bluuebunny/crossref_metadata_2025 huggingface dataset:
P456 Longer-term outcomes in acute severe colitis
Authors: CAMPBELL R , Haddock R , Parman K , MacDonald J , Seenan J P
Published: January 2020

Background

Acute severe ulcerative colitis (ASUC) is a medical emergency. Rescue medical therapy is increasingly used in steroid-refractory patients but has historically been considered to delay rather than prevent colectomy. We have previously described short-term outcomes from our unit of cases of ASUC, as defined by Truelove and Witt’s criteria, over a 1 year period (July 2016 to June 2017). Data on longer-term outcomes is now available.

Methods

Electronic patient records (EPRs) of cases included in the original study were reviewed. Outcomes including readmission rates, need for colectomy, steroid use, medical escalation and rates of biochemical remission (as defined by faecal Calprotectin (FC) <250μg/l) were recorded.

Results

In total, 58 cases (51 patients) were included in original cohort. 19 failed initial medical therapy with steroids with 10 successfully treated using rescue medical therapy thus avoiding colectomy. Only 1/10 required subsequent colectomy during our median follow-up period of 32 months.

29/51 (56.9%) patients settled with steroids alone. 3 died of unrelated causes so were excluded from further analysis. Further oral steroids were prescribed in 53.8% (14/26).

6 patients were already receiving an immunomodulator (azathioprine or mercaptopurine) prior to initial presentation. 75% of the remainder (15/20) were discharged on aminosalicylates as their only maintenance therapy but the majority (60%, 9/15) subsequently required medical escalation with only 30% (6/20) continuing aminosalicylate monotherapy. 1 colectomy also occurred in this group.

17 readmissions occurred in 12 patients with the majority (52.9%, 9/17) within 1 year. At the end of follow-up two out of three patients (66.7%, 12/18) were considered to be in biochemical remission (FC <250 μg/l).

Conclusion

Rescue medical therapy for ASUC provides sustained benefit with the vast majority avoiding delayed colectomy. Patients admitted with ASUC have significant readmission rates, particularly within 1 year with frequent need for further steroids and/or escalation of medical therapy. Long-term remission rates are high but aminosalicylate monotherapy is rarely adequate to achieve this. All patients with an adequate response to treatment for ASUC should be considered for initiation of immunomodulator and/or biologic Rx prior to discharge. ASUC patients should be considered for more intensive follow-up and early, aggressive medical escalation. An enhanced inpatient liaison service and early review clinic is planned to support this.
P458 Association between adalimumab serum levels and level of remission in Crohn’s disease
Authors: Hambli S , Rogeau S , Duveau N , Nachury M , Branche J , Gérard R , Wils P , Lauriot Dit Prevost C , Lambin T , Desreumaux P , Labalette M , Pariente B
Published: January 2020

Background

Adalimumab (ADA) is effective as induction and maintenance therapy in Crohn’s disease (CD). Serum ADA levels have been shown to be correlated with clinical remission. Therapeutic goals have evolved based on the notion of ‘treat to target’ and the aim is to achieve deep remission. The objective of this study was to consider the association between serum ADA levels and clinical, biological, endoscopic and iconographic remission in CD.

Methods

From October 1, 2016 to December 31, 2018, all CD patients receiving ADA who had a serum ADA level test with anti-ADA antibodies (AAA) detection were consecutively included. We compared serum ADA levels between the following groups: patients with and without clinical remission, patients with biological remission and those with a CRP >5mg/l, patients with endoscopic remission and those with ulcerations and patients with iconographic remission and those with active radiological lesions. In addition, we defined optimal cut-off values to reach these therapeutic targets by analysing ROC curves.

Results

Three hudred and four patients were included corresponding to a total of 445 assays. Indications for the ADA assay were mainly for persistent disease activity in 308 (69%) samples. An immunosuppressant was initially associated with ADA treatment in 154 (35%) samples and 75 (17%) assays were performed under combotherapy. ADA concentrations were higher in patients who started ADA in combotherapy (8.3 vs. 6.6 μg/ml, p = 0.005), but not in patients treated by combotherapy at the time of dosing (8.7 vs. 7.1 μg/ml, p = 0.12). Serum levels of ADA were significantly higher in patients in remission compared with patients with active disease for clinical remission (7.9 vs. 6.3 μg/ml, p = 0.015), biological remission (9.5 vs. 5.1 μg/ml, p <0.001), endoscopic remission (10.1 vs. 6.1 μg/ml, p <0.001) and luminal iconographic remission (9.1 vs. 6.8 μg/ml, p = 0.04). ROC curves and the areas under the curve (ASC) were analysed to determine optimal cut-off values of serum ADA levels to predict these different levels of remission: 6.45 μg/ml (AUC 0, 56, p = 0.027) for clinical remission, 7.35 μg/ml (AUC 0.67, p < 0.001) for biological remission, 9.75 μg/ml (AUC 0.64, p = 0.002) for endoscopic remission and 7.80 μg/ml (AUC 0.58, p = 0.04) for luminal iconographic remission.

