bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOP35 Monitoring of mucosal T cells subsets under biotherapies in IBD: responders exhibit a phenotype similar to healthy controls
Authors: Hammoudi N , Perez K , Hassid D , Tran Minh M L , Gornet J M , Baudry C , Lourenco N , Gergaud B , Chardiny V , Bonnet J , Le Bourhis L , Allez M 
Published: January 2020

Abstract

Background
A dysregulated T-cell response is involved in the pathophysiology of inflammatory bowel diseases (IBD). T cells expressing the NKG2D activation receptor are implicated. Here, we investigated changes in intestinal T lymphocyte subsets overtime in patients treated by biotherapy for active disease.

Methods
In this prospective single-centre study, patients with IBD who have started a biotherapy (Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab) for active disease were included. Mucosal biopsies in the inflamed segment were taken during endoscopies before treatment initiation (W0) and in the same location 14 weeks (W14) and 52 weeks (W52) after inclusion. Control biopsies were taken from 16 patients without IBD (7 ileal and 9 colonic). Immunophenotyping of isolated lymphocytes was performed by flow cytometry at each timepoint. Correlation with endoscopic response was evaluated. For Crohn’s disease (CD), the response was defined by a 50% decrease of the CDEIS score. For ulcerative colitis (UC), the response was defined by a 2 points decrease of the UCEIS

Results
Between February 2016 and November 2018, 85 patients were included. Forty-four were male (52%). Forty had an active CD with the most inflamed segment located for 28 in the colon and 12 in the ileum. Thirty-nine patients had active UC and 6 pouchitis. An anti-TNF was started for 51 patients (60%), Vedolizumab for 16 patients (19%) and Ustekinumab for 18 (21%). Lymphocytes phenotyping was performed at inclusion for the whole cohort, at W14 for 67 patients (79%) and at W52 for 49 patients (58%). Data concerning endoscopic response was available for all patients.
At W0, IBD patients displayed higher rates of CD4 T cells and lower rates of CD8 T cells than controls (medians: 31% vs. 48% for CD4, p &lt; 0.001 and 52% vs. 37% for CD8, p &lt; 0.001 respectively). Endoscopic responders experienced a normalisation of these mucosal populations as compared with non-responders (W14: 58% vs. 45% for CD4, p = 0.005 and 40% vs. 28% for CD8, p = 0.03; W52 56% vs. 43% for CD4, p = 0.01 and 27 vs. 43% for CD8, p = 0.003). Results remained significant when splitting the cohort in CD and UC patients. Before treatment initiation, IBD patients displayed lower expression of NKG2D on CD8 T cells (78% vs. 94%, p &lt; 0.001). At W52, endoscopic responders presented significantly higher expression of this marker on CD8 T cells compared with non-responders (85% vs. 68%, p &lt; 0.001). Results remained significant in UC and CD patients.

Conclusion
The intestinal T cells of IBD patients with active disease present an increase of the CD4 to CD8 T-cell ratio and lower expression of NKG2D on CD8 T cells reflecting engagement of this receptor in inflammation. These T-cell parameters are normalised in endoscopic responders but not in non-responders
DOP39 The first prospective, multicentre, randomised controlled trial on discontinuation of infliximab in ulcerative colitis in remission; endoscopic normalisation does not guarantee successful withdrawal
Authors: Kobayashi T , Motoya S , Nakamura S , Yamamoto T , Nagahori M , Tanaka S , Hisamatsu T , Hirai F , Nakase H , Watanabe K , Matsumoto T , Tanaka M , Abe T , Suzuki Y , Watanabe M , Hibi T 
Published: January 2020

Abstract

Background
Anti-tumour necrosis factor (TNF)-α agents are the mainstay of the long-term treatments for refractory ulcerative colitis (UC). However, there is no prospective randomised controlled trial evaluating if anti-TNF-α agents can be discontinued in UC patients in remission.

