bluuebunny/crossref_metadata_2025 huggingface dataset:
P533 Predictors of sustained remission after infliximab de-escalation in patients with inflammatory bowel diseases
Authors: Kantasiripitak W , Outtier A , Thomas D , Sabino J , Vermeire S , Ferrante M , Dreesen E
Published: January 2022

Background

Infliximab (IFX) de-escalation (i.e., extending the dosing interval and/or decreasing the dose) has been attempted in patients with inflammatory bowel disease (IBD) who sustained treatment response following an earlier IFX escalation. We aimed to identify predictors of sustained disease remission after IFX de-escalation.

Methods

Data of 30 adult patients (17 Crohn’s disease [CD], 13 ulcerative colitis [UC]), who underwent IFX de-escalation following earlier escalation, were retrospectively collected from a single-centre database search. All patients were in steroid-free clinical (two-item patient-reported outcome [PRO2] ≤1 [UC] and ≤8 [CD]) and biological (C-reactive protein <5 mg/L and faecal calprotectin <250 mg/kg) remission at IFX de-escalation. The primary endpoint was sustained steroid-free clinical and biological remission during one year after de-escalation. Predictors at baseline (i.e., demographic, clinical, and biological characteristics, the IFX trough concentration (TC), and IFX clearance (CL) [estimated using a posteriori prediction with the Dreesen model1; NONMEM v7.5]) were identified using univariate Cox regression analysis (P<0.05). Markers for steroid-free combined clinical and biological remission at the infusions during the study period (secondary endpoint) were evaluated using a multivariable generalised linear model (mGLM).

Results

The percentage of patients who sustained steroid-free clinical and biological remission gradually decreased over time to 57% at 180 days and 37% at 360 days (Fig 1). A lower baseline PRO2 was predictive for attaining the primary endpoint (P=0.039), regardless of IBD type. One unit increase in PRO2 increased the probability of losing remission by 17% (95% CI: 0.8%-36%). The IFX TC at baseline was similar between patients with and without sustained remission during the first year (median 6.8 [IQR 6.0–7.6] mg/L and 6.0 [5.1–9.2] mg/L, respectively; P>0.05). Throughout the study period, neither IFX TCs nor IFX CLs predicted attaining the primary endpoint (P >0.05).

At the fifth infusion, patients who did not attain the secondary endpoint had a higher IFX CL (P=0.025), but the IFX TC was not different (Fig 2). In mGLM, the estimated IFX CL, but not the IFX TC itself, was identified as a predictor for attaining the secondary endpoint (P=0.016). A 0.1-unit increase in IFX CL (L/day) increased the probability of losing remission 3,227-fold.

Conclusion

Lower PRO2 at IFX de-escalation predicted a higher chance of sustained remission. Monitoring the IFX CL using a Bayesian forecasting software tool may provide more insight into disease activity than monitoring the IFX concentration as such. A prospective study is awaited to confirm our findings (MODIFI; NCT04982172).

Reference

1. Dreesen BJCP. 2020
P536 Comparison of outcomes of infliximab biosimilar CT-P13 with infliximab originator in patients with inflammatory bowel disease
Authors: Yüksel I , Baspınar B , Durak M B , Kilic V , Kivrakoglu F , Guven I E , Kosar K , Erdogan C , Alkan A
Published: January 2022

Background

Studies on the efficacy and safety of Infliximab (IFX) biosimilar CT-P13 and IFX originator are needed in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

The aim of this study was to evaluate the short and long-term clinical efficacy and safety of IFX biosimilar CT-P13 compared to IFX originator in adult patients with inflammatory bowel disease (IBD).

Data were retrospectively collected. Therapeutic failure was defined as discontinuation of biological therapy because of primary lack of response (p-LOR), secondary loss of response (s-LOR, including steroid needed, IBD-related hospitalization, IBD-related surgery, and switch to other biotherapy) and serious adverse events (SAE).

Results

252 patients who received IFX were identified between January 2007 and November 2021 (66 IFX biosimilar CT-P13 and 186 IFX originator).

Data were analyzed for 188 CD (62.2% males; 34.6% biologics experienced; 27.7% IFX biosimilar CT-P13 / 72.3% IFX originator and 64 UC (59.4% males; 20.3% biologics experienced; 21.9% IFX biosimilar CT-P13 / 78.1% IFX originator). There were no significant differences between the two groups with respect to all demographic features at the beginning of the treatment (p>0.05). Median follow-up time was 1.58 years and 1.74 years after starting IFX in biosimilar CT-P13 and originator, respectively.

There were no significant differences in the rates of p-LOR (4.5% vs. 5.4%, p>0.999) and SAE (6.1% vs. 15.6%, p=0.078) between IFX biosimilar CT-P13 and IFX originator, while the rate of s-LOR was significantly higher in IFX originator group (13.6% vs. %31.2, p=0.009). Considering all types of s-LOR, we did not detect significant differences between IFX biosimilar CT-P13 and IFX originator in the rates of IBD-related hospitalization (10.6% vs. 15.6%, p=0.430) and IBD-related surgery (7.6% vs. 12.4%, p=0.403). Nevertheless, the rates of steroid needed (0.0% vs. 6.5%, p=0.040), and switch to another biotherapy (4.5% vs. 19.4%, p=0.008) were significantly higher in IFX originator.

There were also no significant differences in terms of these outcomes between concomitant immunomodulator therapy and monotherapy within IFX biosimilar CT-P13 and IFX originator (p>0.05).