Conclusion

High levels of ADA are associated with clinical, biological, endoscopic and iconographic remission in CD. Optimal cut-off values of ADA have been identified and increase as deep remission is obtained. These results suggest that serum ADA levels should be considered to be one of the tools in the tight control strategy of CD and adapted according to pre-defined objectives (clinical, biological or mucosal).
P483 Vedolizumab serum drug levels are not associated with clinical outcomes or markers of disease activity in inflammatory bowel disease
Authors: Shields S , Seenan J P , Nowell E , Dunlop A , Galloway P , Macdonald J
Published: January 2020

Background

Treatment options in Inflammatory Bowel Disease (IBD) include anti-TNFα and anti-integrin biologics. Therapeutic drug monitoring (TDM) is used to support clinical decision making and improve treatment outcomes with anti-TNFα drugs infliximab and adalimumab.1,2 It is unclear if TDM can offer similar benefits with vedolizumab (VDZ) and there are no clinical guidelines for using TDM with VDZ3. The aim of this study was to identify if drug levels (DL) are associated with clinical outcomes and markers of disease activity in patients treated with VDZ.

Methods

All VDZ DLs performed since introduction of testing at our unit in December 2018 were retrospectively identified. Target DLs of >30 μg/ml during induction (≤14 weeks since treatment initiation (TI)) and >10 μg/ml in maintenance (>14 weeks after TI) were agreed based on available published data. Dose information, timing of DL, lab results and disease activity scores were obtained from electronic patient records and paired with the DL dose. Calprotectin was included if recorded within 3 months of DL. Patients were classified as in remission or mild, moderate or severe active disease according to partial Mayo Score for ulcerative colitis and Harvey–Bradshaw Index for Crohn’s disease. Sub-analysis was undertaken according to timing of testing in relation to TI.

Results

Sixty pre-dose trough VDZ levels were identified from 41 patients. Median VDZ level was 25.7 μg/ml (<3.5–>70). Median time from TI to first VDL DL was 36 weeks (4.6–184). No relationship was identified between VDZ levels and biochemical markers of disease (Figure 1). Fourteen (23.3%) TDM were performed during induction. 6/14(42.8%) had subtherapeutic DLs; 3 in remission, 1 mild, 2 severe disease. The remaining 8/14(57.1%) had therapeutic DL; 3 mild, 3 moderate, 1 severe disease, 1 unknown. Forty-six (76.7%) TDM were performed during maintenance. Five out of 46(10.9%) had subtherapeutic DLs; 3 remission, 1 moderate disease, 1 unknown. The remaining 41/46(89.1%) had therapeutic DLs; 16 remission, 11 mild, 10 moderate, 3 severe disease, 1 unknown. For both sub-analysis groups, no relationship between disease state and drug level was observed.

Conclusion

The results from this small cohort do not suggest a relationship between serum VDZ levels and clinical outcomes. Further research in larger cohorts is needed to confirm or refute these findings.

References
P495 Usefulness of a capsule endoscopy scoring system in understanding the disease state of Crohn’s disease
Authors: Omori T , Kambayashi H , Murasugi S , Ito A , Yonezawa M , Tokushige K
Published: January 2020

Background

Crohn’s disease (CD) is a pathological condition that develops because of inflammatory and organic changes such as stenosis. The Lewis Score (LS) and Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) are employed for scoring small bowel lesions in CD using small bowel capsule endoscopy (SBCE). However, it remains unclear whether the obtained score can contribute to the understanding of the disease state or the selection of treatment. This study aimed to examine whether the existing scoring systems (LS and CECDAI) and the new Crohn’s Disease Activity in Capsule Endoscopy (CDACE) scoring system proposed by us were useful in understanding the disease state of CD.

Methods

After obtaining the results of intestinal patency evaluations using patency capsules from June 2012 to June 2018, 196 times (108 CD patients) who underwent SBCE were included in this retrospective study. The cut-off values of LS, CECDAI, and CDACE were calculated using the receiver operating characteristic curve to determine the extent of small intestinal lesions and the presence or absence of stenotic lesions. Using the cut-off values, the sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of each scoring system were determined. In CDACE, the small bowel is divided into quartiles, and the degree of inflammation (range: 0–4) for each quantile (range: 0–16) (inflammation score: A), number of quartiles with inflammation (range: 0–4) (range score: B), and degree of stenosis (range: 0–3) (stenosis score: C) were scored; the CDACE score was calculated as follows: A × 100 + B × 10 + C (score range: 0–1643).

Results

For LS, the Se, Sp, PPV, and NPV were 83.7%, 73.5%, 75.9%, and 81.8%, respectively, for inflammation in multiple quantiles (2/3 quantiles or more) (cut-off value: 10) and 94.9%, 90.5%, 71.2%, and 98.6%, respectively, with regard to the presence or absence of stenosis (cut-off value: 196). For CECDAI, the Se, Sp, PPV, and NPV were 93.8%, 86.1%, 82.6%, and 93.4%, respectively, for multiple quantiles (both proximal and distal) (cut-off value: 5) and 51.3%, 87.9%, 51.3%, and 87.9%, respectively, with regard to the presence or absence of stenosis (cut-off value: 11). For CDACE, the Se, Sp, PPV, and NPV were 100%, 82.4%, 78.6%, and 100%, respectively, for multiple quantiles (multiple locations excluding two consecutive zones) (cut-off value: 320) and presence or absence of stenosis was identified in the first digit.

