled, randomised, clinical trial setting. Under an umbrella design, 1000 patients with immune-mediated inflammatory disease have been enrolled at centres in Belgium, Germany, Ireland, Italy, Spain and the UK.

Methods

Eligible patients had been transitioned to SB5 as part of routine treatment following a minimum of, 16 weeks’ treatment with ADL. Data were captured from patient charts retrospectively for, 24 weeks prior to and prospectively and/or retrospectively for, 48 weeks after SB5 initiation. This interim analysis of the Crohn’s disease cohort reports outcome measures including clinical characteristics, disease activity, persistence on SB5, clinical management and safety for patients enrolled at, 32 specialist sites and followed up to the data extract date of October, 5th, 2021.

Results

Of the, 462 patients included in this interim analysis, the majority were enrolled in Germany (n=127), Spain (n=118) and Italy (n=79); Belgium, Ireland and UK enrolled, 56, 46 and, 36 patients, respectively. At time of data extract, 416 patients had completed, 48 weeks of follow-up and, 15 had withdrawn from the study.

The most common reasons driving transition were physician decision, or a mandate from the health authority or payer. At baseline, the majority of patients were in remission or had mild disease as determined by Harvey Bradshaw Index (HBI), and were in remission or stable according to physician opinion. Most patients transitioned to the same SB5 regimen as they had received for ADL (Table 1).

Twenty-four patients reported, 27 serious adverse events (SAE), of which, 4 (anal fistula [n=1], perianal abscesses [n=2] and subileus [n=1]) were considered by the study physician to be related to SB5 administration.

Conclusion

No meaningful change in HBI or SB5 dosing regimen was observed from baseline to Week, 48 after transition from ADL. The number of patients experiencing a treatment-related SAE was low, and no new safety concerns were detected. Thus, transition from ADL to SB5 was generally safe and effective in patients with Crohn’s disease over, 48 weeks of follow-up.

Acknowledgements:

This study was funded by Biogen International GmbH. Statistical services were provided by FGK Clinical Research GmbH, Munich, Germany. Data management services were provided by Worldwide Clinical trial, Research Triangle Park, NC, USA.
P435 High rate of vitamin deficiencies in patients after total proctocolectomy and pouch surgery- results from a prospective cohort
Authors: Elial-Fatal S , Pfeffer-Gik T , Raykhel B , Friedenberg A , Margolis L , Barkan R , Ollech J , Yanai H , Wasserberg N , White I , Dotan I , Godny L
Published: January 2022

Background

Patients with ulcerative colitis (UC) undergoing total proctocolectomy with ileal pouch anal anastomosis (pouch surgery) may be prone to develop nutritional deficiencies. Here we aimed to evaluate the rates of vitamin deficiencies and their risk factors in these patients.

Methods

Patients after pouch surgery were consecutively enrolled in a tertiary referral center. Pouch behavior determined clinically (normal pouch; recurrent acute pouchitis; chronic pouchitis; Crohn’s like disease of the pouch), disease activity, inflammatory markers and serum vitamin D, B12 and folic acid levels were repeatedly assessed. Body mass index (BMI) and the use of dietary supplements were recorded at each visit.

Results

A total of, 136 patients (mean age-, 47.5±16 years, mean BMI-, 24.9±5 Kg/m2, female gender, 58%) underwent, 721 study visits. Average visits/patients:, 5 (range, 1–15); between-visit interval:, 5±4 months. Normal pouch:, 41%, recurrent acute pouchitis, 24%, chronic pouchitis/ Crohn’s like disease of the pouch:, 35%. Vitamin D deficiency (<25 nmol/L) and insufficiency (25–75 nmol/L) were detected in, 6.5% and, 82% of patients, respectively. Vitamin B12 deficiency (<221 pmol/L) was detected in, 29%, and folic acid deficiency (<7 nmol/L) in, 9.5% of patients. After controlling for disease activity and inflammatory markers, vitamin D deficiency was positively associated with pouch age (i.e interval from the ileostomy closure, OR=, 1.47, 95%CI, 1.1–1.9, p=, 0.007). Vitamin B12 deficiency was positively associated with BMI (OR=1.07, 95%CI, 1.001–1.14, p=0.045), and folic acid deficiency was inversely associated with patient’s age (OR=, 0.95, 95%CI, 0.9–0.99, p=0.017). Of patients with vitamin D, B12 and folic acid insufficiencies or deficiencies, only, 60/121 (49.6%), 17/40 (42%), and, 4/13 (30%), respectively, reported the use of appropriate dietary supplements throughout the long-term follow-up.

Conclusion

In a longitudinal follow up of patients with UC after pouch surgery, we detected significant vitamin D, B12 and folic acid deficiencies and identified specific risk factors. Insufficient active correction with dietary supplements was noticed. Screening and improved correction of nutritional deficiencies should be a part of the routine pro-active multidisciplinary care of patients after pouch surgery.
P437 Reoperations and long-term survival of Kock’s continent ileostomy in Inflammatory bowel disease patients: a population based national cohort study from Sweden
Authors: Risto A , Andersson R E , Landerholm K , Bengtsson J , Block M , Myrelid P
Published: January 2022

Background

Kock’s continent ileostomy is an option after proctocolectomy for patients not suitable for ileal pouch anal anastomosis or ileorectal anastomosis. Ulcerative colitis is the most common indication for continent ileostomy. The aim of this study was to evaluate the long-term outcome of continent ileostomy.