Conclusion

In this study, outcomes did not reveal significant differences between IFX biosimilar CT-P13 and IFX originator in terms of the p-LOR and SAE. There was no difference between the two groups in the IBD-related hospitalization and IBD-related surgery, however the rates of steroid needed and switch to another biotherapy were significantly higher in the IFX originator within the s-LORs group. No difference was observed in terms of all outcomes between the two groups treated with monotherapy or concomitant immunomodulator therapy.
P540 Longitudinal Dynamics of Gut Microbiome and Metabolome After Biological Therapy in Inflammatory Bowel Diseases
Authors: Ahmed M , Metwaly A , Hammoudi N , Meng C , Köhler N , Le Bourhis L , Pauling J , Kleigrewe K , Allez M , Haller D
Published: January 2022

Background

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. Biological therapy with monoclonal antibodies has provided significant benefit for patients with IBD, resulting in clinical and endoscopic remission. Gut microbiome alterations were shown to serve as a marker of response to treatment in IBD. The aim of the study is to characterize gut microbiome and metabolome in patients with CD and UC after initiation of biological therapy.

Methods

We studied a prospective cohort of 41 CD and 39 UC patients initiating biological therapy. Biological therapy included anti-TNF (Adalimumab, Infliximab and Golimumab), anti-α4β7 integrin (Vedolizumab) or anti-IL-12/23 p40 antibody (Ustekinumab). One-year follow up showed that up to 60% of the patients achieved clinical and endoscopic remission. Fecal samples and mucosal biopsies were collected both at baseline and 14 or 52 weeks after initiation of therapy. Microbiota and metabolite changes were analyzed using 16S rRNA gene sequencing and targeted/untargeted metabolomics.

Results

Longitudinal profiling of luminal and mucosal bacteria reflected the individual patient-related variations over the study duration. CD and UC patients showed distinct luminal and mucosal bacterial communities. Bacterial dysbiosis was significantly higher in patients with CD than with UC, as shown by community richness and diversity. While fecal microbiota of patients with CD was enriched in Escherichia coli and Bacteroides, both Faecalibacterium and Bifidobacterium were enriched in UC. In contrast to fecal bacterial communities, mucosal bacteria from patients with ileal and colonic CD showed a clear separation of microbial profiles based on disease location. Members belonging to Haemophiles, Fusobacterium, and Escherichia coli were significantly more abundant in IBD patients with active disease. Machine-learning based analysis showed that fecal and biopsy profiles equally classified patients based on their disease subtype, with an area under the curve (AUC)=0.86. Metabolite profiling revealed enrichment of platelet-activating factor and the glycosphingolipid lactosylceramide in inflamed phenotypes. Conversely, enrichment of bile acids, such as deoxy cholic acid, chenodeoxycholic acid and Lithocholic acid was observed in responders or patients during remission.

Conclusion

Gut microbial and metabolomic profiling revealed associations between gut microbial taxonomic or functional profiles and IBD subtypes. The association between enrichment of fatty acids and bile acids and disease activity suggests an important role of these pathways in the development or the resolution of intestinal inflammation.
P541 Effectiveness, safety and durability of vedolizumab in active moderate-severe Crohn’s Disease
Authors: Morales Bermúdez A I , Bracho González M , Gómez Rodríguez P , Olmedo Martín R
Published: January 2022

Background

Vedolizumab (VDZ) has demonstrated efficacy and safety in moderate-severe Crohn’s Disease (CD) in GEMINI registration trials. Nevertheless, the patient profile in actual clinical practice differs from that included in controlled studies so additional data are needed. The primary objective of our study was to evaluate the effectiveness, safety and durability of VDZ in active moderate-severe CD in real clinical practice.

Methods

Unicentric retrospective observational study. All patients treated in our center with VDZ with moderate-severe CD were included. Effectiveness was assessed 16 weeks after treatment iniciation and at the last visit with available data. Remission (RmLE) and steroid-free response (RsLE) were considered to be the achievement of a Harvey-Bradshaw index (HBI) ≤4 or a decrease of at least 3 points from the previous HBI. To evaluate the durability of VDZ, a Kaplan-Meier survival curve was performed. In addition, adverse effects attributable to VDZ during follow-up were recorded.

Results

We included 26 patients whose clinical-demographic features are shown in Table 1. The median follow-up of patients was 52 weeks (IQR= 24–78). At 16 weeks after initiation of VDZ treatment, RmLE and RsLE were achieved in 19.2% and 69.2% of patients respectively. At the last follow-up visit, 27% of patients achieved RmLE with 61.5% presenting RsLE (Figure 1). The probability of retention of VDZ treatment at median follow-up was 57%, not differing significantly between bionaive patients from those with previous failure to other biologic treatments (Figures 2 and 3). There were no serious adverse effects or effects that required discontinuation of VDZ. Three mild adverse effects were documented in 11.5% of patients (arthralgia, dyspnea and a mild viral infection).

Conclusion

In our series of patients, VDZ proved effectiveness and safety in line with that described in other real clinical practice series. The durability of VDZ at one year in this series of refractory CD was also considerable and did not vary according to previous exposure to biologic agents.
P542 Topical tacrolimus versus systemic biological therapy for refractory ulcerative proctitis: a retrospective cohort study
Authors: Crispino F , Michielan A , Tieppo C , Mazza M , Rogger T M , Brinch D , Cappello M , Armelao F
Published: January 2022

Background

Refractory ulcerative proctitis significantly affects patients’ quality of life, because of disabling symptoms such as tenesmus, fecal urgency and rectal bleeding. Immunosuppressive drugs, such as thiopurines and biologics, are recommended by clinical guidelines. Recently, a few studies have suggested that topical tacrolimus can be an effective and safe therapy in inducing clinical remission in these patients. However, there are no comparative data with biologics. The aim of our study was to compare the efficacy and safety of topical tacrolimus versus biological therapy in a retrospective cohort of refractory ulcerative proctitis patients’ followed up in two tertiary IBD clinics.

