bluuebunny/crossref_metadata_2025 huggingface dataset:
P558 Validation of the ‘IBD Disk’ in clinical practice
Authors: FERGUSON A , Ding N , Connell W , Williams J , Wright E , Kamm M , Thompson A , Lust M , Flanagan E , Basnayake C
Published: January 2020

Background

The inflammatory bowel disease (IBD) Disk is a tool that has been developed from the IBD Disability Index in order to objectively measure the degree of disability in patients suffering from IBD. It provides a visual representation of disability state, thereby increasing the ease of application in a clinical setting. Currently, it has not yet been validated in any population. Our primary aim was to hence validate the IBD Disk in a clinical setting.

Methods

40 patients were recruited from an outpatient setting in a tertiary centre in Australia. All patients completed four surveys, the IBD Disk, the IBD Disability Index (IBD-DI), the Hospital Anxiety and Depression Score (HADS) and the Shortened IBD Questionnaire (SIBDQ). Nineteen of these patients then elaborated on their answers in a semi-structured narrative interview based on the IBD Disk. After a consultation with a gastroenterologist, the treating doctors were also asked to fill out an IBD Disk based on their own perceptions of the participant’s degree of disability. The IBD Disk was assessed for its internal consistency, construct validity and factor structure. The qualitative data were analysed and coded using NVIVO and then associated to IBD Disk scores.

Results

Of the patients recruited 48% were female, 30% had ulcerative colitis and 52% were in clinical remission. Average IBD Disk score was 40.75. Our results suggest the IBD Disk is an internally consistent tool for clinical use when assessing disability (Cronbach’s Α = 0.888). This is supported by statistically significant differences in IBD Disk scores between patients in clinical remission and patients with active disease (p = 0.002). There is also a good correlation between the Patient-Reported IBD Disk scores and the IBD-DI scores (r = 0.864), Doctor Perceived IBD Disk scores (r = 0.794) and the HADS Depression score (r = 0.759). IBD Disk scores also negatively correlated with the Shortened IBD Questionnaire (r = −0.864). Qualitative data also correlate well thematically with IBD Disk scores. These results suggest an appropriate system for grading disability status via the IBD Disk is: 0–24 = no disability; 25–49 = mild disability; 50–74 = moderate disability; and, 75–100 = severe disability.

Conclusion

This study supports the use of the IBD Disk as a reliable and valid self-reporting tool in clinical situations. There is strong internal consistency, construct validity, factor structure and qualitative thematic association. However, more data are needed to further validate the IBD Disk. Most significantly though, the IBD Disk is likely to become a valuable tool for the practical assessment of disability in patients with IBD in the near future.
P569 The role of multidrug-resistant infections in IBD patients undergoing surgery
Authors: Colombo F , Lamperti G M B , Antinori S , Corbellino M , Maconi G , Ardizzone S , Foschi D , Sampietro G
Published: January 2020

Background

Inflammatory bowel diseases (IBD) patients are particularly vulnerable to an increased incidence of infections, due to both innate characteristics and prolonged pharmacological therapies as steroids, biologics and antibiotics. Very few data are available in the literature about multidrug-resistant (MDR) infections and previous studies have not taken into account the impact of the surgical treatment on infections. We focused on the identification of risk factors for the development of MDR infections in IBD patients undergoing surgical procedures, we investigated the involved microorganisms, and finally, we proceeded to a costs/complications analysis of the treatment.

Methods

472 consecutive, unselected IBD patients (285 Crohn’s disease and 187 ulcerative colitis) undergoing surgery from 2016 to 2018 in our Tertiary Care Centre were divided into three groups: MDR infections, antibiotics sensitive infections (no-MDR) and no infections.

Results

In 37 CD patients nutritional status (p < 0.0008), preoperative biologics (p < 0.008) and antibiotic therapy (p < 0.001), duration of surgical procedure (p < 0.0001) and preoperative hospitalisation length (p < 0.0001) were risks factors for MDR infection development. In 14 UC patients multidrug-resistant infection was related to age at surgery (p < 0.003), disease duration (p < 0.008), inflammatory/nutritional status (p < 0.04), preoperative antibiotic therapy (p < 0.04), and suture leakage (p < 0,01). In the MDR CD group Gram + cocci (54%) were the most implicated pathogens, with a prevalence of 19% of Enterococcus faecium; while in MDR UC patients Gram – bacilli (59%) were the most involved pathogens, with prevalence of Escherichia coli ESBL+ (47%). The antibiotic therapy cost for the CD group was higher in MDR (3249 €) and no-MDR (924 €) groups vs. non-infected patients (41€). In UC we found higher cost only in the MDR group (1408€ vs. 33€).

Conclusion

Preoperative risk factors involved in the development of MDR infections in IBD patients undergoing surgery were identified. Some factors, such as nutritional status or preoperative antibiotic therapy, were found to be common between CD and UC patients, while some others were found to be specific for UC or CD. Some of these elements appear to be non-modifiable, while some others are part of the multidisciplinary approach, for which further studies are needed to improve the preoperative ‘patient optimisation’ in order to reduce surgical complications.
P571 Self-Medication with steroids in ulcerative colitis: Results of a patient survey
Authors: Mesonero Gismero F , Rodriguez-Lago I , Cañas M , Claudia S , Saldaña R , Feo-Lucas L , Fernandez S , Cea-Calvo L , Juliá B
Published: January 2020

Background

Medical treatment of mild-to-moderate flares of ulcerative colitis (UC) is based on topical and oral mesalazine, steroids or a combination of both. Sometimes self-medication with any of them can occur during a flare and it could interfere with clinical practice. Our aim was to assess the prevalence of self-medication with steroids in UC-patients and the reasons for this behaviour.

