bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP23 Efficacy and safety of vedolizumab SC in patients with moderately to severely active Crohn’s disease: Results of the VISIBLE 2 study
Authors: Vermeire S , Sandborn W , Baert F , Danese S , Kobayashi T , Loftus E V , Bhatia S , Kisfalvi K , Rosario M , Zhang W , D’Haens G 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) is a gut-selective, humanised, monoclonal α 4β 7 integrin antibody for the treatment of patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). VDZ is currently an intravenous (IV) therapy; a subcutaneous (SC) formulation is under development to provide patients with an alternative route of administration for maintenance treatment for UC and CD. Here we present the first data from the phase 3 study of VDZ SC maintenance treatment in CD.

Methods
VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a randomised, double-blind, placebo (PBO)-controlled phase 3 trial of VDZ SC as maintenance treatment in adults with moderately to severely active CD. Patients (n = 644) received open-label VDZ 300mg IV induction therapy at Weeks 0 and 2. At Week 6, clinical responders (defined as patients with a ≥70-point decrease in CD Activity Index [CDAI] from baseline) were randomly assigned to receive vedolizumab SC (108 mg every 2 weeks [Q2W]), or placebo (Q2W) for up to 52 weeks. The primary endpoint was clinical remission at Week 52 (defined as CDAI score ≤150). Rank-ordered secondary endpoints were enhanced clinical response at Week 52 (a drop of ≥100 in CDAI score), corticosteroid (CS)-free clinical remission at Week 52, and clinical remission at Week 52 in anti-tumour necrosis factor (TNF)-naïve patients. Finally, VDZ immunogenicity and predefined adverse events of special interest were assessed.

Results
Patients who responded to VDZ IV induction at Week 6 (n = 409) were randomised to VDZ SC (n = 275) or PBO (n = 134) maintenance and received at least 1 dose of study drug; 61% and 53%, respectively, were previously exposed to anti-TNF therapy. At Week 52, 48.0% of patients on VDZ SC vs. 34.3% on PBO were in clinical remission (p = 0.008, Figure). Enhanced clinical response at Week 52 was reached by 52.0% vs. 44.8% of patients on VDZ SC vs. PBO, respectively (p = 0.167). Among patients on concomitant CS at baseline (VDZ SC, n = 95; PBO, n = 44), 45.3% receiving VDZ SC vs. 18.2% receiving PBO achieved CS-free clinical remission at Week 52. Of anti-TNF-naïve patients (VDZ SC, n = 107; PBO, n = 63), 48.6% vs. 42.9% were in clinical remission at Week 52 in the VDZ SC and PBO arms, respectively. Injection-site reactions were reported for &lt;3% of patients treated with VDZ SC. Serious infections, malignancy, and liver injury were ≤5% for both arms. Anti-VDZ antibodies were detected in 7 (2.5%) patients treated with VDZ SC arm; 4 of 7 patients developed neutralising antibodies. No new safety signals were observed.

Conclusion
Among VDZ IV induction responders, significantly more patients on maintenance VDZ SC than PBO achieved clinical remission at Week 52. The safety findings with VDZ SC remain in line with the known safety profile of VDZ IV in patients with CD.
OP24 A novel subcutaneous infliximab (CT-P13): 1-year results including switching results from intravenous infliximab (CT-P13) in patients with active Crohn’s disease and ulcerative colitis
Authors: Ben-Horin S , Leszczyszyn J , Dudkowiak R , Lahat A , Gawdis-Wojnarska B , Pukitis A , Horynski M , Farkas K , Kierkus J , Kowalski M , Ye B D , Reinisch W , Lee S J , Kim S H , Kim M R , Kim Y A , Kim H N , Schreiber S 
Published: January 2020

Abstract

Background
Two randomised controlled trials of a novel subcutaneous (SC) formulation of infliximab in patients with active rheumatoid arthritis1 and in patients with active Crohn’s disease (CD) and ulcerative colitis (UC)2 confirmed comparable clinical efficacy and safety of CT-P13 SC with CT-P13 intravenous (IV) up to Week 30. We now present the efficacy, pharmacokinetics (PK) and safety of CT-P13 SC over 1-year in the active CD and UC trial, including the outcomes of switching from CT-P13 IV to CT-P13 SC.

