bluuebunny/crossref_metadata_2025 huggingface dataset:
P480 Efficiency and safety of endoscopic balloon dilatation of ileocolonic anastomotic strictures in patients with Crohn’s disease: A multicentric retrospective study
Authors: Lukáš M , Kolar M , Vasatko M , Klvana P , Leksa V , Dyntr J , Baca L , Pipek B , Bahnikova B , Summerova S
Published: January 2020

Background

Ileocolonic resection is the most common surgery in Crohn’s disease (CD). However, stricture formation in the anastomosis is considered to be a frequent cause of significant morbidity in CD and a reason for reoperation. Endoscopic balloon dilatation (EBD) is an established modality for non-surgical treatment of strictures in CD, however, summary data from the Czech Republic are lacking.

Methods

All EBDs of CD anastomotic strictures performed in the 7 centres from the Czech Republic between January 1, 2013, and May 30, 2019, were included. Demographics, disease characteristics, concomitant medication and procedure outcomes were analysed. Technical success was defined as an ability to pass the endoscope through the site of the stricture following the procedure. Complications included perforation and bleeding with the need for intervention or hospitalisation. Kaplan–Meier and logistic regression analysis were performed.

Results

In total, 615 procedures performed in 282 patients, 52.1% males, were included. Mean age at the time of the first procedure was 41.9 ± 12.7 years and mean disease duration was 14.5 ± 8.4 years. Single dilatation was performed in 47.9% of patients, 52.1% requested repeated interventions (2–10, median 2). Cumulative probability of redilatation at 6 months, 1 year and 3 years was 20.2% (95% CI 14.8–26.2%), 31.8% (95% CI 26.5–37.2%) and 59.4% (95% CI 55.5–63.0%) respectively. Cumulative probability of a need for reoperation at 6 months, 1 year and 3 years was 4.4% (95% CI 0.5–16.9%), 8.2% (95% CI 2.3–19.3%) and 14.8% (95% CI 7.1–25.2%) respectively. Technical success was reached in 81.1% of procedures and relief of symptoms in 86.7%. The success of the procedure was dependent on the age of the patient (OR 0.98; 95% CI 0.96–0.99), smoking (OR 0.57; 95% CI 0.32–0.98) and concomitant immunosuppression use (OR 1.99; 95% CI 1.31–3.02). Complications occurred in 2.6% of the procedures. Reintervention until 6 months after the procedure was needed in 26.7% of cases, out of which repeated dilatation in 21.3% of cases and early surgery took place in 5.4% of cases. The technical success (OR 0.44; 95% CI 0.29–0.67) and repeated dilatation (OR 1.57; 95% CI 1.09–2.27) were significantly associated with the need for reintervention until 6 months.

Conclusion

In a large multicentric Czech cohort, the EBD in Crohn’s disease anastomotic strictures was proven to be safe and effective with results comparable to the available international data.
P489 Are patients with inflammatory bowel disease receiving an adequate immunisation?
Authors: Simian D , Núñez P , Flores L , Figueroa C , Ibáñez P , Kronberg U , Lubascher J , Pizarro G , Quera R
Published: January 2020

Background

Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunisations in IBD and identify possible associated factors.

Methods

A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary centre in Chile, between April – June 2019. Demographic and clinical data were obtained from the hospital IBD registry, approved by the local IRB. Patients were asked to answer a vaccine survey and complementary information was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p <0.05).

Results

A total of 243 patients were included (Table 1). The influenza vaccine rate has significantly increased (Figure 1), reaching 67% in 2019, being higher in women (66% vs. 34%; p 0.045) and patients in biological therapy (BT) (29% vs. 14%; p 0.011) (Table 1). Vaccination rates are shown in Figure 2. Combination of Influenza/Hepatitis B/Pneumococcus vaccines was administered in 56 patients (23%), significantly higher in patients with BT and with fewer years of IBD. Forty patients received a live virus vaccine, 18% were on immunomodulatory treatment. The survey showed that 57 patients (23%) have not been immunised with any vaccine, mainly due to lack of time, lack of medical prescription and high cost.

Conclusion

In this cohort, vaccination rates are low, however, adherence to Influenza vaccine has increased. Immunisation should be considered early by the multidisciplinary team, educating patients about its importance.
P494 The efficacy and safety of adalimumab for patients with moderately to severely active ulcerative colitis and predictors of response in Korea
Authors: Shin Shin S , Park S J , Kim Y , Im J P , Kim H J , Lee K M , Kim J W , Jung S A , Lee J , Kang S B , Shin S J , Kim E S , Kim Y S , Kim T O , Kim H S , Park D I , Kim H K , Kim E S , Kim Y H , Kim D H , Teng D , Kim J H , Kim W Y , Choi C H
Published: January 2020

Background

The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC).

Methods

We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method.

