bluuebunny/crossref_metadata_2025 huggingface dataset:
P430 Feasibility and reliability of gastrointestinal ultrasound in pregnant inflammatory bowel disease patients
Authors: de Voogd F , Joshi H , Van Wassenaer E , D’Haens G , Gecse K
Published: January 2020

Background

Disease activity during pregnancy in women with inflammatory bowel disease (IBD) is associated with miscarriage, preterm delivery and low birth weight. Monitoring disease activity throughout the pregnancy is therefore important. Gastrointestinal ultrasound (GIUS) has a high potential as a point-of-care tool for monitoring disease activity in IBD as it has been shown to correlate well with endoscopy and magnetic resonance imaging. However, data are scarce on the use of GIUS in IBD throughout pregnancy. The aim of this prospective study is to determine the feasibility and reliability of GIUS in pregnant IBD patients.

Methods

Patients were included when visiting the outpatient IBD pregnancy clinic. At each trimester, clinical and biochemical disease activity was evaluated and GIUS was performed. Feasibility was assessed by the ability to visualise each bowel segment (terminal ileum (TI), ascending (AC), transverse (TC), descending (DC) and sigmoid colon (SC)). Reliability was evaluated by using clinical and biochemical disease activity as a gold standard. This was defined as a Harvey–Bradshaw Index ≥4 in Crohn’s disease (CD) or a Simple Clinical Colitis Activity Index ≥5 in ulcerative colitis and a faecal calprotectin (FCP)³ 250 mg/g. Bowel wall thickness (BWT) of > 3 mm in the colon and > 2mm in the terminal ileum was considered as signs of active inflammation on ultrasound. A Mann–Whitney U-test and chi-square were used for statistical analysis.

Results

Thirty-two IBD patients (54% CD) were studied. Both a GIUS and FCP was available in 18, 11 and 6 patients for the first, second and third trimester, respectively. Eleven of 32 (34%) patients had clinically active disease at least at one time point during the pregnancy. Table 1 shows the visibility per segment. When the active disease was defined as an FCP ≥ 250 mg/g, GIUS could distinguish active from the non-active disease in the first, second and third trimester with a sensitivity of 80%, 75% and 75% and specificity of 85%, 86% and 100%, respectively.

FCP levels were significantly higher in patients with an active disease on GIUS regardless of the trimester (mean 1095.5 ± 1453.8 mg/g vs. 265.25 ± 649.8 mg/g, p < 0.0001).

Conclusion

GIUS is accurate to distinguish active from the quiescent disease in pregnancy. Feasibility to visualise the TI and the SC decreased during the second and third trimester, although active disease could still be detected. Consequently, GIUS is feasible and reliable to assess disease activity throughout pregnancy in IBD.
P432 Effects and safety of a colon-long absorbing budesonide product in patients with mild to moderate ulcerative colitis
Authors: Pigniczki D , Szántó K , Rutka M , Farkas K , Bálint A , Bor R , Fábián A , Szepes Z , Molnár T
Published: January 2020

Background

Budesonide is an oral corticosteroid, which is widely used in moderate-to-severe ulcerative colitis (UC) to obtain and maintain remission in those cases, where 5-aminosalicylic-acid was ineffective. Unlike previous forms of budesonide absorbing from the ileal and ascending colon region, the new-generation budesonide-MMX contains a formula, that allows absorption throughout the whole colon, and therefore in the whole potentially inflamed area in UC. We aimed to evaluate the effects and safety of budesonide-MMX in our UC patients who meet the above mentioned therapeutic demands in a real-life study.

Methods

We enrolled 22 patients with mild to severe UC in this single-centre prospective study until August of 2019. Patients received 9 mg oral budesonide-MMX once daily until 8 weeks. Laboratory parameters (cholesterol, triglyceride, CRP) and serum hormone levels (parathormone [PTH], dehydroepiandrosterone [DHEA] and cortisol) were monitored before and after the 8-week therapy to follow metabolic and hormonal changes. During these visits, body composition analysis was also performed with InBody 770 machine to observe the adverse steroid effects of budesonide-MMX in respect of body fat mass, body mass index, protein content of the body and bone mineral content. Disease activity was followed by the partial Mayo (pMayo) score. Statistical analysis was performed by paired t-test and Wilcoxon signed-rank test with SigmaPlot 1.25.

Results

The total of 22 patients (age: 44.4 ± 15.1 years, 6 male and 16 female patients) had received the 2-month budesonide-MMX therapy (2.0 ± 0.3 months). Mean disease duration was 8.3 years. By the end of follow-up, 15 (68.2%) patients experienced remission and 7 patients (31.8%) were primary non-responders. The disease activity decreased significantly from the mean of 3.95 to 1.64 (p < 0.001). No significant changes were observable in case of any body composition analysis parameter. Regarding the laboratory parameters, serum cholesterin level showed a significant increase (p < 0.001), while triglyceride and CRP showed did not show significant changes. Serum cortisol levels were elevated (p < 0.001), while PTH and DHEA showed no significant decrease. Only two patients experienced side effects: one of them hypertonia, headache and acnes, while the other patient experienced mild diarrhoea. One patient had a relapse during the treatment.

