bluuebunny/crossref_metadata_2025_split huggingface dataset:
P491 De-escalation of dose-intensified anti-TNF therapy in IBD patients in sustained deep remission
Authors: Chu I , Little R , Sparrow M , Ward M 
Published: January 2020

Abstract

Background
Data on outcomes following de-intensification of anti-TNF therapy in inflammatory bowel disease (IBD) are limited and concerns about relapse limit the willingness to de-escalate. This study aimed to evaluate rates of successful de-escalation at 12 months and to determine factors that may predict success.

Methods
Single-centre retrospective study of IBD patients on dose-intensified infliximab (IFX) or adalimumab (ADA) for secondary loss of response. De-escalation was considered in patients achieving sustained biomarker normalisation. Patients were followed for 12 months post-de-escalation and classified as ‘successes’ if remaining on reduced dose anti-TNF or ‘failures’ if requiring re-escalation, steroids, surgery or enrolment into a clinical trial. Patient demographics, disease characteristics, biomarkers (faecal calprotectin (FCP), C-reactive protein (CRP), albumin), anti-TNF drug levels and thiopurine metabolites were collected.

Results
Of 24 patients (20 CD, 4 UC), 18 received IFX and 6 received ADA. Patients on IFX were de-escalated to 5 mg/kg 8-weekly (89%) or 10 mg/kg 6-weekly (11%), while patients on ADA were de-escalated to 40 mg fortnightly (83%) or 40 mg weekly (17%). Fifteen out of 24 (63%) patients were successes 12 months post-de-escalation. Of the 9 failures, median time to failure was 6 months (IQR 4.6–9.9) – 6/9 failures required re-escalation of anti-TNF therapy and 3/9 entered a clinical trial. Re-escalation successfully recaptured response in 6/6 (100%) patients after a median of 1.4 years follow-up (IQR 1.1–2.3). Albumin at de-escalation was higher in the success group compared with failures (38 g/l vs. 36 g/l, p = 0.025). There was no significant difference in CRP, FCP, anti-TNF drug level or 6-TGN level between the two groups. There was no difference in IFX levels between successes and failures at the time of de-escalation (5.5 vs. 7.5, p = 0.524) as well as 6 months (3.1 vs. 5.1, p = 0.628) and 12 months (3.2 vs. 6.1, p = 0.457) post de-escalation. There were insufficient data for ADA drug level comparison post-de-escalation.

Conclusion
Nearly two-thirds of patients remained on reduced anti-TNF dosing at 12 months post-de-escalation. All patients who failed de-escalation were recaptured after dose re-escalation. Other than albumin, no baseline predictors for the success or failure of de-escalation could be identified, although cohort size is small, follow-up was short and the majority of patients achieved sustained biomarker normalisation prior to de-escalation. De-escalation may be considered in patients on intensified anti-TNF therapy in sustained deep remission.
P492 Use of bowel ultrasound to assess disease activity in Crohn’s disease patients after induction therapy with infliximab
Authors: Frias Gomes C , Neto Nascimento C , Pereira F , Caldeira A , Sousa R , Arieira C , Xavier S , Monteiro S , Dias de Castro F , Leite S , Cotter J , Santos A A , Cravo M , Torres J , Palmela C 
Published: January 2020

Abstract

Background
Objective goals are needed to guide patient management and assess treatment efficacy in patients with Crohn’s disease (CD). Bowel ultrasound (US) is a widely available, non-invasive and inexpensive technique increasingly being used in these patients. The use of bowel wall thickness (BWT) has been proved to be an accurate measure for assessing disease activity and response to therapy. Recent studies show a rapid improvement of BWT after 3-month of therapy. Our aim was to evaluate BWT variation after induction therapy with infliximab (IFX) in CD patients and correlate BWT with clinical and laboratory parameters.