Methods

An anonymous cross-sectional survey was developed by representatives of the Spanish working group on Crohn’s disease and UC (GETECCU), the Spanish nursing working group on Inflammatory bowel disease (IBD) (GETEII) and the Spanish associations of patients with CD and UC (ACCU). A link to the online survey was distributed to adult UC patients through 50 Spanish IBD units as well as in the ACCU webpage. Participants voluntarily answered to the survey based on their own experiences.

Results

A total of 546 patients were included, 61% women, mean age 40 years old. Half of them (51%) were followed-up by IBD specialists, while 47% by general gastroenterologists. Thirty-six (6.6%) patients self-medicated with steroids. The main reasons to self-medicate with steroids were the need for quick relief of symptoms (n = 20, 56%), fear of worsening (n = 17, 47%) and difficulty for getting a medical appointment or being previously prescribed by the doctor (n = 9, 25%, both). Sixty-four per cent of them self-medicate once per year, while 8% self-medicate more than three times per year. Of these patients, 175 (32%) reported that self-medication lasted less than one month, while in 9 (18%) lasted for more than 3 months. Factors related to self-medication with steroids were the increased number of flares (p < 0.001), living with someone who uses oral steroids (p = 0.04), keeping the steroids left after finishing the treatment (p < 0.001), and prescription of corticosteroids in case of worsening by the primary care doctor (p = 0.02). Self-medication was less frequent in those patients who were attended by an IBD specialist (11, 3%), compared of those followed by an internal medicine physician (2, 33%), (p = 0.007), or by a general gastroenterologist (n = 23, 9%), (p = 0.02). Multivariate analysis showed that a higher number of flares [OR 7 (95% CI: 1–32), p < 0.001] and being attended by a general gastroenterologist [OR 0.08 (95% CI=0.01–0.5), p = 0.007] were both associated with a greater frequency of self-medication.

Conclusion

Self-medication with steroids is not a common practice in patients with UC from Spain. However, there is still room for improvement in clinical practice. Characteristics of the healthcare system and the disease may influence the rate of self-medication in UC patients.

This project was endorsed by GETECCU, GETEII, ACCU and funded by MSD Spain.
P578 Inter-observer agreement of an expert panel for gastrointestinal ultrasound in ulcerative colitis
Authors: de Voogd F , Wilkens R , Gecse K , Allocca M , Novak K , Lu C , D’Haens G , Maaser C
Published: January 2020

Background

Gastrointestinal ultrasound (GIUS) is increasingly performed in inflammatory bowel disease to assess disease activity and treatment response. It is promising as an effective point-of-care imaging tool since it correlates well with endoscopy and other cross-sectional imaging modalities. Previous studies showed moderate to substantial interobserver agreement in Crohn’s disease. However, in ulcerative colitis (UC) inter-observer agreement for GIUS has not yet been evaluated. Therefore, we conducted a study to assess inter-observer agreement in UC.

Methods

Thirty patients with UC (five with clinically quiescent and 25 with active disease) were included in this study. Cine-loops were recorded for the sigmoid colon (SC) in a longitudinal and cross-sectional axis in B-mode and in colour Doppler mode. Cine-loops were scored by five independent raters blinded for clinical disease activity. The cine-loops were scored for bowel wall thickness (BWT), Doppler activity (0=no activity, 1=small spots limited to the bowel wall, 2=long stretches within the bowel wall, 3=long stretches within and outside of the bowel wall), inflammatory fat, bowel wall stratification, loss of haustration and lymph nodes (present or absent). The intraclass correlation coefficient was used for the assessment of bowel wall thickness. Fleiss’ kappa was used for all nominal variables and weighted Cohen’s kappa was used for all ordinal variables.

Results

Inter-observer agreement was good for bowel wall thickness (ICC: 0.7, 95% CI: 0.51–0.83, p < 0.0001) [1] and moderate for Doppler signal (k=0.57, 95% CI: 0.37–0.77, p < 0.0001) [2]. When Doppler signal was interpreted as absent (0) or present (1–3) the observed agreement was almost perfect (k=0.81, 95% CI: 0.69–0.92). For inflammatory fat the observed agreement was moderate (k=0.42, 95% CI: 0.29–0.58, p < 0.0001). Inter-observer agreement was fair for the presence of lymph nodes (k=0.35, 95% CI:0.20–0.49, p < 0.0001) and loss of stratification (k=0.22 95% CI: 0.09–0.35, p < 0.001). Agreement was slight for loss of haustrations (k=0.15, 95% CI: 0.00–0.29, p = 0.046).

Conclusion

GIUS is a reliable imaging modality with good to moderate interobserver agreement for BWT, vascularisation and fatty wrapping in UC. These ultrasonographic parameters are important features to distinguish active from quiescent disease.

References
P581 Allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulas in Crohn’s disease: First real-life experiences
Authors: Schreiner P O , Biedermann L , Rogler G , Turina M , Cabalzar D
Published: January 2020

Background

Since treatment of perianal fistulas in patients with Crohn’s disease (CD) has low durable fistula closure rates even with optimal medical and surgical therapy, new therapies are needed. According to a pivotal phase 3 study program, darvadstrocel, a mesenchymal stem cell therapy, appears to be a promising new treatment option after failure or incomplete response to biologics and immunosuppressive agents. However, until now, no data on the real-life efficacy of darvadstrocel is available.

