bluuebunny/crossref_metadata_2025 huggingface dataset:
P638 Stenotic Crohn’s disease
Authors: El Ouardi W , Nawal L , Imane B , Camelia B , Mohamed B , Fatima Zahra A
Published: January 2020

Background

The treatment of Crohn’s stenosis appears to be codified and complex, it depends on the inflammatory or fibrous type of stenosis. The purpose of our study was to describe the clinical, epidemiological and therapeutic characteristics of Crohn’s disease in its stenotic form and to determine the failure factors for the treatment of stenotic CD.

Methods

This is a descriptive and analytical monocentric retrospective study, involving 900 Crohn’s patients, 189 of whom had stenotic CD. The statistical analysis is performed using the SPSS 22.0 software.

Results

The average age was 32± 11 years. Followed for an average of 48 months[12–96].Sex ratio=1.14F/1H. 44(23.3%) were smokers and 29(15.3%) had a previous of appendectomy.Symptomatology was Koenig syndrome in 107 cases(56.6%), occlusive syndrome in 40 cases(21.2%), constipation in 31 cases(16.4%), vomiting in 7 cases(3.7%) and 4 cases(2.2%) asymptomatic.The localisation of stenosis was ileocaecal in 118 patients(62.4%), hail in 32 patients(16.9%), colic in 17 cases(9%), anal in 15 cases(7.9%) and high in 7 cases(3.7%).Stenosis was unique in 160 cases(84.7%) and multiple in 29 cases(15.3%). 117 patients (62%) had a short stenosis <5 cm and 72 patients (38%) had a stenosis >5 cm. The fibrous nature of stenosis was in 86 patients (45.5%) and inflammatory in 103 (54.5%). 40 patients (21.2%) had an associated fistulizing behaviour. Anoperineal manifestations (MAP) in 58 cases (30.7%). Therapeutically speaking:80 patients (42.3%) were treated with corticosteroids, 10 patients (5.3%) with anti-TNFa, 3 patients (1.6%) with immunosuppressants (IS), 12 cases (6.3%) with endoscopic dilation and 84 cases (44.4%) were operated. The course was marked by a good response in 53 cases (28%), the appearance of fistula± abscess in 25 cases (13.2%), intestinal obstruction in 13 cases (6.9%) and recurrence of stenotic disease in 98 cases (51.9%).There is a difference in management between fibrous and inflammatory stenosis:corticosteroids(1.2%vs98.8%),anti-TNF(10%vs90%), dilation(100%vs0%), surgery(84.5%vs15.5%), this difference is statistically significant(p < 0.001). In multivariate analysis and by adjusting for confounding parameters, it appears that only MAP, ileocaecal location and fistulizing behavior are associated with treatment failure with [OR = 3.2; IC = 1.4–7.7; p = 0.005], [OR = 0.17; IC = 0.3–0.9; p = 0.037], [OR = 2.6; IC = 1.02–6.6; p = 0.04].

Conclusion

There was a statistically significant difference (p < 0.001) in terms of response to corticosteroid and anti-TNF treatments, as well as the use of surgery and dilatation between fibrous and inflammatory stenosis. And treatment failure was related to: MAP association [OR = 3.2; IC = 1.4–7.7; p = 0.005], ileocaecal localisation of stenosis [OR = 0.17; IC=0.3–0.9; p = 0.037] and fistulizing behavior[OR = 2.6;IC = 1.02–6.6;p = 0.04]
P639 Outcomes of a clinical psychology intervention in a UK IBD service
Authors: Eldridge F , Strongili K , Parkes M , Raine T
Published: January 2020

Background

Patients with IBD experience significant psychological distress. A variety of interventions to ameliorate this distress have been studied. However, to date, no European study has assessed the impact on patients of a clinical psychologist embedded within the IBD team. Clinical psychology is uniquely characterised by its use of a patient/therapist collaborative formulation to guide and select from a variety of evidenced-based psychological therapeutic treatment options. Such an approach is likely to be particularly beneficial for patients with IBD who may present with a wide range of needs from adjustment at diagnosis to coping with symptoms, adhering to treatment protocols and managing an on-going relationship with a medical team.