Methods

Consecutive patients with refractory ulcerative proctitis who started rectal tacrolimus 2 mg o.d. or biologics were enrolled between 2018 and 2020. Ulcerative refractory proctitis was defined as active disease up to 20 cm beyond the anal verge and endoscopic Mayo score ≥2 failure to both topical and oral mesalamine and corticosteroids. Primary endpoints were clinical response and remission after 8 and 54 weeks of treatment. Secondary endpoints were endoscopic remission after 54 weeks and the rate of adverse events. Clinical response was defined as a decrease in partial Mayo score of ≥3 points, plus either a decrease in rectal bleeding subscore of ≥1 or an absolute rectal bleeding score of ≤1. Clinical remission was defined as a partial Mayo score ≤2, while endoscopic remission as a Mayo endoscopic subscore ≤1.

Results

25 patients were enrolled (17 males, mean age 52.0±17.2 years, mean disease duration 11.6±9.0 years, mean partial Mayo score 6.7±1.3; mean endoscopic Mayo score 2.6±0.2). 10 patients were treated with rectal tacrolimus, 15 with biologics (antiTNFs=12; vedolizumab=3). There were no differences at baseline between the two groups. At week 8, 64.0% of patients had a clinical response, while 32.0% obtained clinical remission. At week 54, 80.0% were on clinical response and almost half of the patients were on clinical and endoscopic remission. No significant difference in clinical and endoscopic response and remission rates was observed in the two groups except for a trend toward significance in favour of biologics in the rate of concomitant topical corticosteroid use at 8 weeks (p = 0.06). Two patients experienced biologics related-side effects, while no one had tacrolimus related-ones.

Conclusion

In this real-world two centers experience, both rectal tacrolimus and systemic biological therapy seem to have comparable efficacy in inducing and maintaining remission in refractory ulcerative proctitis patients. Topical tacrolimus can be a safer and cheaper therapeutic option. Our results need confirmation in prospective and larger studies.
P546 Minimal risk of lymphoma despite long term use of azathioprine in patients with Inflammatory Bowel Disease: a longitudinal cohort analysis from Northern India
Authors: Ranjan M K , Kante B , Vuyyuru S K , Kumar P , Mundhra S K , Golla R , Sharma R , Das P , Sahni P , Makharia G , Kedia S , Ahuja V
Published: January 2022

Background

Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn’s Disease (CD). Reported effectiveness and tolerability rates have been variable across studies. Moreover, there are only sparse data in the Asian population regarding the long-term efficacy and safety of azathioprine (AZT).

Methods

Records of 5351 patients followed up at IBD clinic, All India Institute of Medical Sciences, New Delhi from 2004–2020 were evaluated retrospectively. Azathioprine efficacy was defined as no requirement of surgery, hospitalizations, anti TNFs agents, and minimum steroid (≤1 course in 2 years) requirement on follow-up. Safety was evaluated in terms of long-term adverse events and the development of malignancy.

Results

Of 5351 patients with IBD, 1093 who received AZT for > 3 months (UC=788 [proctitis-1.9%, left-sided colitis-44.9%, pancolitis-53.1%], CD=305 [inflammatory-42.6%, stricturing-46.9%, fistulizing-10.5%]) were included (60.8%-males; mean age at disease onset-31.69±12.34 years) (Table1). Follow-up and treatment duration on AZT were 7(4–12) years and 39.41±40.27 months respectively. Mean initiation and maintenance dose of AZT was 1.09±0.45 mg/kg and 94.82±21.29, respectively. One,3,5, and 10 years relapse free survival was 85%,79%,76%, and 64%; 87%, 82%, 79% and 72%; and 78%, 72%, 68% and 61% in overall cohort, UC and CD patients, respectively (Log-rank P=0.001 between UC and CD). Three hundred fifty-nine [UC:249(31.6%); CD:110(36.07%); P=0.158] patients developed adverse events (AE), commonest was myelosuppression (23.42%) followed by gastrointestinal intolerance (2.97%), flu like illness (1.7%), and arthralgia/myalgia (1.37%) (Table 2). Myelosuppression was the commonest cause of AZT withdrawal. No patient (including 254 patients on AZT for ≥5 years) developed lymphoma or non-melanoma skin cancer. Adverse events free course in entire cohort, and in UC and CD are shown in fig.1 and 2 respectively.

Conclusion

Long-term Azathioprine monotherapy in patients with IBD is safe with minimal risk of lymphoma and non-melanoma skin cancer.
P560 Application of a clinical decision support tool for predicting outcomes with vedolizumab therapy in patients with inflammatory bowel disease: A KASID multicenter study
Authors: Kim K , Hong S W , Park J H , Hwang S W , Park S H , Yang D H , Byeon J S , Myung S J , Yang S K , Yoo J H , Boo S J , Kim E S , Lee J , Kim K O , Ye B D
Published: January 2022

Background

A clinical decision support tool (CDST) has been developed and validated for predicting outcomes of vedolizumab (VDZ) therapy for patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively. We aimed to validate each CDST for predicting outcomes and need for drug optimisation in patients with inflammatory bowel disease (IBD).

