bluuebunny/crossref_metadata_2025 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

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

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

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

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 <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

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 < 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 <0,01) and anxiety (p <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

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

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

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.
P610 Optimising biological therapy in inflammatory bowel disease patients: the role of a virtual biological clinic
Authors: REES J , Maher C , Jones J , Slater J , Bates B , Rattehalli D , De Silva S
Published: January 2020

Background

The National Institute of Clinical Excellence (NICE) recommends that patients with inflammatory bowel disease (IBD) taking biologic agents are reassessed every 12 months, to determine whether continuation of therapy is appropriate. Only those with evidence of ongoing active disease, determined by clinical symptoms, biochemical markers, endoscopic or radiological investigations, should continue with therapy. With the increasing use of biologics, this represents a major challenge and may result in biologic agents being inappropriately continued, at significant cost to the NHS. A virtual biologics MDT (VMDT), consisting of 2 IBD consultants and 2 specialist nurses, was launched in 2017 at Russells Hall Hospital (RHH) to address this issue. We aim to evaluate its performance in 2018.

Methods

We performed a retrospective case note review of all patients discussed at the VMDT in 2018. Clinic letters, blood results, endoscopy reports and radiological investigations were examined to determine adherence to NICE guidelines.

Results

Out of a total 223 patients using biologics in 2018, 119 (51.2% male, 79.8% Crohn’s disease, mean age 42.7 years, 57.9% taking adalimumab) were discussed at the VMDT. 67/119 patients were taking a second immunosuppressant agent and out of the remaining 58, 32 had documented evidence of treatment failure or side effects on these agents and 23 were planned to commence them from the MDT. Fourteen patients (11.8%) had their biologic de-escalated post MDT and 5 (4.2%) were switched to a second-line agent. 1 patient’s planned de-escalation was prevented by ankylosing spondylitis. 26/119 patients had no recent or planned radiological or endoscopic reassessment of their disease at 12 months. Of these 26 patients, 17 had ongoing clinical symptoms preventing treatment withdrawal, 2 were de-escalated and 6 had plans to add a second agent prior to reassessment. Only 1 patient continuing treatment had a good indication for de-escalation. Of the 89 patients eligible for therapeutic drug monitoring, 8 were found to have no levels within 12 months of the VMDT (all taking adalimumab). All of these patients were identified at the time and 7 were sent for levels. The remaining patient had their drug discontinued.

Conclusion

The virtual biologics MDT at RHH has been shown to be an effective way of monitoring patients’ disease activity and drug levels, optimising drug therapy and appropriately de-escalating biologic agents. It was only possible to discuss 53.4% of our patients at the virtual MDT and we recommend this service is expanded by allocating a formal monthly session to ensure that all patients can be reviewed. Work is now underway to assess performance in 2019 and follow-up patients who have had their biologics discontinued.
P615 Safety of vedolizumab in the treatment of IBD in a single tertiary centre
Authors: Peruzzi G , Calandrini L , Privitera Hrustemovic H , Salice M , Decorato A , Carbone A , Rizzello F , Belluzzi A , Scaioli E , Calabrese C , Gionchetti P
Published: January 2020

Background

There is a lot of data on Vedolizumab efficacy in the treatment of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD). Despite this, we have little real-world data on its adverse reactions. We aimed to identify and quantify principal adverse reactions in order to assess the safety of the drug.

Methods

UC and CD patients from a single tertiary IBD referral centre receiving Vedolizumab treatment between September 2016 and August 2019 were included. Data were collected prospectively at week 22, 54 and 108. Adverse events were categorised as infections, rheumatic/cutaneous disorders, allergy-related symptoms/anaphylactic shock, serious adverse events and drug discontinuation. Serious adverse events were those that resulted in hospitalisation or death. Discontinuation was due to drug-related effects or IBD complications that persisted despite the treatment or that could be worsened by drug-induced immunodepression.