Methods

All patients with inflammatory bowel disease and a continent ileostomy were identified from the Swedish National Patient Register. Data on demographics, diagnosis, reoperations, and excisions of the continent ileostomy was obtained. Patients with inconsistent diagnostic coding were classified as IBD-unclassified.

Results

Some, 727 patients were identified, 428 (59%) with Ulcerative colitis, 45 (6%) with Crohn’s disease and, 254 (35%) with IBD-unclassified. After a median follow-up time of, 27 (IQR, 21–31) years, 191 (26%) patients had never had revisional surgery. Some, 1,484 reoperations were performed on, 536 (74%) patients, the median number of reoperations was, 1 (IQR, 0–3) per patient. The continent ileostomy was excised in, 77 (11%) patients. Reoperation within the first year after reconstruction was associated with higher rate of revisions (IRR, 2.90 p<0.001) and shorter time to excision (HR, 2.38 p<0.001). Constructing the continent ileostomy after year, 2000 was associated with increased revision and excision rates (IRR, 2.7 p<0.001 and HR, 2.74 p=0.013). IBD-unclassified was associated with increased revisions (IRR, 1.3 p<0.001) and the proportion of IBD-unclassified patients almost doubled from the, 1980s (32%) to after, 2000 (50%).

Conclusion

Continent ileostomy is associated with substantial need for revisional surgery, but most patients get to keep their reconstruction for a long time.
P441 Adalimumab versus ustekinumab as first-line biological in a real-life cohort of moderate-to-severe Crohn’s disease
Authors: Moens A , Verstockt B , Alsoud D , Sabino J , Ferrante M , Vermeire S
Published: January 2022

Background

As therapeutic options in Crohn’s disease (CD) are growing, new challenges including choice of first line therapy arise. Both adalimumab (ADM) and ustekinumab (UST) are effective at inducing and maintaining endoscopic remission in moderate-to-severe CD. Recently, the SEAVUE trial (Sands et al. DDW, 2021) did not show a difference in (steroid-free) clinical remission nor endoscopic remission at week, 52 in biological-naive patients with moderate-to-severe CD. Our aim was to explore if these results withstand in a real world setting of biological-naive CD patients starting their first biological.

Methods

This retrospective cohort study included adult, biological-naive CD patients starting ADM or UST between, 2017–2020 in our tertiary referral centre. Patients were eligible for biological therapy as per reimbursement criteria and all had endoscopy-proven moderate-to-severe disease (at least one ulcer of any size) prior to start of therapy. ADM could be dose optimized. Clinical remission was defined as a Harvey-Bradshaw Index (HBI) <, 5. Endoscopic remission (SES-CD<3) and improvement (≥50% reduction in SES-CD) were assessed at W26-52. Treatment persistence was defined as still being on ADM or UST by the end of follow-up. Missing values were imputed as nonresponses for binary outcomes.

Results

A total of, 70 consecutive biological-naive CD patients were included (38 ADM, 32 UST) and prospectively followed for, 60 (33–104) weeks. Baseline characteristics were similar between both treatment groups (Table, 1). Median (IQR) time to endoscopy was comparable between both groups [ADM, 26 (23–33) vs. UST, 25 (24–45) weeks; p=0.38]. Clinical remission rates, only in patients with active clinical disease at baseline, at week, 26 (ADM:, 72% vs. UST:, 48%, p=0.09) and, 52 (ADM:, 62% vs. UST:, 35%, p=0.09) were numerically but not statistically different between groups. However, ADM was superior to UST in achieving endoscopic remission (61% vs., 31%, p=0.02) and improvement (74% vs., 47%, p=0.03) at week, 26–52. Fifteen (39%) patients in the ADM and, 6 (19%) in the UST group were on steroids at baseline. Numerical differences in steroid-free endoscopic remission (55% vs., 31%, p=0.06) and improvement (68% vs., 47%, p=0.09) rates were seen between ADM and UST at week, 26–52. Rates of treatment persistence were not significantly different between both treatment groups (p=0.31; Figure, 1). The number of adverse events was similar in both groups after one year of therapy (p=0.98).

Conclusion

In a real-world cohort of biological-naive CD patients, ADM seems superior to UST in achieving endoscopic remission and improvement, but no difference was seen in clinical remission at W26-52.
P452 Tofacitinib Effectiveness and Safety as Therapy for Ulcerative Colitis
Authors: McNally M , Keating E , Gray E , McCormick E , Carroll A , Palmer C , Kennedy U , McKiernan S , MacCarthy F , Dunne C , Hartery K , Egan L , Slattery E , Ryan B , McNamara D , O’Connor A , Breslin N , O’Donnell S , Cullen G , Mulcahy H , Sheridan J , Doherty G , Kevans D
Published: January 2022

Background

Tofacitinib is an oral small molecule directed against the JAK/STAT pathway. It is the first JAK inhibitor approved for the treatment of ulcerative colitis (UC) and is licenced for use in moderate to severely active disease. This study aims to evaluate tofacitinib effectiveness and safety in real-world clinical practice for moderate-to-severely active UC.