Methods

We retrospectively analysed 166 patients with IBD (71 with CD, and 95 with UC) treated with VDZ from January 2017 through November 2021 at 6 tertiary referral centres in Korea. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CfCREM) and response (CfCRES), biochemical response (BioRES), endoscopic healing (EH), and need for drug optimisation by CDST-defined response groups (low vs. intermediate to high probability group with a cut-off of 13 points in CD, Table 1A, and 26 points in UC, Table 2A, respectively). CDST was evaluated by area under the receiver operating characteristics curve (AUC) and test performance.

Results

Patients were classified as low (27 with CD, and 28 with UC) and intermediate to high probability group (44 with CD, and 67 with UC). Among CD patients, there showed no significant difference in the response rate of any outcomes between CDST-defined groups. Among UC patients, the rates of CREM (41.0 vs. 18.5%, p=0.040) and EH (56.5 vs. 33.3%, p=0.045) at week 14 were higher among intermediate to high probability group. The rate of drug optimisation during maintenance therapy was also higher in low probability group (54.2 vs. 30.2%, p=0.038). At week 26, CDST for CD discriminated CfCREM with an AUC of 0.656 (sensitivity 87.5%, specificity 43.8%) (Table 1B). Meanwhile, CDST for UC identified CREM with an AUC of 0.606 (sensitivity 83.3%, specificity 37.9%) at week 14 (Table 2B). BioRES of FC was identified with an AUC of 0.649 (sensitivity 84.6%, specificity 45.2%) at week 26. BioRES of CRP was identified with an AUC of 0.660 (sensitivity 68.8%, specificity 63.2%) at week 26, and with an AUC of 0.642 (sensitivity 70.0%, specificity 58.3%) at week 54. Drug optimisation during maintenance therapy was identified with an AUC of 0.620 (sensitivity 54.2%, specificity 69.8%).

Conclusion

Both CDST for CD and UC can be used to help guide VDZ therapy for Korean patients to predict BioRES with a fair discriminant function and moderate sensitivity.
P561 Clinical utility of therapeutic drug monitoring of adalimumab using a point of care test
Authors: Stevens T , Teichert C , Volkers A , Mostafavi Montazeri N , Bahur B , Bray K , D’Haens G
Published: January 2022

Background

Adalimumab (ADL) is a fully human monoclonal antibody against tumor necrosis factor that is approved for the management of inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) of ADL is widely used to ensure adequate blood levels for maintenance of the clinical benefit. This study examined the clinical utility of a point of care (POC) ADL assay to facilitate TDM.

Methods

A fast (<3 min), time-resolved fluorescence resonance energy transfer (FRET) based immunoassay (Procise ADL™) was developed for measuring of ADL and its biosimilars for TDM using 20 µL of finger prick capillary whole blood or serum. To assess its clinical performance we conducted an observational study using stored frozen serum specimens from a nested cohort in a registry population collected over 24 months. Serum samples were thawed and ADL concentrations were measured with Procise ADL™. Adult patients with an established diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) who received maintenance ADL treatment were included. Primary endpoint was loss of response (LOR) defined as any of the following: (i) disease flare defined by documented worsening symptoms and abnormal endoscopy/imaging/biomarker findings leading to discontinuation of ADL; (ii) disease activity leading to change in IBD medication; (iii) increase in fecal calprotectin ≥150 mg/Gr; (iv) IBD surgery or (v) new or recurring actively draining fistula. To be evaluable LOR patients were required to have a study specimen < 60 days prior to the LOR event. Receiver-operating characteristic (ROC) curves were generated to identify optimal cut-off values to discriminate between patients with maintained response vs. LOR.

Results

A total of 84 IBD patients (LOR=37, No LOR= 47) were included in this study. Median ADL trough levels were lower in patients who experienced loss of response compared to patients who did not (median ADL 6.0 μg/mL vs 13. μg/mL, P < 0.001, figure 1). Area-Under-the-ROC Curve (AUC) value for loss of response was 0.822 (figure 2). Optimal ADL trough cut-off value was 8 μg/mL (Table 1).

Figure 1. shows patients losing response to ADL had serum levels significantly lower than those maintaining response

Figure 2. shows ROC curve analysis of the Procise ADL test for the detection of LOR

Table 1. Showsclinical performance of Procise ADL for the detection of LOR at various ADL concentration

Conclusion

IBD patients in disease remission on maintenance ADL therapy with ADL levels below a cut-off 8.0 μg/mL had a 5.34 fold increased risk of LOR compared to those above 8.0 μg/mL. Identifying patients at high risk of LOR with a convenient POC format test enhances the clinical utility of TDM by enabling faster treatment adjustment.
P564 A qualitative exploration of acceptability of long-term use of oral nutritional supplement drinks as partial enteral nutrition in adolescent and adult Crohn’s Disease
Authors: Mu S , Wei Y , Weekes E , Keetarut K
Published: January 2022

Background

Evidence mainly from Japanese cohorts suggests replacing 35–50% of food intake with enteral nutrition known as partial enteral nutrition (PEN) either orally as oral nutritional supplements (ONS) or via nasogastric tube for >1 year can prolong disease remission and increase drug effectiveness in CD. This study aimed to examine patients’ attitude towards the organoleptic properties and perceived barriers and benefits towards long-term ONS usage as PEN by analysing the free text comments from questionnaires. This study will help support our understanding of the feasibility of PEN as a treatment option in CD maintenance by exploring the factors affecting compliance and acceptability and help identify potential areas for improvement.

