bluuebunny/crossref_metadata_2025_split huggingface dataset:
P559 Effect of vedolizumab and ustekinumab on articular manifestations in patients with inflammatory bowel disease refractory or intolerant to anti-TNF therapy: An observational prospective study
Authors: Britschu O , Meyer A , Gottenberg J E , Reimund J M , Caron B 
Published: January 2020

Abstract

Background
The effectiveness of vedolizumab (VDZ), a monoclonal antibody targeting the α4β7 integrin, and ustekinumab (UST), an anti-interleukin-12/anti-interleukin-23 antibody, for the treatment of patients with inflammatory bowel disease (IBD) has been demonstrated. Nearly 50% of patients with IBD have extraintestinal manifestation(s) (EIM). The most frequent are rheumatologic. In contrast to the data available for infliximab (IFX), only retrospective or small studies with contradictory results have been published regarding the effect of VDZ or UST on IBD-associated articular manifestations. The aim of our study was to evaluate the effect of VDZ and UST used in the treatment of Crohn’s disease or ulcerative colitis on associated articular manifestations, compared with patients receiving IFX.

Methods
We conducted a single-centre observational prospective study. All consecutive patients diagnosed with IBD and treated with IFX, VDZ or UST were included and classified into two groups: group 1, not presenting articular manifestations at the baseline, and group 2, having articular manifestations at the inclusion. We evaluated the occurrence of articular manifestations assessed by the BASDAI score in group 1 and the evolution of articular manifestations according to the BASDAI score in group 2. EIM activity was assessed at months 0, 3, 6, 9 and 12. Improvement or worsening of joint manifestations was considered significant if the BASDAI decreased or increased by 10 mm or 20 % in relative value between its initial value and its last available value (M12 or earlier for patients with shorter follow-up times).

Results
From September 2017 to April 2019, 54 patients were included. Twenty-nine patients were analysed in group 1: 9 treated with IFX, 8 with VDZ and 12 with UST. During the follow-up period, 12 (41.4 %) patients in group 1 without EIM at baseline developed articular manifestations: 44.4 %, 50 % and 33.3 % respectively under IFX, VDZ and UST. The mean time from treatment initiation to the development of articular symptoms was 3.3, 3.8 and 2.6 months, respectively on IFX, VDZ and UST. Twenty-five patients were analysed in group 2, 6 treated with IFX, 7 with VDZ and 12 with UST. A significant improvement of the BASDAI score was observed in 50 % of patients treated with IFX, 71.4 % with VDZ and 41.7 % with UST. BASDAI scores were 31.2, 51.8 and 27.9 at M0 and 31.0, 44.7 and 27.5 on average over the entire follow-up for the following treatments respectively: IFX, VDZ and UST.

Conclusion
This prospective study suggests a potential beneficial effect of VDZ and UST on articular manifestations associated with IBD compared with IFX. However, these results need to be confirmed by larger prospective trials.
P562 5-ASA in ulcerative colitis: Are they really needed in the biological therapy era?
Authors: Arieira C , Dias de Castro F , Cúrdia Gonçalves T , Moreira M J , Cotter J 
Published: January 2020

Abstract

Background
Biologic therapy has demonstrated efficacy for induction and maintenance of remission in ulcerative colitis (UC). However, it remains unclear whether oral aminosalicylates (5-ASA) should be continued or stopped after treatment escalation to biologics. The aim of the study was to evaluate differences in inflammatory biomarkers or the occurrence of complications in UC patients being treated with a combination of 5-ASA and biologics vs. biologics alone.

Methods
Retrospective study, including patients with UC and on biologic therapy with a minimum follow-up of 6 months. Collected inflammatory biomarkers were faecal calprotectin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The occurrence of complications was defined as the need of hospitalisation, need of corticosteroids or other top-up therapy, surgery and the occurrence of dysplasia or colorectal cancer.

Results
We included 65 patients with UC, 56.9% female with a mean age of 32.8 (±12.8) years. The median follow-up was 30 (6–132) months. Regarding extension, 61.5% were E3, 35.4% E2 and 3.1% E1. While 44 patients (67.7%) were on 5-ASA and biologics (infliximab = 32, adalimumab = 6, vedolizumab = 6), 21 (32.3%) were on biologics alone (infliximab = 13, adalimumab = 3, vedolizumab = 5). The median duration of biologic therapy was 30 (6–126) months. Regarding baseline characteristics, including age, gender, duration of the disease or biologic therapy and age at UC diagnosis, there were no differences between groups. No differences regarding inflammatory biomarkers were observed – fecal calprotectin (p = 0.39), CRP (p = 0.9) and ESR (p = 0.61). No differences were found regarding complications, namely the need of hospitalisation (p = 0.06) or need of corticosteroids (p = 0.89). Only one patient developed dysplasia (under infliximab and 5-ASA). Any of the included patients needed surgery or developed colorectal cancer.

