bluuebunny/crossref_metadata_2025_split huggingface dataset:
P679 What is the best strategy after failure to anti-TNF? Ustekinumab or other anti-TNF?
Authors: Cerpa Arencibia A , Suarez Ferrer C , Poza Cordón J , Martín Arranz E , Ramírez L , Martín Arranz M D 
Published: January 2020

Abstract

Background
After the appearance of new biologics are more treatment options for first and second-line individualising according to the characteristics of each patient. The efficacy of a second anti-TNF is lower than the initial treatment so a more efficient strategy could change the therapeutic target.

Methods
We included patients with an established diagnosis of Crohn’s disease who were on second-line biological treatment (ustekinumab or anti-TNF) after failure of a first anti-TNF (adalimumab or infliximab) treatment. Only patients in whom the indication was the ‘induction of remission of inflammatory activity’ so those patients in whom the indication was different from the intestinal activity (intestinal manifestations, perianal disease etc.) were selected were not considered valid for analysis. Patients who had undergone intestinal resection alone were included in the study if the indication of second-line biologic treatment was already established and no recurrence prophylaxis thereof.

Results
A total of 56 patients with an established diagnosis of Crohn’s disease stable tracking unit EII La Paz Hospital who were treated with second-line ustekinumab (21 patients, 37.5%) or anti-TNF (35 patients were included, 62.5%) for remission induction. Baseline characteristics of patients and their IBD are summarised in Table 1. The duration of biological treatment at the time of analysis was 1.48 years (SD: 1.2) for ustekinumab group and 3.55 years (SD 3.3) for the anti-TNF group. Ustekinumab group in 16/21 (76.2%) achieved clinical remission, 3/21 (14.3%) had no response while achieving remission (note that in one patient occurred exitus otherwise cause adenocarcinoma páncreas- unable to properly assess drug response), 2/21 patients (9.5%) did not answer. In the group of anti-TNF, 15/35 patients (42.8%) achieved clinical remission, 12/35 patients (34.3%) had response without remission, 8/35 patients (22.9%) No response. These differences between groups reached statistical significance (p = 0.015). Among patients who achieved a response / clinical remission included those wherein assessed by endoscopy identifying intestinal activity no statistically significant differences between groups vs. anti-TNF ustekinumab both SESCD (average 2 vs. 6.3 p = 0, 39) to the Ruttgerts in (mean 2.5 vs. 2, p = 0.67) postsurgical stage. Regarding the response/biological remission found no significant differences in CRP between ustekinumab and anti-TNF (4.55 vs. 5.79, p = 0.68) or with fecal calprotectin (276.25 vs. 268.82, p = 0.94).

Conclusion
In our experience, the second-line treatment with ustekinumab after the failure of a first anti-TNF has better remission rates and response to treatment with a second anti-TNF.
P681 Efficacy of vedolizumab for the prevention of postoperative recurrence in Crohn’s disease: Data from clinical practice from the ENEIDA registry
Authors: Mañosa Ciria M , Hinojosa E , Carbajo A , Castro J , Manceñido N , Calvo M , Núñez Alonso A , P Gisbert J , Nos P , Guardiola J , Sainz E , Sánchez-Rodríguez E , Cañete F , Calafat M , Domènech E 
Published: January 2020

Abstract

Background
Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases, these drugs are contraindicated or have previously failed. Vedolizumab was licensed for CD some years ago but scarce data on its efficacy for the prevention of POR is available.

Methods
All CD patients in whom vedolizumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD, GETECCU). We evaluated the rates of Endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score &gt;i1 and advanced endoscopic POR by &gt;i2.

Results
Twenty-three patients were included; vedolizumab was started after a median time of 23 days (IIQ21-73). Concomitant immunosuppressants were used in 17%; 18% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 13% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. Thirty-four per cent had been exposed to vedolizumab prior to the index surgery (26% within the last 6 months). The median time of follow-up on ustekinumab was 26 months (IQR 11–31). Eighty-three per cent of patients had at least one endoscopic assessment within 18 months after surgery: 40 % had endoscopic POR and 15% advanced endoscopic POR. Additionally, 22% presented clinical POR at the discretion of the treating physician and 9% developed surgical POR.