Methods

A total of 7 CD patients with complex perianal fistulas without luminal disease were treated with local injection of 120 million allogenic adipose-derived stem cells at our academic tertiary referral centre on an outpatient basis. MRI and fistula conditioning with seton loop placement were performed at least 6 weeks pre-operatively. Furthermore, CD remission was confirmed endoscopically in advance.

Results

The mean age of patients was 39.4 years, 86% were male and 29% smokers. The mean duration of fistula manifestation was 8.1 years. All patients (except one treated with tacrolimus) had previously received anti-TNF treatment without fistula healing. One patient had CD of an ileoanal pouch following restorative proctocolectomy. Postoperatively, the secretion from the wounds stopped after a few days and in 2 patients clinically fistula healing occurred already after 4 weeks. In 3 patients the fistulas healed after 6 weeks. One patient developed repeated abscesses without fistula healing. Another patient showed improvement of symptoms but without healing of the fistula at 8 weeks. Interestingly, symptomatic CMV viremia occurred two weeks after darvadstrocel injection in one patient, but his two fistulas healed.

Conclusion

Our initial experience of seven patients treated with darvadstrocel for perianal CD fistulas demonstrates promising results with rapid resolution of local complaints and full clinical healing in five patients until now. Taken together, darvadstrocel appears to be a promising therapeutic option for the challenging group of patients suffering from complex perianal CD fistulas.
P587 Adalimumab in pediatric Crohn’s disease: A long-term multi-centre real-world experience
Authors: Lawrence S , Huynh H , El-Matary W , DeBruyn J , Carroll M , Wine E , Chan J , Jacobson K
Published: January 2020

Background

There is a paucity of data regarding long-term outcomes for adalimumab (ADA) in pediatric Crohn’s disease (CD). We describe the long-term effectiveness of ADA, in achieving clinical and biochemical remission in a Canadian multi-centre pediatric CD cohort. Moreover, we report the effects of prior anti-TNF exposure and use of a concomitant immunomodulator (IM) on durability of clinical and biochemical response. The primary outcome was 24-month corticosteroid (CS) free remission. Secondary objectives included biochemical and faecal calprotectin response over the study period.

Methods

Retrospective review of electronic records of all children aged 3–18 years with CD requiring ADA at 4 centres across Canada (Vancouver, Edmonton, Winnipeg and Calgary) between January 2005 and December 2017.

Results

One hundred and nine children (68% male; median age 13.07 [IQR 10.6–15.1]) with CD (L1 21.7%, L2 28.3%, L3 50%) were included with a median follow-up of 15.9 months [IQR 7.6–24]. Seventy-four patients (67.9%) were anti-tumour necrosis factor (TNF) naïve. Concomitant IM therapy was used in 51 (46.8%). CS free clinical remission at 24 months was observed in 45/66 (68%). Over time, the median PCDAI, CRP, ESR and faecal calprotectin significantly improved (Table 1). During follow-up, 36 (33%) patients discontinued ADA; 6 (5.5%) had primary non-response, 28 (25.7%) had secondary LOR and 2 (1.8%) had intolerance. At 24 months, clinical remission was achieved more frequently in patients who were Anti-TNF naïve (81% vs. 43.5% p 0.002). There was no significant difference in biochemical or faecal calprotectin outcomes between those who were bio-naive or experienced. There was no significant difference in the time to loss of response between those on monotherapy and combination therapy with an IM and ADA (HR 0.64 [95% CI 0.33–1.26] p0.2).

Conclusion

This study demonstrates that ADA is effective and durable in pediatric CD. Over 24 months, clinical, biochemical and faecal calprotectin improvement was seen. In our cohort, clinical response to ADA was greater in anti-TNF naïve compared with anti-TNF experienced patients; however,, biochemical and faecal calprotectin outcomes did not differ. ADA response appears durable with no significant difference in patients on monotherapy or combination therapy.
P591 Therapeutic management in inflammatory bowel disease: Differences in two IBD inception cohorts: 1991–93 and 2010–11 enrolled in the north-west of Spain
Authors: De Castro Parga M L , Hernández V , Sanroman L , Pineda J R , Figueira M , Martinez-Cadilla J , Pereira S , Rodriguez-Prada J I
Published: January 2020

Background

The treatment of IBD has dramatically changed in the last two decades, with the advent of immunosuppressive and biological drugs. The goal of therapy remains to achieve and maintain disease remission, diminishing disease outbreaks as well. Our aim was to show the changes in the therapy management of IBD between 1991 and 2011 at the first disease outbreak and during the first years.

Methods

Retrospective and descriptive study of two inception cohorts of IBD patients aged 15 years or more that were enrolled in the area of Vigo (north-west of Spain) in two European epidemiological studies: EC-IBD performed from 1991 to1993, and EpiCom performed in 2010 and 2011. First disease outbreak includes treatments employed in the first four months from diagnosis of IBD, We review the therapies that were used at 12, 24 and 36 months from These data, and the successive disease flares as well.