Methods

Consecutive patients receiving Tofacitinib for UC in four Irish tertiary referral centres were identified. Baseline clinical data and information on therapy outcomes were collected by retrospective review of electronic patient records. Patients included in the study cohort were older than 18 years of age, had a confirmed diagnosis of UC, had received at least one induction dose of tofacitinib, and had available clinical follow-up. The primary study endpoint was 6-month corticosteroid-free remission rate. Secondary endpoints included 3-month clinical response, inflammatory biomarkers responses to tofacitinib therapy, rates of tofacitinib discontinuation, and side effects. Continuous variables are presented as median [range]. P values < 0.05 were considered significant in all analyses.

Results

Fifty-three UC patients were included; age 40.4 [33.3 – 53.9] years, 66% male, disease duration 5.7 [2.6–10.9] years; follow-up 8.7 [6.4–14.1] months. 43%, 40% and 17% of patients had extensive, left-sided disease and proctitis respectively. At baseline, clinical Mayo subscore was 7 [5–8], CRP 4.0 [1.0–16.7] mg/L and faecal calprotectin 914 [444.0–1000] mcg/g. The 3-month clinical response and 6-month corticosteroid-free remission rates were 69% and 43%, respectively. Following tofacitinib therapy, compared with baseline values, a significant reduction in 3-month clinical Mayo score, 3-month CRP, and post-induction faecal calprotectin was observed, p <0.03 for all comparisons. 36% of patients (n=19) discontinued tofacitinib during study follow-up (time to Tofacitinib discontinuation 1.9 [0.5–18.9] months). Side effects occurred in 26% percent of patients with the majority minor and self-limiting. No cardiovascular or venous thromboembolic events were observed and no hospitalisations occurred due to therapy-related side effects

Conclusion

These data are in concordance with prior studies of tofacitinib effectiveness and safety in real world practice. They demonstrate that, in a cohort of UC patients with significant prior therapy exposure, tofacitinib is an effective therapy with an acceptable safety profile.
P462 Upfront infliximab dose intensification for secondary loss of response in IBD: similar efficacy to dose interval shortening with the added advantage of early clinical and pharmacokinetic predictors of response
Authors: Srinivasan A , De Cruz P , Sam M , Toong C , van Langenberg D
Published: January 2022

Background

The efficacy and pharmacokinetic profile of upfront dose intensification strategies such as re-induction (RI) have not been well described, nor directly compared with more prevalent intensification strategies to address secondary loss of response (LOR) in inflammatory bowel disease (IBD). Hence this study aimed to prospectively compare infliximab RI and 6-weekly dose interval shortening (DIS) with reference to clinical and pharmacokinetic effectiveness, and to identify early predictors of response.

Methods

A prospective multicentre parallel cohort study of consecutive patients with IBD who underwent dose intensification to address secondary LOR using (1) infliximab RI (i.e. repeat week 0,2,6 dosing) followed by 8-weekly maintenance, or (2) 6-weekly DIS, over 30 weeks (6 doses) was undertaken. Primary outcomes were: (1) Clinical response, defined as a decrease in Harvey Bradshaw Index ≥3 or partial Mayo score ≥2 from pre-intensification baseline, assessed at weeks 12 and 32, and (2) Clinical and pharmacokinetic predictors of week 32 response, with serum infliximab samples collected at predefined timepoints (Figure 1). Patients who were dose intensified in the absence of clinical symptoms, were excluded from the primary analysis.

Results

Of 104 patients, 54 underwent RI and 50 underwent 6-weekly DIS (Table 1), including 43 patients from each cohort who were dose intensified to address clinically active disease. Baseline infliximab trough levels prior to RI and DIS (2.03 v 2.02ug/ml, p=0.83) were comparable. Clinical response was similar across both RI and DIS cohorts at weeks 12 (70 v 65%, p=0.89) and 32 (53 v 63%, p=0.51). Multivariate logistic analyses demonstrated that objectively verified active disease at baseline (OR 20.43[2.53–64.94]; p=0.005) and clinical response at week 12 (OR 15.44[1.20–19.97]; p=0.036) were associated with week 32 response, as were week 2 infliximab levels within the RI cohort only (OR 1.34[1.02–1.47]; p=0.036). Following RI, week 2 infliximab levels below 15.6ug/ml (sensitivity 100.0%; specificity 42.9%; AUROC 0.76; p<0.05) were predictive of not achieving clinical response at week 32; potentially indicating that amongst this patient subset, week 12 clinical response may be useful in differentiating between early clinical responders who may benefit from sequential DIS following RI to prevent subsequent non-response, and early clinical non-responders who may benefit from early biologic switching.