Conclusion
About two-thirds of the UC patients under biologics are co-treated with 5-ASA. No differences between UC patients under combination biologics+5-ASA vs. biologics alone were found regarding inflammatory biomarkers or the occurrence of complications. These results raise the question if continuing 5-ASA in UC patients under biologics is really necessary.
P567 Impact of oral ferric maltol and IV iron on health-related quality of life in patients with iron deficiency anaemia and inflammatory bowel disease, and relationship with haemoglobin and serum iron
Authors: Howaldt S , Jacob I , Sampson M , Akriche F 
Published: January 2020

Abstract

Background
Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD) and can significantly impair health-related quality of life (HRQoL). IV iron is currently the main treatment for patients intolerant or unsuitable for standard oral iron. Ferric maltol (FM), a stable oral complex of ferric iron and maltol, is designed to provide efficient iron delivery and minimise formation of free iron in the gut, thus reducing the potential for gastric adverse events. The HRQoL benefits of FM and ferric carboxymaltose (FCM) and their relationship to haematological parameters were analysed using data from a randomised controlled trial.

Methods
Patients with IBD and IDA were randomised to FM (30 mg b.i.d) or IV FCM (as per local SmPC) in an open-label, Phase 3b non-inferiority study (primary endpoint haemoglobin [Hb] responder rate [proportion of patients with ≥2 g/dl increase or normalisation of Hb at week 12]; non-inferiority margin 20%). HRQoL was assessed via the Short Form Health Survey (SF-36). In a post-hoc analysis of patient-level data, Hb, serum iron and HRQoL at baseline and week 12 were summarised descriptively and correlations between HRQoL and haematological parameters were assessed via Pearson’s correlation coefficient (PCC).

Results
250 patients were randomised: 125 to FM and 125 to IV FCM. The primary endpoint was not met. Hb, serum iron and HRQoL all improved following both treatments at Week 12. Improvements in SF-36 physical component summary (PCS) and mental component summary (MCS) scores were slightly greater with FM (difference not statistically significant; Table 1). HRQoL improved across all SF-36 domain scores with both FM and FCM, with no statistically significant differences between treatments (Figure 1). HRQoL (MCS and PCS) improvements were positively associated with increases in Hb and serum iron (Table 1).

Conclusion
FM provides HRQoL benefits at least as great as those with IV FCM, and may, therefore, provide an oral alternative to IV iron in patients with IBD.
P572 Clinical outcomes after discontinuation of anti-tumour necrosis factor-α agents in inflammatory bowel disease patients with clinical remission: KASID multicenter study
Authors: Song J H , Kong S M , Shin J , Seong G , Kang E A , Park S K , Hong S N , Kim Y S , Bang K B , Kim K O , Lee H S , Kang S B , Shin S Y , Song E M , Choi C H , Kim T J , Kim E R , Chang D K , Kim Y H 
Published: January 2020

Abstract

Background
Despite proven efficacy of anti-tumour necrosis factor-α agents (ant-TNF) for inflammatory bowel disease (IBD), some patients have to be discontinuation of anti-TNF for various reasons in a real-world clinical setting. The aim of this study was to evaluate the long-term outcomes and risk factors of relapse after discontinuation of anti-TNF in IBD patients with clinical remission.

Methods
A retrospective multicenter cohort study was conducted at 10 referral hospitals, affiliated in IBD Study Group of the Korean Association for the Study of Intestinal Diseases. The study population comprised patients diagnosed with Crohn’s disease (CD) or Ulcerative colitis (UC) who had been treated with anti-TNF (infliximab (IFX) or adalimumab (ADA)) to induce remission and in whom ant-TNF had been discontinued after clinical remission was achieved. The patients were excluded for follow-up of &lt;12 months after discontinuation of anti-TNF.

Results
A total of 125 IBD patients were eligible. Among them, 109 IBD patients including 71 CD and 38 UC were analyzed and median follow-up period was 56 months (interquartile range, 35–90 months). The reasons of discontinuation of anti-TNF was physician’s decision (n = 32, 29.4%), patient’s own preference (n = 30, 27.5%), anti-TNF-related adverse events/opportunistic infection (n = 18, 16.5%), and other reasons (n = 29, 26.6%). After discontinuation of anti-TNF, relapse occurred in 49 CD patients (69%) and 19 UC patients (50%). Relapse-free survival rate at 1, 2, 3, and 5 years in patients with CD were 11.3%, 31.4%, 46.7%, and 62.5%, respectively, and that in patients with UC was 28.9%, 34.8%, 45.3%, and 60.9%, respectively. Multivariate Cox regression analysis identified the risk of relapse was associated with adalimumab use (vs. infliximab: hazard ratio [HR], 4.41; 95% confidence interval [CI], 1.18–16.41; p = .027) and discontinuation due to physician’s decision (vs. patient’s preference: HR, 0.13, 95% CI, 0.04–0.49, p = .002) in patients with CD, whereas that was decreased in UC patients with mucosal healing (vs. non-mucosal healing: HR=0.07, 95% CI, 0.01–0.58, p = .014). Retreatment with anti-TNF was done in 54 patients (49.5%) and effective in 45 patients(83.3%).