Results

Regarding the management of the first outbreak of UC, we found an increase in the use of topical 5-aminosalicylic acid (5-ASA) and a decrease of topical steroids (p = 0.001) in 2010–2011 cohort. Sulfasalazine was only used in 1991–1993 cohort, and immunosuppressive or biological drugs in 2010–2011 (p = 0.004). Neither ciclosporine nor surgical therapy was used in both cohorts. In the first outbreak of CD there was an increase in the utilisation of systemic steroids (p = 0,004) and a reduction in oral 5-ASA (p = 0,02)) in 2010–2011 cohort. The use of immunosuppressive or biological drugs was found only in 2010–2011 (Table 1). At 12, 24 and 36 months after diagnosis of IBD, more patients had received an immunosuppressive drug, or were in a higher therapeutic step in the 2010–2011 cohort, compared with 1991–93 cohort (p = 0,0001) both in CU and CD (Figure 1). There were no differences in the number of disease outbreaks suffered in these periods of time between both cohorts (Figure 2).

Conclusion

The progressive early use of immunosuppressive therapies at the initial outbreak of IBD, and during the first 3 years of disease is clearly demonstrated, although it was not related to a decrease in disease outbreaks.
P596 Risk of colorectal cancer and other malignancies in association with the use of thiopurines, tumour necrosis factor antagonists or mesalazine
Authors: Timeus S , Laoun R
Published: January 2020

Background

Mesalazine, thiopurines and TNF antagonists play an important role in management of inflammatory bowel disease (IBD). It is generally accepted that longstanding ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). In addition to colorectal cancer, there are data that suggest that IBD is also associated with an increased risk of extra-intestinal malignancies but the results are inconclusive. The evidence concerning the effects of mesalazine on the risk of CRC in IBD patients remains conflicting.

Methods

In this review, cancer-reported outcomes with IBD drugs reported to FAERS (USA) were extracted for adalimumab, infliximab, thiopurines and mesalazine and compared with all other 25’382 drugs in the database. The data were used to calculate reporting odds ratio (ROR) and 95% CI for CRC, lymphoma, Hodgkin’s disease and all cancers outcomes. A sub-analysis was conducted to include patients exposed to mesalazine alone without IBD co-medications.

Results

The databases contained approximately 17 million reports for all drugs of which 401’084 were for adalimumab, 121 562 for infliximab, 11’985 for mesalazine, and 25’286 for thiopurines. Of these, a total of 259 757 concerned cancer-related AEs associated with the drugs under consideration. All IBD drugs were associated with a positive ROR for CRC with infliximab presenting the highest point estimate 8.01 (CI 95% 7.48–8.59) and adalimumab the lowest 2.52 (CI 95% 2.35–2.69). Considering patients exposed to only mesalazine, this association remained positive at 2.39 (CI 95% 1.58–3.59). For lymphoma, all IBD drugs also showed a positive ROR where thiopurines were associated with the highest 7.25 (CI 95% 6.69–7.84) and mesalazine with the lowest 1.46 (CI 95% 1.14 -2.73) point estimate. With regards to patients only exposed to mesalazine, the association showed protective effect, 0.24 (CI 95% 0.13–0.47). For Hodgkin’s disease again all IBD drugs showed a positive ROR where thiopurines were associated with the highest 34.65 (CI 95% 28.88–41.59) and adalimumab with the lowest 4.98 (CI 95% 4.39 -5.65) point estimate. In patients only exposed to mesalazine, no association 0.66 (CI 95% 0.09–4.66) was observed. Considering all cancers only positive ROR were observed where infliximab was associated with the highest 7.31 (CI 95% 7.17–7.45) and mesalazine with the lowest 1.33 (CI 95% 1.17–1.51) point estimate. In patients only exposed to mesalazine, a protective effect 0.73 (CI 95% 0.61–0.88) was observed.

Conclusion

FAERS data showed an association between reported occurrence of cancer and the drugs under consideration. Considering patients only exposed to mesalazine the odds ratio was positive only for colorectal cancer but lower than all other IBD drugs.
P600 Vedolizumab dose optimisation: Findings from a Belgian registry
Authors: Louis E , Muls V , Bossuyt P , Colard A , Nakad A , Baert D , Mana F , Caenepeel P , Vanden Branden S , Vermeire S , D’Heygere F , Strubbe B , Cremer A , Coche J C , Setakhr V , Baert F , Vijverman A , Coenegrachts J L , Flamme F , Hantson A , Wijnen K , Piters E , Hantsbarger G , Dolin P
Published: January 2020

Background

Vedolizumab (VDZ) dose optimisation (DO), by interval shortening from 8-weekly (Q8W) to 4-weekly (Q4W) dosing, is used for patients with secondary loss of response. This report presents outcome data on patients receiving DO in real-world clinical practice in Belgium.

Methods

The Belgian VDZ Registry (ENcePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as Harvey–Bradshaw Index (HBI) <5 or partial Mayo Score (pMS) <2, and clinical response as a 2+ point improvement in pMS or a 3+ improvement in HBI.

Results

During a median follow-up of 19 months from enrolment, 57 (28%) patients (41 CD and 16 UC) received VDZ Q4W due to secondary loss of response. Q4W was mostly used in patients with CD or with prior anti-TNF therapy failure. The median starting point for Q4W dosing was 16 months after the start of VDZ (interquartile range (IQR) 8–27 months) and median duration of Q4W dosing was 4 months (IQR 2–8 months). After changing to Q4W dosing 44% achieved clinical remission, 3% clinical response, and 53% showed no improvement (Table 1).