Results

A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p < 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p < 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis.

Conclusion

Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.
P498 Loss of response of anti-TNF in Crohn’s disease patients single-centre experience
Authors: Atanassova A , Georgieva A C , Mirchev M
Published: January 2020

Background

Despite the timely commencement of the biological treatment, only about 30% will respond to it, and about 1/3 will lose the initial anti-TNF (tumour necrosis factor) response.

Methods

We retrospectively studied the data of 69 Crohn’s disease (CD) patients who started biological treatment with anti-TNF-ADA/ IFX. We excluded patients who are primary nonresponders to IFX/ADA. In patients with induction of clinical response, we investigated and analysed the frequency of subsequent loss of response (LOR) to IFX/ADA. We analysed the possible risk factors that have led to LOR.

Results

Of the 69 patients undergoing biological treatment, 71.01% achieved a clinical response during the course of the follow-up. There is a correlation between the presence of a clinical response and the CD course- x2 = 10.78, p = 0.013, ρ = 0.241, (p = 0.046). Inflammatory phenotype (В1) manifestation among our patients is a factor for achieving a clinical response OR = 3.68 (1.116–11.73), p = 0.021, whereas the presence of a penetrating form is a risk factor for the lack of response OR = 6.13 (1.29–29.01), p = 0.019. The presence of intestinal complications is a risk factor for the lack of response- OR = 3.2 (1.61–6.37), p = 0.001. During the course of the follow-up in 30.61% of cases, we observed LOR (men/women - 86.66%/13.33%, p < 0.05 (p = 0.02), in 60.00 % this was between 1–2 years, on average 20.62 ± 13.07 months from the start of the biological treatment. A total of 46.66% of patients required treatment with another anti-TNF drug due to secondary loss of response. A total of 50% of patients needed a reduction of the dose interval. Over 50.00% of those with LOR have an extensive disease (L3). A total of 40% have В1 and 33% have stricturing (В2) and penetrating (В3) phenotypic expression. In 26.66%, we observed progression of the disease range, and in 46.66% of patients - intestinal complications, none of whom had subsequent surgery. In 21.42% of LOR patients there is a combination of intestinal complications and progression according to disease localisation. 93.33% of CD patients with LOR have a persistence of extraintestinal manifestations (EIMs); those with two or three EIMs predominate. We discovered that gender was a risk factor for loss of response, OR = 8.36 (1.16–60.26), p = 0.005, as is the combination of В2 and В3 form of the disease OR = 14.72 (2.47–87.79), p = 0.003. Patients who lost response during the course of treatment had higher mean faecal calprotectin, CDAI and CRP prior to the initiation of the anti-TNF therapy.

Conclusion

The high activity of the disease measured with CDAI, faecal calprotectin and CRP, male gender, the combination of penetrating and stricturing form during the course of the disease are all risk factors for the loss of response.
P503 Changes in clinical use of vedolizumab are driven by lower drug costs and are associated with better outcomes: a real-life single-centre Spanish experience
Authors: Gonzalez Lama Y , Calvo M , Matallana V , Gonzalez-Partida I , Omella I , Vera M I
Published: January 2020

Background

Vedolizumab (VDZ) has shown efficacy in the treatment of inflammatory bowel disease (IBD). Available data show better outcomes in naïve patients than in AntiTNFa experienced patients, and current ECCO guidelines support first-line use of VDZ since 2017. Nevertheless, reimbursement of VDZ was initially approved in Spain only in patients failing to at least one AntiTNFa agent (except contraindication) until January 2018 when, following a significative decrease in costs of VDZ, reimbursement was approved also in naïve patients. Our aim was to elucidate if our clinical use of vedolizumab have evolved after costs decrease, and if was associated with better clinical outcomes.

Methods

Retrospective review of all VDZ treated patients with at least 6 months of follow-up in a referral IBD Unit of a tertiary centre in Madrid (Spain) since December 2014. Demographics, clinical data and information regarding VDZ treatment were collected.

Results

118 IBD patients included (61(52%) Crohn’s disease, 57(48%) ulcerative colitis): 62(53%) female; median age 48(IQR 32–63) years. 64 patients started VDZ before 2018, 54 since January 2018. Among patients who started VDZ treatment before and after January 2018: 9(14%) and 22(41%) respectively were naïve to antiTNFa (p = 0.001); 38(60%) and 10(18.5%) respectively had previously received at least 2 anti-TNFa agents (p = 0.0001). Among patients who started VDZ treatment before and after January 2018, 25(39%) and 6 (11%), respectively, had VDZ intensified along the follow-up (p = 0.001); 36(56%) and 12(22%) respectively withdrawn VDZ (p = 0.0001); 40(73%) and 15(27%) respectively withdrawn or intensified VDZ along the follow-up (p = 0.0001).