Conclusion
In a small clinical practice cohort, vedolizumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR.
P693 Development and evaluation of i-TRACKER infliximab and i-TRACKER anti-Infliximab kits: fast and innovative chemiluminescent assays for the monitoring of patients treated with infliximab
Authors: Noguier G , Montaillier C , Daviere S , Colombeau L , Parussini E 
Published: January 2020

Abstract

Background
Infliximab, a monoclonal antibody directed against TNFα, is a drug widely used for the treatment of inflammatory diseases (rheumatoid arthritis, Crohn’s disease, etc.). Therapeutic drug monitoring is currently proposed to provide useful information to clinicians to improve the efficacy of the treatment. Theradiag has just developed the innovative i-TRACKER Infliximab and i-TRACKER Anti-Infliximab kits: fast quantifications of Infliximab and Anti-Infliximab antibodies fully automated on the random access i-TRACK10 chemiluminescent analyser.

Methods
Analytical performances were assessed using two types of serum samples: human serum spiked with Infliximab or Anti-Infliximab antibodies, and samples from inflammatory bowel disease patients treated with Infliximab (n = 41). On one hand, Infliximab from serum sample was captured by TNFα coupled magnetic microparticles and Anti-Infliximab polyclonal antibodies conjugated to acridinium ester were used for the detection of Infliximab. On the other hand, Anti-Infliximab antibodies were captured according to Infliximab coupled magnetic microparticles and detected with the use of Infliximab conjugated to acridinium ester. Light emission was linked to the quantity of Infliximab, or anti-Infliximab antibodies, presents in the sample.

Results
Infliximab measurement showed high accuracy (recovery was comprised between 80% and 107%). High precisions were reached for both assays (intra-precision CV were below 8.1% and 2.7% for Infliximab and Anti-Infliximab assays; inter-precision CV were below 11.7% and 4.8% for Infliximab and Anti-Infliximab assays) and no interferences were seen with biologic agents (bilirubin, haemoglobin, lipids, biotin and rheumatoid factors). The dynamic ranges of the assays were 0.3–24 µg/ml for Infliximab quantification and 10–2000 ng/ml for Anti-Infliximab antibodies quantification. i-TRACKER Infliximab and i-TRACKER anti-Infliximab assays were compared with respective LISA-TRACKER assays and showed excellent correlation (R² = 0.94, Slope = 1.04 for Infliximab assay; Spearman’s coefficient correlation was 0.98 for Anti-Infliximab assay).

Conclusion
i-TRACKER kits are innovative assays which exhibit fast (time to results &lt;40 min), accurate (standardised with NIBSC/WHO international standard Infliximab) and reproducible results for the quantification of princeps and biosimilar molecules (CT-P13, SB2). Excellent agreements were observed with respective LISA-TRACKER assays. i-TRACKER kits are valuable tools for the monitoring of patients treated with Infliximab.
P697 Efficacy and safety of ustekinumab in Crohn’s disease: A real-world study from Australia
Authors: Kakkadasam Ramaswamy P , Moattar H , Sawyer E , Edwards J , Shukla D 
Published: January 2020

Abstract

Background
Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved in Australia for the treatment of adults with moderate to severe Crohn’s disease (CD) in 2017. The aim of this retrospective single centre study was to study the efficacy and safety of UST in CD in a real world cohort.

Methods
Patients with CD who began UST therapy between June 2017 and July 2019 were included. UST induction was given as an infusion (6 mg/kg) at week 0 followed by 90 mg subcutaneous injection (SC) at week 8 and 90 mg SC every 8 weeks as maintenance. Primary endpoint (PE) was steroid free clinical remission or steroid free clinical response at week 24. Secondary endpoints (SE) were: endoscopic response or remission, radiological response or remission, biochemical response (CRP &lt; 5 mg/L or Calprotectin &lt;150 μg/g), clinical response or remission at week 52.

