bluuebunny/crossref_metadata_2025 huggingface dataset:
OP07 The epidemiology of inflammatory bowel diseases among immigrants to Denmark: A population-based cohort study
Authors: Agrawal M , Shrestha S , Corn G , Nielsen N M , Frisch M , Colombel J F , Jess T
Published: January 2020

Background

The incidence of inflammatory bowel diseases (IBDs) among immigrants and in countries with historically low IBD risk is rising, implicating environmental risk factors in IBD pathogenesis. The purpose of our study was to determine the incidence rates of Crohn’s disease (CD) and ulcerative colitis (UC), among immigrants to Denmark, a high IBD incidence country, according to the country of birth and age at immigration, in comparison with the corresponding incidence rates in the Danish host population.

Methods

Using the Danish Civil Registration System, we identified all residents in Denmark with a known country of birth between January 1977 and December 2018. First-generation immigrants were persons who, along with parents, were born outside Denmark; second-generation immigrants were Danish-born persons whose parents were born outside Denmark. We recorded immigrants’ (or parents’) country of birth, age at immigration and duration of stay in Denmark. Study participants were followed for CD and UC diagnosis in the Danish National Patient Registry. Incidence rate ratios (IRRs) according to immigration status were estimated using log-linear Poisson regression analysis, and stratified by IBD prevalence in the country of birth (low, intermediate and high), and among first-generation immigrants, by age at immigration and duration of stay in Denmark.

Results

In this cohort of 9,038,025 subjects, among 1,295,518 first-generation and 208,826 second-generation immigrants eligible for inclusion, 4,805 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. The risk of IBD among first-generation immigrants reflected risk in the country of birth (low, intermediate or high, Table 1), and increased with >20 years stay in Denmark (Table 2). Among second-generation immigrants, the risk of CD and UC was comparable to that in Danish natives (Table 1). Younger age at immigration did not impact IBD risk.

Conclusion

In this population-based study, the risk of IBD among first-generation immigrants reflected that in their country of birth, and increased with >20 years stay in Denmark. Among second-generation immigrants, the risk was comparable to native Danes. These findings underscore the role of environmental risk factors in the aetiology of IBD. Further studies to determine risk factors for IBD among immigrants to Denmark are ongoing.
OP09 Immunomodulatory mechanisms of faecal microbiota transplantation are associated with clinical response in ulcerative colitis: early results from STOP-Colitis
Authors: Quraishi M N , Oo Y H , Beggs A , Withers D , Acharjee A , Sharma N , Manzoor S , Hart A L , Gaya D R , Loman N J , Hawkey P M , Gerasimidis K , Hansen R , Gkoutous G , Iqbal T H
Published: January 2020

Background

Studies of faecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. Mechanisms by which FMT modulates inflammation, however, remain unexplored. Through a prospective, open-label pilot of FMT in UC (STOP-Colitis) we conducted a sub-study to explore changes in host colonic mucosal immune cell subsets and gene expression following FMT.

Methods

Patients in this study received eight infusions of FMT over an 8-week period. Colon biopsies and blood were obtained at baseline and at the end of the study. Immunophenotyping of colonic lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) was conducted. RNA sequencing was performed on colon biopsies for differential gene expression analysis followed by multi-omic integration.

Results

Seventeen patients were recruited to this sub-study; of which, 12 completed 8 weeks of FMT per protocol. Response (reduction in MAYO score) was seen in 67% (8/12) of patients. Analysis of colonic LPMC populations revealed a significant increase in regulatory T cells (Tregs, CD4+CD25+CD127lowFoxP3+; Δ 5.02%; p < 0.01), especially effector memory Treg subset (CD4+CD25+CD127-CCR7-CD45RA-; Δ 12%; p < 0.001), gut homing Tregs (CD4+CD25+CD127-CCR7-CD45RA-α4+; Δ 18.55%; p < 0.01) and IL-10 producing CD4 cells (Δ 2.16%; p = 0.04) in responders following FMT. Along with this, there was a significant reduction in mucosal Th17 cell (CD4+CD161+CCR6+; Δ −7.61%; p = 0.017), IL-17 producing CD4 cell (Δ −7.69%; p = 0.05) and CD8 cell (Δ -5.18%; p = 0.04) populations in FMT responders. Colonic mucosal gene expression and pathway analysis demonstrated that response to FMT was associated with significant downregulation of host antimicrobial defence response mainly REG and defensin family of anti-microbial peptides, pathogen-associated molecular pattern binding receptors, proteases, multiple MHC class II genes associated with antigen presentation and proinflammatory immune pathways. There was a significant upregulation of butanoate and propionate metabolic pathways in FMT responders. Analysis of PBMC revealed a significant increase in IL-10 producing CD4 cells suggesting that induction of peripheral immune tolerance is preferentially compartmentalised to the gut mucosa.