Conclusion

Despite similar clinical outcomes across both dose intensification strategies, only upfront dose intensification using infliximab RI was associated with early clinical and pharmacokinetic predictors of response capable of facilitating early dose optimisation and biologic switching.
P465 Is golimumab serum level predictive of clinical remission after intensification for loss of response in patients with ulcerative colitis?
Authors: Fumery M , Nancey S , Filippi J , Altwegg R , Hebuterne X , Boschetti G , Veyrard P , Yzet C , Paul S , Roblin X
Published: January 2022

Background

Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti-TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was therefore to determine a threshold of serum golimumab before intensification predictive of clinical remission after optimization.

Methods

We included consecutive patients with UC and loss of response to golimumab (Mayo score between 6 and 12 and an endoscopic Mayo sub-score> 1) in a prospective multicentric cohort. Patients with loss of response at 50 mg / 4 weeks (W) and 100 mg / 4W underwent therapeutic intensification at 100 mg / 4W and 100 mg / 2W, respectively. Patients were followed prospectively with a first evaluation between weeks 2 and 4 (visit 2) and between weeks 4 and 8 (visit 3) after intensification. Clinical remission was defined by partial Mayo score ≤ 1. Serum level and anti-golimumab antibodies were evaluated at each visit (Lisa Tracker, Theradiag France).

Results

A total of 47 patients (female, 50%; median age, 39 years (IQR, 27–52) treated with golimumab for a median of 20.4 weeks (IQR, 10.7–38.3) were included. The median partial Mayo score was 6 (IQR, 5–7) and the endoscopic Mayo score was 3 (IQR, 2–3). The median golimumab serum level before intensification was 2.23 µg / mL (IQR, 1.02–3.96) and only three patients (6.2%) had anti-drug antibodies. After a total of 50 drug intensification, 23 (48.9%) patients had clinical response (100 mg / 4W: 14/25 (58.3%); 100 mg / 2W: 9/25 (36%)), 10 (21%) clinical remission and 18 (39%) endoscopic response. The median golimumab levels before intensification were respectively 2.17 µg / mL (IQR, 0.97–3.25) and 2.47 (IQR, 1.10–4.05) in responders and non-responders (p = 0.66), and 1.11 µg / mL (IQR, 0.59–2.29) and 2.47 µg / mL (IQR, 1.21–3.83) in patients with and without clinical remission after intensification (p = 0.054). In multivariate analysis, intensification to golimumab 100 mg / 2W (vs 100 mg / 4W) (OR, 0.11 [95%CI, 0.01 - 0.87], p=0.037) and change of golimumab level between V1 and V2 (OR, 1.48 [95%CI, 1.02 - 2.14], p=0.037) were significantly associated with clinical remission after intensification. Only one serious adverse event (infection) was reported during the 24-week follow-up.

Conclusion

In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Change of golimumab level was predictive of clinical remission after intensification.
P470 Real-world characteristics and complications of patients with Ulcerative Colitis receiving conventional therapy in the public healthcare system in Brazil
Authors: Galhardi Gasparini R , Yukie Sassaki L , Lima Martins A , Saad Hossne R , Watanabe de Oliveira R , Yang Santos C , Biatti Barreto T
Published: January 2022

Background

Ulcerative colitis (UC) therapy management is complex and typically begins with conventional therapy (CVT) followed by biologic drugs. For many years, CVTs were the only available option for the treatment of UC in the public healthcare system in Brazil (SUS). Biologic therapy was only available at the end of 2020. This study aimed to observe the real-world intestinal complications (IC) experienced in patients with UC receiving CVT in SUS.

Methods

This study was a secondary analysis of patients (>18 years) with UC (ICD-10 code: K51) who received at least two claims of CVT (index data defined as first CVT), between January 2011 and February 2020, in the DATASUS database. UC IC was defined as at least one claim (after index date) for either: UC-related hospitalisation, pre-defined procedure codes for rectum or intestinal surgeries, pre-defined ICD-10 codes were validated by independent clinical experts (malignant neoplasia of colon, stenosis, haemorrhage, ulcer and other rectum and anus disease, megacolon, functional diarrhea volvulus, intussusception and erythema nodosum). Patients with an anal or rectal fissure or fistula, with <6 months of follow-up from index date, with a CVT claim 12 months before index date or patients treated outside of the public healthcare system, were excluded. Descriptive statistics, annual incidence and incidence rate (IR; per 100 patient-years [PY]) over the available follow-up period were calculated.

Results

In total, 41,229 patients with UC were included (median age, 48 years; 65% women) and the median (interquartile range [IQR]) follow-up period was 3.3 (1.8 - 5.3) years. CVT utilized during follow-up was: mesalazine (87%), sulfasalazine (15%), azathioprine (16%) or methotrexate (1%); the median (IQR) CVT duration was 1.9 (0.8 – 4.0) years. The overall IR of IC was 2.5 per 100 PY during the follow-up period. Of the IC, 54% were related to ICD-10, 20% were related to a procedure and 26% to a UC-related hospitalisation (Table 1).