Conclusion

CECDAI was more likely to predict the extent of inflammation than LS, although it was difficult to determine the presence or absence of stenosis. Based on the scores, CDACE may be a useful scoring system in clinical practice where the disease state of CD needs to be determined.
P516 Daily consumers of drip-filtered coffee have a decreased risk of developing late-onset Crohn’s disease
Authors: Widbom L , Hultdin J , Ekblom K , Karling P , Nilsson L M
Published: January 2020

Background

Coffee is known to impact on colon motility, alter gut-related immune response, and to affect symptoms among inflammatory bowel disease (IBD) patients. In spite of this, the role of coffee as a determinant of IBD is unclear. The aim of this study was to investigate how coffee correlates to the risk of developing late-onset IBD in general, and subdivided into Crohn’s disease and ulcerative colitis.

Methods

This nested case-control study within the large, population-based Northern Sweden Health and Disease Study (NSHDS), included data from 78 patients with IBD and 311 controls matched for age, sex, time and area of sample collection. Cases were included in NSHDS at least one year prior to IBD diagnosis. Coffee consumption was assessed by questionnaire-data, differing between drip-filtered and boiled unfiltered coffee. Risk associations were estimated through conditional logistic regressions.

Results

Results differed between different subgroups of IBD and coffee. Our main finding was a decreased risk of Crohn’s disease in subjects with a daily intake of drip-filtered coffee in comparison with subjects with a less frequent intake (Table). After adjustments for smoking, body-mass-index, educational level and marital status the results remained. Adjusted OR for Crohn’s disease was 0.22; 95% CI 0.07–0.76

Conclusion

Our results indicate potential biochemical differences depending on coffee preparation technique on IBD risk, with possible implications for prevention or treatment. Further studies are warranted.
P547 Inadequate vitamin C status and association with inflammatory biomarkers in adults with active Crohn’s disease
Authors: Wall C , MacFarlane K , Carr A , Day A , Gearry R
Published: January 2020

Background

Micronutrient deficiencies are common in inflammatory bowel disease (IBD) due to the inflammatory burden and changes in dietary intake. Vitamin C, an essential water-soluble antioxidant required for tissue repair and immune function, is found primarily in fresh fruit and vegetables however, this food group is more often avoided by people with IBD compared with the general population. This research aimed to determine serum vitamin C status in subjects with active Crohn’s disease, measure urinary vitamin C excretion in healthy controls (HC) and Crohn’s disease patients before and after exclusive enteral nutrition (EEN) and assess associations between inflammatory markers and vitamin C.

Methods

Stored serum and random urine samples prospectively collected from adults with mild to moderately active Crohn’s disease and adult HC were analysed. Both HC and Crohn’s disease groups received EEN with a known vitamin C content for two weeks. Serum and urinary vitamin C were measured using high-performance liquid chromatography with electrochemical detection. Urinary vitamin C was standardised to urinary creatinine. Non-parametric t-tests and correlations were performed.

Results

EEN was initiated in 38 patients (aged 16 to 39 years old). Inadequate serum vitamin C (<50 µmol/l) was present in 36/38 patients with active Crohn’s disease and 45% had hypovitaminosis C. Baseline C-reactive protein (CRP) was 12 mg/l (range, 3 to 158 mg/l) and faecal calprotectin was 1065 µg/g (range, 60 to 3838 µg/g). Serum vitamin C correlated weakly with CRP (r = −0.30 95% CI: −0.58 to 0.03, p = 0.06) but not with faecal calprotectin. Two weeks of EEN was completed by 30 (79%) patients and 17 (81%) HC. The average vitamin C intake was 168mg/day (range, 108–252 mg/day). Baseline urinary excretion of vitamin C was low in both Crohn’s disease and HC. Following EEN urinary vitamin C excretion increased significantly in both groups (Figure 1).

Conclusion

Patients with active Crohn’s disease had inadequate vitamin C status. EEN increased urinary vitamin C excretion in both Crohn’s disease and HC, suggesting low baseline dietary vitamin C intake and potentially enhanced utilisation. Further research with a larger patient cohort would provide a greater understanding of vitamin C metabolism in active Crohn’s disease.
P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study
Authors: Fischer S , Mesfin S , Klenske E , Schmitt H , Vitali F , Hirschmann S , Ramming A , Zundler S , Rath T , Krebs S , Dörje F , Uter W , Nagore D , Meyer S , Neurath M F , Atreya R
Published: January 2020

Background

SB2 is a biosimilar infliximab approved for the treatment of inflammatory bowel disease (IBD) patients. These are the first prospective data investigating long-term efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in IBD patients.

Methods

This is a prospective, observational cohort study of patients that underwent a switch from infliximab originator to biosimilar SB2 in 2017 as part of routine care at the outpatient Clinic for IBD at the University Hospital of Erlangen, Germany. Long-term safety and clinical effectiveness were recorded over a follow-up period of 18-months. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI) in Crohn’s disease (CD) and the partial Mayo Score (pMS) in ulcerative colitis (UC) patients. C-reactive protein (CRP) was analyzed at every patient visit, and IFX trough-level (TL) and anti-IFX antibodies (ADA) were measured prior to every SB2 administration, using the Promonitor® tests. The occurrence of adverse events was registered at every patient visit.