Conclusion
The discontinuation of anti-TNF was associated with increased risk of relapse. Although retreatment of anti-TNF seems to be effective and safe, the discontinuation of anti-TNF should be carefully considered based on the type of anti-TNF, the reason for discontinuation, and the mucosal healing status.
P594 Increased levels of stress, anxiety and depression among patients with CD and UC
Authors: Laoudi E , Papalouka D , Gkizis M , Kokkotis G , Perlepe N , Vlachogiannakos I , Papakonstantinou I , Bamias G 
Published: January 2020

Abstract

Background
Patients with IBD often report stress and emotional discomfort (anxiety and depression), which lead to a compromise in quality of life. The aim of this study was to report the prevalence and severity of those parameters among patients with CD and UC and correlate them with disease activity, inflammatory biomarkers and demographic characteristics.

Methods
We analyzed data from 86 patients with CD (53 male) and 68 with UC (37 male) who attended our IBD department for routine follow-up. Participants completed the DASS 21 questionnaire (validated Greek version). DASS 21 consists of 21 questions which feed into separate measurement scales for stress, anxiety or depression. Disease activity was measured with the Harvey Bradshaw index (HBI) for CD and Simple Colitis Activity Index (SCAI) for UC.

Results
CD patients. Stress scale: based on validated cutoff values for the general population, 36% of patients had normal scores, 11% mild discount, 14% moderate, 17% severe, and 22% had an extremely severe discount. Anxiety scale: 44% normal, 18% mild, 8% moderate, 6% severe and 24% extremely severe discount compared with the general population. Depression scale: 60% had normal scores, whereas 4% mild, 9% moderate, 6% severe and 23% extremely severe discount. In CD patients, a positive correlation between stress, anxiety, depression and Harvey Bradshaw score were found [Spearman non-parametric correlation: p &lt; 0,001) for all comparisons]. UC patients. Stress scale: 45% had normal scores, 6% mild, 15% moderate, 12% severe and 22% extremely severe discount. Anxiety scale: 5% normal, 12% mild, 15% moderate, 3% severe and 19% extremely severe. Depression scale: scores were normal 68%, mild in 33%, moderate in 12%, and extremely severe in 7% of patients. No correlation was found between DASS 21 and SCAI scores. When the CD and UC groups were compared, no significant differences were found for stress (p = 0,162) and anxiety (p = 0,194). In contrast, scores for depression were higher in CD patients (t-test p = 0,007). Female patients had higher scores for stress (p &lt;0,01) and anxiety (p &lt;0,01) in comparison to male patients with IBD. We did not observe significant correlations between DASS scores and Hb or CRP.

Conclusion
Our results show that a considerable percentage of patients with IBD present with deranged emotional status. We were able to recognise correlations between specific alterations and patient subpopulations. Those findings support the notion that patients with IBD may benefit from psychological interventions.
P597 Pooled safety analyses from Phase 3 studies of filgotinib in patients with rheumatoid arthritis
Authors: Besuyen R , Walker D , Winthrop K , Genovese M , Combe B , Tanaka Y , Kivitz A , Matzkies F , Bartok B , Ye L , Guo Y , Tasset C , Sundy J , Keystone E , Westhovens R , Rigby W , Burmester G 
Published: January 2020

Abstract

Background
Filgotinib (FIL) is an oral, selective Janus Kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, randomised, multicentre studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24).

Methods
The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to a standard of care. W24 safety data from all studies were aggregated and summarised. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities.

Results
3452 patients were evaluated; 2088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups.