Methods

A novel clinical psychology service was established within an existing IBD service at a large UK tertiary centre. Patients were referred either by a gastroenterologist, IBD nurse, or dietician using real-world clinical selection (clinical judgement rather than screening/threshold methods). Patients could also self-refer to the service. After an assessment with the clinical psychologist, patients were assigned as either accepted for intervention, referred to other mental health services or did not require intervention. Intervention involved a range of therapeutic modalities delivered by a clinician with considerable experience of working with long-term physical health conditions.

Results

Of 42 patients referred, 25 (60%) were accepted for intervention, with completion data currently available for 21. Measures of depression, anxiety, work and social adjustment and health-related quality of life were captured for these patients pre-, during and post-intervention, as well as for 93 unselected patients with IBD attending outpatient clinics. Patients selected for intervention recorded moderate to severe scores across these domains that differed significantly from the background population. Post-intervention, patients showed highly statistically significant improvement across all domains with scores that did not differ from the background.

Conclusion

Real-world clinical selection methods appear adequate in identifying patients with greater psychological need than the baseline population. Although limited by our current small sample size, our results suggest that a clinical psychology intervention, embedded within the IBD team, can reduce patient psychological distress in IBD across a range of outcomes.
P640 Moderate to severe endoscopic inflammation is frequent after clinical remission in pediatric ulcerative colitis: A cause for disease extension and relapse?
Authors: Sarbagili Shabat C , Weiner D , Wardi J , Abramas L , Yaakov M , Levine A
Published: January 2020

Background

Pediatric ulcerative colitis (UC) is characterised by low sustained remission rates and frequent extension of disease even if clinical remission is obtained. Current therapy in pediatric UC is driven primarily by clinical response. Extension of disease and high relapse rates may be due to a failure to obtain mucosal healing with treatment despite clinical remission. Our aim was to evaluate this possibility by assessing endoscopic disease activity after remission was obtained.

Methods

Pediatric UC patients with clinical remission, defined as sustained PUCAI < 10 three months after remission was obtained, were prospectively assessed for mucosal healing by endoscopy. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading.

Results

41 children were enrolled after informed consent, 7 were excluded because of a PUCAI score 10–15 at the time of sigmoidoscopy. Thirty-four Sigmoidoscopies were performed 12–20 weeks after reporting clinical remission. Mucosal healing Mayo 0 was present in 15 endoscopies (44%), Mayo 1 was present in 2 endoscopies (6%) and moderate to severe endoscopic scores Mayo 2–3 was present in 17 endoscopies (50%).

Conclusion

About 50% of children assessed for mucosal healing 3–5 months after clinical remission is obtained have residual moderate to severe inflammation. Inadequate endoscopic improvement despite clinical remission may explain disease extension and the high relapse rate in children.
P643 Development of quantitative ultrasonographic activity score in ileal Crohn’s disease
Authors: Livne Margolin M , Amitai M , Klung E , Ungar B , Eliakim R , Ben-Horin S , Carter D , Kopylov U
Published: January 2020

Background

Intestinal ultrasound (IUS) is as an accurate bedside tool for monitoring Crohn’s disease (CD). However, there is no validated quantitative ultrasonographic score for evaluation of the activity of intestinal inflammation in CD. Such a score may facilitate the use of IUS-based monitoring in clinical practice and in clinical trials in CD. For magnetic resonance enterography (MRE), the magnetic resonance index of activity (MaRIA) is most commonly used. Thus, the aim of our study was to correlate IUS data for the terminal ileum with segmental MARIA score for the terminal ileum in order to devise a quantitative inflammatory index for IUS.

Methods

In this retrospective cohort study, the data of CD patients who were followed in the Gastroenterology Department at Sheba medical centre between January 2016 and December 2018 were extracted. Inclusion criteria were age >18 and an interval<3 months between MRE and IUS. MaRIA score for the terminal ileum was compared with ultrasonographic features of inflammation that included: bowel wall thickness (continuous variable), echogenicity of the bowel wall, pseudostratification of the bowel wall layers, inflammatory mesenteric fat and lymph nodes, hyperemia present on colour Doppler flow and complications (nominal variable). A linear regression model that included the significantly correlated variables was constructed.