Methods
After loading doses of IV 5 mg/kg at Weeks 0 and 2, patients were randomised at Week 6 to receive either SC 120 mg (&lt;80 kg) or 240 mg (≥80 kg) every 2 weeks (SC arm), or continued on IV 5 mg/kg every 8 weeks (IV arm). From Week 30, IV 5 mg/kg was switched to either SC 120 or 240 mg based on the patients’ body weight at Week 30. Patients who initially responded but experienced loss-of-response at Week 30 or beyond, were dose-escalated to SC 240 mg every 2 weeks.

Results
A total of 131 patients were randomised (66 to the SC arm and 65 to the IV arm); of whom, 105 (80.2%) patients completed the Week 54 visit (55 in the SC arm and 50 in the IV arm). The mean CDAI and partial Mayo scores decreased over time in the 2 arms until Week 30 and comparable improvement in clinical activity was observed at Week 54 after switching the remaining IV patients to SC (Figure 1 and 2). The rates of clinical response and remission were also maintained at Week 54 and the rate of mucosal healing in combined CD and UC was further improved at Week 54 (Table 1). The mean pre-dose serum concentrations in the IV arm increased to a similar level to SC arm after switching and maintained consistent levels until Week 54 (Figure 3). The safety profiles during the maintenance phase and on or after Week 30 were generally comparable between the 2 arms (Table 1). All of the localised injection site reactions were grade 1 or 2 in intensity and majority of patients recovered without any treatments.

Conclusion
These results of CT-P13 SC 1-year study in active CD and UC show comparable efficacy and safety of the SC and IV formulations, which were not affected by a switch of IV patients to SC route. The PK as manifested by trough concentrations of the drug, increased after switching from IV to SC. These observations support the first infliximab SC formulation as a viable therapeutic agent to expand patients’ treatment options.

References
OP26 The first real-life multicentre prospective validation study of the electronic chromoendoscopy score (Paddington International Virtual ChromoendoScopy ScOre) and its outcome in ulcerative colitis
Authors: Iacucci M , Smith S C , Bazarova A , Shivaji U N , Bhandari P , Cannatelli R , Daperno M , Ferraz J G , Goetz M , Gui X , Hayee B , De Hertogh G , Lazarev M , Li J , Nardone O M , Occhipinti V , Panaccione R , Parra-Blanco A , Pastorelli L , Rath T , Tontini G , Vieth M , Villanacci V , Zardo D , Kiesslich R , Bisschops R , Ghosh S 
Published: January 2020

Abstract

Background
Mucosal healing is an important goal in the treatment of ulcerative colitis (UC). The newly published PICaSSO score characterises subtle mucosal and vascular changes and defines mucosal healing. We aimed to validate in real-life the PICaSSO score and assess its ability to predict relapse.

Methods
Patients with UC were prospectively recruited from 11 international centres. Participating endoscopists experienced in IBD received training on PICaSSO before starting the study. The rectum and sigmoid were examined using iScan 1,2 and 3 (Pentax, Japan) and inflammatory activity was assessed using UCEIS and PICaSSO. Biopsies were taken for the histological assessment using Robarts Histological Index (RHI) and Nancy. Follow-up was obtained at 12 months.

Results
A total of 278 patients were recruited (Table 1). The diagnostic performance in predicting histologic healing is shown in Table 2. When using PICaSSO score of ≤3 for mucosal and vascular architecture the AUROC to predict healing by RHI is 0.79 (95% CI 0.74–0.85) and 0.73 (95% CI 0.68–0.80) respectively and when using the Nancy score the AUROC is 0.78 (95% CI 0.72–0.84) and 0.77 (0.71–0.84). A total PICaSSO score of ≤8 and UCEIS score of ≤1 predicts remission at 12 months with an AUROC of 0.73 (0.65–0.80) and 0.71 (0.64–0.79). A Kaplan–Meier curve shows a favourable survival probability without relapse with a PICASSO score of ≤8 (Figure 1).