Results

Our analysis comprised 200 patients (86 with UC and 114 with CD: 22% female; median age 58,3 years). Adverse effects were reported in 59/200 (29,5%) patients, leading to treatment discontinuation in 21/200 (10,5%) cases: 2 with UC and 19 with CD. Six patients experienced more the one adverse reaction for a total of 69. Rheumatic disorders were observed in 17/69 (24,6%), infections in 17/69 (24,6%) and cutaneous manifestations in 6/69 (8,7%). One patient complained of headache and another subocclusive symptom. One patient had an asymptomatic increase in cholestasis tests. No anaphylactic shock or allergy-related symptoms were reported while 6 patients (6/69, 8,7%) required hospitalisation (especially for infective complications). Vedolizumab discontinuation was due to perianal disease onset or relapse (9/21, 42,8%), infections (6/21, 28,6%) and rheumatic disorders (5/21, 23,8%); in one case we observed uncontrolled hypertension and Ménière syndrome. Treatment was restarted after surgical management and treatment with antibiotics in 3 patients with perianal disease and 1 with community-acquired pneumonia, respectively.

Conclusion

In our experience, Vedolizumab is a well-tolerated drug. Most of the adverse events that occurred in our centre were mild and did not require hospitalisation. In some patients discontinuation was not permanent: we performed it in order to treat the condition that contraindicated the administration and restart treatment.
P624 Maintenance of remission after treatment with Exclusive Enteral Nutrition and Azathioprine in paediatric patients with Crohn’s disease
Authors: Pujol Muncunill G , Pascual-Pérez A I , Dominguez-Sánchez P , Feo-Ortega S , Suárez-Galvis M , Vila-Miravet V , Martin de Carpi F J
Published: January 2020

Background

Several studies have shown the efficacy of Exclusive Enteral Nutrition (EEN) in patients with Crohn’s disease (CD) for the induction of remission. ECCO-ESPGHAN guidelines recommend the use of EEN combined with early use of immunosuppressants in paediatric patients with mild-to-moderate CD. However, there is a lack of data to show its efficacy in the long term to avoid or postpone the use of biological treatment. The aim of our study is to know how many of our patients that have achieved remission with EEN and Azathioprine (AZA), required to step up to biological treatment during the follow-up.

Methods

Retrospective analysis of paediatric patients with Crohn’s disease that were diagnosed at our Unit between 2003 and 2017. We included those patients that achieved clinical remission after treatment with EEN and AZA. We analyse demographics, clinical and follow-up data until February 2019 or until they are transferred to an adult inflammatory bowel disease (IBD) unit.

Results

We included 91 patients that achieved clinical remission after treatment with EEN and AZA (68.1% males; Mean age at diagnosis: 12.29 years; Median age at diagnosis: 13 years (range 8 months-17 years). The mean time of follow-up was 60.45 months (range: 8–165 months). During this period, 66/91 patients (72.5%), had a flare. Seventeen of those patients (20.2%) received a second cycle of EEN, being effective in 7 (41.2%). Mean time from diagnosis until the second cycle of EEN was 13.76 months (maximum: 110 months). Globally, 64.8% of our patients required to step up to biological therapy with a mean time from onset to biologics of 15.3 months (median 9 months). Seventy-two per cent of those who needed biological treatment started Adalimumab (ADA). During the follow-up, 42.2% of the patients with combo therapy could withdraw AZA, being the main reason (76.3%) clinical and endoscopic remission.

Conclusion

Even though EEN is an effective treatment for the induction of the remission in paediatric CD, in the long term we are not able to maintain that remission and an important percentage of patients require to step up to biological therapy. The definition of more strict criteria of remission is necessary in order to establish the most suitable maintenance treatment for each patient.
P630 Complete endoscopic remission is not only associated with higher mucosal concentrations of 5-aminosalicylic acid but also with N-acetyl-5-aminosalicylic acid in patients with ulcerative colitis
Authors: Fukuda T , Naganuma M , Takabayashi K , Hagihara Y , Tanemoto S , Nomura E , Yoshimatsu Y , Sugimoto S , Nanki K , Mizuno S , Mikami Y , Fukuhara K , Suzino T , Mutaguchi M , Inoue N , Ogata H , Iwao Y , Kanai T
Published: January 2020

Background

The mechanisms behind 5-aminosalicylic acid (5-ASA) activity in ulcerative colitis (UC) are known to exert a beneficial effect by acting topically on colonic mucosa. this study investigated whether mucosal 5-ASA and N-acetyl-5-ASA (Ac-5-ASA) concentrations are associated with endoscopic remission.