Conclusion

Lower costs have facilitated earlier use of VDZ in our clinical practice, towards increase use in patients who have failed to one single AntiTNFa agent or even naïve to AntiTNFa. This evolved a pattern of VDZ use is associated with better clinical outcomes in terms of VDZ intensification and/or withdrawn. Price policies facilitating appropriate access to drugs, such as VDZ, should be more easily and quickly acceptable by national health authorities. Patient-centred care demand best use of all available drugs, including VDZ.
P504 Remote cannabis-therapy management platform for IBD patients: performance assessment
Authors: Sweed G , Shapira C , Naftali T
Published: January 2020

Background

Efficient IBD symptomatic control, especially in severe patients, is still lacking while conventional management options agents carry risks for long-term side effects such as malignancy and infections. Only about 60% of IBD patients initially respond to conventional therapy thus, a growing number of IBD patients turn to use medical cannabis to relieve their symptoms. The large selection of cannabis varieties available in the markets, together with lack of evidence-based cannabis therapy guidelines, practically turns cannabis care to a self-medicating hit-or-miss treatment. Yet, despite its large therapeutic window, cannabis care still carries unknown risks of short-and long-term side effects and tolerance. SelfX is a novel cannabis-therapy management web platform, designed to monitor patients in various clinical conditions. It is a cloud-based decision-support physician tool, consisting of personal patient wearable monitoring device, mobile app and physician web portal.

Methods

SelfX capability to detect and alert of IBD patients in need of cannabis treatment protocol change consideration (including cessation of treatment), was examined in a proof of concept observational clinical study. Men and Women aged 18–65 (n = 26) with IBD who were already treated with cannabis prior to the study initiation, and held a valid cannabis license from the Israeli Ministry of Health, were recruited at Meir Medical Center in Israel and completed 6 weeks of remote monitoring. A designated statistical formula developed by our team for change-point detection was applied to alert of any negative clinical trends, including an increase in resting heart rate, decrease in sleep quality, increase in daily self-report IBD scoring system, adverse events and cannabis patterns use.

Results

The study achieved its primary objective to alert in real-time of detected change points which enabled an educated calibration of a personal adaptive alerts function. Study group post hoc analysis revealed significant and informative system performance: 60 objective negative trends alerts, and 27 subjective negative trends alerts were detected in real time.

Conclusion

Currently physicians require a practical tool to monitor short-and long-term safety and efficiency of cannabis use. Our work demonstrates the importance of continuous remote monitoring alongside laboratory routine measurements for IBD patients treated with cannabis. Future interventional studies will expand valuable monitored parameters scope range and will associate monitored data points with personal cannabis patterns use. SelfX platform offers a safety-net and an educated adaptive optimisation tool for continuous remote patients management in real time.
P511 Association of ustekinumab serum concentrations and clinical outcomes: results from the mUST-DECIDE trial
Authors: Bressler B , Sattin B , Williamson M A , Khanna R , Seow C H , Dajnowiec D , Karra K , Gao L L , Afif W
Published: January 2020

Background

Therapeutic drug monitoring is an important adjunct in optimising IBD management in patients treated with anti-TNF therapies. However, it remains unclear whether these principles apply to non-anti-TNF biologic therapies, such as the anti-IL12/23 agent, ustekinumab (UST). A follow-up analysis of the ‘mUST-DECIDE’ study explores the correlation between UST drug level and clinical outcomes.

Methods

111 consecutive UST-treated adult CD patients across 11 sites in Canada from April 2017 to January 2018 were evaluated. Clinical decisions were recorded for all subjects at the single study visit and blood was drawn for TDM (Sanquin, radioimmunoassay). A retrospective chart review was completed in patients who had a follow-up visit ≥ 30 days after the baseline visit. Improved disease control (primary outcome) was defined as a composite assessment outcome meeting ≥ 1 disease control criterion (symptomatic, endoscopic/imaging, biochemical) without any of the non-response criteria (inadequate or loss of response, worsening of any disease control criteria, initiation of any CD-related medications and adverse events). Serum [UST] were categorised as therapeutic, subtherapeutic or uninterpretable based on their position in a 2 compartment PK model [subjects on Q8W dosing were assessed as per the log-linear model which projected a therapeutic level of ≥4.5 µg/ml at 4 weeks and ≥1.0 µg/ml at 8 weeks].

Results

53 patients had a clinical follow-up visit and an interpretable serum [UST]. Patients had refractory disease (89% anti-TNF-exposed, median 16.4 years since diagnosis), but clinically well (66% had baseline HBI <5) on treatment with UST for a median [IQR] of 16.5 [10.4–26.8] months. At baseline, the majority had serum [UST] in the therapeutic range (n = 44/53, 83%). After a median [IQR] of 148 [104–193] days, improved disease control was achieved by 51% of patients at next clinic visit. The outcome appeared independent of achieving therapeutic [UST] at baseline (OR[95% CI] = 0.80[0.19–3.38]). Dose-adjustment occurred in eight (15%) patients and improvements were observed in 75% of these patients. Subgroup analyses failed to detect clinical outcomes that were dependent on therapeutic serum [UST] (Table 1). No new safety signal was observed, no patient samples were positive for antibodies to UST.