Conclusion

Response to FMT is associated with a significant increase in mucosal gut homing Tregs and butanoate metabolism along with a reduction in Th17 cells and multiple anti-microbial defence and proinflammatory pathways. FMT induces change in immune balance in local milieu which leads to clinical response in UC. Exploring microbial mediators in FMT which influence immunometabolism is now under investigation to underpin novel biotherapeutic approaches.
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

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 <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

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 (<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

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

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 <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

Background

Crohn’s disease (CD) is a debilitating autoimmune disease affecting >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 >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 <150) 19/27 patients (70%) achieved clinical response with >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

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

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

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.
DOP44 Cancer risk in a high-incidence inflammatory bowel disease population: a Faroese IBD cohort study
Authors: Midjord J M M , Vang A G , Hammer T , Burisch J , Nielsen K R
Published: January 2020

Background

The association between inflammatory bowel disease and malignancy is still controversial despite many observational studies. The Faroese population exhibits the highest occurrence of inflammatory bowel disease (IBD) in the world. The aim of this study was to investigate the risk of cancer in Faroese IBD patients within the nationwide Faroese IBD cohort.

Methods

This was a nationwide cohort study of all IBD patients diagnosed in the Faroe Islands from 1960 to 2014. Clinical demographics and cancer diagnosis were retrieved from patient files and from the Faroese cancer registry. Patients were followed until the event of cancer, death or emigration. Patients diagnosed with cancer prior to the IBD diagnosis were excluded. Observed numbers of cancer were compared with expected numbers based on ASR(N) (Nordic age- and sex-specific incidence rates) from Nordcan, by multiplying ASR(N) with person-years and follow-up in the study cohort and presented as standardised incidence ratios (SIRs) with 95 % intervals (CIs).

Results

The cohort consisted of 664 incidence IBD patients. After excluding 12 patients with cancer prior to IBD diagnosis, 652 patients with a total follow-up length of 11 476 person-years were included (414 UC with 7.494 patient-years, 128 IBDU with 2.038 patient-years and 110 CD with 1.944 patient-years). A total of 56 patients developed cancer during the follow-up period compared with 39.2 expected cases in the background population. We observed no gender difference. In UC, 33 observed compared with 25.7 expected patients developed cancer (SIR 1.28; 95% CI, 0.88–1.80). In IBDU, 13 observed compared with 6.9 expected patients developed cancer (SIR 1.88; 95% CI 1.00–0.22). In CD, 10 cases were observed compared with 6.6 expected (SIR 1.51; 95% CI 0.73–2.79). The most common types of cancers observed are shown in Table 1.

Conclusion

In this nationwide cohort study, we found no overall risk of cancer in IBD patients in the geographic isolated Faroe Island. However, skin cancer occurred more than expected in IBDU patients. This finding needs to be investigated further including the influence of treatment on cancer risk.
DOP47 The changing pattern of inflammatory bowel disease incidence in Northern France: A continuing increase in the young women (1988–2014)
Authors: CRETIN T , Sarter H , Savoye G , Fumery M , Leroyer A , Dauchet L , Pariente B , Gower-Rousseau C
Published: January 2020

Background

In industrialised countries, inflammatory bowel disease (IBD) incidence rates appear to have stabilised in adults but not in children. The objective was to describe changes in the incidence and phenotype of adult-onset IBD in northern France over a 27-year period.

Methods

We included all patients aged 17 or over at IBD diagnosis, recorded in the EPIMAD population-based registry between 1988 and 2014. Standardised incidence rates for Crohn’s disease (CD) and for ulcerative colitis (UC) were calculated in the population as a whole and by age and sex. Patients were divided into three age groups: 17–39, 40–59, and 60 and over. Disease locations were defined according to the Montreal classification.