Methods
Patients with UC maintained in clinical remission with infliximab (IFX) were prospectively enrolled from 23 specialist centres. Patients confirmed to be in (1) clinical remission for &gt; 6 months, (2) steroid-free and (3) Mayo endoscopic subscore (MES) of 0 or 1 were randomised with stratified factors (MES and use of immunomodulators) into two groups (continue or discontinue IFX) in 1:1. The biopsy was taken from the rectum and Nancy histological Index (NI) was centrally scored at randomisation. The primary endpoint was remission rate at week 48 in full analysis set (FAS). Factors associated with remission at Week 48 were evaluated by logistic regression adjusted for the treatment group. Efficacy and safety of retreatment with IFX after relapse were also evaluated.

Results
A total of 92 patients were included in the FAS and the remission rates at week 48 were 80.4% (95% CI: 66.1–90.6) and 54.3% (95% CI: 39.0–69.1) in IFX-continued and IFX-discontinued groups, respectively (p = 0.008). Although the duration of IFX, use of concomitant immunomodulators, IFX concentration, and MES of 0 at randomisation were not predictive, C-reactive protein and NI were associated with remission at week 48 in FAS (p = 0.039 and 0.019, respectively). Retreatment with IFX lead to remission in 8 out of 12 patients (66.7%) in 8 weeks and was well-tolerated.

Conclusion
This first prospective multicentre randomised controlled trial confirmed that discontinuation of maintenance IFX resulted in the increased risk of relapse but retreatment was effective in UC. Endoscopic normalisation was not sufficient for the successful discontinuation of IFX.
DOP42 Impact of discontinuing thiopurines at anti-TNF initiation in inflammatory bowel disease: A nationwide Danish cohort study
Authors: Bohn Thomsen S , Ungaro R , Allin K , Poulsen G , Mikael A , Colombel J F , Jess T 
Published: January 2020

Abstract

Background
The impact of discontinuing vs. continuing thiopurines at anti-TNF initiation in thiopurine experienced patients with inflammatory bowel disease (IBD) is unclear.

Methods
We used the nationwide Danish registers to establish a national cohort of patients with IBD who received thiopurines prior to initiating anti-TNF during 2003–2014. We compared patients who discontinued vs. continued thiopurine within 90 days of anti-TNF initiation. Our primary outcome was a composite of any clinical event: corticosteroids, hospitalisation, surgery, or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Analyses were adjusted for sex, diagnosis-age, IBD-subtype, disease duration, calendar year, pre-anti-TNF thiopurine duration, and past disease severity including hospitalisations the past year, surgery past 5 years, and corticosteroid use the past year.

Results
Of 6998 anti-TNF exposed, 1602 patients (Crohn’s disease, n = 1000, ulcerative colitis, n = 602) received thiopurines prior to anti-TNF. Of these, 489 (44%) received thiopurines for more than 180 days. At anti-TNF initiation, 503 patients discontinued thiopurines and were followed for a median 3.54 years and 1099 continued thiopurines with a median follow-up of 3.92 years. Discontinuing thiopurines at anti-TNF initiation statistically significantly increased the risk of the composite outcome (aHR 1.25; 95% CI 1.09 to 1.45). Analyses of the individual outcomes revealed a statistically significantly increased risk of later corticosteroid use in thiopurine discontinuers (aHR 1.31; 95% CI 1.11 to 1.56), but no increased risk of the remaining outcomes.
IR; incidence rate, HR; hazard ratio, CI; confidence interval, IBD; inflammatory bowel disease. P-value is the test of interaction between the variable and the treatment groups.

Conclusion
In our nationwide cohort study of patients with IBD, we found that continuing thiopurines after anti-TNF initiation impacted the outcome favourably, especially regarding corticosteroid use. Further studies are warranted to investigate this central clinical question.
DOP57 Vedolizumab has similar efficacy rates in young and elderly patients: A binational, multicentre, retrospective case–control study
Authors: Cohen N A , Plevris N , Kopylov U , Grinman A , Ungar B , Yanai H , Leibovitzh H , Fliss N , Hirsch A , Ritter E , Ron Y , Bar-Gil Shitrit A , Goldin E , Dotan I , Ben-Horin S , Lees C , Maharshak N 
Published: January 2020

Abstract

Background
Treatment of inflammatory bowel diseases (IBD) is associated with multiple side effects, such as malignancies and infections, that may be more common in the elderly population. The aim of this study was to compare the safety and efficacy of vedolizumab (VDZ) in young and elderly patients.