Conclusion

The sub-study did not detect any association between routine serum [UST] and short-term clinical outcomes at the next patient visit. These data broadly suggests that the routine measurement of serum UST in CD patients does not aid in disease management, though further studies across different clinical scenarios (e.g. loss of response) are warranted.
P512 Efficacy of tofacitinib for the treatment of moderate-to-severe ulcerative colitis: real-world data
Authors: XIAO Y , Lakatos P L , Bourdages R , Bitton A , Afif W , Kohen R , Berberi M , Bessissow T
Published: January 2020

Background

A significant proportion of patients do not respond to therapy for moderate to severe ulcerative colitis (UC), including thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-a and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, data on its real-life efficacy remains sparse.

Methods

We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included the rate of biomarker normalisation, corticosteroids-free clinical remission and severe infections. We conducted a multi-centre retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalisation was defined as faecal calprotectin ≤250 μg/g. Severe infection was defined as an infection requiring hospitalisation.

Results

During the study period, 40 patients with UC were started on tofacitinib at 10 mg/kg twice a day. Amongst the patients, 85% (n = 34) had failed ≥1 biologic and 50% (n = 20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment; 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n = 34) and clinical remission occurred in 63.2%(n = 24). At 6 months, clinical response occurred in 73.3% of patients (n = 22) and clinical remission was sustained in 53.33% (n = 16). Biochemical normalisation occurred in 29.0% (n = 11) and 30.0% (n = 9) at 3 and 6 months respectively. Additionally, 63.2% (n = 24) of patients and 43.3% (n = 13) of patients achieved steroid-free clinical remission at 3 and 6 months respectively. In the interim, one patient developed a serious infection requiring discontinuation of the drug.

Conclusion

Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow-up.
P519 Higher anti-TNF α trough levels are not associated with increased radiological response in perianal fistulising Crohn’s disease: A multicentre study
Authors: LEE T , Gilbert L , Srinivasan A , Lee A , van Langenberg D , Martin C , Ding N , Sparrow M
Published: January 2020

Background

Perianal fistulas remain a debilitating and clinically challenging manifestation of Crohn’s disease (CD), given their prevalence and relative treatment resistance. Since the advent of biologic therapy, particularly the anti-TNFα agents infliximab and adalimumab, patient outcomes have improved. Serum trough levels have been associated with mucosal healing in luminal CD. However, the relationship between trough drug levels and healing of perianal fistulas remains less clear, with few studies assessing this cohort, and clinical healing typically defined as the primary endpoint. The aim of this study was to assess the relationship between radiological healing of perianal fistulising Crohn’s Disease (pfCD) on MRI, and serum trough drug levels, in patients treated with anti-TNFα therapy.

Methods

In this multi-centre, retrospective cross-sectional study, patients with pfCD who had trough levels measured within 6 months of a pelvic MRI were included. We collected patient demographics, infliximab and adalimumab trough levels, the presence or absence of anti-drug antibodies, concomitant steroid or antibiotic therapy, and Van Assche scores on MRI. The primary outcome, radiological response, was defined as a Van Assche score of 7 or less, while no response was defined as a score of greater than 7.

Results

A total of 99 patients were included (65 on infliximab, 34 on adalimumab). For patients receiving infliximab, the median drug levels for responders (n = 22) compared with non-responders (n = 43) were 5.5 mg/ml vs. 3.9 mg/ml respectively (p = 0.16). For patients receiving adalimumab, the median drug levels for responders (n = 14) compared with non-responders (n = 20) were 6.3 mg/ml vs. 3.1 mg/ml respectively (p = 0.09). On ROC curve analysis, the AUC for the association between radiological response and infliximab levels was 0.61, while for adalimumab it was 0.67. On quartile analysis, there appeared to be an increased response for increase in infliximab trough level quartile, with the exception of the highest quartile, however this association was not statistically significant (OR 1.36, 95% CI 0.85–2.16, p = 0.20). In comparison, the quartile analysis of adalimumab trough level and response demonstrated an exposure-response relationship (OR 2.24, 95% CI 1.11–4.52, p = 0.02).