Results
Seventy-six patients with CD were included in the study. 64.5% failed ≥1 anti-TNF and 13.1% failed anti-TNF and vedolizumab; 26(34.2%) patients were biologic-naïve. Median follow-up was 61 weeks. Ten patients (13.1%) discontinued UST, and the median time to discontinuation was 48 weeks; eight patients due to loss of response, one patient due to paradoxical worsening of arthralgia, one patient chose to stop treatment. Six patients underwent surgery whilst on UST. At week 12, 48 (63.1%) of patients achieved steroid free clinical remission or response [19/26 (73%) Anti-TNF naive and 29/49 (59%) anti-TNF exposed]; of these patients, 16/19 (84%) in the anti-TNF naive group and 19/29(65.5%) in the anti-TNF exposed group achieved PE. Forty-seven (61.8%) patients achieved PE. At 52 weeks, 68.2% (30/44), 67.5% (27/40), 56.1% (23/41), 69% (29/42) achieved endoscopic, radiological, biochemical and clinical endpoints respectively. Achieving steroid free clinical response or remission at week 12 was associated with achieving PE (79% vs. 42.8%, OR 3.6, p 0.01) and clinical SE (83.3 vs. 58.3%, p 0.001). Patients with B2/3 vs. B1(54% vs. 82%, p 0.09), ≥2 biological failure (72% vs. 33%, p 0.09), CRP &lt; 6 baseline (55 % vs. 67.5%, p 0.3) were less likely to attain PE.

Conclusion
In a real-world cohort, UST appears efficacious and safe in medium and long term, with modest clinical, biochemical, radiological and endoscopic outcomes. Patients who achieve steroid-free clinical remission or response at 12 weeks are more likely to be in clinical remission or response at 24 and 52 weeks.
P706 Adalimumab drug levels at secondary loss of response in Crohn’s disease; are we aiming high enough? A retrospective, international multi-centre study
Authors: Swaine A , Reynolds R , Roblin X , Gibson D , Martin C , Irving P , Sparrow M , Ward M 
Published: January 2020

Abstract

Background
Evidence supporting therapeutic drug monitoring with adalimumab (ADA) in Crohn’s disease (CD) is not as strong as for infliximab. Data examining whether changes in ADA drug exposure after dose intensification are associated with outcomes are lacking. We aimed to explore associations between ADA drug level exposure at loss of response and then at 6 and 12 months and compare these to short term clinical outcomes.

Methods
Retrospective study of adult CD patients who underwent ADA intensification to weekly dosing for secondary loss of response at three tertiary centres between 2013 and 2018. We compared trough ADA drug levels using a drug sensitive ELISA at loss of response and at 6 and 12 months after intensification with paired rates of clinical remission (Harvey Bradshaw Index &lt;5 or Crohn’s Disease Activity Index &lt;150), biochemical remission (C-reactive protein &lt;5 mg/L), objective remission (CRP &lt; 5 mg/L, faecal calprotectin &lt; 150 µg/g or absence of inflammation at endoscopy or imaging) and ADA failure (based on Physicians Global Assessment. We performed comparisons between continuous and categorical data using Fischer’s exact or Mann–Whitney test. A receiver operated curve (ROC) analysis was used to identify target ADA levels associated with outcomes of interest.

Results
In total, 133 CD patients were included; median disease duration 8 years (IQR 4–17), 51% were biologic-exposed and 49% received concomitant immunomodulation. Rates of clinical remission, objective remission and ADA failure were 73.0%, 37.4% and 25.0% at 6 months and 65.8%, 34.0% and 42.8% at 12 months, respectively. Drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders; however increases in drug levels at 6 and 12 months were associated with improved outcomes at these time points (Figure 1). ROC analysis demonstrated that ADA drug levels 6 months after intensification &gt; 8.9, 9.6 and 8.9 µg/ml were associated with clinical remission, objective remission and ADA non-failure respectively. Similar results were demonstrated with ADA drug levels at 12 months after dose intensification (Figure 1).