Among the 17 patients with clinical remission/response on Q4W dosing, 53% de-escalated back to Q8W, and continued with Q8W for a median duration of 12 months, 23.5% remained on Q4W with clinical remission, and 23.5% eventually stopped VDZ due to loss of response. A limitation of this study is that it did not systematically collect data on DO prior to recruitment, hence the proportion of patients receiving DO may be higher than reported here.

Conclusion

These real-world data show DO plays an important role in management of UC and CD. In this study, 28% of patients received DO following the secondary loss of response to Q8W therapy. Forty-seven per cent of patients receiving Q4W subsequently returned to clinical remission or had a clinical response, and half of these patients successfully returned to Q8W VDZ therapy. Controlled studies are warranted, ideally blinded, using more objective endpoint to reveal the true success rate of dose-optimisation.
P606 Exclusive enteral nutrition with a polymeric diet is efficacious in inducing remission in adults with active Crohn’s disease
Authors: Kakkadasam Ramaswamy P , Mutsekwa R , Lan X , Chen Y , Angus R , Moattar H , Edwards J , Shukla D
Published: January 2020

Background

Exclusive Enteral nutrition (EEN) is not routinely used as induction therapy for adults with active Crohn’s disease (CD)due to limited adherence and palatability. The aim of this study was to assess the efficacy, tolerability and safety of EEN in adult patients with CD.

Methods

Retrospective analysis of data from patients with active CD who underwent induction therapy with EEN at a single centre from January 2018 to July 2019. All patients who completed at least 4 weeks of polymeric EEN diet were included in the final analysis. Primary Endpoint (PE) was steroid-free clinical remission (CDAI ≤150) or response (100 point decrease in CDAI) at the end of therapy. Secondary endpoint (SE) was achievement of biochemical remission (CRP <5 mg/l or Calprotectin <150 μg/g) at 8–10 weeks.

Results

Sixty-three patients were initiated on EEN, 50 patients who completed at least 4 weeks of EEN were included in the final analysis. Mean age was 42.4 years, 25 (50%) were females. Mean CDAI score at baseline was 260. Forty per cent of patients were on concurrent biologics and 66.6% were on concurrent immunomodulators. At the completion of EEN, 72% (36/50) of patients achieved PE (29 remission, 7 response). SE was achieved in 65.7% (23/35) of patients. EEN duration ≥ 6 weeks was more likely to achieve PE (75% vs. 55.5%, OR 2.7, P 0.01) and SE (71% vs. 25%, OR 7.3, P 0.001).EEN duration < 6 weeks and current smoking were less likely to achieve PE and SE. Patients with concomitant steroid use at baseline had PE of 77.7% (vs. 68.8% with EEN alone; OR 0.9, P 0.5), and SE of 66.6% (vs. 60.9% with EEN alone, OR 0.77, P 0.74). Disease location, behaviour, sex, disease duration, concurrent biologic use or concurrent immunomodulator use did not affect the PE or SE. Six patients reported adverse effects (3 nausea,2 diarrhoea,1 constipation). Male sex, ileal location, B2/B3 phenotype were more likely to complete a 6 week EEN course.

Conclusion

Polymeric EEN is well-tolerated, safe and efficacious in inducing remission in adults with active CD. EEN duration of ≥ 6 weeks has better outcomes. EEN alone or in combination with steroids induces remission in adult patients with active CD. Further controlled trials using polymeric EEN are necessary.
P617 Mesenchymal stromal cells of bone marrow reduce the risk of postoperative recurrence of Crohn’s disease
Authors: Knyazev O , Kagramanova A V , Lishchinskaya A , Parfenov A
Published: January 2020

Background

Crohn’s disease (CD) in the form of terminal ileitis occurs in approximately 1/3 of CD patients and is often complicated by the formation of ileum stricture or ileocecal valve. The operation of choice is resection of ileocecal Department with the formation of ileo of ascendants. Depending on the combination of risk factors, as well as on the effectiveness of previous anti-relapse therapy, patients after surgery should be stratified into groups with different risks of postoperative recurrence. The objective of the study was to evaluate the effectiveness of mesenchymal stem/stromal cells (MS/SC) as anti-relapse therapy in patients with low-risk CD after ileocecal resection.

Methods

Thirty-six patients with CD in the form of terminal ileitis with a stricture of the terminal ileum with signs of intestinal obstruction after the ineffectiveness of the course of conservative therapy (application of GCS) underwent resection of the ileocecal Department with the formation of ileo-ascendoanastomosis. All patients had a low risk of postoperative recurrence of Crohn’s disease. However, the first group of patients aged 19 to 58 years (Me-29) (n = 18) received MS/SC. The second group of patients aged 20 to 68 years (Me-36) (n = 18) received mesalazine 4 gr/day. The follow-up period was 60 months. The monitoring was carried out by endoscopic picture and/or CT-enterography, C-RP level, faecal calprotectin (FCP). Average baseline CRP in the first group was 29.5 ± 3.2 mg/l, in the second – to 27.75 ± 3.0 (p = 0.73), the level of the FCP in the first group 1019.4 ± 97.2 mkg/g, in the second – 998.8±127.3 mkg/g (p = 0,9).