The overall annual incidence of IC was 2.9%, 2.6% and 2.5% in the first, second and third year after index, respectively (Table 2).

Over the first 3 years, the annual IR of UC-related hospitalisations ranged from 0.8% to 1.1%, for ICD-10 related events 0.9%-1.2% (anus and rectum disease, and malignant neoplasia of colon most frequently reported) and for procedure-related events 0.6%-0.7% (intestinal resection and polyp removal were the most frequent procedures).

Conclusion

The IR of IC was constant along the use of CVT. This study suggests the need to consider additional strategies for intestinal complications associated with the management of UC in Brazil, including but not limited to biologics.
P498 Sources of excess steroid prescriptions and clinical adverse outcomes associated with steroid excess: The Leeds Steroids study
Authors: Rosiou K , Carbonell J , Dolby V , Monfared N , Selinger C
Published: January 2022

Background

This retrospective study aims to determine steroid prescription practice across primary and secondary care, quantify the proportion of primary care prescriptions communicated to secondary care, and assess outcomes associated with excessive steroid use.

Methods

The study cohort consists of all patients attending IBD clinics under Leeds Teaching Hospitals from 1/1/2016 to 31/12/2017 with linked primary care records. Data were extracted from the hospital’s electronic health record. Steroid excess was defined based on ECCO guidelines. Cases with excess were reviewed to determine if escalation was implemented, appropriateness of escalation, timeliness of that (within 6 weeks of steroid course) and whether steroid excess was unavoidable.

Results

2246 patients were included in the study (Mage: 47.26 y; 47.6% male; 46.4% CD, 46.8% UC; 36.2% of CD patients on thiopurines, 26.3% on biologics; 78.8% of UC patients on 5-ASA, 21.4% thiopurines, 5.6% biologics). During the study period 32.9% of patients were exposed to steroids (77.4% of steroid prescriptions issued for IBD, 27.5% of prescriptions for IBD originating from primary care).

Significantly more prescriptions from secondary care were of appropriate dose and duration compared to primary care (84.7% vs 40.7%, p<0.001). Secondary care was made aware within six weeks of steroid initiation in 60.3% of steroid courses prescribed by primary care. 49.5% of patients flared after being prescribed steroids from primary care, compared to 39.1% from secondary care, p=0.003.

Steroid excess was observed in 14.5% of patients and was related to IBD in 76% of them. In patients with steroid excess due to their IBD; excess was acted upon in 82.8% of patients (77.5% had treatment escalation). Escalation was considered appropriate in 98.9% of patients however, it was timely in 62.4% of patients and steroid excess was unavoidable in 47.6%.

Patients with steroid excess due to IBD had significantly more hospital admissions for IBD (p<0.001), hospital admissions for infections (p=0.036) and more antibiotic courses prescribed by GP (p=0.023) compared to patients without steroid excess.

Conclusion

Steroid prescribing for IBD flares originating from primary care is common however, steroid dose and duration are frequently inappropriate, and more than one third of courses are not communicated to secondary care in a timely manner. A significantly higher amount of patients flare again after being prescribed steroids by primary care. Finally, over 50% of steroid excess is potentially avoidable and steroid excess is related to negative consequences such as IBD admissions, admissions for infections and antibiotic prescriptions.
P499 Accessing ultrasonographic transmural healing in patients with Crohn’s disease after induction therapy with infliximab: should we aim for higher infliximab trough levels?
Authors: Morão B , Frias Gomes C , Revés J , Cúrdia Gonçalves T , Freitas M , Castro F , Moreira M J , Cotter J , Pereira F , Caldeira A , Sousa R , Coelho R , Macedo G , Macedo C , Ferreira M , Glória L , Torres J , Palmela C
Published: January 2022

Background

Higher infliximab trough levels (ITL) have been shown to be associated with better rates of clinical remission and mucosal healing. Transmural healing (TMH) assessed by cross-sectional imaging [such as intestinal ultrasound (IUS)] is emerging as a potential target in Crohn′s disease (CD) treatment, but whether there is any relation with ITL remains unclear. Our goal was to investigate the association between ITL and bowel wall thickness (BWT) in patients with CD after induction therapy with IFX.

Methods

Prospective multicentric cohort study of CD patients who started IFX in mono or combination therapy. Patients performed IUS and ITL at weeks 0 and 14. TMH was defined as BWT ≤3 mm in the most affected segment. A ROC curve was plotted to determine the best cut-off point of ITL to predict TMH. Chi-square test, Mann-Whitney test and Spearman correlation were performed to assess the ITL relation with BWT.