Methods

Data was obtained from 105 (55 males) aged 34.9 (±15.4) CD patients in remission (HBI<5) from University College London Hospital. Questionnaires with free-text comments were transcribed and analysed using qualitative content analysis using NVivo software. Thematic analysis was used to identify patterns of meaning within and between questionnaires and to identify key themes. Codes were derived through inductive (i.e. data-driven) and deductive approaches, reflecting the thematic guidelines and objectives of the study.

Results

A total of 86 (81%) of participants left at least one free text comment. There was a total of 501 comments. Comments related to participants’ perceived attitudes towards taking ONS drinks as PEN were divided into six themes: motivation, sensory perceptions, physiological consequences, social impact, practical experience and perceived compliance. Most patients were willing to stick with ONS drinks as PEN for a short period of time ≤3 months and expected significant therapeutic benefits. Taste fatigue, prolonged use and requirement to drink large volumes may reduce long-term adherence. In addition, storage space, cost and the perceived negative impact on normal social life were also considerations for patients.

Conclusion

Long term use of ONS drinks as PEN in CD patients is influenced by a number of physiological, social and sensory factors suggesting a complex interaction of variables are involved in the perceived attitudes towards their long-term use. Consideration should be given to developing multiple flavours of ONS to prevent taste fatigue, adapting ONS formulations to improve palatability and improving convenience of use. Monitoring by healthcare staff and better education to inform patients on the clinical benefits are suggested as necessary components for future interventions to improve ONS drinks acceptability as PEN.
P580 Early intestinal ultrasound assessment predicts endoscopic response and remission on anti-TNF treatment in Crohn’s Disease – a prospective longitudinal cohort study
Authors: de Voogd F , Bots S , Gecse K , Gilja O H , D’Haens G , Nylund K
Published: January 2022

Background

In the assessment of treatment response in Crohn’s Disease (CD) objective measures are superior to clinical improvement. Intestinal ultrasound (IUS) is an emerging modality with high accuracy to detect CD disease activity. Less is known about early transmural changes at IUS in treatment follow-up. Therefore, we aimed to investigate conventional IUS and contrast-enhanced ultrasound (CEUS) parameters and how they are associated with endoscopic treatment response.

Methods

In this longitudinal prospective cohort study, consecutive patients with active CD according to the simplified endoscopic score (SES-CD≥3) starting anti-TNF-α treatment were included. We recorded clinical, biochemical, IUS and CEUS parameters at baseline (T0), after 4–8 weeks (T1) and at 12–34 weeks (T2). IUS parameters were scored as previously established1. The SES-CD was scored per segment by a gastroenterologist immediately after endoscopy. The bowel segment with highest SES-CD score and thickest wall on IUS was identified. At T2, endoscopic response (decrease SES-CD≥50%) and endoscopic remission (SES-CD=0) were scored per segment. IUS and CEUS were scored blindly by two readers using recorded videos.

Results

40 patients were included (Table 1) with 23 completing follow-up. The other 17 patients had side-effects and stopped treatment (n=9), underwent bowel surgery (n=5) or were lost to follow-up (n=3). At T2, 14 reached endoscopic remission, 17 had endoscopic response. The absolute decrease in BWT at T1 and T2 paralleled endoscopic response (Figure 1). Decrease in BWT of 18% at T1 (Fig 2) predicted endoscopic response accurately (OR: 10.8, 95%CI: 1.7–69.0, p=0.012). For T2, 29% decrease in BWT (Fig 2) was most accurate to determine endoscopic response (OR: 37.5, 95%CI: 2.8–507.5, p=0.006). At T2, a BWT of 3.2 mm was most accurate (AUROC: 0.940, 95%CI: 0.862–1.000, p<0.0001, sensitivity: 92%, specificity: 85%) to determine endoscopic remission (OR: 39.4, 95%CI: 7.7–202.6, p<0.0001). Normalization of Colour Doppler Signal (CDS) (no signal or single vessel) (OR: 13.8, 95%CI: 1.3–147.8, p=0.03) or Wash-out Rate (WoR) at CEUS (1 dB increase: OR: 0.8, 95%CI: 0.60–0.96, p=0.019) added significantly to BWT to determine endoscopic remission at T2.

Conclusion

Decrease of BWT 4–8 weeks after treatment initiation predicted endoscopic response later during follow-up. In addition, we have provided accurate cut-off values for (Δ)BWT associated with endoscopic response and remission at different time-points. CDS or WoR were both of additional value to determine endoscopic remission after 12–34 weeks. As CEUS is time consuming, CDS might be sufficient in the close follow-up of CD patients.

Reference

1. Novak et al, JCC 2021
P583 Ustekinumab during pregnancy in patients with inflammatory bowel disease: a prospective multicenter cohort study
Authors: Avni Biron I , Mishael T , Zittan E , Livne M , Zinger A , Tzadok R , Goldenberg R , Kopylov U , Ron Y , Hadar E , Helman S , Ollech J , Farkash R , Pauker M , Yanai H , Dotan I , Bar-Gil Shitrit A
Published: January 2022

Background

The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Maintaining remission from conception to delivery is associated with improved pregnancy outcomes, and continued drug therapy throughout pregnancy is often needed. Data regarding pregnancy outcomes in patients with IBD treated with ustekinumab (UST) are limited. We aimed to assess maternal, pregnancy, and neonatal outcomes in patients with IBD treated with ustekinumab (UST).