Conclusion
Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD.
P598 Incidence of venous thromboembolic events in patients with ulcerative colitis treated with tofacitinib in the ulcerative colitis clinical development programme: An update as of May 2019
Authors: Sandborn MD W J , Panés J , Sands B E , Reinisch W , Modesto I , Su C , Steinwurz F , Lawendy N , Koram N , Kwok K , Jones T V , Thorpe A J , Quirk D , Danese S 
Published: January 2020

Abstract

Background
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of UC. In data analysed from a large, ongoing (data cut-off February 2019 [a]; database unlocked; data may be subject to change), post-authorisation safety study in patients with RA (≥50 years; ≥1 cardiovascular risk factor; enrolled on a stable dose of MTX), the incidence rate (IRs; unique patients with events per 100 pt-years [PY]) of pulmonary embolism (PE) in patients treated with tofacitinib 10mg BID (0.54 [95% CI] 0.32, 0.87]) was numerically higher compared with 5 mg BID (0.27 [0.12, 0.52]) and statistically different from TNFi (0.09 [0.02, 0.26]). Corresponding IRs for deep vein thrombosis (DVT) were 0.38 (0.20, 0.67), 0.30 (0.14, 0.55) and 0.18 (0.07, 0.39).1 UC is a known risk factor for DVT and PE. Subsequently, updates to the tofacitinib prescribing information have been made, with venous thromboembolism added as a warning and adverse drug reaction. Here, we provide an update on the incidence of DVT and PE in the tofacitinib UC clinical development programme, as of May 2019.2

Methods
DVT and PE events were evaluated from 4 randomised placebo-controlled studies (Phase [P]2/P3 induction studies and P3 maintenance study) and an ongoing, open-label, long-term extension (OLE) study.3,4 Three cohorts were analysed: Induction, Maintenance and Overall (patients receiving tofacitinib 5 or 10mg BID in P2/P3/OLE studies; patients were categorised based on the average daily dose: predominant dose [PD] 5 or 10 mg BID).

Results
1157 patients were evaluated for DVT and PE, with 2581 PY of tofacitinib exposure and up to 6.8 years’ treatment. In the Induction and Maintenance Cohorts, 2 patients had DVT and 2 had PE; all were receiving placebo at the time of the event (tables). In the Overall Cohort, DVT occurred in 1 pt and PE in 4 patients during the OLE study, after ≥7 months of treatment; all patients had received PD 10 mg BID (83% of Overall Cohort received PD 10 mg BID) and had other (non-UC) risk factors for venous thrombosis (tables).

Conclusion
IRs in the Overall Cohort have remained stable since the previously reported data cut.2 All of the events in tofacitinib patients (PD 10 mg BID) occurred during the OLE study and all had other (non-UC) risk factors for thromboembolic events. This analysis is limited by sample size and duration of drug exposure; further study is needed. [a] The tofacitinib 10mg BID arm of the study was discontinued in February 2019 and patients who re-consented and chose to remain in the study were switched to the 5 mg BID arm.

References
P608 Endoscopic treatment of enterocutaneous fistulas in Crohn’s disease patient
Authors: Yzet C , Le Mouel J P , Hakim S , Brazier F , Fumery M 
Published: January 2020

Abstract

Background
The management of enterocutaneous fistulas (ECF) in Crohn’s disease (CD) patients is complex and requires a multidisciplinary approach. Despite the advent of anti-TNF, the majority of patients still need surgical management. The aim of this study was to report the feasibility of endoscopic treatment of ECF in CD patient.

Methods
We prospectively identified CD patients with an ECF who failed to conventional medical therapies. Demographic and clinical data were collected retrospectively. Under general anaesthesia, a colonoscopy was performed to identify the fistula. At the discretion of the operator, an Ovesco® clip under or hemostatic clip were placed on the top of the fistula, with radiological opacification control. Technical success was defined by the clip placement on the EFC. The clinical success was defined by the closure of the fistula (defined by the absence of emission of stool or gas by the cutaneous orifice).

Results
Eight patients (female, 75 %, median age 45 years (interquartile range (IQR), 33–51)) were identified. Regarding the EFC, they evolved from a median of 3 months (IQR, 1.75–5.5) before the endoscopic management. The fistulas were localised on the ileocolonic anastomosis for 7 patients, and on the stomach in one. Two patients had an endoscopic activity, as defined by the presence of ulcer(s). Seven patients were treated with an OVESCO clip and one with Boston® resolution 360 hemostatic clips. Thirteen endoscopic procedures were performed, with a median number of 1 procedure/patient (IQR, 1–2). Technical success was observed in 100% of cases. Clinical success at 3 months was observed in 75% of cases (6/8 patients). After a median follow-up of 8 months (IQR, 5–12), 2/6 patients in clinical success underwent a new procedure due to EFC recurrence at respectively 4 and 7 months due to a clip migration. Among the 2 failures, one patient underwent a second colonoscopy with a new Ovesco® placement and the other was treated with fibrin glue. In both cases the procedure was ineffective. No complication related to the clip insertion was observed.

Conclusion
This demonstrates |, for the first time, the feasibility and short-term effectiveness of endoscopic clips for the treatment of EFC in CD patients. New prospective studies should confirm these results.