Conclusion

Trough infliximab and adalimumab levels in patients who achieved radiological response were not significantly higher compared with those who did not, however quartiles analyses demonstrated trends toward an exposure-response relationship, in particular for adalimumab. The association between trough levels and radiological response could be further characterised with a larger, and ideally longitudinal, study.
P521 Infection of the anal canal by human papillomavirus in Crohn’s disease
Authors: Guzela V , Sobrado Júnior C , Nadal S , Nadal C R , Villa L L , Gonçalves A P , Boarini L R , Nahas S C , Cecconello I
Published: January 2020

Background

Compare the frequency of subclinical papillomavirus (HPV) in the anal canal os Crohn′s disease (DC) patients to a control group by smear cytology and polymerase chain reaction (PCR) and hybridisation and to assess whether there is correlation with the presence of immunosuppression and anal manifestations of the disease, besides establishing the agreement between the two diagnostic methods used.

Methods

Two groups were selected, one with DC and others to be the control population. All the individuals were submitted to smear cytology (two brushes inserted in sequence in the anal canal) and a third one preserved for molecular analysis (PCR and hybridisation). The cytology was classified according to Bethesda criteria as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL). The molecular analysis was considered with HPV present or absent and types 16 and high-risk HPV group identified.

Results

During sixteen months, 104 patients underwent anal cytology collection for smear preparation and HPV molecular method detection. The control group consisted of 41 individuals and the DC of 63 patients (32 immunocompetent and 31 immunosuppressed). ASCUS and LSIL represented respectively 26.8% and 22.0% of the control patients and 28.6% and 39.7% of the Crohn′s patients, with no statistically significant difference between the groups. HPV was identified in 17.1% of patients in the control group and 27% of patients with CD by the molecular method, being predominantly high risk in both groups. In a subanalysis considering Crohn’s disease patients with and without immunosuppression and the control group, there was no statistical difference between the frequencies detected by PCR and hybridisation (p = 0.084) as well as the anal manifestation of Crohn’s disease. The Kappa coefficient for agreement between smear anal cytology and HPV identification by PCR and hybridisation was -0.127 in the total sample.

Conclusion

In this study, is possible to conclude that in the sample studied there was no difference between subclinical HPV anal infection between control patients and Crohn’s disease group evaluated by both cytology and hybridisation and immunosuppression and anal impairment did not influence these results either. Anal cytology and hybridisation did not show agreement represented by the Kappa coefficient in this population.
P524 Administration and monitoring of biologic therapy in patients with inflammatory bowel disease: A national Danish survey
Authors: Volmar S , Wildt S , Munck L K
Published: January 2020

Background

Administration and monitoring of biologic therapy to patients with inflammatory bowel disease (IBD) is an increasing burden in gastroenterology outpatient clinics. The aim of this study was to compare the present organisation of biologic therapy to IBD patients in Denmark with the published evidence.

Methods

A national online survey using SurveyXact was send to all outpatient clinics administering biologic treatment to IBD patients in Denmark in March 2019. It focused on infusion time, post infusion observation and biochemical control of treatment with biologic drugs. A systematic literature search covering the same topics was performed on PubMed in May 2019.

Results

21 of 23 clinics completed the survey. Infusion time for infliximab induction was 2 h in all clinics and was reduced to 30 min or 1 h in 60 % and 40% of clinics respectively after ≥ 10 infusions. Vedolizumab infusion time was 30 min in 90% of clinics from start. Ustekinumab infusion time was 1 h in 90% of clinics. Observation time after intravenously administered biologics varied considerably. Only half of the clinics discharged patients on infliximab without post-infusion observation from the start of maintenance treatment increasing to 80% of clinics after ten infusions. About half of the clinics observed patient on vedolizumab maintenance for at least 30 min after 5 infusions. Ten clinics discharged patients immediately after the initial ustekinumab infusion. In 30–60% of clinics, patients were observed 20–120 min after subcutaneous injection of ustekinumab, adalimumab or golimumab. Twenty clinics controlled laboratory parameters prior to every maintenance treatment with infliximab and vedolizumab, no matter of infusion interval, while patients on injection therapy with adalimumab, golimumab and ustekinumab had biochemical tests taken every second to third months. Only two clinics measured trough values and antibodies against biologics routinely and adjusted the dose accordingly to the trough value. The systematic literature search identified 26 relevant articles. These showed that infliximab infusion time of 30 minutes is safe and questioned the necessity of post-infusion observation. There was no consensus on the frequency of biochemical control in patients on biologics.

Conclusion

Reduction and harmonisation of infusion time, post-infusion and post-injection observation time for patients on biologics could release patient and staff resources.
P527 A review of adverse events associated with immunosuppressive treatments in inflammatory bowel disease patients
Authors: Tassone D , Ding N
Published: January 2020

Background

Medical therapies that suppress various pathways involved in inflammation comprise the mainstay of inflammatory bowel disease (IBD) treatment. Adverse events, including the development of serious infection and malignancy, have been associated with these therapies. This study evaluates the current evidence regarding serious adverse events associated with immunosuppressive agents in the IBD patient population.