Methods

In a multicenter, prospective, cohort study, women with IBD treated with UST during conception and pregnancy were recruited between 2019–2021. Outcomes were compared between patients treated with: UST, anti-tumor necrosis factor (TNF)-a, and non-UST,non anti-TNF therapy (thiopurines or mesalazine) or no therapy. UST treated patients were matched to controls in a 1:2 ratio according to age, BMI, and number of previous pregnancies. Newborns were followed up-to 12 months.

Results

Pregnant patients recruited: 129, 27-UST; 52- anti-TNF; 30-non-UST, non anti-TNF 20- no therapy (the latter 50=conventional control group).

The vast majority (96.9%) had Crohn’s disease (CD). Patients treated with UST compared to those treated with anti-TNF or conventional therapy, showed a trend towards longer disease duration (11 vs 7 vs 6 years, respectively, p=0.06), higher proportion of smokers (30.8% vs 5.9% vs 0%, respectively, p<0.001), higher rate of previous exposure to infliximab(77.8% vs 52.0% vs 14.5%, p<0.001), adalimumab (92.6% vs 66.7% vs 22.0%, p<0.001), and vedolizumab (48.1% vs 5.8% vs 4.0%, p<0.001) and higher rate of disease activity at conception (59.3% vs 15.4% vs 8%, p<0.001). Most of the patients treated with UST(n=25, 92.5%), continued therapy throughout pregnancy. New flares during pregnancy were comparable (15.2% vs 45.5% vs.39.4%, p-0.92).

Among UST-treated patients, pregnancy outcomes included: two spontaneous abortions, 4% of of preterm labor and low birth weight, one congenital anomaly (tetralogy of Fallot) (4%), and 42% cesarean section. Maternal outcomes, specifically obstetric complications and hospitalizations, pregnancy, and neonatal outcomes were comparable between treatment groups. Rates of newborn 1st-year infections, hospitalizations, and developmental delay were also comparable.

Conclusion

Pregnant patients with IBD treated with UST comprise a highly refractory group, with high rates of disease activity at conception. Their pregnancy and neonatal outcomes were favorable, and comparable to those in patients treated with anti-TNF or conventional therapy.
P585 Examining faecal incontinence and its impact on health-related quality of life in patients with Crohn’s perianal fistulas: results from a multi-country burden of illness study
Authors: Karki C , Athavale A , Hantsbarger G , Lee K , Milicevic S , Perovic M , Raven L , Sajak-Szczerba M , Sharpe E , Tozer P
Published: January 2022

Background

Perianal fistulas (PAF) are a common complication associated with Crohn’s disease (CD), and patients with Crohn’s perianal fistulas (CPF) are more likely to experience faecal incontinence (FI) than patients with CD without PAF (non-PAF CD). A global study was conducted to assess the burden of illness in patients with CPF compared with patients with non-PAF CD. Here, we present data on the level of FI and its impact on quality of life (QoL).

Methods

This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as having non-PAF CD (cohort 1) or CPF without PAF-related surgery (cohort 2) or CPF with PAF-related surgery (cohort 3). Validated, general and disease-specific patient-reported outcome data were collected using a 45-min IRB/EC-approved web-enabled questionnaire. The level of FI was evaluated using the Revised Faecal Incontinence Score (RFIS) (1–20 scale, 0 = no incontinence, 4-week recall period) and the impact of FI on QoL in patients who had experienced FI using the Fecal Incontinence Quality of Life (FIQL) (1–5 scale, 1 = lower QoL). Data were analysed using descriptive statistics.

Results

Of the 929 patients recruited (cohort 1, n = 620; cohort 2, n = 174; cohort 3, n = 135), 58–69% were male and 55–67% were aged 21–40 years across all cohorts. A significantly higher proportion of patients in cohort 3 than cohort 1 had severe Crohn’s disease as classified by a physician (18% vs 9%, respectively; p < 0.05). Overall, 47% of patients reported experiencing FI and completed both the RFIS and FIQL. Significantly higher proportions of patients in cohorts 2 and 3 had experienced FI than in cohort 1 (59% and 59% vs 40%, respectively; p < 0.05), and a significantly higher proportion were currently experiencing FI in cohort 3 than in cohorts 1 and 2 (69% vs 37% and 45%, respectively; p < 0.05). Mean RFIS scores were significantly higher (worse) in cohorts 2 and 3 than cohort 1 (9.5 [p < 0.05] and 10.6 [p < 0.001] vs 8.2, respectively). Patients in cohort 2 had significantly lower (worse) FIQL scores than those in cohort 1 across three FIQL domains (lifestyle [2.2 vs 2.4], depression/self-perception [2.1 vs 2.3], embarrassment [2.2 vs 2.4]; p < 0.05), whereas patients in cohort 3 only reported significantly lower FIQL scores compared with cohort 1 in the embarrassment domain (2.2 vs 2.4; p < 0.05).

Conclusion

In this study almost half of the patients experienced faecal incontinence. Among those who experienced faecal incontinence, patients with PAF experienced a significantly higher impact on their quality of life compared with patients without PAF.
P592 Effectiveness and safety of thioguanine in thiopurine-naïve Inflammatory Bowel Disease patients
Authors: Crouwel F , Bayoumy A B , Mulder C J J , Peters J H C , Boekema P J , Derijks L J J , De Boer S Y , van de Meeberg P C , Ahmad I , Buiter H J C , de Boer N K
Published: January 2022

Background

Currently thioguanine is considered as off-label rescue therapy for Inflammatory Bowel Disease (IBD) after conventional thiopurine failure. This study aimed to determine the safety, effectiveness and 12-month drug tolerability of thioguanine in thiopurine-naïve IBD patients.