Results

A total of 148 IBD patients (96 CD, 52 UC) was enrolled. The median duration of previous infliximab treatment before the switch was 29 months (range 1.0–110.0). Median disease activity in CD was an HBI of 3 (0–16) at switch (baseline), 2 (0–13) at month 6, 3 (0–15) at month 12 and 2.5 (0–11) at month 18. Median disease activity in UC was a pMS of 0 (0–6) at baseline, 1 (0–4) at month 6, 1 (0–4) at month 12 and 1 (0–5) at month 18. The median TL for all IBD patients was 6.3 mg/ml (0.1–33.7) at baseline, 5.0 mg/ml (0.1–34.3) at month 6, 6.3 mg/ml (0.1–35.8) at month 12 and 5.1 mg/ml (0.1–35.4) at month 18. CRP for all IBD patients was 2.2 mg/l (0.1–45.6) at baseline, 2.2 mg/l (0.1–90.4) at month 6, 2.3 mg/l (0.1–169.5) at month 12 and 2.7 mg/l (0.1–19.8) at month 18. In the 18-month follow-up period, 12/103 (11.7%) of patients who were ADA-negative at baseline developed ADA post-switch. Altogether, 40 (27%) IBD patients discontinued SB2 treatment during the 18-month follow-up period (4 anaphylaxis, 20 loss of response, 7 non-serious and 9 serious adverse events), 2 paused during pregnancy, 1 discontinued in clinical remission, 10 were lost to follow-up (7 change of physician, 3 unknown). Serious adverse events comprised 3 malignancies (breast and prostate carcinoma, neuroendocrine malignancy), 1 liver abscess and 5 intestinal surgical procedures (1 perforation, 1 ileus, and 3 stenoses).

Conclusion

Switching from IFX originator to biosimilar SB2 was not associated with an increase in disease activity. No clinically meaningful changes in IFX trough levels or immunogenicity were identified. Altogether, SB2 was well tolerated in a real-life setting.
P554 Dietary practices and beliefs of patients with inactive ulcerative colitis: A prospective UK study
Authors: Crooks B , McLaughlin J , Limdi J K
Published: January 2020

Background

Our understanding of the aetiopathogenesis of inflammatory bowel disease (IBD), in particular the impact of environmental factors, remains limited. The role of diet in IBD appears to be of particular importance to patients. The dietary habits of the IBD population with inactive disease have scarcely been reported. We describe the dietary practices of patients with inactive ulcerative colitis (UC) and the information resources which guide these beliefs.

Methods

We developed a questionnaire assessing demographics, dietary practices and the use of information resources in patients with inactive UC (defined as a PRO2 score ≤ 1 (rectal bleeding subscore = 0)). This is being prospectively administered to 200 consecutive patients with inactive UC.

Results

Data from 168 patients are available to date. Mean patient age is 54 years, 58% male and 89% Caucasian. Mean disease duration is 12 years. Disease extent is 20% E1, 43% E2 and 29% E3. Sixty-three per cent of patients report no relapse in the last year. 32% consider diet to be an initiating factor for their UC and this is based on their own experience (93%), the internet (30%) and a gastroenterologist’s advice (22%). 39% of patients feel that diet has previously triggered a relapse of their disease, the most commonly reported triggers being spicy foods (45%), alcohol (38%), fatty foods (38%), coffee (27%) and milk products (26%). Fifty-four per cent of patients avoid certain foods, at least sometimes, to prevent relapse. Spicy foods are most frequently avoided (76%) followed by fatty foods (65%), alcohol (53%), coffee (46%), carbonated drinks (44%), milk products (42%) and red meat (36%). Female patients are significantly more likely to restrict their diet in an attempt to prevent a relapse of their UC (p = 0.002). A fifth of patients consume specific foods or nutritional supplements to prevent a UC relapse, most commonly probiotics or turmeric. Fifty-seven per cent of patients believe that the recommended diet in disease remission is different to that in relapse however less than half of patients report being able to find specific dietary advice for UC. Dietary recommendations are most commonly sourced via the internet.

Conclusion

A significant proportion of patients with inactive UC have strong beliefs pertaining to diet and specific dietary triggers. Credible sources of dietary information for IBD patients remain lacking. A high prevalence of self-imposed dietary restriction may risk nutritional deficiency in such patients and impact upon the quality of life. More data and mechanistic explanations are needed to understand the complicated relationship between dietary components and gut inflammation. A larger dataset will be presented at conference proceedings.
P555 Frequent disease relapse after withdrawal of infliximab in IBD patients with sustained remission
Authors: Gordon H , Murray J , Tailor F , Goh S A , Lindsay J O
Published: January 2020

Background

In the UK, NICE guidance requires an annual review of TNF antagonists with the withdrawal of therapy in patients in confirmed remission. This study assesses the outcome of this practice in patients with Crohn’s disease (CD) and ulcerative colitis (UC) who received infliximab at a large referral centre. The primary outcome is relapse-free survival. Secondary objectives include evaluation of predictors of relapse, and response to subsequent therapy.