Results

We included 57 patients, 30 (53%) of whom were men with mean age of 36±15 years. Disease extension according to Montreal classification was L1 in 19 (33%), L2 in 8 (14%) and L3 in 30 (53%) patients; 6 (11%) patients also had L4 extension and 19 (33%) patients had perianal disease. Disease behavior was B1 in 36 (63%), B2 in 13 (23%) and B3 in 8 (14%) of patients. Most patients (61%) were under immunomodulators and 15 (26%) were under corticosteroids when infliximab was started; most (88%) were naïve for infliximab. At week 0, all patients had endoscopic activity and 97% had increased BWT at the most affected segment. The most affected segment on IUS at week 0 was the terminal ileum in 38 (67%) patients and the ascending, transverse, descending and sigmoid colon in 5 (9%), 2 (3%), 7 (12%) and 5 (9%) patients, respectively. There was a very good agreement between IUS and colonoscopy for evaluation of the most affected segment at baseline (kappa 0.81, p<0.001). Median ITL at week 14 was 4.30 μg/ml (IQR 0.01–21). TMH at week 14 was achieved in 13 (23%) patients. ITL and BWT at week 14 were negatively correlated, with a fair correlation (r=-0.3, p=0.03). The AUC of ITL for BWT was 0.661 (best cut-off value 7.65, sensitivity 54%, specificity 89%). ITL ≥7.65 μg/ml was associated with higher rates of TMH (44% vs 15%, OR 4.47 [95%CI 1.2–16.4], p=0.04).

Conclusion

In our cohort of CD patients completing induction therapy with infliximab, higher ITL were associated with higher ultrasonographic transmural healing rates. The best cut-off for predicting TMH was ITL above 7.65μg/ml.
P507 Need for surgery in patients with ulcerative colitis in the era of biologic therapy
Authors: Zamora Olaya J M , Aparicio-Serrano A , Gómez Pérez A , Ortiz Chimbo D S , Rodríguez Tirado M I , Soto Escribano P , Marín Pedrosa S , Iglesias Flores E , Benítez J M
Published: January 2022

Background

The aim of the present study is to evaluate the impact of anti-TNF drugs on the need for surgery among patients with ulcerative colitis (UC). Secondary objectives: to compare needs for medical treatment before surgery, indications for surgery and surgery-free survival.

Methods

Observational, retrospective and single-center study that includes patients with UC who have required surgery for inflammatory bowel disease (IBD). Two cohorts of UC patients were analyzed: cohort-1 (pre-antiTNF) with a diagnosis of UC between 1995–2000, and cohort-2 (post-antiTNF) diagnosed after the approval of anti-TNF between 2010–2015. Patients were followed up to the event (surgery) or at least five years since UC diagnosis. Demographic variables related to UC and surgery were collected. Kaplan-Meier curves were performed to compare the surgery-free survival in both cohorts. The ENEIDA registry was used to identify the patients.

Results

A total of 32 patients underwent surgery were included (18 in cohort 1 and 14 in cohort 2). The mean age at UC diagnosis was significantly lower in cohort 1 (31.3 vs 46.4 years, p=0.015), and the proportion of smoking patients was higher in cohort 1 (27.8% vs 0%, p=0.053). There were no differences between the two cohorts in the extent of UC and extraintestinal manifestations. Surgery rates were 3.7% in cohort-1 and 4.7% in cohort-2. Overall, there were no differences in colectomy rates in both cohorts (Figure 1). However, the median time from UC diagnosis to surgery was significantly longer in cohort-2 (21 vs. 1 months, p<0.05) (Figure 2). Regarding the surgery timing, the proportion of urgent surgery was higher in cohort-1 (61% vs 43%, ns); while in cohort-2, scheduled surgery predominated (50% vs 18%, ns). In the subgroup of patients who underwent scheduled surgery, the surgery free time was significantly longer in cohort-2: 67 vs 12 months (p=0.01) (Figure 3). Regarding surgical indications, cohort-1: 78% acute severe colitis or acute complications and 22% refractory to medical therapy; cohort-2: 43% Acute Severe Colitis/complications. A high proportion of patients in both cohorts required ostomy (temporary or definitive). Pre-surgery medical treatment needs cohort-1 vs cohort-2: steroids (100% vs 71%, p=0.028), immunosuppressants (5.6% vs 57%, p=0.002).

Figure 1. Surgery -free survival at 5-years follow-up.

Figure 2. Kaplan-Meier curves of time from UC diagnosis to surgery.

Figure 3. Kaplan-Meier curves of time until scheduled surgery.

Conclusion

Surgery rates in UC patients remain stable in the post-antiTNF era. However, the arrival of antiTNF drugs allows a longer surgery-free survival, lower preoperative steroids requirements and less need for urgent surgery.
P514 Optimising response to infliximab in the management of perianal Crohn’s disease
Authors: Shah R , Anandbaskaran S , Hart A , Tozer P
Published: January 2022

Background

Perianal Crohn’s Disease (PCD) remains a refractory phenotype of Crohn’s Disease (CD)1. Despite initial demonstration of the benefit of infliximab (IFX) in PCD over 20 years ago2, it remains clear how IFX treatment can be optimised for PCD patients3. In this retrospective observational study, a cohort of PCD patients based at St Mark’s Hospital was reviewed to understand their disease-journeys whilst on treatment with IFX.