Conclusion

In our study, budesonide-MMX proved to be safe by bringing up a low number of side effects, while more than two-thirds of the patients could reach remission with this short-term therapy. Hormonal changes were not mentionable, although the drug’s effects on serum lipid content have to be examined further.
P444 The impact of azathioprine on inflammatory bowel disease patients’ overall health-related quality of life: a single-centre retrospective cohort study
Authors: ALRUTHIA Y , Alsharif W , Almuaythir G , Alrasheed H , Alharbi O , Azzam N , Almadi M , Saeed M , HajkhderMullaissa B , Aljebreen A
Published: January 2020

Background

The Ulcerative Colitis (UC) and Chron’s Disease (CD) are two debilitating Inflammatory Bowel Diseases (IBD) with an immense negative impact on patients’ health-related quality of life (HRQoL). Although several studies have examined the efficacy of different drugs in the management of IBD, none of these studies has assessed their impact on HRQoL among IBD patients in low incidence areas, such as Saudi Arabia. Therefore, the aim of this study was to examine the impact of Azathioprine, which is one of the commonly utilised immunosuppressive drugs, on HRQoL among a sample of IBD patients in Saudi Arabia.

Methods

This was a single-centre retrospective cohort study in which adult patients (≥18 years) with a confirmed diagnosis of UC or CD and no malignancies were identified in the hospital IBD registry. Patients’ HRQoL was assessed using the EuroQol five-dimensions- 3-level (EQ5D) at baseline as well as six months after initiation of therapy. The overall HRQoL was assessed using the Visual Analogue Scale (VAS) of the EQ5D. Multiple linear regression analysis was conducted to examine the impact of Azathioprine on patients’ EQ5D VAS scores at the six-month follow-up visit controlling for their baseline EQ5D VAS scores, duration of illness, sex, diagnosis (CD or UC), comorbidities, number of prescription medications, and the use of biologics (e.g., infliximab, adalimumab), 5-aminosalicylic acid (5-ASA), and steroids.

Results

Out of 220 IBD patients who were recruited, 160 patients met the inclusion criteria and were included in the study. About 56% of the patients had CD and 44% had UC. The mean age of the patients was 27 years and 54% of them were female. The majority of the patients (77%) did not have any comorbidities. Approximately 63% of the patients were on Azathioprine, and only 4% of them were on Azathioprine monotherapy. The majority of those on Azathioprine were on combination therapy with 5-ASA (78%), steroids (80%), and biologics (69%). Patients on Azathioprine were more likely to report higher overall HRQoL scores at the six-month follow-up visit compared with their counterparts on other therapies (β = 9.35; 95% CI: 0.486–18.22; p = 0.003).

Conclusion

The use of Azathioprine was associated with a positive impact on IBD patients’ HRQoL controlling for their baseline overall HRQoL scores as well as a myriad of covariates. Future studies should examine the cost-effectiveness of Azathioprine in comparison to other therapeutic agents in the management of IBD.
P448 Dose adjustment in patients with moderate-to-severe ulcerative colitis: results from the UNIFI maintenance study long-term extension
Authors: Danese S , Panaccione R , Peyrin-Biroulet L , Marano C , O’Brien C D , Zhang H , Zhou Y , Johanns J , Scherl E , Leong R W L , Rowbotham D S , Arasaradnam R P , Sands B E
Published: January 2020

Background

The UNIFI randomised-withdrawal maintenance study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients (patients) with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment during the long-term extension (LTE).

Methods

At Week (Week) 0 of the 44 weeks maintenance study, 523 patients who had responded to IV UST induction were randomly assigned in a 1:1:1 ratio to placebo (PBO) SC, UST SC 90 mg q12w, or 90 mg q8w. Patients who completed the maintenance study were eligible to enter the LTE if the investigator thought they would benefit from continued treatment. PBO patients were discontinued from the LTE after the maintenance study was unblinded and the analysis was complete. Based on investigator’s clinical judgement of UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Week 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). PBO patients were only eligible for dose adjustment before unblinding. Patients were assessed for symptomatic remission (SR), partial Mayo scores, and inflammatory markers ≥16 weeks after dose adjustment.

Results

Symptomatic remission was maintained through Week 92 among patients treated with UST regardless of dose adjustment in the LTE (Figure). Overall, 40 (28.4%) and 37 (25.9%) patients in the q12w and q8w groups, respectively, underwent dose adjustment (or sham dose adjustment) prior to Week 92 of the LTE. Among patients who received dose adjustment at Week 76 or before and had data ≥16 weeks after dose adjustment, symptomatic remission was observed in 70.0% in the q12w-to-q8w group and 71.4% in the q8w-to-q8w group, the majority of whom were in symptomatic remission at the time of the dose adjustment (Table). The safety profile of UST in patients who received dose adjustment was generally consistent with the overall safety profile of UST.

Conclusion

Patients may benefit from UST dose adjustment to q8w. However, the majority of UST-treated patients were in SR at the time of dose adjustment in this study. No new safety signals were observed among patients who dose adjusted.
P462 Efficacy of ustekinumab for the prevention of postoperative recurrence in crohn’s disease. Data from clinical practice from the eneida registry
Authors: Mañosa Ciria M , Fernandez-Clotet A , Hernández-Camba A , Muñoz Pérez R , Iborra M , Sierra M , Márquez L , Delgado-Guillena P , Busquets D , Van Domselaar M , Girona E , Sánchez-Rodríguez E , Martín-Arranz M D , Lorente R , Casas-Deza D , Boscá M , Cañete F , Calafat M , Domènech E
Published: January 2020

Background

Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases these drugs are contraindicated or have previously failed. Recently, ustekinumab was licensed for CD but no data on its efficacy in the prevention of POR is still available.