Conclusion
This real-life validation study shows the PICaSSO score can predict accurately histological healing and long-term remission and can be a useful tool in the management of UC.
OP27 Long-term safety and efficacy of risankizumab treatment in patients with Crohn’s disease: Final results from the Phase 2 open-label extension study
Authors: Ferrante M , Feagan B G , Panés J , Baert F , Louis E , Dewit O , Kaser A , Duan W R , Gustafson D , Liao X , Wallace K , Kalabic J , D’Haens G R 
Published: January 2020

Abstract

Background
Efficacy and safety of the IL-23 inhibitor risankizumab (RZB) have been assessed in patients with moderate-to-severe Crohn’s disease (CD) following induction/maintenance treatment.1,2 Responders to RZB in a Phase 2 induction/maintenance study2,3 could enrol in an open-label extension (OLE), NCT02513459.4 Final safety and efficacy results from this RZB OLE study are reported here.

Methods
Patients achieving clinical response (CResp) (decrease from baseline [BL] in CD Activity Index [CDAI] ≥100) without remission (CRem) (CDAI &lt;150) after Period 2 (Week 26) or CResp/CRem after Period 3 (Week 52) of the preceding study1 received open-label 180 mg subcutaneous (SC) RZB every 8 weeks (Q8W) for up to 206 weeks. Patients who lost CResp/CRem at screening of the OLE were re-induced with open-label 600 mg IV RZB at Weeks 0, 4, and 8. Patients receiving re-induction treatment only received subsequent 180 mg SC RZB Q8W if they regained CResp/CRem following re-induction. A centrally read ileocolonoscopy was performed yearly. Treatment-emergent adverse events (AEs) were collected up to 20 weeks after the last RZB dose. CRem and endoscopic remission (ER [CD Endoscopic Index of Severity (CDEIS) ≤4 or CDEIS ≤2 for patients with isolated ileitis at BL]) were reported up to Week 152. Non-responder imputation (NRI) and observed case analysis were used for binary endpoints.

Results
Sixty-five patients with CD were enrolled in the OLE, with 4 patients re-induced. At BL of the preceding study, median (range) age was 34 (19–67) years and median (range) disease duration was 10 (2–38) years. Sixty patients (92%) were previously exposed to TNF antagonists. In the OLE, median (range) exposure to RZB was 1014.0 (114–1317) days. Twenty-one (32%) patients prematurely discontinued RZB, including 6 (9%) who had developed an AE. AEs were reported in 60 (92%) patients; 23 (35%) experienced serious AEs. The most common AEs were nasopharyngitis (31%), gastroenteritis (23%), and fatigue (20%). Serious infections were reported in 6 (9%) patients and opportunistic infections in 3 (5%) patients. No tuberculosis, malignancies, or deaths occurred. At Week 0 of the current study, 47 (72%) patients were in CRem and 27 (42%) patients had ER. Both CRem and ER were sustained up to Week 152 (Table).

Conclusion
In this final analysis of patients with CD receiving long-term open-label RZB treatment, the safety profile of RZB remained consistent with previous data² with no new safety signals. Clinical and endoscopic remissions were sustained.

References
DOP01 Exclusive enteral nutrition for the treatment of adult Crohn’s disease
Authors: Shukla D , Purcell L , Palmer M , Pillay L 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) is a debilitating autoimmune disease affecting &gt;40 000 Australians. Exclusive enteral nutrition (EEN) is an effective, risk-free therapy in children with CD, offering an ~80% success rate. Despite similar efficacy in adults, including the potential to decrease the need for high-risk steroids and surgery, adherence remains an unresolved obstacle for its use, with withdrawal rates of up to 40% (Wall 2013). Lack of dietetic expertise and support for adults on EEN were identified as primary barriers (Wall 2013). This prospective, single-centre, observational study aimed to assess the impact of a 6-week EEN model of care on disease symptoms, nutrition and inflammatory markers. We also assessed if &gt;80% of adults with CD could adhere to EEN.

Methods
Adults with active CD were treated with oral EEN for six weeks between March 2018 and September 2019 which uniquely included weekly specialist Dietetic support. EEN is the provision of 100% of a patient’s nutritional requirements via a nutritionally complete liquid formula. Paired assessment at baseline and EEN completion occurred for Crohn’s disease activity index (CDAI), calprotectin, C-reaction protein (CRP), platelets, albumin, white cell count, weight and calprotectin using paired t-tests. The primary outcome measure was disease activity using CDAI.