Methods

We performed an analysis of our multicenter, retrospective cohort study including thiopurine-naïve IBD patients treated with thioguanine as first-line maintenance therapy without concomitant biological therapy. Clinical effectiveness was defined as a sustained clinical response (based on physician’s global assessment) without the (re-)initiation of concurrent biological therapy, corticosteroids or a IBD-related surgical intervention. All adverse events that occurred during follow-up were categorized by the Common Terminology Criteria for Adverse Events. Elevation of two concurrent liver tests were categorized as drug-induced liver injury.

Results

A total of 103 IBD patients (female 61%, Crohn’s disease 52%) were included with a median daily thioguanine dose of 20mg and median 6-thioguanine nucleotide (6-TGN) levels of 635 pmol/8x108 RBC (IQR 425–1100). Clinical effectiveness at 12 months was observed in 60 out of 99 patients (61%) and 80% of patients were still using thioguanine 12 months after initiation. Four patients did not reach the 12-month follow-up period but were in remission at time of data collection. Of the responding patients at 12 months 88% (N=53) remained responsive until the end of follow-up (median follow-up period 28 months, IQR 17–40 months).

Forty-nine patients (48%) developed adverse events (grade 1 or 2), of which 24% graded as moderate (grade 2) and none as severe. Seven patients ceased therapy due to the occurrence of adverse events. Adverse events consisted mainly of elevated liver tests (26%) and gastrointestinal complaints (17%). An infection was documented in three patients, none of them requiring hospitalization. Pancytopenia occurred in two other patients with 6-TGN levels of respectively 2900 and 140 pmol/8x108 RBC. None of the included patients had signs of (noncirrhotic) portal hypertension or underwent a liver biopsy during follow-up.

Conclusion

This is the first cohort study that reports on the safety and effectiveness of first-line thioguanine maintenance therapy in IBD. Thioguanine therapy was, 12 months after initiation, still used by 80% and clinically effective in 61% of thiopurine-naive patients. Adverse events were relatively common but mainly mild (grade 1) and the discontinuation rate related to adverse events was lower than observed during conventional thiopurine therapy. No signs of (noncirrhotic) portal hypertension were reported
P607 Efficacy and safety of tofacitinib in Ulcerative Colitis patients with extraintestinal manifestations in OCTAVE Open
Authors: Rubin D T , Vavricka S R , Armuzzi A , Dubinsky M C , Sharara A I , Modesto I , Fellmann M , Liguori G , Lawendy N , Cadatal M J , Lichtenstein G R
Published: January 2022

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Data from OCTAVE Induction 1&2 and OCTAVE Sustain demonstrated that a history of extraintestinal manifestations (EIMs) was shown not to influence the efficacy of tofacitinib 10 mg twice daily (BID).1 We explored the efficacy and safety of tofacitinib in patients (pts) with and without a history of EIMs in the open-label, long-term extension study, OCTAVE Open.

Methods

Efficacy and safety (treatment-emergent serious adverse events of interest) data from OCTAVE Open (NCT01470612) were analysed by history of EIMs. Tofacitinib dose in OCTAVE Open was based on baseline remission status; pts in remission received tofacitinib 5 mg BID; all others received 10 mg BID. The frequency of pre-defined prior and active EIMs at OCTAVE Open baseline (peripheral arthritis [PA]; sacroiliitis; ankylosing spondylitis [AS]; myopathy; pyoderma gangrenosum; erythema nodosum; scleritis, episcleritis; uveitis, iritis; oral ulcer/stomatitis; and thromboembolic disorder) and new occurrences of EIMs at Month (M)36, or at early termination, were evaluated in pts with non-missing data.

Results

In OCTAVE Open, 113/935 (12.1%) had EIMs at baseline (7/174 [4.0%] tofacitinib 5 mg BID; 106/761 [13.9%] tofacitinib 10 mg BID). Pts with EIMs were more likely to be female (61.1%), have a total Mayo score of ≥3 (93.8%) at OCTAVE Open baseline and have disease duration ≥6 years (60.2%), prior tumour necrosis factor inhibitor failure (61.9%), prior immunosuppressant treatment (86.7%) or corticosteroid use (54.0%) at induction study baseline, compared to those without EIMs (38.8%, 78.7%, 49.6%, 50.9%, 74.5% and 43.9%, respectively). There was no consistent trend in the proportions of pts with and without EIMs at baseline who met the OCTAVE Open efficacy endpoints (Table 1). Tofacitinib 5 and 10 mg BID had comparable safety in pts with or without EIMs at baseline (Table 2). In pts with EIMs at baseline, the most frequent active EIMs were PA (51/113 [45.1%]), sacroiliitis (6/113 [5.3%]), oral ulcer/stomatitis (5/113 [4.4%]), myopathy (4/113 [3.5%]) and AS (4/113 [3.5%]). At M36, 4/428 [0.9%] had new occurrences of PA and there were no new occurrences of sacroiliitis (0/468 [0%]), oral ulcer/stomatitis (0/460 [0%]), myopathy (0/469 [0%]) or AS (0/469 [0%]).

Conclusion

The presence or absence of a history of EIMs at baseline did not impact the long-term efficacy and safety of tofacitinib in pts with UC. New occurrences of EIMs were infrequent.