Results

After 24 months in the first group of patients the average level of C-RP was 9.5 ± 1.9 mg/l, in the second group 17.8 ± 3.3 mg/l (p = 0.027). The level of the FCP in the first group 98.0 ± 12.1 mkg/g, in the second 121.7 ± 14.2 mkg/g (p = 0.27). After 24 months of follow-up, 1 (5.5%) patient from the first group (n = 18) had a relapse that required the appointment of GCS. In the second group, relapse occurred in 4 (22.2%) patients out of 18 (RR 0.25; 95% CI 0.031–2.025; p = 0.15). After 60 months in the first group of patients, the average level of C-RP was 10.76 ± 2.1 mg/l, in the second group 19.2 ± 3.5 mg/l (p = 0.039). The level of the FCP in the first group of 100.4 ± 13.7 per mkg/g, in the second 191.7 ± 24.9 mkg /g (p = 0.002). After 60 months of follow-up, 1 (5.5%) patients from the first group had a relapse. In the second group, relapse occurred in 8 (22.2%) patients out of 18 (RR 0.125; 95% CI 0.017–0.9; p = 0.008).

Conclusion

The use of mesenchymal stem/stromal cells (MS/SC) as anti-relapse therapy in patients with low-risk CD after ileocecal resection significantly reduces the risk of postoperative recurrence of CD.
P619 Efficacy of zinc acetate hydrate administration for zinc deficiency in patients with inflammatory bowel disease: a multi-centre retrospective study
Authors: Sakurai K , Katsurada T , Otagiri S , Yamanashi K , Nagashima K , Onishi R , Nishimura H , Ito T , Furukawa S , Maemoto A , Sakamoto N
Published: January 2020

Background

Zinc deficiency is common in patients with inflammatory bowel disease (IBD), and the frequency is about 42.1% in Crohn’s disease (CD) and 38.5% in ulcerative colitis (UC). Patients with IBD with serum zinc deficiency are more likely to have adverse disease-specific outcomes. However, there are few studies about the effect of administering zinc preparations in IBD patients with zinc deficiency. The purpose of this study was to investigate the efficacy of zinc acetate hydrate (Nobelzin®︎) preparation for patients with IBD with zinc deficiency.

Methods

56 IBD patients who were treated with Nobelzin®︎ for zinc deficiency from March 2017 to November 2019 were analyzed. We conducted a multicenter retrospective observational study to investigate changes in serum zinc concentration or changes in disease activity before and after administration and their contributing factors.

Results

Among 56 cases, 4 cases were excluded due to self-interruption of internal use, and 52 cases (39 cases of CD, 13 cases of UC) were included. The median observation period was 27.5 (13–47) weeks, the median serum zinc concentration before administration was 58.5 (50.8–65.3) μg/dl, and the average of starting dose of Nobelzin®︎ was 67.8±31.1 mg/day. Nobelzin®︎ administration normalised serum zinc concentration(Zn ≥80 μg/dl) in 94.2 % (49/52) of patients. The median administration period required for normalisation of serum zinc concentration was 5 (3–8) weeks. In the group of CD patients who achieved zinc normalisation, the median CDAI score significantly improved after the normalisation from 171.5 to 129.5 (p < 0.001). Similarly, the partial Mayo score in the same group of UC significantly improved after the normalisation (p = 0.035). There were 77.6 % patients who did not have additional treatment without Nobelzin®︎ administration until zinc was normalised. In CD patients of this group, the median CDAI score significantly improved after the normalisation from 152 to 120 (p = 0.029). All 3 cases in which zinc normalisation was not achieved within the observation period were CD cases, and they had a history of multiple surgeries, changes in biologics, or a long medical history. In one patient, side effects of Nobelzin®︎ administration were observed and these were abdominal discomfort and nausea. During the observation period, serum copper concentration was measured in 27 patients after administration of Nobelzin®︎, and one patient presented with copper deficiency.

Conclusion

Our findings show that administration of zinc acetate hydrate preparations may be effective in improving zinc deficiency and contribute to improve disease activity in IBD patients with zinc deficiency.
P620 Maintenance of clinical remission with SB5 biosimilar after switch from adalimumab originator: Real-life experience of a tertiary referral centre
Authors: Dragoni G , Pieraccini A , Bagnoli S , Caini S , Macrì G , Rogai F , Milani S , Galli A , Milla M
Published: January 2020

Background

Adalimumab (ADM) biosimilars have been demonstrated as safe and effective as the ‘originator’ in trials for other autoimmune disorders, but real-life evidence in inflammatory bowel diseases (IBD) is lacking. The aim of the study was to demonstrate maintenance of clinical remission (CR) after switch from ADM ‘originator’ to biosimilar SB5.

Methods

Data were retrospectively collected from November 2018 to September 2019. All IBD patients in CR after at least 6 months of ‘originator’ and switched to SB5 were included. The primary outcomes were maintenance of CR at 6 months after switch (defined as Partial Mayo Score 0–1 for ulcerative colitis and Harvey–Bradshaw Index ≤4 for Crohn’s disease) and overall comparable safety. A historical cohort of patients treated only with the ‘originator’ was included for comparison, using a Cox regression model with a time-varying covariate.

Results

In total, 96 patients were included. Baseline characteristics of the cohort are reported in Table 1. Maintenance of CR after 6 months of switch was reported in 89/96 (92.7%) patients. Levels of C-reactive protein (CRP) significantly increased over time from baseline to 6 months (from 2.67 ± 2.61 to 4.98 ± 5.81 mg/dl, p = 0.03), but no difference between the two time points was found when considering a relevant flare only for CRP above the lab cut-off (5 mg/dl). A comparison of CR persistence over time between ‘originator’ cohort and SB5 ‘switching’ cohort did not show any statistical difference (Hazard Ratio 1.07, 95% CI 0.57 – 2.01). With regard to adverse events, SB5 showed an overall safety profile, with only 2/96 (2.1%) patients interrupting the treatment due to anti-TNF-induced psoriasis. In 42/96 (43.8%) of patients, at least one injection site reaction was reported; only in one case a re-switch to ‘originator’ was needed for local intolerance.