Methods
This is a binational, multicentre, retrospective, case–control study consisting of patients from multiple centres in Israel and from Edinburgh, UK. IBD patients in whom VDZ treatment was initiated during 2015–2019, and were followed for at least 14 weeks, were included in the study according to their age groups: ≤40 years or ≥60 years. Patients were matched for disease duration, classification and severity.

Results
We recruited 144 patients (82 CD and 62 UC) to the elderly cohort and 140 patients (83 CD and 57 UC) to the young cohort. The respective average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years. Elderly patients had significantly more cardiovascular, metabolic and respiratory co-morbidities and had less prior exposure to anti-TNF agents compared with the young cohort (CD: 51% vs. 88%, p &lt; 0.001; UC: 47% vs. 70%, p = 0.03). Clinical and endoscopic responses were comparable between the groups at Weeks 14 and 52 among elderly and young (Week 52 remission: CD: 40% vs. 35%, p = 0.7; UC: 48% vs. 51%, p = 0.84) (Figure 1). However, the use of more than one anti-TNF agent was an independent predictor of poor response and remission rates to VDZ at all time points among the elderly (OR 0.13; 95% CI 0.03–0.69). A total of 49 adverse events were documented, 23 (16%) in the young cohort and 26 (18%) in the elderly cohort (p = 0.5). Overall there were significantly more infections in the elderly cohort (3 (2%) vs. 17 (12%), p = 0.002) and included nasopharyngeal, urinary, skin and Clostridium difficile infections. None of them was fatal but one patient stopped treatment due to urinary sepsis. There were significantly more non-specific adverse events such as headache and myalgia in the young cohort (8% vs. 2%, p = 0.03). Six patients (4%) in the young cohort required drug discontinuation due to adverse events compared with 4 patients (3%) in the elderly cohort (p = 0.5). The reasons for discontinuation were similar between the groups.

Conclusion
VDZ is equally effective in elderly and young IBD patients. This study shows an increased risk of overall infections in the elderly cohort, it is unclear whether these are related to VDZ treatment or the age and background diseases of these patients. In elderly patients, the use of VDZ before anti-TNF therapy may improve response and remission rates.
DOP60 Vedolizumab treatment persistence and safety in an extended access program (XAP)
Authors: Danese S , Subramanian K , Van Zyl J , Adsul S , Lindner D , Roth J , Vermeire S 
Published: January 2020

Abstract

Background
Vedolizumab, a gut-selective, α 4β 7 integrin antagonist, has been established as an effective and safe treatment for patients with UC or CD in the GEMINI phase 3 program and long-term safety (LTS) study. An extended access program (XAP) was initiated to provide continued access to patients who were benefiting from vedolizumab in GEMINI LTS and to monitor safety. We now report persistence and safety results from a 2-year data analysis.

Methods
Vedolizumab XAP (NCT02743806) is a phase 3b/4 prospective, open-label, multinational interventional study. A rollover from GEMINI LTS (NCT00790933) to the XAP, patients reduced dosing frequency from vedolizumab 300 mg IV every 4 weeks (Q4W) to every 8 weeks (Q8W) or remained on vedolizumab 300 mg IV Q4W if medically indicated. This 2-year data analysis assessed persistence on Q8W dosing after dosing frequency reduction, need for escalation to Q4W dosing, incidence of relapse (defined as dose escalation, study withdrawal due to adverse event, loss of adequate benefit from vedolizumab, or increased corticosteroid [CS] or immunomodulator dose), and safety 2 years after rollover from GEMINI LTS.