Methods

All CD patients in whom ustekinumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a prospectively maintained database of the Spanish Working Group in IBD –GETECCU-). We evaluated the rates of endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score >i1 and advanced endoscopic POR by >i2.

Results

Thirty patients were included; ustekinumab was started after a median time of 60 days (IIQ 31–90). Concomitant immunosuppressants were used in 17%, 27% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 23% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. In total, 36% of them had more than one risk factor. 50% had been exposed to ustekinumab prior to the index surgery (46% within the last 6 months). The median time of follow-up on ustekinumab was 17 months (IQR 11–21). Fifty-six per cent of patients had at least one endoscopic assessment within 18 months after surgery: 58% had endoscopic POR and 23% advanced endoscopic POR. Additionally, 13% presented clinical POR at the discretion of the treating physician and none developed surgical POR.

Conclusion

In a small clinical practice cohort, ustekinumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR. Unfortunately, the lack of early endoscopic monitoring is still frequent despite the recommendations from guidelines.
P472 Optimising the development of apps for the management of inflammatory bowel disease and participation in clinical trials
Authors: Hussain F , DeLegge M , Copeman M , Gallagher M B , Stewart T , Georgiev G
Published: January 2020

Background

Patients interested in participating in Ulcerative Colitis (UC) and Crohn’s Disease (CD) clinical trials must be in the flare to qualify for enrollment. Digital technology can be used to help detect flares based on patient-reported symptoms, share information electronically with their physicians, and increase the likelihood of eligibility on clinical trials. Moreover, early detection and treatment of flares is key to patient management and outcomes.

Methods

IQVIA utilised an electronic survey to solicit input from adult patients with UC and CD, in the USA, regarding the optimum design of an app to both detect flares for participation on clinical trials and assist physicians with patient management. Patient input was critical to designing the app with features that would help manage disease, increase communication with their physicians, and increase opportunities for participation in clinical trials.

Results

Data were collected for 134 patients with IBD (70% 46 years or older and 28% 26–45 years old). Only 23% of respondents had previously downloaded an app to help manage their IBD, however, 78% were interested. 85% would find capturing flares and electronically sharing symptom information with their doctors useful to monitoring and managing their IBD. And 88% would find notifications about clinical research studies useful. More than 61% would be likely to go to this app when they first have symptoms of a flare and enter symptoms every day. 55% would be likely to download an app that would monitor IBD flares to see if they may qualify for a clinical research study. Of those with an interest in participation in clinical research, 27% had already participated in a study. Of this same group, 92% would be likely to download an app if it would also track IBD symptoms. Inclusion of functionality for food, stress, mood, exercise and compliance were recommended by patients to assist in elucidating factors that may cause flares.

Conclusion

Patients are very interested in using an app that would help detect flares, though only a minority do so at present. They are supportive of entering symptoms and related information on a daily basis, but also expanding to inclusion of other factors which may be relevant to flares for individuals. The results of this survey were influential in the recent development of an IBD app.
P486 Assessing the efficacy of biologics in ucerative colitis: a real-life, observational retrospective multicentre study with propensity score analysis (AURORA): Focus on patients naive to biologics
Authors: Cassinotti A , Mezzina N , Di Paolo D , Lenti M V , Bezzio C , Stradella D , Mauri M , Zadro V , Cortellezzi C , Ricci C , Casini V , Radice E , Massari A , Ardizzone S , Pastorelli L , Di Sabatino A , Manes G , Caprioli F , Vecchi M , Tari R , Occhipinti P , Fichera M , Invernizzi P , Parravicini M , Segato S , Pace F , Testoni P A , Tinelli C , De Silvestri A
Published: January 2020

Background

Recently, comparative trials among biologics in ulcerative colitis (UC) provided conflicting results on their reciprocal superiority or equivalence. Therefore, in patients naive to biologics, the first-choice biological drug is uncertain.

Methods

In a retrospective, real-life, multicentre inception cohort study involving 11 Italian IBD tertiary centres, all consecutive patients, naive to biologics, treated with adalimumab (ADA), infliximab biosimilar (CTP-13), golimumab (GOL) or vedolizumab (VDZ) after their postmarketing approval (2014–2018) for moderate–severe active UC, were followed up for 1 year or until relapse. All drugs were compared with each other and to naive patients treated with IFX-originator (IFX-O, Remicade) in 2013–2014 as a reference group. A propensity score analysis was performed. The primary endpoint was the 1 year relapse-free, optimisation-free, steroid-free remission, defined as Mayo score ≤2, with bleeding subscore = 0, no relapse after first clinical remission and no optimisation with dose intensification or steroids courses. Multiple further secondary endpoints were analysed (Table 1).

Results

Two hundred ninety-six naive patients (ADA = 56, CTP-13 = 73, GOL = 60, VDZ = 34, IFX-O = 73) were included. The primary end-point was achieved in similar percentages in all groups, irrespective of optimisation. IFX-O and ADA had similar rates of clinical remission achieved once during the follow-up but higher rates than GOL and VDZ. The 1-year relapse rate, however, was lower with VDZ than ADA, GOL and IFX-O. Treatment failure for primary/secondary no response was higher with GOL than IFX-O and ADA. Treatment failures for intolerance were similar among all drugs. CTP-13 performed differently than the originator for some secondary end-points.