Methods

A systematic search was conducted in September 2019 by combining three key research themes: inflammatory bowel disease, immunosuppression, and adverse events. For this systematic review, adverse events are defined as either the development or recurrence of malignancy or the development of serious infection necessitating hospital admission.

Results

There is a demonstrated association between thiopurine use and increased risk of both nonmelanoma skin cancer (NMSC) or lymphoma. The length of thiopurine exposure required to increase NMSC risk is, however, unclear. Of the papers reporting on exposure length and NMSC risk, the thiopurine exposure duration required to result in a statistically significant increase in NMSC risk varied from 6 months to 5 years. Among the studies retrieved, there is a lack of consensus on malignancy risk associated with the use of anti-TNF agents. From 5 studies on malignancy risk associated with the use of anti-TNF agents, one concluded that malignancy risk is increased while three concluded that risk is unchanged from baseline. The fifth study is inconclusive on any possible association. Confounding by past or concurrent thiopurine exposure remains an issue. There is a clear association between combination therapy with both thiopurines and anti-TNF agents and increased malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Anti-integrin agents were not found to be associated with an increase in adverse effects when compared with placebo, while nil studies on ustekinumab were retrieved. Individual studies on infection risk do not consistently stratify infections according to severity, limiting any analysis.

Conclusion

An established association between thiopurine use and increased risk of both lymphoma or NMSC exists. However, the duration of thiopurine exposure necessary to increase NMSC risk is uncertain. There is a lack of consensus on whether anti-TNF agents increase malignancy risk due to confounding from past or concurrent thiopurine exposure. Combination therapy increases malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Limited studies on the newer biologic therapies were retrieved. Finally, evidence which stratifies infections according to severity is lacking.
P529 Natural history and management strategies of ulcerative colitis (UC) in a paediatric population: A 10-year review in a tertiary paediatric gastroenterology centre
Authors: Sonnino M , Ocholi A , ElZein A , Saliakellis E , Pensabene L , Borrelli O , Kiparissi F
Published: January 2020

Background

Paediatric UC can be severe with high colectomy rates. We describe clinical practice, management strategies and determine whether an accelerated approach can influence the natural history of UC.

Methods

Retrospective study reviewing paediatric UC patient’s records diagnosed January 2009–June 2019. Demographics, diagnosis, auxology, extra-intestinal manifestations, medical/surgical treatment and therapeutic drug monitoring (TDM) data were recorded.

Results

Fifty-two patients were diagnosed with UC, 23 females. Median age at diagnosis 10 years (range: 1–15). Median follow-up: 40.5 months (range: 1–125). At diagnosis, 85% received 5-aminosalicylates (5ASA), 82% steroids, 51% azathioprine. Within 1 year, 94% received steroids, 90% azathioprine and 69% biologics (Infliximab (IFX) and Adalimumab (ADA)), mean months after diagnosis: 18.4 ± 16.8. Seventy-six per cent were monitored with a proactive approach (TDM). Seventy-one per cent developed antibodies towards IFX after an average of 9.2 months (concomitant treatment with immunomodulators), 27% to ADA after an average of 15.2 months. Treatment at 1 year: 80% 5ASA, 70% AZA, 8% MTX, 13% IFX, 13% ADA and 4% sirolimus. At 1-year follow-up, steroid treatment dropped from 82% to 24% (p < 0.001), steroid-free remission rate 76%. Rate of first relapse 19% within 3 months, 38% within 6 months and 61.5% within 12 months. The latest endoscopy available (mean: 41.6 ± 25.2 months): 19% mucosal remission, disease limited to rectum: 15%. Disease regression 40%, stable 23% and progression 6%. Extra-intestinal manifestations 27%; three cerebrovascular events. No patients manifested lymphoproliferative disease. Only three patients underwent surgery, colectomy rate 6%. We compared patients who initiated azathioprine at diagnosis (51%, early group) and after 1 month (44%, late group). No surgery in the early group, two in the late group. Steroid use was higher in the early group (95% vs. 61%, p = 0.013). There were no differences in the mean number of steroid courses, PUCAI, treatment escalation, flares, family history, UCEIS, blood exams at diagnosis and growth parameters. At 1-year follow-up, the mean PUCAI was double in the late group, CRP was double in the early group (18.3 ± 24.9 vs. 7.3 ± 10.0, p = 0.2). The need to escalate treatment at 2 years was correlated to ESR (p = 0.05) and PUCAI at 1 year (p = 0.04), steroid courses (p = 0.049) and AZA dose at 1 year (p = 0.04). We found a significant difference in patients receiving adalimumab (0 vs. 6, p = 0.005). AZA doses were similar in both groups.