Reference

1. Rubin DT et al. Therap Adv Gastroenterol 2021; 14: 1–12.
P635 Incidence, prevalence, disease phenotype and maximal therapeutic step in Ulcerative Colitis patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem County cohort
Authors: Lakatos L , Gonczi L , Golovics P , Pandur T , David G , Erdelyi Z , Szita I , Lakatos P L
Published: January 2022

Background

Recent trends indicate a change in the epidemiology of inflammatory bowel disease (IBD) with previously low incidence areas now reporting progressive rise. The number of epidemiological population-based studies are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to analyze the incidence and disease phenotype at diagnosis, and the maximal therapeutic step distributions during follow-up in a prospective population-based database from Veszprem Province, including incident ulcerative colitis (UC) patients diagnosed between January 1, 2007 and December 31, 2018.

Methods

Data of 467 incident UC patients were analyzed (male/female:236/231; median age at diagnosis:36 years(y)[IQR: 25–54]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The source of age- and gender-specific demographic data for statistical analysis was derived from the results of a national population census in 2011.

Results

Adjusted mean incidence rate was 11.02(CI95%:10.1–12.1)/105 person-years in this 12 year period[males:11.53(CI95%:10.2–13.1)/105; females:10.54(CI95%:9.3–12.0)/105]. Prevalence rate was 283.51(CI95%:265.7–300.7)/105 persons in 2011 and 317.79(CI95%:298.8–335.8) in 2015. For detailed annual incidence rates and age-specific mean incidence rates see Figure 1 and 2. Peak onset age in UC was 20–29 years of age. Diagnostic delay from symptom onset was ≥1year in 19.1%, and ≥3 years in 4.1% of the patients. Disease extension was proctitis(E1) in 22.3%, left sided colitis(E2) in 43.9%, and extensive colitis(E3) in 33.8% of the patients at diagnosis. Patients with extensive colitis were younger(32.9y,SD:16.6) at diagnosis compared to patients with proctitis(40.1y,SD:15.9;p<0.001) or left sided colitis(44.0y;SD:19.1;p<0.001). Extraintestinal manifestations were as follows: hepatic5.4%(PSC 2.1%), arthritis10.7%, ocular0.9%, skin3.6%. Active smokers at diagnosis were 12.6%. Distribution of maximal therapeutic steps during the course of follow-up (8.34y,SD: 3.5) were 5-ASA in 46.9%, systemic corticosteroids in 16.3%, immunosuppressive therapy in 19.3%; anti-TNF biologic therapy in 12.2% and other biologic therapy in 4.3%.

Conclusion

The incidence of UC in this 12 year period was high, comparable to high-incidence areas in Western European countries, and comparable to previous data from the Veszprem cohort, while prevalence rates continue to rise compared to our previous data.(Lakatos 2011, IBD). Disease extension at diagnosis and distribution of highest treatment step was comparable to European population-based data.(Burisch 2019, JCC).
P660 Knowledge, attitudes, and awareness of contraceptive choices in women with Inflammatory Bowel Disease
Authors: Liu E , Jatale R , Farraye J , Cannon R , Woodhams E , Farraye F , Limdi J K
Published: January 2022

Background

Active inflammatory bowel disease (IBD) at conception is associated with adverse pregnancy outcomes. Published literature suggests that almost a quarter of women with IBD do not use any form of contraception putting them at risk of unplanned pregnancy. Recent guidelines emphasise the importance of antenatal care in IBD patients, but contraception counselling and risk assessment are not addressed. Our aim was to explore the contraceptive knowledge, attitudes and preferences of women with IBD.

Methods

A 34-item questionnaire was prospectively administered to 245 consecutive female IBD patients aged 18–45 attending gastroenterology clinics. Disease control was measured using the validated IBD Control questionnaire, and contraceptive preferences assessed by the Contraceptive Features Survey.

Results

Of the 245 participants (see table 1), mean disease duration was 6.5 years, median IBD control score was 16.9 (range 0- 26), and 152 (62%) respondents had previously been pregnant. Almost three quarters of respondents (n=176) reported currently using contraception, and 41 (17%) were using highly effective contraceptives. The most commonly used contraceptives were oral birth control pills (27%) and barrier methods (18%). Participants who identified as Caucasian (74%) were more likely than those who identified as Asian (37%) to use contraception (p=0.0009). Patients who did not plan to conceive in the future were more likely to use contraception (p=0.0365). However, of the 58% (n=143) who had either no plans to conceive in the future or were unsure, 23% were not using any form of contraception, and 83% were not using a highly effective contraceptive. Current biologic therapy was significantly associated with highly effective contraceptive use (p=0.0275). Contraceptive features most important to women were effectiveness (78%), ease of use (76%), few or no side effects (68%) and not detracting from sexual enjoyment (65%). Only 25% patients (n=61) recalled discussing reproductive issues with their IBD clinician, however, 86% stated they would feel comfortable having this discussion. Women wished to receive family planning counselling from their IBD nurse (81%), General practitioner (77%), IBD doctor (68%), and gynaecologist (47%).

Conclusion

A quarter of patients in our cohort were not using any contraception and the majority were not using a highly effective form potentially increasing their risk of unplanned or mistimed pregnancy. Participants desired a contraceptive that was effective, easy to use and with minimal side effects. Our findings reflect the need for further studies to improve informed decision making with contraceptive counselling, to improve the overall quality of care for women with IBD.