Conclusion
ADA drug levels at loss of response are not associated with subsequent 6 or 12 month outcomes. However, measurement of subsequent ADA drug levels at 6 and 12 months post escalation demonstrates that higher levels (with a target threshold between 7.7–10.9μg/ml) were associated with favourable outcomes. This study suggests that performing TDM subsequent to dose escalation of ADA has a role in predicting outcomes. Further, prospective studies dosing to target ADA drug levels are therefore needed.
P723 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: Results from the GO-LEVEL study
Authors: Samaan M , Cunningham G , Tamilarasan G , Rawstron K , Hawash K , Beltran L , Ray S , Mawdsley J , Anderson S , Sanderson J , Arkir Z , Irving P 
Published: January 2020

Abstract

Background
The exposure–response relationship associated with the use of golimumab for UC has been previously demonstrated in the PURSUIT trial programme. A significant association between serum golimumab concentrations (SGC) and favourable outcomes was observed during both induction and maintenance therapy. However, data regarding the optimal therapeutic SGC threshold is limited.

Methods
GO-LEVEL was an open-label, phase IV, investigator initiated study (NCT03124121) which included a prospective cohort of UC patients commencing golimumab induction therapy, as well as a cross-sectional cohort receiving maintenance treatment (&gt;18 weeks from initiation).
Patients commencing induction therapy all had disease activity objectively confirmed and were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare, or during stable remission. Clinical disease activity was evaluated using SCCAI and PRO2, and biochemical activity using FC and CRP. Combined clinical-biochemical remission was defined as SCCAI&lt;3 as well as FC&lt;250ug/g. SGC and anti-golimumab antibodies (AGA) were measured using a drug-sensitive ELISA (LISATRACKER, Theradiag). Fishers exact or Mann–Whitney U were used to compare groups, ROC analysis to identify therapeutic thresholds and Spearman’s rank coefficient (rs) for correlations.

Results
Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined remission at week 6. The median SGC of those in combined remission was significantly higher than those who were not (5.0 vs. 3.1 μg/ml, respectively, p = 0.03). ROC curve analysis demonstrates 3.8 μg/ml as the optimal therapeutic threshold to achieve combined remission at week 6 (sensitivity 0.71, specificity 0.65, AUC 0.72). Significant, inverse correlations were also observed between week 6 SGC and PRO2, CRP and FC (rs −0.41 (p = 0.01), −0.47 (p = 0.004) and −0.40 (p = 0.02), respectively). However, week 6 SGC did not predict outcomes at week 10 or 14.

Sixty-four patients were included in the maintenance cohort; 32 (50%) were in combined remission, 32 were not. The median SGC of those in combined remission was significantly higher (3.0 vs. 2.1 μg/ml, respectively, p = 0.003). ROC curve analysis demonstrates 2.4 μg/ml as the optimal therapeutic threshold to achieve combined remission (sensitivity 0.73, specificity 0.66, AUC 0.71).

No AGA were detected in either cohort.

Conclusion
GO-LEVEL offers further evidence of the exposure-response relationship with golimumab. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested SGC therapeutic thresholds of 3.8 μg/ml at week 6 and 2.4 μg/ml during maintenance.
P730 Effectiveness and safety of endoscopic balloon dilation of colorectal strictures in Crohn’s disease
Authors: TILMANT M , serrero M , Poullenot F , Bouguen G , Pariente B , Altwegg R , Basile P , Filippi J , Vanelslander P , Buisson A , Vuitton L , Desjeux A , Laharie D , Le Balch E , Nachury M , Boivineau L , Savoye G , Hebuterne X , Poincloux L , Lamrani A , Fumery M 
Published: January 2020

Abstract

Background
Endoscopic balloon dilation (EBD) is widely used to manage Crohn’s disease (CD) ileal stricture. However, data of EBD on inflammatory bowel diseases (IBD) colorectal strictures are scarce.

Methods
We performed a retrospective study in 9 tertiary centres, including all consecutive IBD patients who underwent EBD for native or anastomotic colorectal stricture between 1999 and 2018. Outcomes were rate of technical success defined by a passable stricture at the end of the EBD, clinical success defined by a passable and asymptomatic stricture and colonic resection at the end of follow-up. Factors associated with EBD success were also investigated by logistic regression.