Conclusion

Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year in patients naive to these drugs. IFX originator and ADA appear more effective in the induction phase, while patients responders to VDZ had more prolonged clinical remission. Some differences on secondary questionable outcomes between IFX biosimilar and originator have been observed.
P487 Development and validation of a new patient-reported outcome measure for Crohn’s perianal fistula: Crohn’s anal fistula quality-of-life (CAF-QoL) scale
Authors: Adegbola S , Dibley L , Sahnan K , Tozer P , Wade T , Verjee A , Sawyer R , Mannick S , McCluskey D , Yassin N , Phillips R , Norton C , Hart A
Published: January 2020

Background

Crohn’s perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments, and despite recommendations by a recent global consensus, there are currently no specific patient-derived quality of life (QoL) tools to measure outcomes including response to treatment, in patients with Crohn’s perianal fistulas. Exploratory qualitative work has demonstrated that Crohn’s perianal fistulas reduce QoL far beyond restricting daily and sexual activities, and a patient-centred, patient-derived tool is needed. We present a patient-reported outcomes measure (PROM) for this complicated disease phenotype.

Methods

A 35 item draft questionnaire was generated using information from: (a) unstructured qualitative patient interviews, exploring the experience of living with Crohn’s perianal fistulas; (b) a consensus exercise analysing outcomes from a systematic review of studies assessing medical, surgical and combined (medical/surgical) treatment of Crohn’s perianal fistula; and (c) a patient and public involvement meeting. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale, HADS and the United Kingdom version of the Inflammatory Bowel Disease Questionnaire, UK-IBDQ), and reliability and responsiveness assessed by test-retest analysis.

Results

Data from 211 patients contributed to the development of the CAF-QoL scale, following the collation of items including patient experience interviews, a systematic review and a consensus exercise involving 187 stakeholders (patients, gastroenterologists, surgeons, IBD specialist nurses, radiologists). Internal consistency was good with Cronbach’s α of 0.88. Analysis aided reduction of the questionnaire to 26 items that demonstrated good internal consistency, good stability (intra-class correlation 0.98) and good construct validity and responsiveness with positive correlation with the UK IBDQ and HADS.

Conclusion

A disease-specific PROM to assess clinical outcome (i.e. QoL) as baseline and following interventions in patients with Crohn’s anal fistula—the CAF-QoL—is ready for use. Translation and cross-cultural validation will aid wider international dissemination.
P491 De-escalation of dose-intensified anti-TNF therapy in IBD patients in sustained deep remission
Authors: Chu I , Little R , Sparrow M , Ward M
Published: January 2020

Background

Data on outcomes following de-intensification of anti-TNF therapy in inflammatory bowel disease (IBD) are limited and concerns about relapse limit the willingness to de-escalate. This study aimed to evaluate rates of successful de-escalation at 12 months and to determine factors that may predict success.

Methods

Single-centre retrospective study of IBD patients on dose-intensified infliximab (IFX) or adalimumab (ADA) for secondary loss of response. De-escalation was considered in patients achieving sustained biomarker normalisation. Patients were followed for 12 months post-de-escalation and classified as ‘successes’ if remaining on reduced dose anti-TNF or ‘failures’ if requiring re-escalation, steroids, surgery or enrolment into a clinical trial. Patient demographics, disease characteristics, biomarkers (faecal calprotectin (FCP), C-reactive protein (CRP), albumin), anti-TNF drug levels and thiopurine metabolites were collected.

Results

Of 24 patients (20 CD, 4 UC), 18 received IFX and 6 received ADA. Patients on IFX were de-escalated to 5 mg/kg 8-weekly (89%) or 10 mg/kg 6-weekly (11%), while patients on ADA were de-escalated to 40 mg fortnightly (83%) or 40 mg weekly (17%). Fifteen out of 24 (63%) patients were successes 12 months post-de-escalation. Of the 9 failures, median time to failure was 6 months (IQR 4.6–9.9) – 6/9 failures required re-escalation of anti-TNF therapy and 3/9 entered a clinical trial. Re-escalation successfully recaptured response in 6/6 (100%) patients after a median of 1.4 years follow-up (IQR 1.1–2.3). Albumin at de-escalation was higher in the success group compared with failures (38 g/l vs. 36 g/l, p = 0.025). There was no significant difference in CRP, FCP, anti-TNF drug level or 6-TGN level between the two groups. There was no difference in IFX levels between successes and failures at the time of de-escalation (5.5 vs. 7.5, p = 0.524) as well as 6 months (3.1 vs. 5.1, p = 0.628) and 12 months (3.2 vs. 6.1, p = 0.457) post de-escalation. There were insufficient data for ADA drug level comparison post-de-escalation.

Conclusion

Nearly two-thirds of patients remained on reduced anti-TNF dosing at 12 months post-de-escalation. All patients who failed de-escalation were recaptured after dose re-escalation. Other than albumin, no baseline predictors for the success or failure of de-escalation could be identified, although cohort size is small, follow-up was short and the majority of patients achieved sustained biomarker normalisation prior to de-escalation. De-escalation may be considered in patients on intensified anti-TNF therapy in sustained deep remission.
P492 Use of bowel ultrasound to assess disease activity in Crohn’s disease patients after induction therapy with infliximab
Authors: Frias Gomes C , Neto Nascimento C , Pereira F , Caldeira A , Sousa R , Arieira C , Xavier S , Monteiro S , Dias de Castro F , Leite S , Cotter J , Santos A A , Cravo M , Torres J , Palmela C
Published: January 2020

Background

Objective goals are needed to guide patient management and assess treatment efficacy in patients with Crohn’s disease (CD). Bowel ultrasound (US) is a widely available, non-invasive and inexpensive technique increasingly being used in these patients. The use of bowel wall thickness (BWT) has been proved to be an accurate measure for assessing disease activity and response to therapy. Recent studies show a rapid improvement of BWT after 3-month of therapy. Our aim was to evaluate BWT variation after induction therapy with infliximab (IFX) in CD patients and correlate BWT with clinical and laboratory parameters.