Results

17,686 incident adult-onset IBD cases were recorded, including 10,206 cases of CD (58%), 6,839 cases of UC (38%) and 641 cases of IBD unclassified (IBDU; 4%). The mean [95% CI] annual incidences of adult-onset IBD, CD, UC, and IBDU were 13.5 per 105 [13.3–13.7], 7.5 per 105 [7.4–7.7], 5.4 per 105 [5.3–5.6] and 0.51 per 105 [0.47–0.55] respectively. The median [IQR] age at diagnosis was lower in CD (28 [22–40]) than in UC (36 [27–49]) (p < 0.0001). The median [IQR] age at diagnosis was lower in women than in men: 28 [21–39] vs. 29 [22–40] in CD (p < 0.0001), and 33 [26–45] vs. 39 [28–51] (p < 0.0001) in UC. The incidence of IBD rose from 11.5 per 105 in 1988–1990 to 12.9 per 105 in 2012–2014 (p = 0.053). The incidence of CD steadily increased from 5.5 to 7.9 per 105 (average percent change per year [APC] +1%; [0.5;1.4]; p < 0.0001), whilst that of UC was stable at 5.0 per 105. The largest increase was seen in young women: APC of +2.0% per year for CD (p < 0.0001) and +1.7% per year for UC (p < 0.0001) in the 17–39 age group, and APC of +1.1% per year for both disease (p = 0.019 for CD and p = 0.024 for UC) in the 40–59 age group. The sex ratio did not vary for CD but changed from 0.70 in 1988–1990 to 1.10 in 2012–2014 for UC (p = 0.001). Among CD patients having undergone a full assessment of the ileum and colon, ileal locations increased from 19% to 26% for L1 (p < 0.0001) and from 50% to 58% for L3 (p < 0.0001), while L2 locations decreased from 31% to 16% (p < 0.0001). In the UC group, the proportion of patients with E1 location decreased from 42% to 34%, whereas the proportion with E3 location increased from 19% to 28% (p < 0.0001).

Conclusion

In a large, population-based study over a period of 27 years, we found that the incidences of CD and UC in the young women in northern France are still rising quickly. Our present results suggest that one or more environmental factors may significantly predispose women to IBD in our region. Among patients with CD, we observed an increase in ileal involvement and a concomitant decrease in colonic involvement.
DOP56 Ustekinumab maintained clinically meaningful improvement in health-related quality of life in patients with moderate to severe ulcerative colitis: Results from the UNIFI long-term extension
Authors: Sandborn W J , Rowbotham D S , Leong R W L , Han C , Zhou Y , Zhang H , Johanns J , Marano C , Danese S
Published: January 2020

Background

The UNIFI maintenance study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients with moderately–severely active UC who had responded to IV UST induction. Previously, we reported that health-related quality of life (HRQoL) improvements achieved after UST induction were maintained through Week 44 with UST maintenance. Here, we evaluated HRQoL through Week 92 in patients who continued UST maintenance in the long-term extension (LTE).

Methods

Patients who completed the maintenance study were eligible to continue their maintenance treatment regimen (placebo [PBO], UST90mg q12w, or UST90mg q8w) in the LTE if the investigator thought they could benefit from continued treatment. PBO patients discontinued from the LTE after the maintenance study was unblinded. Per investigator discretion, patients could receive a single dose adjustment (UST q12w to q8w or UST q8w to q8w [sham dose adjustment]) starting at Week 56. The Inflammatory Bowel Disease Questionnaire (IBDQ) is a 32-item questionnaire with a total score ranging from 32 to 224. Higher scores indicate better HRQoL, a score ≥170 indicates remission, and a change ≥16 was defined as clinically meaningful. General health was assessed using SF-36. A change ≥5 points in physical and mental component scores was defined as clinically meaningful. In this analysis, patients who dose adjusted were considered treatment failures.

Results

Most patients who received UST in the LTE maintained the improvements in IBDQ and SF-36 that were achieved after induction (Tables 1 and 2) through Week 92. Overall, 158 of 284 patients (55.6%) who received UST were in IBDQ remission at Week 92, and 114 of 169 patients (67.5%) who were in IBDQ remission at maintenance baseline were in IBDQ remission at Week 92. Of the 284 patients, 179 (63.0%) achieved a ≥16-point improvement in IBDQ score from induction baseline to Week 92. Of 250 patients who achieved a ≥16-point improvement from induction baseline to maintenance baseline, 154(61.6%) maintained a ≥16-point improvement at both Weeks 44 and 92. For SF-36, 142 of 284 patients (50.0%) had a ≥5-point improvement from induction baseline to Week 92 in the physical component score, while 128 of 284 (45.1%) had a ≥5-point improvement in the mental component score.

Conclusion

The majority of patients who were treated with UST in the LTE generally maintained improvements in IBDQ and SF-36 scores that were achieved after IV induction.
DOP58 Tofacitinib for ulcerative colitis: Results of the ICC Registry, a nationwide prospective observational cohort study
Authors: Biemans V B , Sleutjes J A M , de Vries A C , Bodelier A G , Dijkstra G , Oldenburg B , Löwenberg M , van Bodegraven A A , van der Meulen-de Jong A E , de Boer N K , Srivastava N , West R L , Römkens T , Horjus Talabur Horje C S , Jansen J M , Hoekstra J , Weersma R K , van Schaik F D , Hoentjen F , Pierik M J
Published: January 2020

Background

Tofacitinib is a janus kinase 1 and 3 inhibitor approved for the treatment of ulcerative colitis (UC). Real-world evidence is needed to evaluate the effectiveness, usage and safety in daily practice.