Results
Fifty-seven patients (25 women, median age: 36 years, InterQuartile Range, 31–48) were included. All patients had CD and 42 (74%) had symptomatic stricture. Regarding the 60 strictures, 52 (87%) were native and the most frequent location was left colon (27%). 39 (65%) measured less than 5 cm, 57 (95%) were non-passable by the scope and 35 (58%) ulcerated. Among the 161 EBD performed (median number of dilatations per strictures: 1, IQR 1–3), technical success was observed in 123 (76%) EBD. One perforation occurred (0.6% per EDB and 2% per patient). After a median follow-up of 4.3 years [IQR 2.0–8.4], 24 patients (42%) underwent colonic resection, 9 (16%) had symptomatic strictures non-passable by the scope, 11 (19%) had asymptomatic non-passable strictures and 13 (23%) had asymptomatic strictures passable by the scope. One colon lymphoma and one colorectal cancer were diagnosed (3.5% of patients), respectively on endoscopic biopsies and at the time of surgery. None factor was associated with technical, clinical success, or surgery including therapeutic modification.

Conclusion
EBD of CD-associated colorectal strictures is feasible, efficient and safe as more than 50% of patients avoid surgery.
P736 Utility of infliximab serum concentration in inflammatory bowel disease treatment in real world practice at Hospital Universitario de Canarias
Authors: Carrillo Palau M , Alonso-Abreu I , Ramos-Lopez L , Fernando G N , Hernandez Alvarez-Buylla N , Hernandez-Perez A , Medina-Chico S , Quintero E 
Published: January 2020

Abstract

Background
Anti-TNF drugs are effective treatments for the management of inflammatory bowel disease (IBD) but treatment failure is common. The aim of this study was to investigate the association between inflammatory biomarkers, serum concentrations of IFX and antiIFX antibody concentration during induction and maintenance treatment and to investigate the association with disease activity and response to treatment in our patients from 2017 to 2019.

Methods
Retrospective observational study. We enrolled patients receiving IFX from March 2017 until March 2019. Demographic data, disease characteristics, previous medical treatments and surgeries were recorded. Clinical Activity Index (Harvey Index and Parcial Mayo Score) and CRP, faecal calprotectine (FC) and endoscopy or radiological activity were recorded at baseline, and at 6, 12 and 24 months of treatment. IFX serum concentrations and anti-IFX antibody concentration were measured at the end of induction (week 8) and during follow-up (6, 12 and 24 months).

Results
One hundred and eighty-one IBD patients were treated during the study period, and 175 patients were included: 128 (73.1%) Crohn’s disease (CD), 46 (26.3%) ulcerative colitis (UC) and 1 (0.6%) indeterminated colitis (IC). 95 male, 85 female, mean age 45 years (±15); 93% were naive to IFX. 73.6% started IFX combined with inmunomodulator treatment. At week 0, 80% had an active disease (Global Physician Assessment), 58.8% had CRP &gt;5 μg/dl and 62% had FC &gt; 150 mg/kg. At 12 months, 126 patients continued under IFX, and 68% had an stable disease and 44% were intensified. Thirty-six per cent had CRP &gt; 5 μg/dl and 37% FC&gt;150 mg/kg. At 24 months, 90 patients continued with IFX, from which 80% were stable and 43% were intensified.38% had CRP &gt;5 μg/dl and 26% FC &gt;150 mg/kg. Patients with post-induction (week 8) serum IFX concentration &gt;7 μg/ml had more stable disease (p: 0.04) at that moment and IFX serum concentration &gt; 3 μg/ml at 18 months was corelationated with no inflammation at endoscopy or radiology (p: 0.025). In the multivariate analysis stenosant phenotype and CRP &lt; 5 mg/dl at 6 months were relationated with early stop of IFX treatment (&lt;1 year).

Conclusion
Our study shows that IFX levels &gt;7 μg/ml correlates with a better clinical response. Disease phenotype and inflammatory parameters could influence in long time maintenance treatment. Drug-level monitoring and measurement of baseline inflammatory parameters may improve the management of IBD.