Methods

IBD patients who ceased infliximab due to remission at annual review were identified. Demographics and clinical characteristics were collected from electronic patient records. Disease activity from 3 months prior to cessation and throughout follow-up was recorded; active disease was defined as CRP>10, faecal calprotectin>50, endoscopic activity or radiological activity. Relapse was defined as the aforementioned markers of activity with clinician documentation of relapse. Immunomodulator use, active disease prior to cessation, age at diagnosis and ethnicity were analysed in patients who had completed 6, 12, 18 and 24 months of follow-up. Survival analysis and logistical regression were undertaken with SPSS®. In patients who relapsed, steroid use and future biologic use was evaluated. Analysis was undertaken for total IBD, CD and UC.

Results

66 cases were identified (CD:UC = 40:26, F:M =28:38, Asian:Black:Caucasian:Multiracial/Unknown = 13:3:45:5). Median follow-up was 18.1 months (IQR 9.07–41.71). Failure free survival was: all IBD; 14.65 months (IQR 8.38–25.23), CD; 13.08 months (IQR 7.66–25.23) and UC; 14.65 months (IQR 5.91–22.47). Relapse rates of patients who completed follow-up at each time point are presented in Table 1:

No predictors of disease relapse were identified at any time point. Thirty-seven patients experienced relapse, of whom 40.5% (15/37) were prescribed steroids, 86.5% (32/37) restarted a biologic and 67.7% (25/37) restarted infliximab. Of those who have completed infliximab induction, 56.5%(13/23) recaptured response to standard dose and a further 13.0% (3/23) required 10mg/kg. Alternative therapy was required in 30.4% (7/23).

Conclusion

Within 24 months of cessation 73.1% patients relapsed. The majority of these restarted a biologic. However, only 56.5% of patients who restarted infliximab responded to standard dose. With additional costs of newer biologics and morbidity of disease flare and steroid use, routine withdrawal of TNF antagonists should only occur after careful consideration.
P565 Efficacy and safety of long-term treatment with ustekinumab in moderate–severe ulcerative colitis patients with delayed response to ustekinumab induction: Results from UNIFI 2-year long-term extension
Authors: Sands B E , Abreu M T , Leong R W L , Marano C , O’Brien C D , Zhang H , Zhou Y , Johanns J , Rowbotham D , Hisamatsu T , Arasaradnam R P , Scherl E , Danese S , Peyrin-Biroulet L
Published: January 2020

Background

Ustekinumab (UST) has been shown to induce and maintain clinical response and remission in moderate–severe UC patients in the UNIFI study. In the UNIFI maintenance study, the primary randomised population consisted of patients who were in clinical response 8weeks after UST induction treatment. Patients who had a delayed response to induction were also eligible for the maintenance study but were not included in the randomised analysis set. Here, we present the efficacy and safety of UST maintenance among delayed responders who were treated in the UNIFI long-term extension(LTE).

Methods

UNIFI was a single protocol of induction and randomised withdrawal maintenance studies in patients with moderate–severe UC who failed conventional or biologic therapy(including TNF antagonists and/or vedolizumab). Delayed responders were patients who were not in clinical response to UST IV induction at Week8 but achieved response at Week16 following a single UST90mg SC dose at Week8. These patients entered the maintenance study and continued to receive UST90mg SC q8w. Patients who completed Week44 evaluations were eligible to enter LTE continuing to receive UST90mg SC q8w. Efficacy in delayed responders to UST(who were treated in LTE) was evaluated over time through Week92 and safety through Week96.

Results

116 delayed responders to UST induction were treated in the LTE, including 58 who had previously failed biologic therapy and 58 who had not failed biologic therapy, 54 of whom were bio-naïve. Symptomatic remission(defined as stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) rates in delayed responders to UST induction increased from maintenance baseline to Weeks 44 and 92 (Table 1). Similar trends were seen within the biologic failure subgroups; although, rates among patients who had not failed biologics (primarily bio-naïve) were greater than those of patients who had failed biologics. Among the 79.3% (n = 92/116) of delayed responders to UST in symptomatic remission at Week 92, 94.6% (n = 87/92) were corticosteroid free. Safety data for randomised and non-randomised patients treated in UNIFI LTE is in Table2. The safety profile for UST in delayed responders was generally similar to that observed among patients randomised to UST; no new safety signals were observed.

Conclusion

Delayed responders to UST treatment maintained symptomatic remission through Week 92 with UST90mg SC q8w and the majority did so in the absence of corticosteroids.
P570 The burden of anaemia remains significant over time in patients with inflammatory bowel disease at a tertiary referral centre
Authors: Singh Singh K , Al-Khoury A , Kurti Z , Gonczi L , Golovics P , Kohen R , Afif W , Wild G , Seidman E , Bitton A , Bessissow T , Lakatos P
Published: January 2020

Background

Anaemia is an important complication and/or extra-intestinal manifestation of inflammatory bowel disease (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the occurrence of anaemia and the frequency of anaemia screening over time, at a tertiary referral IBD centre.

Methods

We retrospectively reviewed the occurrence of anaemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre (MUHC) IBD centre. Consecutive patients presenting with an outpatient visit (‘index visit’) between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were captured.