Conclusion

We suggest that an accelerated step-up approach may reduce colectomy rates in paediatric UC patients. Further multi-centre studies are needed to confirm our findings.
P530 Cost-effectiveness of vedolizumab SC vs. adalimumab for moderately to severely active ulcerative colitis
Authors: Diakite I , Schultz B , Carter J , Snedecor S , Turpin R
Published: January 2020

Background

Intravenous vedolizumab (VDZ IV) is approved for the treatment of moderately to severely active ulcerative colitis (UC). Subcutaneous VDZ (VDZ SC) was studied in the VISIBLE 1 trial (NCT02611830) and is under review by the US Food and Drug Administration for maintenance treatment. VARSITY (NCT02497469) is the first head-to-head trial to compare 2 biologics (VDZ IV vs. adalimumab SC [ADA]) in UC. We evaluated the cost-effectiveness of VDZ SC vs. ADA from a US payor perspective using efficacy data from these trials.

Methods

We used a cohort decision tree model with a time horizon up to 2 years. Simulated cohorts included patients with and without prior biologic therapy who initiated treatment with VDZ IV (300 mg in weeks 0, 2, and 6) or ADA (day 1: 160 mg; day 15: 80 mg) for a 6 week induction period. Initial responders went on to maintenance treatment with VDZ SC (108 mg every 2 weeks) or ADA (40 mg every 2 weeks); maintenance remitters continued treatment for 2 years. Patients with inadequate response to induction, or serious adverse drug reaction (ADR) switched to treatment with biologics (tofacitinib, infliximab, or golimumab). Patients who were intolerant to biologics received corticosteroids with or without curative surgery. The relative effectiveness of VDZ IV vs. ADA was derived from network meta-analyses of published randomised controlled trials. Model outcomes included total direct medical costs associated with drug acquisition, administration, routine monitoring, toxicity management, ADRs, and cost per remission achieved. Costs (eg, drug, monitoring, healthcare resource utilisation, administration) are expressed in 2019 US$.

Results

Based on our model, VDZ SC was associated with greater clinical response (52.92% vs. 45.07%) and remission at year 2 (22.49% vs. 14.36%) compared with ADA. Total direct medical costs per patient over 2 years were $98,034 for VDZ SC and $137,007 for ADA. After 2 years of treatment, more patients were in remission with VDZ SC than ADA for lower overall costs.

Conclusion

The clinical foundation for this model is built primarily on evidence from clinical trials of adults with moderately to severely active UC. This allowed us to extrapolate clinical outcomes out to 2 years and estimate direct medical costs over that time. These modelled outcomes indicated that treatment with VDZ IV followed by VDZ SC is more effective and less costly for remission compared with initiation with ADA.
P535 Effects of the Janus Kinase 1 (JAK1)-selective inhibitor filgotinib on circulating cytokines and whole-blood genes/pathways of patients with moderately to severely active Crohn’s disease (CD)
Authors: Roblin X , Serone A , Yoon O K , Zhuo L , Grant E , Woo J , Liu J , Galien R , D’Haens G
Published: January 2020

Background

A Phase 2 study of the JAK1-selective inhibitor filgotinib (FIL) dosed at 200 mg once daily for 10 weeks in moderately to severely active CD (FITZROY, ClinicalTrial.gov #NCT02048618) demonstrated significantly higher clinical remission rates compared with placebo,1 and early decrease in systemic and mucosal inflammation biomarkers that was more pronounced in endoscopic responders.2 We investigated baseline (BL) correlation of whole-blood transcriptome pathway activities with clinical disease indexes and circulating cytokines. The effect of FIL on changes in disease-related pathways in responders and nonresponders was also explored.

Methods

PAXgene blood samples were collected from 104 CD patients at BL and Week 10 (W10). RNA was sequenced (Illumina HiSeq 2500) after globin depletion (ThermoFisher GlobinClear). Differential gene expression analysis was performed using the limma R package,3 and Hallmark pathway4 activity scores were calculated using a single-sample Gene Set Enrichment Analysis (ssGSEA).5 All correlations were performed using the Spearman method.

Results

At BL, pathways with activity scores positively correlated with Simple Endoscopic Score for Crohn’s Disease (SES-CD) were immune (IL6/JAK/STAT3, inflammatory response), metabolic, and reactive oxygen species (ROS). These were also positively correlated with systemic inflammation (CRP, SAA, IL6, and OSM) and epithelial turnover (IL22, C4M2, and C3M) markers. Ten weeks of FIL treatment led to significant decreases in these pathways in endoscopic responders (50% reduction in SES-CD) (Figure), whereas there were no significant changes by placebo treatment. While interferon (IFN) response pathway scores showed a weak correlation (rho < 0.2) with SES-CD at BL, they are significantly reduced by FIL treatment, particularly in FIL responders.

Conclusion

In whole blood, inflammation, metabolic, and ROS pathways are reduced by FIL in endoscopic responders at W10, while a reduction in IFN response pathways was observed in all patients regardless of endoscopic response.