Methods

UC patients in whom tofacitinib was started in 15 hospitals (8 academic, 7 non-academic) participated in the ICC Registry: a Dutch prospective, observational registry. Visits were planned at baseline, Week 12, and 24. Patients with both clinical (Short Clinical Colitis Activity Index (SCCAI) >2) and objective disease activity (endoscopy (Mayo >0), C-reactive protein (CRP) >5 mg/l or faecal calprotectin (FCP) >250 µg/g) were included. In this study, corticosteroid-free clinical remission (SCCAI ≤2), biochemical remission (FCP ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, dose optimisation, and effect on lipids were determined at Week 24. Only patients from centres with routine endoscopic follow-up (regardless of symptoms) were analysed to determine endoscopic remission (Mayo = 0) at Week 12. All analyses were done on an intention-to-treat basis.

Results

In total, 111 UC patients (95% anti-TNF, 60% vedolizumab, 4% ustekinumab exposed) were followed for a median of 24 weeks (IQR 12–26). All patients had both active clinical and objective disease (SCCAI 8 (IQR 5–11), FCP 1800µg/g (IQR 633–2682)). Corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29%, 25%, and 19%, respectively. Endoscopic remission was achieved in 21% of patients (n = 33) at Week 12. Prior vedolizumab exposure was associated with a lower remission rate at week 24 (OR 0.33, 95% CI 0.11–0.94) in multivariable analysis. In total, 36 patients (88 per 100 patient-years) experienced tofacitinib-related adverse events (most common: cutaneous lesions and headache) of which 6 patients (18 per 100 patient-years) discontinued treatment. No thromboembolic events were reported. We observed 4 cases of herpes zoster re-activation but no severe infections (requiring hospitalisation). During follow-up 14 hospitalisations and 5 (4.5%) colectomies were performed. Cholesterol, HDL, and LDL increased between baseline and week 12 (18% (95% CI 9–26, n = 35), 18% (95% CI 8–28, n = 35) and 27% (95% CI 14–39, n = 35), respectively). At week 24, 33% of patients used 10 mg twice daily.

Conclusion

Tofacitinib is an effective treatment for UC after anti-TNF and/or vedolizumab failure. We did observe a relatively high rate of adverse events in this refractory UC cohort.
DOP59 Maintenance of remission with tofacitinib in patients with ulcerative colitis: Updated results of a subpopulation analysis from an open-label, long-term extension study, OCTAVE Open
Authors: Colombel J F , Osterman M T , Ibanez P , Thorpe A J , Zhang H , Lawendy N , Su C , Reinisch W
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety were demonstrated in 3 Phase 3, randomised, placebo-controlled studies in patients with moderate to severe UC.1 An ongoing, Phase 3, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) included patients from OCTAVE Induction 1 and 2 and OCTAVE Sustain.

Methods

We present data (as of May 2019) from the ‘maintenance remission’ subpopulation in the OLE study who were in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore of 0) at Week 52 of OCTAVE Sustain (having received tofacitinib 5 or 10 mg twice daily [BID]). These patients received tofacitinib 5 mg BID as per protocol in the OLE study. Efficacy data up to Month 36 of the OLE study (as observed and with non-responder and last observation carried forward imputation [NRI-LOCF]) are presented for this subpopulation. Safety data are reported for all patients who received tofacitinib 5 mg BID in the OLE study.

Results

Of 944 patients receiving ≥1 dose of tofacitinib in the OLE study, 163 were in remission at Week 52 of OCTAVE Sustain (mean age 45 years; 46.0% female). Of these, 66 (40.5%) and 76 (46.6%) received tofacitinib 5 and 10 mg BID, respectively, in OCTAVE Sustain, and 21 (12.9%) received a placebo. In total, 67/163 (41.1%) patients discontinued the OLE study, 16 (9.8%) due to adverse events (AEs) excl. worsening UC and 15 (9.2%) due to insufficient clinical response. Among patients that continued, efficacy (Table) was maintained over 36 months and was similar irrespective of the dose received in OCTAVE Sustain. Of 175 patients who received tofacitinib 5 mg BID (incl. 163 from the maintenance remission subpopulation), 152 (86.9%), 33 (18.9%) and 20 (11.4%) had AEs, serious AEs and severe AEs, respectively. The most frequent treatment-emergent AEs (TEAEs) were worsening UC (41 patients, 23.4%) and nasopharyngitis (38 patients, 21.7%). Six (3.4%) patients receiving tofacitinib 5 mg BID had serious infections, 11 (6.3%) had herpes zoster (non-serious and serious), 4 (2.3%) had opportunistic infections, 2 (1.1%) had major adverse cardiovascular events and 5 (2.9%) had malignancy (excl. non-melanoma skin cancer). No deep vein thrombosis, pulmonary embolism or deaths were reported in patients receiving tofacitinib 5 mg BID.