Methods

This single-centre, prospective cross-sectional study was conducted between March 2018 and February 2019. Patients with UC who were treated with 5-ASA medications for at least 8 weeks prior to sigmoidoscopy were enrolled. All participants underwent sigmoidoscopy without pre-treatment, and biopsies were performed to extract approximately 10 mg of tissue from the sigmoid colon and rectum. Mucosal concentrations of 5-ASA and Ac-5-ASA were measured using liquid chromatography with tandem mass spectrometry. The main endpoint was defined as the difference in mucosal concentrations of 5-ASA and Ac-5-ASA according to the level of either the Mayo endoscopic subscore (MES) or the ulcerative colitis Endoscopic Index of Severity (UCEIS).

Results

Mucosal concentrations were analysed in 50 patients. In the sigmoid colon, the median 5-ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥1 (6.4 ng/mg) (p = 0.019). The median 5-ASA concentration in patients with UCEIS ≤1 (16.4 ng/mg) was also significantly higher than in patients with UCEIS ≥2 (4.63 ng/mg) (p = 0.047). Interestingly, the concentration of Ac-5-ASA was higher in patients with an MES of 0 (21.2 ng/mg) than in patients with an MES≥1 (5.81 ng/mg) (p = 0.022). Similarly, the Ac-5-ASA concentration was significantly higher in patients with a UCEIS≤1 (21.1 ng/mg) compared with that in patients with a UCEIS≥2 (7.8 ng/mg) (p = 0.048). Furthermore, we compared the concentrations of 5-ASA in patients receiving the maximum dose of the three different formulations (time-dependent, pH-dependent, or multimatrix system 5-ASA). 5-ASA concentrations in both sigmoid colon and the rectum tended to be lower in patients receiving time-dependent 5-ASA than patients receiving pH-dependent 5-ASA or multimatrix system 5-ASA, but the difference was not significant.

Conclusion

Although Ac-5ASA, a metabolite of 5-ASA is thought to have few pharmacological effect, this study demonstrated that patients with complete endoscopic remission had higher mucosal concentrations of not only 5-ASA but also Ac-5-ASA than patients with mild-to-moderate endoscopic severity. This result may be explained by the fact that Ac-5-ASA remains as a metabolite of 5-ASA after contributing to the suppression of inflammation in patients with endoscopic remission.
P658 A pooled analysis of serum phosphate measurements and transient decreased phosphate levels in 45 interventional trials with ferric carboxymaltose
Authors: Stein J M , Schiefke I , Göhring U M , Fabien V , Rosano G
Published: January 2020

Background

ECCO guidelines acknowledge the limitations of oral iron for iron deficiency anaemia in IBD and recommend first-line IV iron in patients with active disease. Ferric carboxymaltose (FCM) is approved for iron deficiency when oral iron is ineffective/inappropriate. FCM has shown benefit in RCTs, and as with other IV irons, is known to cause a transient decrease in serum phosphate (PO4), which in most cases is asymptomatic. The aim of this pooled analysis was to characterise the frequency, duration, risk factors, and clinical signs of hypophosphataemia (HP) across 45 interventional trials with FCM.

Methods

15,080 subjects were included (FCM n = 8,245; controls n = 6,835). 12,683 had post-baseline serum PO4 measurements (FCM n = 6,879), which were pooled by time-point, clinical characteristics, dose, and iron parameters. Serum PO4 thresholds were: 2.5–<4.5 mg/dl (normal), 2.0–<2.5 mg/dl (mild decrease), 1–<2.0 mg/dl (moderate), and <1 mg/dl (severe). Logistic regression analysis was used to identify predictors of HP. MedDRA terms were interrogated for reported and potential clinical signs of HP.