Results

1356 and 1293 CD and UC patients [disease duration: 12 (IQR:6–22) and 10 (IQR: 5–19) years] were included in the 2 periods. The prevalence of moderate or severe anaemia at referral/diagnosis (15.4% and 8.5%) and during the follow-up (11.1% and 8.1%) was higher in CD than in UC patients, with a decrease of anaemia in CD patients between the 2 periods. The prevalence of any anaemia at follow-up was 22.4% and 18.7% in CD and in UC, while 82.7% of patients were tested at least once for anaemia during a 6-month period. UC patients with more extensive disease, treated with steroids or biologics at the time of referral but not during follow-up, active disease, or an elevated calprotectin at the time of assessment, and CD patients with active disease, elevated CRP or calprotectin at the time of assessment, with complicated disease, perianal involvement, previous respective surgery or colonic disease location, had a higher risk of anaemia. Intravenous iron therapy was prescribed in 46 patients (46.8% patients (37/79) with moderate or severe anaemia) with 72.3% having active disease (CD: 65.2%, steroid 83.3%, biological therapy: 78.6%, CRP: 97.8%, FCAL: 73.9%) in the second cohort. 91.3% of patients receiving intravenous iron had an extensive evaluation of anaemia pre- and post-therapy (CBC, ferritin, transferrin, TSAT, B12, folate). Anaemia improved by >2g/l in 56.5% after 4–6 weeks (intravenous iron dose >1000mg in 87% of patients). Four patients required a blood transfusion.

Conclusion

Anaemia occurred frequently in this IBD cohort, at referral to the centre and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anaemia regularly and with accurate anaemia workup in patients prescribed intravenous iron therapy, yet the targeted management of moderate to severe anaemia was suboptimal.
P579 Randomised open-label controlled trial of ciprofloxacin/doxycycline/hydroxychloroquine combination compared with standard budesonide in active Crohn’s disease (APRICOT)
Authors: Rhodes J M , Subramanian S , Flanagan P , Horgan G , Martin K , Mansfield J , Parkes M , Hart A , Dallal H , Iqbal T , Butterworth J , Culshaw K , Probert C
Published: January 2020

Background

Mucosal E. coli are increased in Crohn’s disease (CD). They replicate within macrophages where they are inaccessible to penicillins and gentamicin. Hydroxychloroquine is successfully used together with doxycycline, typically for 12 months, to treat Whipple’s disease. It raises macrophage intra-vesicular pH and inhibits replication of bacteria , including E. coli that require an acid pH. Ciprofloxacin and doxycycline are also effective against E. coli replicating inside macrophages.

Methods

Adult patients with active CD (CDAI>220 plus CRP≥5mg/l and/or faecal calprotectin >250 μg/g) were randomised to receive either standard oral budesonide (Entocort CR 9mg/day for 8 weeks, 6mg/day for 2 weeks, 3mg/day for 2 weeks) or antibiotics/hydroxychloroquine (AB/HCQ) - oral ciprofloxacin 500mg bd, doxycycline 100mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by continuation of doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for a further 20 weeks. The use of anti-TNF in the previous 3 months was an exclusion. Primary endpoint parameters were remission at 10 weeks, remission maintained through to 24 weeks, and remission maintained through to 52 weeks. Secondary endpoints included remission and/or response (fall in CDAI of >70) at 10 weeks and remission at 4 weeks. Patients who failed to respond by 10 weeks were invited to cross-over onto the alternative therapy.

Results

59 patients were recruited across 8 sites, lower than target (100) because recruitment slowed due to widening access to biologics. Including cross-over, 39 patients received AB/HCQ and 39 received budesonide. No significant differences were seen comparing AB/HCQ with budesonide at 10, 24 or 52 weeks on either intention-to-treat or per-protocol analysis (see table). Withdrawals by 10 weeks due to adverse events were seen in 16 AB/HCQ, - including nausea (3), photosensitivity (2), Achilles pain (2) and activity of CD (4); and 7 budesonide. Although not significant when analysed per protocol, when patients on AB/HCQ who responded at 10 weeks and later remitted were included, 9/24 patients were in remission at 24 weeks and 4/23 at 52 weeks. No correlation was seen between response to AB/HCQ and ASCA/OmpC status.

Conclusion

The longer-term remissions seen in some patients receiving AB/HCQ are encouraging and a larger phase 3 study is justified.
P583 The prevalence of side effects to immunomodulators and biologics in patients with Crohn’s disease intestinal failure compared with Crohn’s disease without intestinal failure
Authors: Bouri S , Geldof J , Willsmore J , Donnelly S , Gabe S , Hart A
Published: January 2020

Background

Treatment of Crohn’s disease (CD) involves medications and surgery but experiencing medication side effects (SE) limits medical options. The aim of this study was to compare SE experienced by patients with CD and intestinal failure (CD-IF) vs. CD without IF as this may contribute to a higher surgical requirement.

Methods

A single tertiary centre retrospective analysis was performed on CD-IF patients on parenteral nutrition due to short-bowel syndrome vs. small bowel CD without IF. Patients with CD without IF were selected from consecutive clinics who lived in the local catchment area.