References
P536 Early prediction of intravenous corticosteroid therapy failure in moderate–severe ulcerative colitis
Authors: Croft A , Lord A , Radford-Smith G
Published: January 2020

Background

An episode of acute severe ulcerative colitis (UC) is a watershed event during the disease course with a heightened risk of colectomy during and following these episodes.1 The prompt identification of these events followed by the early implementation of appropriate treatment is essential to obtaining the best clinical outcomes for these unwell patients. The majority of published risk scores predicting the important clinical outcomes of intravenous corticosteroid therapy failure and colectomy-by-discharge rely on clinical data from days 1–3 of therapy.2 There is a paucity of tools that allow for a simple and individualised prediction of risk of corticosteroid therapy failure during the earliest stages of admission.

Methods

Data were prospectively obtained from 349 presentations of moderate–severe UC requiring hospital admission to a tertiary referral hospital. The failure of intravenous corticosteroid therapy was strictly defined by the (Oxford) Day 3 and Day 7 criteria.3 Seventeen clinical, laboratory and endoscopic variables all available within 24 h of hospital presentation were assessed for their ability to differentiate intravenous corticosteroid therapy responders from non-responders. A stepwise generalised linear model was formulated based on the results of the initial univariate analyses.

Results

Intravenous corticosteroid therapy failure occurred in 208/349 (60%) of presentations. The formulated risk score included the variables of oral corticosteroid therapy failure, bowel frequency and serum albumin concentration with or without the Mayo endoscopic subscore (MES). With the addition of the MES, the area under the curve (AUC) of the risk score was 0.758. When the positive predictive value of the score (threshold) for correctly predicting intravenous corticosteroid therapy failure was set at 85%, 105/275 (38%) of presentations with available data were identified as high risk for corticosteroid therapy failure (Figure 1).

Conclusion

This practical risk assessment tool provides clinicians with a personalised prediction of the likelihood of success of a course of intravenous corticosteroid therapy in moderate–severe UC. It enables the identification of individuals at high risk of treatment failure who may be suitable for consideration of early treatment escalation or screening for appropriate clinical trials.

References
P549 A virtual clinic enhances the quality use of anti-TNF dose intensification and rates of treatment success using a treat-to-target approach compared with standard outpatient care in Crohn’s disease
Authors: Srinivasan A , van Langenberg D R , Little R , Sparrow M P , De Cruz P , Ward M G
Published: January 2020

Background

Virtual clinics (VC) represent a novel model-of-care which promote quality use of biologics and facilitate a treat-to-target (T2T) approach. We aimed to evaluate the clinical and process-driven outcomes of intensified anti-TNF therapy for secondary loss of response (SLoR) in a VC compared with standard outpatient care (SoC).

Methods

A retrospective multicenter, parallel observational cohort study of patients with Crohn’s disease (CD) who underwent anti-TNF dose intensification to address SLoR with up to 2-years of follow-up was undertaken. Objective assessments of disease activity and anti-TNF trough levels at SLoR then during subsequent 6-month semesters were compared longitudinally between VC and SoC groups. ‘Anti-TNF escalation success’ was the primary endpoint, defined as achieved when two consecutive 6-month semesters of objective assessment demonstrated inactive disease. Dose intensification was defined as ‘appropriate’ if there was both objective evidence of disease activity, plus anti-TNF trough levels at or below the lower limit of the therapeutic range prior to intensification. ‘Treatment escalation failure’ was defined by the occurrence of one or more of biologic switching, discontinuation or further intensification; recommencement of corticosteroids, or IBD-related surgery.

Results

149 patients (69 VC vs. 80 SoC) underwent infliximab (n = 94) or adalimumab (n = 55) dose intensification with similar baseline patient, disease and treatment characteristics between cohorts. The median duration of follow-up post dose-intensification was 1.9 and 1.5 years for the SoC and VC cohorts respectively (p = 0.37). There were higher rates of appropriate dose intensification (82.6 vs. 40.0%, p < 0.01) across the VC cohort. Higher proportions of anti-TNF escalation success (60.9 v 35.0%, p < 0.01), biomarker remission (i.e., C-Reactive Protein (<5mg/l) and faecal calprotectin (<150 μg/ml) normalisation, log-rank tests, p = 0.06 and p < 0.01 respectively), tight disease monitoring (84.1 vs. 28.8%, p < 0.01) and de-escalation of intensified therapy (21.3 vs. 10.0%, p = 0.03) were also achieved by the VC cohort following dose-intensification.

Conclusion

This study favoured a VC-led model of care over standard outpatient-based IBD care in facilitating an effective T2T approach to CD management. A VC model of care improved quality use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and encouraged more frequent anti-TNF dose de-escalation. Moreover, tight semester-based monitoring using a T2T-based strategy facilitated by the VC was associated with improved treatment outcomes.