Methods
Prospective cohort multicentre study including patients with active CD starting IFX therapy. Clinical disease activity was assessed using the Harvey–Bradshaw index (HBI). C-reactive protein (CRP) and faecal calprotectin (FC) were measured both at week 0 and after induction therapy (week 14), and infliximab trough levels (ITL) were measured at week 14. Bowel ultrasound was performed at week 0 and 14, BWT from the worst segment was selected for analysis. Abnormal BWT was defined has higher than 3mm in any bowel segment.

Results
We included 10 patients with CD (80% males; median age 29 (21–64) years). According to Montreal classification, most patients were A2 (7/10), had ileocolonic disease (L1 20%; L2 20%; L3 60%) and an inflammatory phenotype (B1 60%; B2 20% and B3 20%). Most patients were anti-TNF therapy naive (80%), and combination therapy was used in 80%. Before IFX (week 0) median HBI was 2 (IQR 1.75–5.25), CRP 1.10 mg/dl (IQR 0.65–3.50) and FC 802 μg/g (IQR 324–1336). The terminal ileum was the most affected segment identified by the USA (5/10), followed by ascending colon (2/10) descending colon (2/10) and sigmoid colon (1/10). Median BWT was 4.6 mm (IQR 3.6–6.4). After induction therapy (week 14), all patients were in clinical remission (HBI&lt;5) except for one in whom IFX dose was increased to 10 mg/kg. Laboratory remission (CRP &lt; 0.5 mg/dl and FC &lt; 250 μg/g) was present in 50% of patients. US response (measured by a reduction in BWT of at least 0.5 mm) was observed in 70% of patients, with US remission (normalisation of BWT in the most affected segment) in 30%. At week 14, 70% of patient had ITL &gt; 3 μg/ml. Median BWT at week 14 was higher in patients with ITL &lt; 3 μg/ml (6.25 vs. 2.98 mm, p = 0.048).

Conclusion
The majority of our patients showed a US response (reduction in BWT) after 14 weeks of infliximab, suggesting that reduction in BWT could be an early marker of response to therapy. US evaluation after induction therapy can be a helpful tool to monitor disease activity and guide patient management in CD patients in our daily practice.
P496 Feasibility and safety of single incision laparoscopic surgery for patients with complex Crohn’s disease
Authors: LI Y , Liu B , Yao D , Zheng L , Zhou Z , Huang Y , Duan Y 
Published: January 2020

Abstract

Background
Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multi-port laparoscopic surgery. Recently, this technique has been applied to Crohn’s disease (CD); however, the application of a laparoscopic approach for complex CD, which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the feasibility and safety of SILS for patients with the complex disease and to compare its clinical results in patients with complex disease.

Methods
We investigated the feasibility and safety of SILS in sixty patients who underwent SILS for CD were divided into two groups: those with the complex disease (complex group, n = 30), and those with a simple disease (simple group, n = 30). The perioperative data were analysed and compared between the groups.

Results
The mean operative time and blood loss were 130.5 ± 28.3 min (range 105–166 min) and 230 ± 58 ml (range 116–410 ml) in the complex group, and 113.4 ± 21.5 min (range 95–151 min) and 72 ± 19ml (range 58–115 ml) in the simple group. There were no significant differences in the operative time between the two groups (p = 0.083, &gt;0.05), but the blood loss was significantly greater in the cases of complex group (p = 0.025, &lt;0.05). Two patients in the complex group required conversion to open surgery for a retroperitoneal fistula and recurrent CD disease. There were no conversions in the simple group. The frequency of postoperative complications was similar in the two groups. The length of the hospital stay was also similar in the two groups. Although the rate of conversion tended to be higher in the complex group, the rate of postoperative complications and length of hospital stay did not differ significantly between the groups (p = 0.061, &gt;0.05).