Results
A total of 311 patients (142 UC, 169 CD) from GEMINI LTS enrolled in the XAP. Median (range) duration of exposure to vedolizumab prior to the XAP was 8.0 years (5.2–10.0) for patients with UC and 7.5 years (5.4–9.9) for patients with CD. Of patients with UC and CD, 93.0% and 84.6%, respectively, reduced dosing frequency to Q8W at XAP start, and 87.3% and 77.5%, respectively, remained on Q8W after 2 years. At baseline, 93.0% of all patients with UC and 88.2% of all patients with CD were in CS-free remission; patients who maintained Q4W dosing at baseline had lower CS-free remission rates (62.5% in UC and 69.2% in CD). Of patients who initiated Q8W dosing at enrolment in the XAP, 95% had no relapse for ≥6 months (97.0% UC, 93.7% CD; Table 1). Only 7.3% of patients required dose escalation to Q4W, and 11.6% experienced relapse during the 2-year follow-up. Times to dose escalation and relapse were similar in patients with UC and CD (Figures 1 and 2). At 2 years, 4 of 8 patients with UC and 4 of 12 patients with CD who required dose escalation to Q4W discontinued vedolizumab early due to loss of benefit or adverse events. Adverse events related to vedolizumab were infrequent; no new or serious events attributed to vedolizumab were reported.

Conclusion
High patient persistence on Q8W vedolizumab was observed in the first 2 years after reduction of dosing frequency in the XAP. Overall, there were low rates of Q4W dose escalation and CD or UC disease relapse. The safety profile was consistent with previous reports with no new signals observed.
N25 Outcomes of a GP outreach programme to offer colonoscopic surveillance for IBD patients being managed in primary care
Authors: Windak H , Cairnes V , Chanchlani N , Desmond C , Hamilton B , Heerasing N , Hendy P , Simeng L , Kennedy N A , Goodhand J , Ahmad T , Gordon C 
Published: January 2020

Abstract

Background
Colonoscopic surveillance in IBD patients can reduce the development of colorectal cancer (CRC) and the rate of CRC-associated death. We recently reported that 27% of IBD patients living in East Devon are managed exclusively in primary care of whom about 23% maybe eligible for colonoscopic surveillance. We devised an outreach programme, whereby we invited primary care physicians to enrol these patients in a colonoscopic surveillance programme.

Methods
In December 2017, we contacted 37 general practices, where 161 patients with UC who were eligible for surveillance had been identified. Each practice was sent a letter explaining the goals of the project, a link to the National Institute for Healthcare and Clinical Excellence (NICE) guidance for CRC surveillance in IBD patients and patient information booklets. We informed the practices of their eligible patients and asked them to refer patients for secondary care IBD consults if appropriate. We included an outcome form that captured whether the patient was referred, was deemed inappropriate for surveillance, had surveillance elsewhere, had declined surveillance, or was no longer registered at the practice.

Results
Sixty-five percent of practices (24/37) responded and we received responses for 57 of 161 (35%) potentially eligible patients. Thirty-five (61%) patients were referred to our IBD service; 7 (12%) patients declined surveillance; 7 (12%) patients were deemed by their GP to be unfit for surveillance and 5 (10%) were no longer registered at the identified GP practice; 2 (4%) had surveillance arranged elsewhere and 1 (2%) patient had died. Amongst the 35 patients referred to secondary care; 22 (63%) underwent surveillance colonoscopy, 12 (34%) declined surveillance after discussion or did not attend their booked appointments and one is awaiting colonoscopy. Half of patients who had a colonoscopy had active inflammation. We diagnosed one CRC He was an elderly man with a locally invasive signet ring caecal tumour, without distant metastases, who went onto to have a curative right hemicolectomy without complication.

Conclusion
Patients with longstanding IBD are frequently managed exclusively in primary care and maybe overlooked for colonoscopic CRC surveillance. There is a need to implement processes to facilitate identification and recall of patients eligible for surveillance across primary and secondary care.
N28 Effectiveness of pre-biologic screening for viral hepatitis and HIV
Authors: Clarke M , Goodhand J , Ahmad T , Cairnes V , Kennedy N A 
Published: January 2020

Abstract

Background
Biologic treatments can reactivate viral hepatitis and HIV. Prior to starting biologic therapy, the ECCO guidelines recommend patients are screened for chronic viral infection. We recently diagnosed a patient treated with adalimumab with HIV. As a consequence we sought to assess the effectiveness of our screening process for viral infections and to identify factors linked to non-testing

Methods
We screened our pharmacy dispensing records and IBD database for all patients currently treated with biologic therapies. We then cross-referenced our virology records for HIV, Hepatitis B (HBV) and Hepatitis C (HCV) screening. We used our IBD database and clinical records to record demographic and clinical factors associated with non-testing.