Conclusion

SB5 is safe and effective in maintaining CR after switching from the ‘originator’. Injection site reaction is a frequent but usually manageable side effect. Larger multi-centre cohort and endoscopic assessment are needed to confirm the initial findings.
P625 Kinetics and outcomes of transmural healing in patients with Crohn’s disease treated with anti-TNF therapy
Authors: Pastaud C , Hordonneau C , Lambert C , Vignette J , Pereira B , Buisson A
Published: January 2020

Background

Transmural healing is a promising target in Crohns’ disease (CD) but remains poorly investigated. We aimed to evaluate the kinetics of transmural healing in CD treated with anti-TNF and to assess whether transmural healing is associated with more favourable outcomes.

Methods

It was a retrospective study from an MRI database of 449 patients performing MRI for luminal CD. Inclusion criteria were: CD patients older than 18 years-old receiving anti-TNF therapy, with an objective sign of inflammation on morphological evaluation (endoscopy or cross-sectional imaging), who underwent at least one MRI examination to assess therapeutic efficacy and follow-up longer than 6 months. Patients treated with anti-TNF agents for treat isolated perianal lesions were excluded. We used a statistical model based on imputation according to the last observation carry forward and clinical relevance. Each CD MRI lesions were then assessed every month during the first year. For segmental analysis, we used a division into six segments (jejunum, ileum, right colon, transverse colon, left/sigmoid colon and rectum). Transmural healing was defined as no MRI lesions.

Results

Overall, 148 patients were included. Among them, 81 were female (55.7%), 43 (34.4%) were current smokers and 56 (37.8%) had prior intestinal resection. The median CD duration at baseline was 7.6 years [1.4–15.2]. At baseline, 80 patients (54.4%) were anti-TNF-naïve. During the study, 69 patients (46.6%) were treated with infliximab, 77 patients (52%) received adalimumab while only 2 patients (1.4%) were treated with golimumab A combination therapy with thiopurines or methotrexate was found in 108 patients (74.0%) and 30 patients (20.3%) received concomitant steroids at the time of inclusion. Among 148 patients and 303 MRIs, 387 segments were analyzed. The rate of transmural healing was optimal between M6 and M8 and plateaued from the eighth month. The kinetics of transmural healing in CD patients treated with anti-TNF agents is presented in Figure 1.

Among the 148 patients with CD, 29 patients underwent intestinal resection (19.6%), 32 patients (21.6%) required an hospitalisation due to CD and 61 patients (41.2%) discontinued anti-TNF for therapeutic failure. In multivariable analyses, transmural healing was associated with decreased risk of surgery (HR=0.19[0.04–0.86];p = 0.03) and anti-TNF discontinuation (HR=0.42 [0.21–0.84]; p = 0.01) while we observed a trend for decrease risk of CD-related hospitalisation (HR=0.56[0.22–1.43];p = 0.23).

Conclusion

Transmural healing, which is associated with better outcomes in CD, can be achieved in more than half of patients with CD. The best time to assess transmural healing was between 6 to 8 months after starting anti-TNF therapy.
P631 Predictors of vedolizumab treatment persistence in bio-naïve ulcerative colitis patients
Authors: Ritter T E , Sarles H E , Mehta S A , Van Anglen L J
Published: January 2020

Background

Vedolizumab (VDZ) is increasingly being positioned as first-line biologic therapy for the treatment of inflammatory bowel disease (IBD) in adults, particularly for ulcerative colitis (UC). Identifying a certain subset of bio-naïve UC patients most likely to benefit from VDZ and remain on long-term maintenance therapy is important. The purpose of this study was to evaluate predictors of VDZ treatment persistence at 12 months in real-world clinical practice.

Methods

We performed a retrospective review of all adult (≥18 years) bio-naïve UC patients started on VDZ at US gastroenterology physician office infusion centres. Data collection included baseline demographics, VDZ therapy, concomitant oral agents, disease severity, and disease activity scores using the partial Mayo score (pMayo). Disease severity was characterised by prior IBD-related surgery and IBD-related healthcare resource utilisation within 1 year of VDZ initiation. Clinical response was assessed at baseline, 6 weeks, and 14 weeks and defined as a pMayo reduction of ≥2 points. Patients were divided into two cohorts, those persisting on VDZ at 12 months and those discontinuing VDZ prior to 12 months. Logistic regression analysis was used to determine predictors associated with persistence.

Results

A total of 141 UC patients receiving VDZ as first-line biologic therapy were identified: mean age 44 ± 14.5 years, male gender 82 (58%), median disease duration 5.5 (IQR 1.6–13.3) years. VDZ treatment persistence at 12 months was observed in 102 (72%) patients (Figure 1). The remaining 39 patients discontinued VDZ within the first 12 months. Amongst those who discontinued VDZ, reasons included lack or loss of response in 35 (90%), antibodies in 3 (8%), and intolerance in 1 (3%). In the logistic regression analysis, the only factor associated with VDZ treatment persistence was clinical response at 14 weeks (OR 6.5 [95% CI 2.9–14.5]). No other variables (age, gender, smoking status, disease duration, concomitant oral agents, or severity of illness) influenced persistence at 12 months.