Conclusion
SILS may be feasible and safe for carefully selected patients with complex CD.
P506 Increased risk of anti-drug antibodies to a second anti-TNF in patients who developed antibodies to the first anti-TNF
Authors: Yanai H , Amir S , Avni Biron I , Tsadok Perets T , Shamir R , Dotan I , Assa A 
Published: January 2020

Abstract

Background
Evidence regarding predisposition to develop anti-drug antibodies to a second anti-TNF in patients with inflammatory bowel diseases (IBD) who previously developed antibodies to a first anti-TNF (either infliximab or adalimumab) is conflicting. We aimed to assess the rates of such consecutive immunogenicity.

Methods
The medical records of all patients with IBD followed at the Rabin and Schneider Medical Centers (all ages) from 2014 to 2019, who were treated with an anti-TNF agent were reviewed. Clinical data including age at diagnosis, gender, disease type, concomitant use of immunomodulators, as well as drug trough levels (TLs) and anti-drug antibodies (ADAs) for both agents were registered. Patients who switched from one anti-TNF to another and had comprehensive clinical and pharmacokinetic data were assessed for consecutive immunogenicity.

Results
Overall, 1570 patients were tested for TLs and ADAs (infliximab, n = 702, 45%). Rates of positive infliximab ADAs were 31%, and positive adalimumab ADAs were 13%. We identified 55 eligible patients (Crohn’s disease = 52, ulcerative colitis = 2, IBD unclassified = 1; females = 26 [47%]; mean age at diagnosis 26.5 ± 13 years). Of 29 patients with infliximab as the first anti-TNF, 25 (86%) had positive ADAs. None of the 4 patients without ADAs against infliximab developed ADAs against consequent adalimumab, whereas 7/25 (28%) of patients with positive ADAs against infliximab developed ADAs against adalimumab, significantly higher than the overall immunogenicity rate of adalimumab (28% vs. 13%, p = 0.03). Of the 26 patients who were switched from adalimumab to infliximab, 10 (38%) had positive ADAs. Out of 16 patients with negative ADAs against adalimumab, 5 (31%) developed ADAs against consequent infliximab whereas 7/10 (70%) of patients with positive ADAs against adalimumab developed ADAs against infliximab, significantly higher than the overall immunogenicity rate of infliximab (70% vs. 31%, p = 0.008). The overall rate of immunogenicity against the second anti TNF following a switch due to immunogenic failure was 39%. Only 33% of patients were treated with concomitant immunomodulators after an immunogenicity driven switch. Clinical data, as well as TLs and ADA, were comparable in children and adults.

Conclusion
The rate of consecutive immunogenicity in anti-TNF treated patients is significantly higher than the overall immunogenicity against the first anti-TNF. This higher rate of consecutive immunogenicity may be associated with a predisposition to developing anti-drug antibodies to anti-TNF agents. It may also be a consequence of the relatively low rates of combination therapy following an immunogenic failure.
P509 Vedolizumab levels in breast milk: Results from a prospective, postmarketing, milk-only lactation study in nursing mothers with inflammatory bowel disease
Authors: Sun W , Fennimore B , Beaulieu D B , Arsenescu R , Stein A , Chen J , Lin T , McKnight S , Rosario M , Lirio R A 
Published: January 2020

Abstract

Background
The safety of inflammatory bowel disease (IBD) medications during lactation is of significant interest and relevance to female patients of childbearing potential. Available data regarding the safety and transfer of biologic agents via breast milk are limited to case reports. Vedolizumab has a well-established, positive benefit-risk profile in adult IBD patients. Literature data show that vedolizumab is detectable in human milk.

Methods
A prospective, postmarketing, phase 4, open-label, milk-only lactation study was conducted to assess vedolizumab concentrations in breast milk from lactating women with IBD who were on an established vedolizumab maintenance regimen (300 mg intravenous [IV] every 8 weeks [Q8W] or an alternative dose frequency). Maternal milk samples were serially collected throughout the dosing interval on Days 1 (predose and 1 h after the end of vedolizumab infusion), 4, 8, 15, 29, and 57 to allow the estimation of drug excreted in milk relative to the maternal dosage. Maternal safety data were also collected.