Methods

Prospective cohort multicentre study including patients with active CD starting IFX therapy. Clinical disease activity was assessed using the Harvey–Bradshaw index (HBI). C-reactive protein (CRP) and faecal calprotectin (FC) were measured both at week 0 and after induction therapy (week 14), and infliximab trough levels (ITL) were measured at week 14. Bowel ultrasound was performed at week 0 and 14, BWT from the worst segment was selected for analysis. Abnormal BWT was defined has higher than 3mm in any bowel segment.

Results

We included 10 patients with CD (80% males; median age 29 (21–64) years). According to Montreal classification, most patients were A2 (7/10), had ileocolonic disease (L1 20%; L2 20%; L3 60%) and an inflammatory phenotype (B1 60%; B2 20% and B3 20%). Most patients were anti-TNF therapy naive (80%), and combination therapy was used in 80%. Before IFX (week 0) median HBI was 2 (IQR 1.75–5.25), CRP 1.10 mg/dl (IQR 0.65–3.50) and FC 802 μg/g (IQR 324–1336). The terminal ileum was the most affected segment identified by the USA (5/10), followed by ascending colon (2/10) descending colon (2/10) and sigmoid colon (1/10). Median BWT was 4.6 mm (IQR 3.6–6.4). After induction therapy (week 14), all patients were in clinical remission (HBI<5) except for one in whom IFX dose was increased to 10 mg/kg. Laboratory remission (CRP < 0.5 mg/dl and FC < 250 μg/g) was present in 50% of patients. US response (measured by a reduction in BWT of at least 0.5 mm) was observed in 70% of patients, with US remission (normalisation of BWT in the most affected segment) in 30%. At week 14, 70% of patient had ITL > 3 μg/ml. Median BWT at week 14 was higher in patients with ITL < 3 μg/ml (6.25 vs. 2.98 mm, p = 0.048).

Conclusion

The majority of our patients showed a US response (reduction in BWT) after 14 weeks of infliximab, suggesting that reduction in BWT could be an early marker of response to therapy. US evaluation after induction therapy can be a helpful tool to monitor disease activity and guide patient management in CD patients in our daily practice.
P496 Feasibility and safety of single incision laparoscopic surgery for patients with complex Crohn’s disease
Authors: LI Y , Liu B , Yao D , Zheng L , Zhou Z , Huang Y , Duan Y
Published: January 2020

Background

Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multi-port laparoscopic surgery. Recently, this technique has been applied to Crohn’s disease (CD); however, the application of a laparoscopic approach for complex CD, which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the feasibility and safety of SILS for patients with the complex disease and to compare its clinical results in patients with complex disease.

Methods

We investigated the feasibility and safety of SILS in sixty patients who underwent SILS for CD were divided into two groups: those with the complex disease (complex group, n = 30), and those with a simple disease (simple group, n = 30). The perioperative data were analysed and compared between the groups.

Results

The mean operative time and blood loss were 130.5 ± 28.3 min (range 105–166 min) and 230 ± 58 ml (range 116–410 ml) in the complex group, and 113.4 ± 21.5 min (range 95–151 min) and 72 ± 19ml (range 58–115 ml) in the simple group. There were no significant differences in the operative time between the two groups (p = 0.083, >0.05), but the blood loss was significantly greater in the cases of complex group (p = 0.025, <0.05). Two patients in the complex group required conversion to open surgery for a retroperitoneal fistula and recurrent CD disease. There were no conversions in the simple group. The frequency of postoperative complications was similar in the two groups. The length of the hospital stay was also similar in the two groups. Although the rate of conversion tended to be higher in the complex group, the rate of postoperative complications and length of hospital stay did not differ significantly between the groups (p = 0.061, >0.05).

Conclusion

SILS may be feasible and safe for carefully selected patients with complex CD.
P506 Increased risk of anti-drug antibodies to a second anti-TNF in patients who developed antibodies to the first anti-TNF
Authors: Yanai H , Amir S , Avni Biron I , Tsadok Perets T , Shamir R , Dotan I , Assa A
Published: January 2020

Background

Evidence regarding predisposition to develop anti-drug antibodies to a second anti-TNF in patients with inflammatory bowel diseases (IBD) who previously developed antibodies to a first anti-TNF (either infliximab or adalimumab) is conflicting. We aimed to assess the rates of such consecutive immunogenicity.

Methods

The medical records of all patients with IBD followed at the Rabin and Schneider Medical Centers (all ages) from 2014 to 2019, who were treated with an anti-TNF agent were reviewed. Clinical data including age at diagnosis, gender, disease type, concomitant use of immunomodulators, as well as drug trough levels (TLs) and anti-drug antibodies (ADAs) for both agents were registered. Patients who switched from one anti-TNF to another and had comprehensive clinical and pharmacokinetic data were assessed for consecutive immunogenicity.