Methods

A cohort of 59 patients with PCD on treatment with IFX as of January 2020 were identified from a prospective database of IFX treated patients. Twenty-seven patients were classed as fluctuating IFX levels and underwent disease-journey analysis. Detailed qualitative analysis of individual patients journeys were carried out to correlate IFX levels, where available, to C-Reactive Protein (CRP), Magnetic Resonance Imaging (MRI) and Examinations Under Anaesthetic (EUA). These journeys were then graphed as a timeline for each of these patients.

Results

Four disease-journeys have been selected to exemplify key learning points in the management of PCD.

Graph 1: Improving drainage and reducing inflammatory burden with EUA can help to recover IFX levels and regain disease control. This suggests a well-timed EUA can have a synergistic effect on treatment with IFX.

Graph 2: In a subgroup of patients, optimised medical therapy with IFX alone remains adequate to perianal fistula healing.

Graph 3: Patients may benefit from temporary dose escalations with IFX to recapture response and to improve disease burden.

Graph 4: Some patients require longer periods of dose-escalated therapy as seen in this graph & higher IFX levels may be required for radiological healing.

Conclusion

These cases highlight interesting learning points and can help to manage complicated PCD patients. Further work is needed to determine how significant the link is between improvement in IFX levels post-EUA and how this correlates with the overall clinical picture of the patient.

References

1. Sahnan K, Adegbola SO, Fareleira A, Hart A, Warusavitarne J. Medical-surgical Combined Approach in Perianal Fistulizing Crohn’s Disease (CD): Doing it Together. Curr Drug Targets. 2019;20(13):1373–1383.

2. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999;340:1398–405.

3. Kotze PG, Shen B, Lightner A, Yamamoto T, Spinelli A, Ghosh S, Panaccione R. Modern management of perianal fistulas in Crohn’s disease: future directions. Gut. 2018 Jun;67(6):1181–1194.
P518 Partial enteral nutrition use for Crohn’s disease management: a systematic review
Authors: Jatkowska A , White B , Gkikas K , Seenan J P , MacDonald J , Gerasimidis K
Published: January 2022

Background

Exclusive enteral nutrition (EEN) is an established treatment for the induction of clinical remission in children with active Crohn’s disease (CD). However, the benefit of partial enteral nutrition (PEN), in which only some diet is replaced with enteral nutrition, is not well-documented for the management of CD. This review explored the effectiveness of PEN as sole or adjunctive induction and maintenance therapy in patients with CD.

Methods

The protocol for this review was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/ protocol ID: CRD42021239325). Literature search was conducted using PubMed, Ovid Embase, Cochrane Controlled Register of Trials and Cumulative Index to Nursing and Allied Health Literature electronic bibliographic databases. Eligible study designs included: randomised control trials (RCTs), prospective, retrospective, and case control studies. Level of evidence was assessed with CASP tools with an emphasis on study design, and assessment of compliance and objective disease activity biomarkers. Two researchers evaluated each paper separately and when needed, consensus was resolved by a third.

Results

56 articles met the inclusion criteria, grouped under the following 6 distinct areas for PEN use in CD: 1) induction treatment; 2) maintenance treatment; 3) prevention of post-operative recurrence; 4) prevention of loss of response (LOR) to anti-TNFα therapies; 5) nutritional rehabilitation; 6) improvement of quality of life (QOL). Low-quality evidence suggests PEN may improve disease activity in patients with active CD; treatment efficacy was observed to be better in studies using higher proportions of energy intake from PEN. Good quality evidence suggests PEN combined with exclusion diets may be effective in active CD. However, most available studies originated from a single research group, and the additional benefits of exclusion diets over PEN are unclear, particularly as most studies used either high PEN volumes (>75% of energy requirements), or EEN prior to PEN initiation. Good quality evidence shows that PEN at high volumes (≥35–50%) may prolong medically or surgically induced remission and improve the nutritional status of patients with malnutrition or growth delay. Low-quality evidence suggests that PEN may improve response and remission rates to infliximab therapy in CD. Three retrospective studies found that concomitant PEN with anti-TNFα therapies could prevent LOR. Some evidence indicates that PEN is associated with better QOL in patients with active disease or in remission.

Conclusion

PEN may have a beneficial role in various aspects of CD management; however, more robust data including RCTs are needed before specific recommendations can be made.
P524 Compared efficacy of ustekinumab and anti-TNF agents as first-line biological therapy in luminal Crohn’s disease
Authors: Riviere P , Kanters C , Ni A , Pellet G , Hupe M , Aboulhamid N , Poullenot F , Bitton A , Zerbib F , Lakatos P , Afif W , Laharie D , Bessissow T
Published: January 2022

Background

Real-life data on the efficacy of ustekinumab as first-line therapy for the treatment of moderate to severe Crohn’s disease (CD) is lacking. The objective of this study was to compare the clinical remission rate at 3 months of patients treated by ustekinumab or anti-TNF agents as first-line biological therapy.