Results
A total of 11 patients were enrolled in the study. Vedolizumab was detectable in the majority of milk samples collected on Days 1 and 57, and in all samples collected at other time points. Following receipt of vedolizumab 300 mg IV on Day 1, the vedolizumab milk concentration increased with a median time to peak concentration (Cmax) of 3–4 days, and subsequently decreased exponentially. For the 9 patients on the Q8W regimen, median Cmax was 0.213 µg/ml (range, 0.098–0.561 µg/ml); the geometric mean daily infant dosage, calculated using average concentration over 8-week dosing interval (0.13 µg/ml), was 0.02 mg/kg/day with a corresponding geometric mean percentage of maternal dosage consumed in breast milk by infants of 21%. The maternal safety profile was acceptable and similar to that observed in previous adult studies. Leveraging the mean trough serum concentration of 11.2 µg/ml from historical studies of vedolizumab, the ratio of mean milk concentration (trough, 0.05 µg/ml; peak, 0.25 µg/ml) to serum concentration was approximately 0.4%-2.2%, which is consistent with published data for vedolizumab and comparable with several other monoclonal antibody therapeutics for IBD. Published vedolizumab studies also showed no increase in general or gastrointestinal tract infections in the infants exposed to vedolizumab in breast milk, and exposed infants reached their acceptable development milestones through up to 10 months of follow-up.

Conclusion
Vedolizumab was found to be present in human breastmilk at a low level. The impact of vedolizumab IV administration during breastfeeding is expected to be minimal.
P510 Dose escalation of subcutaneous vedolizumab in patients with ulcerative colitis: A post hoc analysis of the VISIBLE trial data
Authors: Sandborn W , Wolf D , D’haens G , Jansson J , Chen J , Uddin S , Candela N , Lasch K , Kisfalvi K 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ), a gut-selective, α 4β7 integrin monoclonal antibody, is approved for intravenous (IV) administration to patients with moderate-severe ulcerative colitis (UC). Subcutaneous (SC) VDZ was evaluated for maintenance therapy for UC in VISIBLE 1, a double-blind, placebo-controlled, Phase 3 study, and its open-label extension (OLE). We evaluated the efficacy of increasing dose frequency of VDZ SC from every-2-weeks (Q2W) to weekly administration (QW) after treatment failure (disease worsening or need for rescue medication).

Methods
In VISIBLE 1 (NCT02611830; EudraCT 2015-000480-14), a Q2W dosing regimen was used for patients with UC who achieved clinical response at week 6 (after open-label IV VDZ inductions at weeks 0 and 2) and were randomised to maintenance treatment with VDZ SC. Patients who did not respond at week 6 but responded by week 14 rolled over to the VISIBLE OLE (NCT02620046; EudraCT: 2015-000482-31) and received Q2W VDZ SC dosing. In VISIBLE 1 and the OLE, 2 groups of patients experienced dose escalation: (1) patients who entered the VISIBLE OLE study on a Q2W VDZ dosing regimen but experienced disease worsening and were escalated to QW dosing (OLE Q2W/QW); and (2) patients who experienced treatment failure during Q2W VDZ treatment in VISIBLE 1, rolled over to OLE, and were escalated to a QW dosing regimen (VISIBLE 1 treatment failure). Efficacy was evaluated by clinical remission and response rates after dose escalation using partial Mayo scores at the visits in the Visible OLE study. In this interim analysis, not all patients continuing in the trial had not completed all study visits. Only patients who had completed a given visit (evaluable patients) were included in the analyses for that visit.

Results
Of the 54 patients who received dose escalation 52% were male. Mean age was 39 years, mean UC duration was 7.4 years; 76% had severe disease activity (Mayo 9–12) at baseline, and 43% had prior anti-TNF therapy failure (Table 1). Of the patients with dose escalation, 27.1% (13/48 evaluable patients) recaptured clinical remission 16 weeks after dose escalation and 10.8% (4/37 evaluable patients) were in clinical remission after 48 weeks (Table 2). A similar trend was observed for clinical response rates in this patient population.