Conclusion

Almost three-fourths of bio-naïve UC patients treated with vedolizumab experienced treatment persistence at 12 months. Our data suggest that response to induction may be used to predict those who will remain on maintenance therapy.
P632 Vedolizumab dose escalation in patients with inflammatory bowel disease experiencing loss of response: A systematic review and meta-analysis of real-world evidence
Authors: Varghese D , Patel D , Martin S , Luo M , Ursos L , Lirio R , Wang S
Published: January 2020

Background

Moderately to severely active inflammatory bowel disease (IBD), featured as Crohn’s disease (CD) and ulcerative colitis (UC) collectively, is commonly treated with biologic therapies. A proportion of patients experience loss of response (LOR) over time. The approved dose of vedolizumab (VDZ), 300 mg every 8-week (Q8W), is known to be safe and effective in the treatment of UC and CD. In an open-label long-term safety study (GEMINI LTS), patients who experienced LOR during maintenance benefitted from dose escalation to an every 4-week (Q4W) regimen. Clinical response and remission were regained in 41% and 28% respectively in UC patients (N=32) and 47% and 32% respectively in CD patients (N=57) through 52 weeks of escalated dosing. The aim of this study was to conduct a meta-analysis of existing real-world evidences to evaluate the effectiveness of VDZ dose escalation to Q4W in IBD patients experiencing LOR to Q8W dosing.

Methods

A systematic literature review was performed using PubMed and Embase databases for articles and conference abstracts from January 2014 through January 2019 for real-world studies reporting clinical outcomes to VDZ dose-escalation among adult patients with UC or CD. Relevant congresses were also screened for accepted abstracts through June 2019. Summary estimates for the proportion of regained response and remission were synthesised under a random effect model (given considerable heterogeneity as measured by I2 statistic) using the DerSimonian-Laird approach.

Results

The search yielded a total of 842 citations from the databases and 12 citations from hand searching. Of these, 5 full-text articles and 1 abstract were included in the meta-analysis. The 6 study cohorts included a total of 297 patients with IBD. The random-effects pooled regained response rate from the 6 studies was 56.5% (95% confidence interval [CI], 44.9%–67.5%) within 52 weeks (figure). Subgroup analysis showed a regained response rate of 62.7% (95% CI,52.8%–71.6%) when measured within 30 weeks vs. 50.2% (95% CI, 38.3%–62.2%) when measured after 30 weeks. Of the 6 studies, 2 reported remission rates that were included in the pooled analysis among 203 patients experiencing LOR. The random-effects pooled estimate of recaptured remission was 42.4% (95% CI, 25.1%–61.8%) within 52 weeks.

Conclusion

More than half of IBD patients who experienced LOR during maintenance phase after initial response to VDZ Q8W dosing regained response on the escalated Q4W regimen within 52 weeks. These findings and the data from the open-label clinical trial support the benefits of VDZ dose escalation among patients experiencing LOR to Q8W dosing.
P636 Changes in peripheral helper T-cell was associated with sustained response to a 12-week EEN therapy in active Crohn’s disease: A pilot study
Authors: Guo K , Gong W , Zheng T , Li W , Fang M , Xie H , Wang G , Gu G
Published: January 2020

Background

Exclusive enteral nutrition (EEN) is an effective solution in inducing remission in patients with active Crohn’s disease (CD). However, the underlying mechanism is not completely clear. Evidence is accumulating that potential beneficial in regulating the inflammatory immune response of CD, a chronic inflammation dominated by pathogenic TH1 and TH17 cells. We investigated the relationship between changes of circulating helper T cell and clinical response in CD during treatment with EEN.

Methods

Sixty-eight adults with active CD treated successfully with EEN were prospectively study. Peripheral helper T cell (Th1, Th2, Th17 and Treg) were evaluated using flow cytometry from baseline to Weeks 4 and 12. We also determine the prognostic value of the ratio of delta Th cell at Weeks 4 to baseline (△Th w4-w0) in patients receiving EEN. Mucosal healing was assessed with endoscopy at baseline and Week 12.

Results

Treatment with EEN significantly improved disease activity scores and laboratory biochemical markers measured at Weeks 4 and 12 compared with baseline (p < 0.05 and p < 0.001). After the initiate of EEN, we observe early modulating effects of EEN on helper T-cell percentages, especially in Treg cell. Furthermore, we found a long-term increase in Treg cell percentages in patients who sustained response to EEN during follow-up. Mean increases of Treg cell from baseline in patients sustained response were significantly larger in a patient who loss of response (p < 0.01). Receiver operating characteristic (ROC) analysis to predict sustained response at 12 weeks showed area under the curve (95% confidence interval) of Treg cell at 4 weeks (Treg w4) and change in Treg cell from baseline to 4 weeks (△Treg w4-w0) to be 0.75 (0.56–0.87) and 0.84 (0.63–0.92), respectively. Logistic regression analysis confirmed that △Treg w4-w0 (31.8%) after the EEN was significant independent predictive factors for sustained response. Mucosal healing at Week 12 was achieved by 97.1% of patients who long-term increase of Treg cell compared with 51.5% of those temporary raise (p < 0.001).

Conclusion

EEN resulted in rapid improvements in laboratory markers and early increase in Th subsets percentages. Early increase of Treg cell predicts a sustained response to EEN and mucosal healing. Monitoring of Treg cell may help predicts the sustained clinical response and course.