Results

Overall, 1570 patients were tested for TLs and ADAs (infliximab, n = 702, 45%). Rates of positive infliximab ADAs were 31%, and positive adalimumab ADAs were 13%. We identified 55 eligible patients (Crohn’s disease = 52, ulcerative colitis = 2, IBD unclassified = 1; females = 26 [47%]; mean age at diagnosis 26.5 ± 13 years). Of 29 patients with infliximab as the first anti-TNF, 25 (86%) had positive ADAs. None of the 4 patients without ADAs against infliximab developed ADAs against consequent adalimumab, whereas 7/25 (28%) of patients with positive ADAs against infliximab developed ADAs against adalimumab, significantly higher than the overall immunogenicity rate of adalimumab (28% vs. 13%, p = 0.03). Of the 26 patients who were switched from adalimumab to infliximab, 10 (38%) had positive ADAs. Out of 16 patients with negative ADAs against adalimumab, 5 (31%) developed ADAs against consequent infliximab whereas 7/10 (70%) of patients with positive ADAs against adalimumab developed ADAs against infliximab, significantly higher than the overall immunogenicity rate of infliximab (70% vs. 31%, p = 0.008). The overall rate of immunogenicity against the second anti TNF following a switch due to immunogenic failure was 39%. Only 33% of patients were treated with concomitant immunomodulators after an immunogenicity driven switch. Clinical data, as well as TLs and ADA, were comparable in children and adults.

Conclusion

The rate of consecutive immunogenicity in anti-TNF treated patients is significantly higher than the overall immunogenicity against the first anti-TNF. This higher rate of consecutive immunogenicity may be associated with a predisposition to developing anti-drug antibodies to anti-TNF agents. It may also be a consequence of the relatively low rates of combination therapy following an immunogenic failure.
P509 Vedolizumab levels in breast milk: Results from a prospective, postmarketing, milk-only lactation study in nursing mothers with inflammatory bowel disease
Authors: Sun W , Fennimore B , Beaulieu D B , Arsenescu R , Stein A , Chen J , Lin T , McKnight S , Rosario M , Lirio R A
Published: January 2020

Background

The safety of inflammatory bowel disease (IBD) medications during lactation is of significant interest and relevance to female patients of childbearing potential. Available data regarding the safety and transfer of biologic agents via breast milk are limited to case reports. Vedolizumab has a well-established, positive benefit-risk profile in adult IBD patients. Literature data show that vedolizumab is detectable in human milk.

Methods

A prospective, postmarketing, phase 4, open-label, milk-only lactation study was conducted to assess vedolizumab concentrations in breast milk from lactating women with IBD who were on an established vedolizumab maintenance regimen (300 mg intravenous [IV] every 8 weeks [Q8W] or an alternative dose frequency). Maternal milk samples were serially collected throughout the dosing interval on Days 1 (predose and 1 h after the end of vedolizumab infusion), 4, 8, 15, 29, and 57 to allow the estimation of drug excreted in milk relative to the maternal dosage. Maternal safety data were also collected.

Results

A total of 11 patients were enrolled in the study. Vedolizumab was detectable in the majority of milk samples collected on Days 1 and 57, and in all samples collected at other time points. Following receipt of vedolizumab 300 mg IV on Day 1, the vedolizumab milk concentration increased with a median time to peak concentration (Cmax) of 3–4 days, and subsequently decreased exponentially. For the 9 patients on the Q8W regimen, median Cmax was 0.213 µg/ml (range, 0.098–0.561 µg/ml); the geometric mean daily infant dosage, calculated using average concentration over 8-week dosing interval (0.13 µg/ml), was 0.02 mg/kg/day with a corresponding geometric mean percentage of maternal dosage consumed in breast milk by infants of 21%. The maternal safety profile was acceptable and similar to that observed in previous adult studies. Leveraging the mean trough serum concentration of 11.2 µg/ml from historical studies of vedolizumab, the ratio of mean milk concentration (trough, 0.05 µg/ml; peak, 0.25 µg/ml) to serum concentration was approximately 0.4%-2.2%, which is consistent with published data for vedolizumab and comparable with several other monoclonal antibody therapeutics for IBD. Published vedolizumab studies also showed no increase in general or gastrointestinal tract infections in the infants exposed to vedolizumab in breast milk, and exposed infants reached their acceptable development milestones through up to 10 months of follow-up.

Conclusion

Vedolizumab was found to be present in human breastmilk at a low level. The impact of vedolizumab IV administration during breastfeeding is expected to be minimal.
P510 Dose escalation of subcutaneous vedolizumab in patients with ulcerative colitis: A post hoc analysis of the VISIBLE trial data
Authors: Sandborn W , Wolf D , D’haens G , Jansson J , Chen J , Uddin S , Candela N , Lasch K , Kisfalvi K
Published: January 2020

Background

Vedolizumab (VDZ), a gut-selective, α 4β7 integrin monoclonal antibody, is approved for intravenous (IV) administration to patients with moderate-severe ulcerative colitis (UC). Subcutaneous (SC) VDZ was evaluated for maintenance therapy for UC in VISIBLE 1, a double-blind, placebo-controlled, Phase 3 study, and its open-label extension (OLE). We evaluated the efficacy of increasing dose frequency of VDZ SC from every-2-weeks (Q2W) to weekly administration (QW) after treatment failure (disease worsening or need for rescue medication).