Conclusion
Increasing the frequency of VDZ SC dosing to QW recaptured lost response to treatment for some patients. These are interim results of the OLE study; further follow-up during the ongoing OLE will provide more insight into the long-term efficacy and safety of dose escalation with VDZ SC.
P525 Rheumatoid arthritis treatment with filgotinib: Week 156 safety and efficacy data from a phase 2b open-label extension study
Authors: Besuyen R , Kavanaugh A , Westhovens R , Winthrop K , Lee S , Greer J , DeZure A , An D , Ye L , Sundy J , Meuleners L , Alten R , Genovese M 
Published: January 2020

Abstract

Background
Filgotinib (FIL) is an oral, selective Janus kinase inhibitor, shown to be effective and well tolerated in patients (pt) with rheumatoid arthritis (RA) and other inflammatory diseases (IBD/AS/PsA). DARWIN 3, an ongoing, open-label, long-term extension of phase 2b studies evaluates the longer-term safety and efficacy of FIL in RA.

Methods
The study evaluated pt outcomes for methotrexate (MTX) inadequate responders completing the 24-week DARWIN 1 (FIL+MTX) and DARWIN 2 (FIL monotherapy) studies. We present an interim analysis at week 156 following FIL 200 or 100 mg/day treatment. Event rate: total events/total years of exposure of FIL; Exposure: until data cut-off in patients on the study at the time of analysis.

Results
Eight hundred and seventy-seven patients completed the parent studies. Seven hundred and thirty-nine enrolled in DARWIN 3 (497 DARWIN 1, 242 DARWIN 2); most DARWIN 1 and 2 patients were female (81.5%, 81.8%), white (75.3%, 74.8%); mean age was 53 and 52 years, respectively. Mean baseline MTX dose in the FIL+MTX group: 16.8mg/week. At week 156, 59.9% of patients remained on study. Most common reasons for discontinuation were adverse events (26.5%) and subject request (9.1%). Total exposure to FIL was 2203 pt-years; mean exposure ± standard deviation (SD): 3.04 ± 1.22 years for FIL+MTX and 2.86 ± 1.21 years for FIL monotherapy. Treatment-emergent adverse events (TEAEs): 419 (84.3%) patients on FIL+MTX and 203 (83.9%) patients on FIL monotherapy; serious TEAEs occurred in 45 (9.1%) and 33 (13.6%), respectively. Adverse event of special interest (AESI) rates remained low at week 156 (Table 1). Grade ≥3 toxicities in &gt;1% of patients were decreased lymphocytes (4.2%/1%), decreased neutrophils (1.0/1.2%), increased fasting triglycerides (2.2/0%) and decreased fasting triglycerides (0/3.3%) for FIL+MTX/FIL monotherapy respectively. 5 deaths occurred (FIL+MTX: 2, FIL monotherapy: 3) none after week 132. Clinical efficacy was shown at week 156 in both FIL+MTX and FIL monotherapy groups, using observed cases as measured by ACR20 (87.2% and 89.7%)/ACR50 (72.4 and 63.0)/ACR70 (45.5 and 40.0) DAS28(CRP) ≤3.2 (69.0 and 64.7) and DAS28(CRP) &lt;2.6 (53.4 and 45.6).

Conclusion
FIL was generally well tolerated; no new safety signals emerged. No safety differences observed in patients receiving FIL+MTX or FIL monotherapy. Efficacy was sustained up to week 156 in both treatment groups.
P526 Body mass index and response to TNF-α inhibitors in inflammatory bowel disease
Authors: Nordin F , Shadbolt B , Subramaniam K 
Published: January 2020

Abstract

Background
Obesity is an emerging issue in the care of patients with inflammatory bowel disease (IBD). The aim of the study was to evaluate whether the response to TNF-α inhibitors (infliximab and adalimumab) could be influenced by body mass index (BMI) in IBD. Unlike adalimumab (ADA), a recombinant humanised IgG antibody against (TNF-α), the dosing of infliximab (IFX); a monoclonal chimeric antibody is weight-based.

