bluuebunny/crossref_metadata_2025_split 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

Abstract

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 &lt;5 mg/L and faecal calprotectin &lt;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&lt;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&gt;0.05). Throughout the study period, neither IFX TCs nor IFX CLs predicted attaining the primary endpoint (P &gt;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

Abstract

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&gt;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&gt;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&gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt; 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

Abstract

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

Abstract

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 (&lt;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 &lt; 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 &lt; 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.