Results

2,760 FCM subjects (40.1%) with normal PO4 at baseline developed HP (PO4 <2.5 mg/dl) on study. PO4 levels normalised in 1,705 subjects (61.8%); mean time to normalisation (±SD) was 40.7 days (±35.31). PO4 normalisation during follow-up did not occur in 177 subjects (0.06%). Independent risk factors for moderate/severe HP within 12 weeks of treatment included treatment setting (gastroenterology or neurology vs. women’s health), lower baseline ferritin level, maximum single-dose, advanced age, lower weight at baseline (all p < 0.0001), multiple doses vs. single dose (p = 0.0003), and higher cumulative dose (p = 0.0005). ‘Hypophosphataemia’ as a MedDRA term was approximately 10-fold more frequent with FCM than controls (2.2% vs. 0.2% with other IV irons). Potential clinical signs of HP were not more frequent with FCM vs. controls (Table) and were not associated with nadir levels of serum PO4. 4 of 49 FCM subjects (8.2%) who had nadir PO4 below 1 mg/dl had a potential clinical sign of HP, vs. 126/1,569 (8.0%) with 1–<2.0 mg/dl, 113/1,229 (9.2%) with 2.0–<2.5 mg/dl and 411/4,032 (10.2%) with ≥2.5 mg/dl. Among subjects with PO4 <2.5 mg/dl, serious cardiac disorders classified as potentially related to HP occurred in 14 FCM subjects (0.5%), 1 (0.7%) other IV iron, and 2 (4.4%) oral iron.

Conclusion

HP is recognised as a common adverse drug reaction with FCM as with several other IV iron preparations. This analysis shows that the transient decreases in PO4 levels were more frequent in patients receiving multiple and/or large doses of FCM but were not associated with an increased rate of potential signs/symptoms of HP.
P664 The impact of vedolizumab on extra-intestinal manifestations in inflammatory bowel disease patients: A real-life experience of a single-centre cohort
Authors: TRUYENS M , Geldof J , Dewitte G , Glorieus E , Varkas G , Elewaut D , Lobaton Ortega T
Published: January 2020

Background

Vedolizumab (VDZ), a gut-specific anti-integrin, is approved as a treatment for moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Extra-intestinal manifestations (EIMs) are frequently associated with inflammatory bowel disease (IBD). However, the effect of VDZ on EIMs remains unknown. The aim of the current study was to describe the prevalence of EIMs in IBD patients at VDZ initiation, the evolution during continued treatment as well as the occurrence of new EIMs.

Methods

A single-centre study was performed in IBD patients who were started on VDZ between May 2010 and February 2019. Retrospectively, the physician-reported EIMs and intestinal disease activity (clinical and endoscopic) were assessed at baseline, 6 months and 1 year after the start of VDZ.

Results

The cohort consisted of 134 patients, including 77 CD patients, 56 UC patients and 1 patient with unclassified IBD. At VDZ initiation EIMs were assessed in 127 patients and 17.3% had ≥ 1 EIM: 9 hepatic EIMs (2 patients with toxic hepatitis, 2 with autoimmune hepatitis and 5 with PSC), 7 arthropathies (6 patients with axial spondyloarthropathy and 1 with peripheral arthritis), 3 non-further specified axial or peripheral arthralgias and 3 cutaneous EIMs (urticaria, psoriasis and erythema nodosum). Clinical evolution of the EIMs is reported in Table 1, assessment of intestinal disease activity in Table 2. During follow-up, 23 new EIMs were seen, mainly arthralgia, which was often transient. VDZ was stopped in 39/130 (30%) patients due to active intestinal disease in 32 patients, patients’ choice (n = 1) or because of deep disease remission (n = 1). In five patients, VDZ was stopped because of insufficient control of EIM.

Conclusion

A good clinical intestinal response was observed. However, the clinical evolution of EIMs appears unaffected by the use of VDZ in our cohort. Prospective data are needed to confirm these results.
P667 Combined therapy of perianal fistulas with autologous adipose-derived stem cells
Authors: Surowiecka A , Łodyga M , Durlik M , Grażyna R
Published: January 2020

Background

Autologous adipose-derived stem cells (ADSCs) are pluripotent medical stimulatory cells. In damaged tissues, they activate regeneration by secretion of various growth factors, anti-inflammatory cytokines and migration factors. Autologous ADSCs are harvested from subcutaneous fat tissue.

Methods

The aim of our study was to create a protocol of combined surgical and biologic treatment of perianal fistulas followed with transfer of autologous ADSCs into fistulas. It was a prospective study. We selected patients diagnosed with Crohn’s disease with perianal fistulas, confirmed in MRI or transanal US, with no symptoms of abscess formation. In this protocol, we started from fistulas setoning. Afterwards, two courses of biologic agents were conducted. In the next step, autologous ADSCs were harvested from subcutaneous fat tissue and transferred to inactive fistulas. We used Arthrex®system to acquire ADSCs. Further courses with biologic agents followed the ADSCs transfer. To evaluate the outcomes we used Pikarky’s Perianal Crohn’s Disease Activity Index. A good resolution was defined as fistula closure, incomplete healing as partial resolution without complete closure and fistula reactivation as no resolution.