Methods

In VISIBLE 1 (NCT02611830; EudraCT 2015-000480-14), a Q2W dosing regimen was used for patients with UC who achieved clinical response at week 6 (after open-label IV VDZ inductions at weeks 0 and 2) and were randomised to maintenance treatment with VDZ SC. Patients who did not respond at week 6 but responded by week 14 rolled over to the VISIBLE OLE (NCT02620046; EudraCT: 2015-000482-31) and received Q2W VDZ SC dosing. In VISIBLE 1 and the OLE, 2 groups of patients experienced dose escalation: (1) patients who entered the VISIBLE OLE study on a Q2W VDZ dosing regimen but experienced disease worsening and were escalated to QW dosing (OLE Q2W/QW); and (2) patients who experienced treatment failure during Q2W VDZ treatment in VISIBLE 1, rolled over to OLE, and were escalated to a QW dosing regimen (VISIBLE 1 treatment failure). Efficacy was evaluated by clinical remission and response rates after dose escalation using partial Mayo scores at the visits in the Visible OLE study. In this interim analysis, not all patients continuing in the trial had not completed all study visits. Only patients who had completed a given visit (evaluable patients) were included in the analyses for that visit.

Results

Of the 54 patients who received dose escalation 52% were male. Mean age was 39 years, mean UC duration was 7.4 years; 76% had severe disease activity (Mayo 9–12) at baseline, and 43% had prior anti-TNF therapy failure (Table 1). Of the patients with dose escalation, 27.1% (13/48 evaluable patients) recaptured clinical remission 16 weeks after dose escalation and 10.8% (4/37 evaluable patients) were in clinical remission after 48 weeks (Table 2). A similar trend was observed for clinical response rates in this patient population.

Conclusion

Increasing the frequency of VDZ SC dosing to QW recaptured lost response to treatment for some patients. These are interim results of the OLE study; further follow-up during the ongoing OLE will provide more insight into the long-term efficacy and safety of dose escalation with VDZ SC.
P525 Rheumatoid arthritis treatment with filgotinib: Week 156 safety and efficacy data from a phase 2b open-label extension study
Authors: Besuyen R , Kavanaugh A , Westhovens R , Winthrop K , Lee S , Greer J , DeZure A , An D , Ye L , Sundy J , Meuleners L , Alten R , Genovese M
Published: January 2020

Background

Filgotinib (FIL) is an oral, selective Janus kinase inhibitor, shown to be effective and well tolerated in patients (pt) with rheumatoid arthritis (RA) and other inflammatory diseases (IBD/AS/PsA). DARWIN 3, an ongoing, open-label, long-term extension of phase 2b studies evaluates the longer-term safety and efficacy of FIL in RA.

Methods

The study evaluated pt outcomes for methotrexate (MTX) inadequate responders completing the 24-week DARWIN 1 (FIL+MTX) and DARWIN 2 (FIL monotherapy) studies. We present an interim analysis at week 156 following FIL 200 or 100 mg/day treatment. Event rate: total events/total years of exposure of FIL; Exposure: until data cut-off in patients on the study at the time of analysis.

Results

Eight hundred and seventy-seven patients completed the parent studies. Seven hundred and thirty-nine enrolled in DARWIN 3 (497 DARWIN 1, 242 DARWIN 2); most DARWIN 1 and 2 patients were female (81.5%, 81.8%), white (75.3%, 74.8%); mean age was 53 and 52 years, respectively. Mean baseline MTX dose in the FIL+MTX group: 16.8mg/week. At week 156, 59.9% of patients remained on study. Most common reasons for discontinuation were adverse events (26.5%) and subject request (9.1%). Total exposure to FIL was 2203 pt-years; mean exposure ± standard deviation (SD): 3.04 ± 1.22 years for FIL+MTX and 2.86 ± 1.21 years for FIL monotherapy. Treatment-emergent adverse events (TEAEs): 419 (84.3%) patients on FIL+MTX and 203 (83.9%) patients on FIL monotherapy; serious TEAEs occurred in 45 (9.1%) and 33 (13.6%), respectively. Adverse event of special interest (AESI) rates remained low at week 156 (Table 1). Grade ≥3 toxicities in >1% of patients were decreased lymphocytes (4.2%/1%), decreased neutrophils (1.0/1.2%), increased fasting triglycerides (2.2/0%) and decreased fasting triglycerides (0/3.3%) for FIL+MTX/FIL monotherapy respectively. 5 deaths occurred (FIL+MTX: 2, FIL monotherapy: 3) none after week 132. Clinical efficacy was shown at week 156 in both FIL+MTX and FIL monotherapy groups, using observed cases as measured by ACR20 (87.2% and 89.7%)/ACR50 (72.4 and 63.0)/ACR70 (45.5 and 40.0) DAS28(CRP) ≤3.2 (69.0 and 64.7) and DAS28(CRP) <2.6 (53.4 and 45.6).

Conclusion

FIL was generally well tolerated; no new safety signals emerged. No safety differences observed in patients receiving FIL+MTX or FIL monotherapy. Efficacy was sustained up to week 156 in both treatment groups.
P526 Body mass index and response to TNF-α inhibitors in inflammatory bowel disease
Authors: Nordin F , Shadbolt B , Subramaniam K
Published: January 2020

Background

Obesity is an emerging issue in the care of patients with inflammatory bowel disease (IBD). The aim of the study was to evaluate whether the response to TNF-α inhibitors (infliximab and adalimumab) could be influenced by body mass index (BMI) in IBD. Unlike adalimumab (ADA), a recombinant humanised IgG antibody against (TNF-α), the dosing of infliximab (IFX); a monoclonal chimeric antibody is weight-based.