Results
Twenty-seven eligible CD patients were identified. Most patients (85%, n = 23/27) successfully adhered to EEN treatment (45 ± 13 years, 63% female, 52% had Calprotectin ≥100). The patients were further subdivided as per Montreal classification (L1:n = 12; L2:n = 3; L3:n = 12) and 93% were on medications such as steroids (n = 9/27), immunosuppressives (n = 19/27) and biologics (n = 16/27). After EEN, 74% (n = 20/27) achieved clinical remission (CDAI &lt;150) 19/27 patients (70%) achieved clinical response with &gt;70-point reduction in CDAI score and most (77%) patients achieved greatest improvement in CDAI score in the well-being section. A trend showed that 37% (p = 0.087) more patients with L2 and L3 CD achieved clinical response through CDAI than L1 CD patients. Calprotectin also showed a trend for improvement (-23(-65230-150) µg, p = 0.067, n = 20). No differences were observed in CRP, white cell count, or albumin (p = 0.262–0.433, n = 12–13); however, platelets showed a trend for improvement (-26(-156-46) µl, p = 0.071, n = 12) and weight reduced by −2.4(3.2) kg (p = 0.001). Few (30%, n = 8/27) patients changed medications during EEN treatment. No significant side effects were observed.

Conclusion
EEN may be achievable for most adults with additional professional support and has merit in assisting patients with clinical improvement of CD.
DOP12 Efficacy of ustekinumab for ulcerative colitis through 2 years: Results of the UNIFI maintenance study and long-term extension
Authors: Panaccione R , Sandborn W J , Sands B E , Marano C , O’Brien C D , Zhang H , Johanns J , Zhou Y , Peyrin-Biroulet L , Hisamatsu T , Danese S 
Published: January 2020

Abstract

Background
Ustekinumab (UST) is a mAb to IL-12/23p40 that is approved for moderate-to-severe ulcerative colitis (UC). The UNIFI maintenance study evaluated SC UST through 1 year in patients who responded to UST IV induction. Patients who completed the maintenance study could enter a long-term extension (LTE) through 220weeks. Here, we report the efficacy of UST through 92weeks for patients randomised in the maintenance study.

Methods
Patients who were in clinical response 8weeks after UST induction were randomised to SC PBO (n = 175), UST 90mg q12w (n = 172), or UST 90mg q8w (n = 176). All patients who completed Week 44 were eligible to enter and continue in the LTE at the investigator’s discretion. Subsequent to completion of the maintenance study at Week 44, unblinding occurred and patients who were receiving PBO were discontinued from the LTE. During the LTE, patients were eligible to receive dose adjustment (q12w to q8w or q8w to q8w [sham dose adjustment]) starting at Week 56 based on investigator assessment of their UC disease activity. Symptomatic remission (stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0) and partial Mayo remission (partial Mayo score ≤2) were evaluated through Week 92. Analyses of symptomatic remission and partial Mayo over time included all patients randomised in maintenance and were performed separately, with dose adjustment as part of the treatment experience (ie, not a treatment failure) and with adjustment considered as a treatment failure.

Results
Symptomatic and partial Mayo remission were sustained through Week 92, with no clinically meaningful differences between the q12w and q8w dose groups (Figure 1 and 2). When dose adjustment was considered to be part of the treatment experience (ie, not a treatment failure), 66.1 % and 67.0% of patients randomised to q12w and q8w, respectively, were in symptomatic and partial Mayo remission at Week 92 (Figure 1). When dose adjustment was considered to be a treatment failure in the analysis, 53.2% and 54.0% of patients were in symptomatic and partial Mayo remission, respectively (Figure 2). The safety profile of UST through Week 96 was consistent with that previously reported for 1 year.

Conclusion
The efficacy of UST in patients with moderate-to-severe UC has maintained through 92weeks with q12w or q8w SC dosing when dose adjustment was considered to be part of the treatment experience.
DOP22 Certification of integral care IBD Units: Evaluation of a certification program (CUE)
Authors: Barreiro-de Acosta M , Gutierrez A , Zabana Y , Beltran B , Calvet X , Chaparro M , Domènech E , Esteve M , Panés J , Gisbert J P , Nos P 
Published: January 2020

Abstract

Background
Spanish inflammatory bowel disease (IBD) group (GETECCU) mission is to promote healthcare, teaching and research of excellence. Our vision is to establish standards of quality of care and generate a mark of excellence and reliability for IBD patients and the different agents involved in all its processes. The aim of this study was evaluate the impact of a program for certification of IBD units (CUE program).