Results

In a preliminary study we collected data of 10 patients. The mean volume of lipoaspirate was 30 ml. The mean amount of ADSCs transferred was 4 ml. The mean operative time was 90 min. The early observation time varied from 1 to 3 months. In all cases, these were bifurcated complex and trans-sphincteric fistulas. There were no cases of no resolution. Early results were promising with almost all cases of good resolution. However, longer observation is required.

Conclusion

Autologous adipose-derived stem cells in combination with surgical setoning and biological agents are a good alternative for patients with perianal manifestation of Crohn’s disease.
P676 Faecal monitoring is useful in monitoring treatment response in anti-TNF-treated patients
Authors: Farkas K , Szántó K J , Kata D , Földesi I , Ferenci T , Rutka M , Pigniczki D , Bor R , Fábián A , Szepes Z , Nagy F , Molnár T
Published: January 2020

Background

Faecal drug concentration is not routinely measured as per therapeutic drug monitoring strategies in inflammatory bowel disease (IBD) patients receiving anti-TNF therapy. However, our previous research work suggested the importance of faecal drug monitoring of anti-TNF agents since active disease may be present in spite of normal serum anti-TNF levels. The aim of the present study was to examine the correlation between faecal calprotectin and faecal infliximab (IFX) concentration and to evaluate the cut-off value of faecal drug concentration in the respect of faecal calprotectin in patients treated with maintenance IFX therapy.

Methods

Consecutive patients with IBD receiving maintenance IFX therapy at 1st Department of Medicine, University of Szeged were enrolled in the present study. Faecal samples were obtained before the subsequent IFX infusion. Faecal calprotectin and IFX concentrations were determined with ELISA. The correlation between faecal calprotectin and faecal IFX concentration was statistically assessed.

Results

Sixty-seven IBD patients were enrolled. Female/male ratio was 49%–51%. Sixty-five point six% of the patients were diagnosed with Crohn’s disease and 34.3% with ulcerative colitis. Mean disease duration was 14.9 years (SD 9.7) at the time of analysis. Mean duration of IFX therapy was 42.3 month (SD 31.6). Twenty-eight point three% of the patients received escalated IFX therapy. Mean faecal calprotectin concentration was 545.7 µg/g (SD 379.4 µg/g). Mean faecal IFX concentration was 1 ng/ml (SD 1.3). Faecal calprotectin and faecal IFX concentration showed significant correlation (r=0.37, p = 0.002). A cut-off value of faecal IFX level of 0.6 ng/ml was determined at faecal calprotectin concentration of 500 µg/g.

Conclusion

According to our results IFX is detectable in the faeces at a calprotectin concentration of 500 µg/g. The cut-off value for faecal IFX concentration proved to be 0.6 ng/ml. Simultaneous determination of faecal anti-TNF and faecal calprotectin concentration is supposed to have a higher benefit in the evaluation of response to IFX therapy.
P685 Healthcare resource use associated with ferric maltol and IV iron treatment for iron deficiency anaemia in patients with inflammatory bowel disease
Authors: Howaldt S , Jacob I , Sampson M , Akriche F
Published: January 2020

Background

Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD). IDA imposes a substantial economic burden on healthcare payers resulting primarily from increased medical costs and increased rates of hospital admission. Most guidelines recommend oral iron as first-line treatment, with IV iron if oral supplementation is ineffective or poorly tolerated. Intolerance to ferrous (Fe2+) oral iron is common in patients with IBD. Ferric maltol (FM), a stable oral complex of ferric (Fe3+) iron and maltol, is designed to reduce exposure to elemental iron and thus limit gastrointestinal damage. This analysis compares the Healthcare resource use (HCRU) associated with oral FM and IV ferric carboxymaltose (FCM) treatment.

Methods

Patients with IBD and IDA (haemoglobin [Hb] ≥8.0 g/dl and ≤11.0 g/dl for women or ≥8.0 g/dl and ≤12.0 g/dl for men, and ferritin <30 ng/ml or ferritin <100 ng/ml with transferrin saturation <20%) 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. The primary endpoint was Hb responder rate (proportion of patients achieving a ≥2 g/dl increase or normalisation of Hb at week 12); the margin for non-inferiority was 20%. HCRU was assessed based on the total costs of iron therapy (including drug costs and administration), and the number of hospital/outpatient visits during the initial 12-week study period. Costs of IV FCM and FM were applied to a German setting.