Results

94 CD-IF and 94 CD patients were included. The proportion of female patients was 56.4% (CD-IF) and 46.8% (CD); mean age was 51.2 (CD-IF) and 41.5 years (CD); mean duration of disease 24 years (CD-IF) and 16 years (CD). Most CD-IF patients had multiple resections. In the CD group, 50 patients never had surgery, 22 had 1 resection, and 9 had 2 or more. From the past medication history for these patients, the proportion in whom a medication was stopped due to SE was similar for CD-IF and CD for azathioprine, mercaptopurine and vedolizumab (Table 1). There were no SE to ustekinumab. Patients in the CD-IF group had a preceding history of significantly more SE to anti-TNF therapy and methotrexate were observed in CD-IF group, of which allergies were most frequent. In the CD group, 2 patients previously had an allergic reaction to infliximab whereas, in the CD-IF group 6 patients had a history of anaphylaxis and 5 an allergy to infliximab, 1 had an allergy to adalimumab and 3 to methotrexate (Table 2). Data on drug levels amongst those with allergy events were limited (due to prior availability of testing); of those tested, 1 had positive antibodies and 1 did not. The frequency of non-response and loss of response was similar between the two groups for each medication.

Conclusion

The frequency of SE to immunomodulators and biologics was similar between CD and CD-IF, except for anti-TNF therapy and methotrexate due to more allergy/anaphylaxis events in CD-IF. The frequency of these reactions may have caused an earlier shift towards surgical treatment. 92/94 CD-IF patients were diagnosed prior to 2014; it would be useful to review the incidence of CD-IF before 2014 (pre-vedolizumab and ustekinumab) vs. the new biological era.
P592 Frequency and causes of prolongation of the induction course of tofacitinib in patients with ulcerative colitis in conditions of real clinical practice
Authors: Knyazev O , Kagramanova A , Lishchinskaya A , Parfenov A
Published: January 2020

Background

Tofacitinib is a selective immunosuppressant, the first representative of the Janus kinase family inhibitors, which has a high selectivity against other kinases of the human genome. According to the results of the study, tofacitinib inhibits JAK-1, JAK-2 and in high concentrations-JAK-3 and tyrosine kinase-2. The drug is registered in Russia for the treatment of patients with ulcerative colitis. According to the instructions for medical use, in patients with incomplete response to the induction course, it is possible to conduct an additional 8 weeks of therapy at an induction dose of 10 mg 2 times a day. The objective of the study was to identify the frequency and reasons for the need to prolong the induction course of tofacitinib in patients with ulcerative colitis.

Methods

35 patients with ulcerative colitis (UC) who received tofacitinib were observed in the Department of inflammatory bowel diseases. Patients were divided into two groups. Group 1 (n = 10) of patients were bionaive. The second group of patients (n = 25) had previous experience of treatment with one or more anti-TNF-α drugs. The necessity of prolongation up to 16 weeks of induction course of tofacitinib was assessed in patients with an insufficient clinical response at week 8 of therapy (reduction of partial index of Mayo less than 30%) and lack of normalisation of laboratory parameters (CRP, haemoglobin, FCP). The comparative analysis was carried out by the method of four-field tables using nonparametric statistical criteria.

Results

In the follow-up period among group 1 UC patients (n = 10) who had not previously received anti-TNF-α drugs, the need for a prolonged induction course of tofacitinib was not required in any patient (0%). In the second group of patients (n = 25), previously treated with anti-TNF-α drugs, a prolonged induction course of tofacitinib was required in 9 (36%) patients (x2-4.484; p = 0.028).

Conclusion

The need for prolongation up to 16 weeks of the induction course of tofacitinib in patients with ulcerative colitis b is significantly higher in patients who have previously received one or more anti-TNF-α drugs.
P605 Eight-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients
Authors: Cassieri C , Pica R , Avallone E V , Brandimarte G , Zippi M , Crispino P , De Nitto D , Lecca P G , Vernia P , Pica R , Corazziari E S
Published: January 2020

Background

Azathioprine (AZA) and thiopurine are widely used for induction and maintenance of remission in steroid-dependent patients with inflammatory bowel disease (IBD). The aim of this study has been to investigate its efficacy and safety in maintaining steroid-free remission in steroid-dependent IBD patients eight years after the institution of treatment.

Methods

Data from consecutive IBD outpatients referred in our Institution, between 1985–2017, were reviewed and all patients treated with AZA were included in this retrospective study. AZA was administered at the recommended dose of 2–2.5 mg/kg.

Results

Out of 2992 consecutive IBD outpatients visited in the index period, AZA was prescribed to 446 patients, 245 (54.9%) were affected by Crohn’s disease (CD) and 201 (45.1%) by ulcerative colitis (UC). One hundred and ninety-six patients with a follow-up < 96 months were excluded from the study. Two hundred and fifty patients were evaluated, 140 (56%) with CD and 110 (44%) with UC. One hundred and thirty-eight (55.2%) were male and 112 (44.8%) female (average age of 35.48 ± 14.26 SD years, range 14–74 years). Eight year after the institution of treatment, 123 (49.2%) patients still were in steroid-free remission (82 CD vs. 41 UC, 58.6% and 37.3%, respectively, p = 0.0009), 71 (28.4%) had a relapse requiring retreatment with steroids (29 CD vs. 42 UC, 20.7% and 38.2%, respectively, p = 0.0030), 56 (22.4%) discontinued the treatment due to side effects (29 CD vs. 27 UC, 20.7% and 24.5%, respectively). The loss of response from first to eighth year of follow-up was low, about 21%.