Methods
Identification of quality indicator for certification of IBD Units was based on CUE Delphy methodology that finally selected 53 quality indicators (12 structure, 37 process and 4 results), which were subjected to a normalisation process (Calvet X et al. JCC 2014; 8: 240–51). This process consisted of face-to-face protocoled meetings with a committee of experts that proceeded to defined/justified the use of each indicator considering objectiveness and the measure of compliance. Applications for certification in the program are made voluntarily through the GETECCU secretariat. From GETECCU, the candidate units are counselled through a consulting round before an audit drill and finally, the formal audit carried out by an independent certifying agency. This audit consists of the review of all selected indicators and includes a review of 40 random medical records. If 80–90% compliance is achieved, the qualification of ‘advanced’ is obtained and the unit is re-certified in 2 years. If it exceeds 90%, the rating is ‘excellence’ and the unit has to be re-certified in 3 years. An anonymous survey was conducted among certified units to assess satisfaction with the program

Results
The CUE program started in 2017. As of November 2019, there are 53 IBD units adhered to the certification nationwide program, of which 42 have already been audited and 40 certified. Twenty-three units achieved the qualification of excellence (56%), 17 achieved an advanced qualification and 5% had not passed the certification. The remaining 11 are currently in the process of being audited. After an IBD Unit achieve the certification an act of official delivery is carried out with the presence of patient associations, public care authorities and the board of GETECCU. Results are published in the State Official Gazette. Survey main results were the average perceived improvement, averaged as 8.5, out of 10. The most important aspect of improvement is data recording followed by health and patient satisfaction results

Conclusion
The establishment of quality standards certification programmes in multidisciplinary units improves the quality of care offered to IBD patients. The acceptance among the health community for adherence to these projects is very high despite being voluntary. The support of patient associations and managers is essential to value these types of projects
DOP43 The risk of extra-intestinal cancer in inflammatory bowel disease (IBD): A systematic review and meta-analysis of population-based cohort studies
Authors: Lo B Z S , Zhao M , Vind I , Burisch J 
Published: January 2020

Abstract

Background
Patients with Crohn’s disease (CD) and ulcerative colitis (UC) are at increased risk of developing intestinal cancer compared with the background population. However, less is known about the risk of extra-intestinal cancers (EICs). A previous meta-analysis did not find an increased overall risk of EICs but was limited by the scarcity of available studies and the short length of follow-up in those cohorts. The aim of this study was to conduct a systematic review and meta-analysis of population-based cohorts assessing the risk of EICs in inflammatory bowel disease (IBD) patients.

Methods
A systematic literature search was carried out. Only population-based studies reporting on the prevalence or incidence of EICs were included. All studies were screened (603), and included studies were quality assessed by two investigators (BL, MZ). Studies eligible for meta-analysis were pooled for events, expected events or events in a control-population, and the length of follow-up in patient-years. A meta-analysis of the overall and site-specific risk of EICs and a stratified analysis of the cohorts (according to whether there were most patients followed before or after the year 2000) were conducted.

Results
In total, 36 studies were included in the systematic review and 14 studies were included in the meta-analysis. The majority of the studies reporting on the overall risk of EICs in their respective cohort were inconclusive due to lack of power. In the meta-analysis, the overall risk of EICs was found to be increased in both CD (IRR: 1.45 [1.26, 1.67]) and UC (IRR: 1.15 [1.02, 1.31]) patients (Figures 1 and 2). The stratified analysis showed a significant increased risk of EICs among CD patients both before (IRR: 1.58 [1.09, 2.28]) and after (IRR: 1.47 [1.28, 1.69]) the year 2000, while no increased risk was found among UC patients. Assessing site-specific EICs, both CD and UC patients demonstrated an increased risk of skin and hepatobiliary malignancies. Furthermore, CD demonstrated an increased risk of haematological and lung malignancies (Figures 3 and 4).

Conclusion
In conclusion, this systematic review and meta-analysis demonstrated that IBD patients, both CD and UC patients, are at an increased risk of developing EICs; both overall and at specific sites. The transition of the millennium did not increase the risk of EICs in CD or UC patients. However, more studies with longer follow-up are needed to assess the true risk of EICs posed by IBD.