Conclusion

Most patients in remission at Week 52 of OCTAVE Sustain maintained efficacy with tofacitinib 5 mg BID over 36 months in the OLE study. Similar efficacy was observed for patients whose dose was reduced from tofacitinib 10 mg BID in OCTAVE Sustain to 5 mg BID in the OLE study, vs. those who received 5 mg BID throughout both OCTAVE Sustain and the OLE study. No new safety risks were identified.

Reference
N23 Concerns of patients with inflammatory bowel disease in the process of disease management
Authors: Mohsenizadeh S M , Manzari Z S , vosoghinia H , Ebrahimipour H
Published: January 2020

Background

Inflammatory bowel diseases (IBD) are among the most common disorders that cause poor quality of life and impose a lot of social and economic burden on patients and their family. Therefore, identifying the main concerns of these patients in the management of the disease is very important for designing a specific care plan. The aim of this study was to explaining the concerns of patients with IBD in the process of disease management.

Methods

This research was carried out using thematic analysis method. Sixteen patients with at least one year of IBD were interviewed individually by semi-structural questions. Their main concerns in the management of the disease were analysed.

Results

The main concerns of patients with IBD were categorised into four main groups as follows: mental (negative attitude toward disease, encounter with disease, tolerance of tough condition, maladaptation, acceptance and denial of disease), behavioural (avoidance of situations, out-of-home planning, physical activity, diet, seeking information, seeking the best treatment), socioeconomic (weak support, high cost of treatment, confidentiality of the disease), and biomedical (supplying medicine and experiencing surgery). These concerns have a substantial impact on patients’ ability regarding the reconciliation of their living with disease.

Conclusion

By identifying the concerns of patients with IBD in their disease management process, nurses can develop care programmes and interventions to meet the essential needs of these patients.
N27 What people want! Exploring inflammatory bowel disease patients’ perspectives on healthcare professionals addressing sexual well-being
Authors: Fourie S , Czuber-Dochan W , Norton C
Published: January 2020

Background

Inflammatory bowel disease (IBD) affects every aspect of one’s life, yet no routine assessment for the impact on sexuality is made. Our aim was to explore patients’ perspective on healthcare professionals (HCPs) addressing sexuality/sexual well-being concerns.

Methods

This was a qualitative narrative study. Inclusion criteria were any sexual orientation and with known IBD for longer than 18 months. Data were collected via semi structured interviews and anonymous narrative accounts submitted via Google Forms. Thematic analysis was used to analyse the data.

Results

Fourteen adults, 4 male and 10 female, took part. Eleven participants were from the UK, one from the USA of America and one for South Africa. The following main themes and subthemes were identified: I cannot imagine talking about my sex life (a difficult topic; there is not enough time), Those who talked about sex, talked badly (nobody volunteered information; badly handled conversations), Still living whilst unwell (sex is an important part of my life; sex issues break down relationships, medicalised body), IBD ruined my sex life (feeling unattractive; feelings of shame and embarrassment), I feel unheard (HCPs don’t open the discussion; sex not taken seriously), I’m a person, not my IBD (holistic approach to care; time, space and ways to talk about sex). The findings reflect the importance of sexual well-being to those living with IBD, the experiences of such conversations, barriers to conversations with HCPs on sexual well-being, and suggestions on how HCPs should address their unmet needs. The importance of discussing intimacy and sexuality was emphasised, as participants felt their sexual well-being was considerably affected by IBD. The majority reported that HCPs did not initiate discussions on sexual well-being, nor did they understand the impact of IBD on sexual well-being, with a distinct accent on the perceived lack of a holistic approach to their care. Therefore, participants made suggestions for practice, such as provision of information related to sexual well-being in the form of leaflets, additionally to HCPs raising the issue.

Conclusion

Our findings indicate that communicating on sexuality/sexual well-being is a problematic area of IBD care. HCPs must be cognisant of the sexual well-being concerns and needs of those living with IBD, who want this topic discussed routinely, as part of a holistic approach to their clinical care.