Results
As of September 2019 we were treating 453 patients with a biopharmaceutical drug in whom pre-treatment testing for viral hepatitis and HIV is recommended. Amongst whom, 50 (11%), 22 (5%) and 24 (5%) patients had not been tested for HIV, HBV or HCV, respectively.
Our patient with HIV had inflammatory ileocolonic Crohn’s disease and been treated with combination azathioprine and adalimumab since October 2016. He was in clinical remission at the time of HIV diagnosis (July 2018). We stopped his azathioprine and adalimumab and he was commenced on antiretroviral therapy. After 13 months’ follow-up, he had not developed immune reconstitution syndrome or had a flare of his Crohn’s disease. Moving forwards, the identified unscreened patients currently on biologic treatment are being tested at the earliest opportunity. Patients receiving infusions of biopharmaceuticals are being screened with their verbal consent at the time of their next infusion. Patients receiving subcutaneous treatments are being screened at their next appointment.

Conclusion
Comprehensive review of our biologic-treated patients revealed that 11% had not been screened for HIV and/or chronic viral hepatitis.
DOP75 Efficacy of tofacitinib dose escalation to 10 mg BID in patients with UC after completing maintenance therapy in remission and losing response: Data from OCTAVE open-label, long-term extension study
Authors: Rubin D T , Dubinsky M C , Panés J , Wu D C , Lawendy N , Guo X , Lai C , Kwok K , Su C , Salese L 
Published: January 2020

Abstract

Background
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in patients with moderate to severe UC in three Phase 3 studies.1 Here, we investigated outcomes in a subpopulation of the ongoing, open-label, long-term extension study (OLE) (OCTAVE Open; NCT01470612; May 2019; database not locked), including maintenance of remission patients receiving tofacitinib 5 mg twice daily (BID) who were dose-escalated to 10 mg BID due to flare.

Methods
Analysis included the maintenance remission–dose-escalation subpopulation: patients who achieved remission at Week 52 in OCTAVE Sustain (tofacitinib 5 or 10 mg BID, or placebo), entered OLE (5 mg BID), but were dose-escalated to 10 mg BID due to flare (based on total Mayo score [MS]; local read endoscopy). Remission: total MS ≤2 with no subscore &gt;1, and rectal bleeding (RB) subscore 0. Dose escalation during OLE was permitted if patients experienced a flare, defined as ≥3 increase from maintenance study baseline total MS and ≥1 increase in RB and endoscopic subscore (ES; unless ES=3 at baseline and remained 3) after ≥8 weeks of treatment in OLE. Kaplan–Meier for estimation of time to dose escalation was assessed in all OLE maintenance remission population relative to OLE baseline. Partial MS remission (≤2 with no subscore &gt;1; no ES) assessed at Months (M)3, 6, 9 and 12 post-dose-escalation; mucosal healing (MH; ES ≤1) and remission assessed at M12 post-dose-escalation. Adverse events (AEs) also assessed.

Results
Of the 944 patients enrolled in OLE, 162 were in remission at baseline and received tofacitinib 5 mg BID, and 41 were dose-escalated to 10 mg BID due to flare (22 had prior TNFi failure). The cumulative proportion of patients with dose escalation was 4.3%, 10.6%, 12.6% and 13.2% at M3, 6, 9 and 12 of OLE, respectively. Partial MS remission was 75.0% at M3, and partial MS remission, MH and remission were 95.0%, 63.6% and 57.6%, respectively, at M12 post-dose escalation (Table). One case each of serious infection, herpes zoster (non-serious; opportunistic infection) and malignancy were reported (see Table).

Conclusion
For patients with moderate to severe UC who entered OLE in remission, received tofacitinib 5 mg BID but flared and were dose-escalated to 10 mg BID, response was recaptured for most by M3 post-dose-escalation and remission was recaptured in the majority by M12. Safety in this subpopulation was generally consistent with that observed in the overall tofacitinib UC programme.2 Due to the small sample size and open-label nature, results should be interpreted with caution.

References