Results

250 patients were randomised: 125 to FM and 125 to IV FCM. The primary endpoint was not met. Mean (standard deviation; SD) total treatment costs per patient in the FM and IV FCM arms were €302.27 (€80.68) and €489.37 (€147.19) respectively. Eighty-seven per cent of FM patients were still receiving treatment at week 12, and 45% and 36% of IV FCM patients required a repeat course of IV iron at weeks 4 and 12, respectively. The mean (SD) number of hospital/outpatient visits during the study period for patients receiving IV FCM was 2.30 (0.88) and the total dose of IV FCM received was 1621 mg (491 mg).

Conclusion

Total per patient drug costs were approximately 1.6 times higher for treatment with IV FCM than FM. The total cost of IV FCM is not only influenced by the higher drug cost, but additional costs associated with IV administration which was required to be carried out in a hospital or outpatient setting. FM has no additional costs or resource use associated with administration and is, therefore, less of a burden on local healthcare systems. FM is associated with substantially lower HCRU than IV FCM, and may provide a cost-effective oral alternative to IV iron in patients with IBD.
P688 Effect of golimumab induction therapy on histologic disease profile in patients with moderate to severe ulcerative colitis: Results from the randomised, placebo-controlled Phase 3 PURSUIT-SC trial
Authors: Johansson T , Weinstein C , MEEHAN A , Tzontcheva A , Xu P , Marano C , de Hertogh G
Published: January 2020

Background

Histologic improvement is an emerging goal in ulcerative colitis (UC) management. We previously demonstrated in the 6-week, multicentre, randomised, placebo-controlled, double-blind Program of Ulcerative colitis Research Studies Utilising an Investigational Treatment [PURSUIT-SC] Phase 3 trial that SC induction therapy with the tumour necrosis factor-α inhibitor, golimumab (GLM), led to statistically significant and clinically meaningful improvements in the signs and symptoms of UC compared with placebo, including clinical remission, mucosal healing, and improved health-related QoL, in patients with moderate to severe active UC.1 In the present report, we explored the histologic effects of GLM induction therapy in PURSUIT-SC by examining data from a prespecified histology sub-study.

Methods

The Phase 3 PURSUIT-SC trial evaluated the safety and efficacy of induction therapy with GLM in 774 patients with moderate to severe UC disease activity (defined as Mayo scores of 6–12, including an endoscopic subscore of ≥ 2). Patients were randomised 1:1:1 to receive SC induction treatment with placebo at Weeks 0 and 2, GLM 200 mg at Week 0 followed by 100 mg at Week 2 (GLM 200–>100 mg), or GLM 400 mg at Week 0 followed by 200 mg at Week 2 (GLM 400–>200 mg). Rectal biopsies were collected during endoscopy at screening and Week 6 in those randomised patients who consented to participate in the histology sub-study (N=98). During the screening endoscopy, two adjacent biopsies were collected 15 to 20 cm beyond the anal verge in an area that was most representative of the inflammation observed. At Week 6, two additional biopsies were to be obtained from the same location biopsied at screening. Biopsies were graded using the Geboes Score (GS) by a single expert gastrointestinal histopathologist, who was blinded to subject, treatment and study visit. The GS comprises seven histologic grades assessing structural changes and inflammatory disease activity. Higher GS grade scores indicate more severe histologic disease.

Results

Evaluable biopsy data were available in 89 patients (placebo, n = 30; GLM 200–>100 mg, n = 30; GLM 400–>200 mg, n = 29). At Week 6, compared with placebo, treatment with GLM induction therapy led to a decrease in the proportion of biopsies with GS grade scores of > 1 and an increase in the proportion of biopsies with GS grade scores of ≤ 1, with the greatest improvements being observed in the GLM 400–>200 mg group (figure).

Conclusion

The findings of this exploratory histologic sub-study in the PURSUIT-SC trial suggest that GLM induction therapy led to an improvement in histologic disease activity compared with placebo in patients with moderate-to-severe UC.

Reference