Methods

We identified a cohort of patients with IBD at a single centre, naïve to biologic therapy and stratified them according to their weight and BMI. The primary outcome is the first occurrence of loss of response defined as clinical deterioration requiring hospitalisation, surgery, corticosteroid use, dose escalation or discontinuation of therapy and/or evidence of activity on endoscopy. Patients were followed up for 4 years. Multivariate analysis with logistic regression were used to compare variables.

Results

There was a total of 104 IBD patients; 51% (n = 53) were males and the median age was 40 years (19–76 years). The majority (n = 89; 85.6 %) had Crohn’s disease and the rest (n = 15; 14.4%) were diagnosed with ulcerative colitis. The median BMI was 24.5 kg/m2 (13.4–41.5 kg/m2). Patients had been diagnosed with IBD for a total median duration of 13 years (1–50 years). The majority of patients were not active smokers (n = 92; 88.5%) with the rest being current smokers (n = 12; 11.5%). Of the 104 patients, there were an equal number of patients in the IFX (n = 52) and ADA (n = 52) groups. There were no differences in the demographics, types of disease and BMI distribution in the two groups.

In terms of loss of response, type of drug (IFX/ADA) was not found to be a significant risk factor (p = 0.250) along with the type of IBD (p = 0.420), age (p = 0.612) and gender (p = 0.600). However, the duration of disease was a significant factor (p = 0.026). There was a trend of accelerated time to loss of response for patients with BMI ≥30 kg/m2, in ADA group, but not significant (p = 0.314) compared with IFX of the same BMI group (Figure 1). For BMI <30 kg/m2 in both groups, there was no difference in time to loss of response (p = 0.259). However, patients on ADA with BMI ≥30 kg/m2 had a significant loss of response compared with patients on IFX with BMI <30 kg/m2 (adjusted HR 5.6; p = 0.038).

Conclusion

BMI appears to be important in predicting loss of response in IBD however we found no overall association between increased BMI and accelerated loss of response. Further larger studies are needed to evaluate the relationship of BMI and loss of response to ADA.
P533 Long-term quality of life after minimally invasive surgery for Crohn’s disease
Authors: Angriman I , Bordignon G , Sciuto E , Zini O , Bortoli N , Gruppo M , Bardini R , Ruffolo C , Scarpa M
Published: January 2020

Background

Risk of surgery is among the highest-rated concerns among Crohn’s disease (CD) patients. Quality of life is often worsened by intestinal surgery. This study aimed to assess the possible predictors of long-term quality of life after minimally invasive surgery for ileal, colonic or ileocolonic CD.

Methods

Data of all the 72 consecutive patients operated from 2010 to 2018 for CD were retrieved and 72 patients who had ileal, colonic or ileocolonic resection were selected and interviewed with the Cleveland Global Quality of Life (CGQL) questionnaire and the Body Image Questionnaire (BIQ). Disease activity was defined as the Harvey–Bradshaw Index (HBI). Comparisons between laparoscopic and open groups were carried out with non-parametric tests and log-rank test.

Results

Seventy-two patients who had laparoscopic ileal, colonic or ileocolonic resection and had a follow-up greater than 1 year were interviewed. The total CGQL score was associated with clinical disease activity at the moment of the interview (rho = −0.61, p < 0.0001) and to the presence of extraintestinal complication (rho = 0.28, p = 0.03). At multivariate analysis, disease activity at the moment of the interview and the presence of extraintestinal complication confirmed to be independent predictors of long-term quality of life.

Conclusion

Long-term quality of life after minimally invasive intestinal surgery is essentially predicted by current disease activity. Thus, it is crucial to prevent clinical CD recurrence
P534 Qualitative perspectives of parent and child participants from a trial of faecal microbiota transplant for paediatric ulcerative colitis
Authors: Popov J , Hartung E , Hill L , Chauhan U , Pai N
Published: January 2020

Background

Faecal microbiota transplant (FMT) is being studied across a range of therapeutic indications including ulcerative colitis (UC). Pediatric patients may have unique perspectives on microbiome-based therapeutics given their younger age, fewer comorbidities, and greater susceptibility to microbial influences. We recently conducted the first randomised-controlled trial (RCT) of FMT for pediatric UC (PediFETCh Trial) and conducted qualitative interviews of child participants and their parents. This study aims to describe the experiences and perceptions of these children who received FMT, and their parents.

Methods

Participants in the PediFETCh Trial (ClinicalTrials.gov: NCT02487238) were invited to participate in face-to-face, semi-structured interviews. Interviews were audiotaped, transcribed, and analyzed using open coding (NVivo 12 Pro).

Results

8 pediatric participants and 8 parents were interviewed. Data were summarised across 4 domains and 11 composite themes (Table 1). Most children and parents saw FMT as a ‘safe, natural’ treatment. Prior to enrollment, children were concerned about receiving ‘someone else’s poo’ and potential physical discomfort, while parents were concerned about transmission of enteric infections and psychiatric diseases. Both groups felt their decision to pursue FMT was influenced by frustration with lack of response to medications, and fear of medication-related side effects. Following completion of the study, most children and parents had no concerns about potential side effects of FMT, and children reported feeling ‘completely normal’. Children were split between preferring FMT or medication therapies. The convenience of medications was valued, while others favoured FMT for its symptomatic improvement and perceived naturality. It was noted that some alternative healthcare practitioners did not support patients’ desire to pursue FMT.

Conclusion

Our study offers valuable insight into the experiences of receiving FMT in pediatric participants and their parents. This data suggest a high rate of acceptance and interest in FMT-based therapeutics in this population and offers strategies to improve the delivery of FMT in future pediatric-focused RCTs.