Conclusion

Eight years after the onset of treatment about 50% of patients did not require further steroid courses. After the first-year loss of response was low in seven subsequent years. In the present series, the maintenance of steroid-free remission was significantly higher in CD than in UC patients. The occurrence of side effects leading to the withdrawal of AZA treatment has been low.
P612 Dietary practices and beliefs of British South Asians with inflammatory bowel disease: A prospective UK study
Authors: Crooks B , McLaughlin J , Limdi J K
Published: January 2020

Background

The increasing incidence of inflammatory bowel disease (IBD) in newly industrialised countries and immigrant populations appears to outpace that which genetic influences alone could instigate. Environmental factors, in particular, the western diet, are therefore implicated in its aetiopathogenesis. Limited data exist on the dietary practices of the migrant South Asian population with IBD. We aim to describe the dietary practices of British South Asian IBD patients and information resources utilised to guide these beliefs.

Methods

A prospective, cross-sectional, questionnaire-based study is being conducted across hospitals in the UK. Two-hundred South Asian patients with IBD are being recruited to complete a questionnaire regarding demographics and dietary practices.

Results

Data from 118 patients are available to date. Mean patient age is 43 years (51% female). Sixty-five per cent have ulcerative colitis (UC) and 33% Crohn’s disease (CD). Fifty-one per cent are of Indian ethnicity, 37% Pakistani and 10% Bangladeshi. Forty-nine per cent of patients were born in the UK to parents who were born outside of the UK and 51% of patients were born outside the UK. Mean disease duration is 10.5 years. Forty-six per cent considered diet to be an initiating factor in their IBD, based on their own experience (85%) as well as information from internet resources (31%) and other patients with IBD (19%). Fifty-nine per cent of patients felt that diet had triggered a relapse of their disease. Most commonly reported foods were spicy (69%) and fatty foods (47%), milk products (44%) and red meat (37%). Eighty-six per cent of patients avoided certain foods in an attempt to prevent an IBD ‘flare’. Most frequently avoided foods were spicy foods (76%), fatty foods (69%), red meat (60%), coffee (55%), carbonated drinks (54%) and milk products (53%). One in four patients had tried a specific exclusionary diet, with 13% having tried a gluten-free diet in the absence of coeliac disease, to manage their symptoms. Just over a half of patients reported being able to find specific dietary advice for IBD, most commonly via the internet. Over half of patients avoided eating the same meal as their family or eating out to prevent relapse of their IBD. 1 in 3 consumed certain foodstuffs or nutritional supplements to prevent a relapse of IBD, most commonly turmeric in 25% of these patients.

Conclusion

Dietary restriction may be highly prevalent amongst the British South Asian IBD community with a high proportion reporting diet as an initiating factor and trigger for disease flares. Studies on immigrant populations may hold valuable clues regarding the influence of migration, environmental influences and drift from traditional cultural practices on IBD aetiopathogenesis and related symptoms. A larger dataset will be presented at conference proceedings.
P618 Post-operative Crohn’s disease patients undergoing colonoscopy require significantly more analgesia and sedation compared with a non-IBD population
Authors: Rowan C , Janjua M , Foley C , Burke J , Boland K , O’Toole A
Published: January 2020

Background

Rates of surgical intervention in Crohn’s disease have declined. However, a significant proportion of patients still require surgical resection and have been shown to have higher post-op pain scores and analgesia requirements. The aim of this study was to assess sedation requirements and comfort scores of post-operative Crohn’s disease patients at endoscopy.

Methods

Patients with a previous intestinal resection undergoing colonoscopy in 2017 were identified using an electronic reporting system. Data regarding patient demographics, disease characteristics, sedation requirements, comfort scores and endoscopy reports were collected. Patients with Crohn’s disease were compared with a non-IBD post-op population.

Results

n = 153 patients were included. n = 56 Crohn’s disease, n = 2 UC and n = 95 non-IBD patients underwent colonoscopy. Patient characteristics in Table 1.

13.6% of patients had a documented history of chronic pain or other relevant conditions that may affect comfort scores. 68.3% of patients with Crohn’s disease were on therapy at the time of endoscopy. The median dose of midazolam administered was 3 mg (IQR 2–4 mg); median fentanyl dose was 50 μg. (IQR 50–75 μg). The median dose of Midazolam was significantly higher in patients with Crohn’s disease (3 mg IQR 3–4 mg vs. 3 mg IQR 2–3; p = 0.006). The median dose of fentanyl required was also significantly higher in post-operative Crohn’s patients (50 μg IQR 50–100 μg vs. 50 μg; p = 0.001). The median comfort score in Crohn’s disease patients was higher (indicating more discomfort) when compared with the non-IBD cohort. (median score 2 and 1 respectively) There was no significant difference in the proportion of patients with chronic pain or multiple intestinal resections (p = 0.84 and p = 0.142).

There was a statistically significant difference in comfort scores;n = 19 Crohn’s disease patients (39.6%) had comfort score 1, compared with n = 70 non-IBD patients (71.4%) (p = 0.04). There was no significant difference in the median doses of midazolam or fentanyl when comparing Crohn’s disease patients with and without active endoscopic disease. (p = 0.07 and p = 0.10 respectively).

Conclusion

Patients with Crohn’s disease undergoing colonoscopy in the post-operative setting have significantly higher analgesia requirements. Comfort scores are significantly worse when compared with non-IBD patients who have had similar intestinal resections. Endoscopists should use techniques, e.g. CO2 insufflation in addition to medication to ensure comfort amongst patients with Crohn’s disease.