Methods

We conducted a two-center retrospective study including biologic-naïve patients starting either ustekinumab or an anti-TNF agent for CD between January 2016 and December 2019. The primary endpoint was clinical remission at 3 months after therapy initiation, defined as a Harvey Bradshaw Index (HBI) < 4 without steroids, need for CD-related surgery or treatment discontinuation due to treatment failure or intolerance. Secondary endpoints were remission at 12 months and time to drug withdrawal. Patients treated with ustekinumab were matched 1:3 to patients receiving anti-TNF agents using a propensity score including age, CD duration, smoking status, CD location according to the Montréal classification and history of perianal disease.

Results

208 patients [104 (50%) female, median age (InterQuartileRange) 30 years (23–47)] were included, 156 (75%) patients starting anti-TNF (95 (45%) adalimumab and 61 (29%) infliximab) and 52 (25%) ustekinumab and followed for a median (IQR) duration of 39 (22–52) months. Median (IQR) CD duration was 21 (6–104) months and 45 (22%) patients had previously undergone a CD-related surgery. At inclusion, the median (IQR) HBI was 5 (2–8) and 83 (39%) patients were receiving oral corticosteroids.

After matching, remission rates at 3 months were 25/45 (56%) patients in the ustekinumab group versus 102/135 (76%) in the antiTNF group [p=0.01, odds ratio (OR) 0.40 (Confidence Interval (CI) 95% 0.20, 0.82)]. At 12 months, remission rates were 26/41 (63%) patients in the ustekinumab group versus 99/123 (81%) in the antiTNF group (p=0.03). No difference was observed in terms of time to drug withdrawal (p=0.25). Rates of drug persistence at 12 months were 89% in patients treated with ustekinumab and 87% in those treated with antiTNF, respectively. Similar rates of adverse events were observed in the two groups (13% versus 13%, p>0.9). In the antiTNF group, 3/156 (2%) adverse events leading to hospitalization were observed compared to 0/52 (0%) in the ustekinumab group (p=0.6).

Conclusion

In this retrospective cohort, we found that anti-TNF agents as a first-line biological therapy led to higher rates of remission at 3 and 12 months in biologic-naïve patients with Crohn’s disease than ustekinumab.
P526 Measurement of thiopurine metabolites concentrations after one week of treatment does not predict treatment failure in Inflammatory Bowel Disease patients
Authors: Deben D , Van Moorsel F , Creemers R , Winkens B , Bus P , Pierik M , Simsek M , De Boer N , Wong D , Van Bodegraven A
Published: January 2022

Background

Conventional thiopurines such as azathioprine (AZA) and mercaptopurine (MP) remain drugs of choice in maintaining remission and corticosteroid sparing in inflammatory bowel disease (IBD). Early discontinuation of thiopurine therapy occurs frequently, due to slow onset of effect and a relatively high frequency of early adverse drug reactions (ADR). Some ADR such as hepatotoxicity and gastro-intestinal complaints are associated with the thiopurine metabolite concentrations 6-thioguanine nucleotides (6-TGN) or 6-methylmercaptopurine ribonucleotides (6-MMPR), in particular elevated 6-MMPR concentrations or unfavorable 6-MMPR/6-TGN ratios.

Early measurement of thiopurine metabolites may help to optimize thiopurine therapy in IBD. The aim of this study was to assess the predictive value of thiopurine metabolite measurement one week after thiopurine therapy initiation on discontinuation during the first three months of therapy.

Methods

This was a multicenter prospective observational study in the Netherlands. Consecutive IBD patients who initiated thiopurine therapy were included and measurement of thiopurine metabolites was performed after 7 days (6 – 8) of treatment (T1). Patients were monitored for 12 weeks to document occurrence of ADR and early treatment discontinuation. Switching to an alternative thiopurine or adding allopurinol (as co-medication) was also considered as treatment discontinuation (to prevent ADR). 6-MMPR concentrations and 6-MMPR/6-TGN ratios were separately analyzed (Mann-Whitney U-tests) regarding therapy discontinuation within 12 weeks. P-values of ≤0.05 were considered statistically significant.

Results

In total, 255 patients were included, of which 83 were excluded due to either missing blood samples on T1 (n=54), dose adjustments within 12 weeks (n=25) or a delayed T1 measurement (n=4). Of the remaining 172 patients, 79 patients were male (46%), 102 patients had Crohn’s disease (59%) and 157 patients were treated with MP (91%). In total, 88 (51%) patients continued thiopurine therapy and 84 patients (49%) discontinued therapy within 12 weeks. Median 6-MMPR concentrations (1,295 versus 1,589 pmol x 108 red blood cells) and 6-TGN/6-MMPR ratios (8.8 versus 11.4) did not differ significantly between patients who continued versus discontinued therapy within 12 weeks (Figures 1 and 2).

Conclusion

In this study thiopurine metabolites at T1 did not relate to discontinuation of thiopurine therapy within 12 weeks. We will conduct additional pharmacodynamic studies to corroborate our hypothesis that early metabolite measurements may be of individual patients’ benefit.