Methods
We identified a cohort of patients with IBD at a single centre, naïve to biologic therapy and stratified them according to their weight and BMI. The primary outcome is the first occurrence of loss of response defined as clinical deterioration requiring hospitalisation, surgery, corticosteroid use, dose escalation or discontinuation of therapy and/or evidence of activity on endoscopy. Patients were followed up for 4 years. Multivariate analysis with logistic regression were used to compare variables.

Results
There was a total of 104 IBD patients; 51% (n = 53) were males and the median age was 40 years (19–76 years). The majority (n = 89; 85.6 %) had Crohn’s disease and the rest (n = 15; 14.4%) were diagnosed with ulcerative colitis. The median BMI was 24.5 kg/m2 (13.4–41.5 kg/m2). Patients had been diagnosed with IBD for a total median duration of 13 years (1–50 years). The majority of patients were not active smokers (n = 92; 88.5%) with the rest being current smokers (n = 12; 11.5%). Of the 104 patients, there were an equal number of patients in the IFX (n = 52) and ADA (n = 52) groups. There were no differences in the demographics, types of disease and BMI distribution in the two groups.
In terms of loss of response, type of drug (IFX/ADA) was not found to be a significant risk factor (p = 0.250) along with the type of IBD (p = 0.420), age (p = 0.612) and gender (p = 0.600). However, the duration of disease was a significant factor (p = 0.026). There was a trend of accelerated time to loss of response for patients with BMI ≥30 kg/m2, in ADA group, but not significant (p = 0.314) compared with IFX of the same BMI group (Figure 1). For BMI &lt;30 kg/m2 in both groups, there was no difference in time to loss of response (p = 0.259). However, patients on ADA with BMI ≥30 kg/m2 had a significant loss of response compared with patients on IFX with BMI &lt;30 kg/m2 (adjusted HR 5.6; p = 0.038).

Conclusion
BMI appears to be important in predicting loss of response in IBD however we found no overall association between increased BMI and accelerated loss of response. Further larger studies are needed to evaluate the relationship of BMI and loss of response to ADA.
P533 Long-term quality of life after minimally invasive surgery for Crohn’s disease
Authors: Angriman I , Bordignon G , Sciuto E , Zini O , Bortoli N , Gruppo M , Bardini R , Ruffolo C , Scarpa M 
Published: January 2020

Abstract

Background
Risk of surgery is among the highest-rated concerns among Crohn’s disease (CD) patients. Quality of life is often worsened by intestinal surgery. This study aimed to assess the possible predictors of long-term quality of life after minimally invasive surgery for ileal, colonic or ileocolonic CD.

Methods
Data of all the 72 consecutive patients operated from 2010 to 2018 for CD were retrieved and 72 patients who had ileal, colonic or ileocolonic resection were selected and interviewed with the Cleveland Global Quality of Life (CGQL) questionnaire and the Body Image Questionnaire (BIQ). Disease activity was defined as the Harvey–Bradshaw Index (HBI). Comparisons between laparoscopic and open groups were carried out with non-parametric tests and log-rank test.

Results
Seventy-two patients who had laparoscopic ileal, colonic or ileocolonic resection and had a follow-up greater than 1 year were interviewed. The total CGQL score was associated with clinical disease activity at the moment of the interview (rho = −0.61, p &lt; 0.0001) and to the presence of extraintestinal complication (rho = 0.28, p = 0.03). At multivariate analysis, disease activity at the moment of the interview and the presence of extraintestinal complication confirmed to be independent predictors of long-term quality of life.

Conclusion
Long-term quality of life after minimally invasive intestinal surgery is essentially predicted by current disease activity. Thus, it is crucial to prevent clinical CD recurrence