Results

Forty-two patients with established Crohn’s disease were included. A stepwise multiple regression model was constructed to predict MaRIA score using US features. Two variables were found to be independently significant in the explanatory model, terminal ileum thickness (r = 0.68, p = 0.001) and US fat proliferation (r = 0.45, p = 0.019). A model was constructed as follows: MaRIA = 7 + 2.5 * TI US thickness (mm) + 7 * US fat proliferation (0 = no, 1 = yes). This model has an R2 of 0.51 for explaining the variability in the results.

Conclusion

Quantitative IUS measurements are significantly correlated with segmental MaRIA score in the terminal ileum; a simple computational model for prediction can be constructed; however,, the accuracy of such model to predict segmental MaRIA was moderate. Additional work to develop quantitative IUS parameters in CD is merited.
P646 Utilisation of indocyanine green fluorescence imaging for Crohn’s disease following intestinal resection
Authors: Duan Y , Li Y
Published: January 2020

Background

Growing evidences have shown that there are important advantages related to the utilisation of indocyanine green fluorescence imaging (ICG-FI) to reduce the risk of postoperative anastomotic leakage (AL) in colorectal surgery. However, the impact of ICG-FI on postoperative AL of Crohn’s disease (CD) following intestinal resection has not been investigated.

Methods

This is a retrospective study of consecutive CD patients who were treated with intestinal resection and anastomosis at a single institution between January 2017 and August 2019. The cohort was divided into 2 groups, those with ICG-FI compared with those without ICG-FI for intestinal resection. ICG was administered intravenously with a bolus of 5 mg, and the intestinal perfusion was evaluated by a SPY Elite system. Their baseline characteristics and perioperative outcomes were further analysed.

Results

No adverse reactions were recorded. Of the 88 CD patients who underwent intestinal resection, 36 patients underwent ICG-FI during intestinal resection, while 52 CD patients who underwent routine intestinal resection were from a prospectively maintained database. The 2 groups were similar in terms of patient demographics, immunosuppressive medication use, and the procedural factors. In patients with ICG-FI, poor perfusion of the bowel judged by ICG-FI led to additional intestinal resection in 25% (9/36). ICG-FI reduces the AL rate from 13.5% (7 leaks) of non-ICF-FI group to 8.3% (3 leaks) in ICG-FI group (p = 0.456). Forty-four (50%) patients had previous intestinal resection. Overall, 10 anastomotic leaks were identified (11.4% leak rate). There were 2 leaks (4.5%) detected in patients with no previous intestinal resection, compared with 8 leaks (18.2%) identified in patients with a history of previous intestinal resection (p = 0.044). The number of previous resections correlated with increasing risk for AL (correlation coefficient = 0.998). In univariate analysis, steroid use, CRP level and preoperative weight loss >10% in 6 months were independently associated with AL.

Conclusion

ICG-FI is applicable to intestinal resection for CD and may play a role in perfusion-related AL. A large prospective randomised trial should be warranted.
P647 Post-marketing evaluation of reported adverse events of a multi-strain probiotic product confirms that change in manufacturing site had no impact on safety profile
Authors: Panetta V , Simonelli I , Bacchieri A , Papetti S , De Stefani E , Colombo S
Published: January 2020

Background

In 2016, the manufacturing site of the multi-strain probiotic product VSL#3 changed. The present work is aimed at verifying if this change had an impact on the safety profile of the product.

Methods

The safety reports from post-marketing surveillance in the USA received by Alfasigma in the years 2014–2015 were compared with those received in the years 2017–2018. 2016 was not considered, because the product on the market during this year could likely come from both manufacturing sites. VSL#3 is sold in the US market as a medical food. Most of the reports were from consumers and were not medically confirmed. However, this happened in both periods, so no bias is introduced in the comparison. Each single safety report contained one or more adverse events (AEs), coded with MedDRA. The comparison between the two periods concerned primarily the number of safety reports in relation to the number of units sold. Given the similarity of trends between the total number of safety reports and sales in the two periods, the frequencies of the AEs and serious AEs were also compared at the System Organ Class (SOC) and Preferred Term (PT) level.

Results

More than 70% of subjects reporting an AE were women in both periods under comparison; mean age was 58; phone was the most frequent means (overall 76%). Table 1 summarises the main results. Sales and number of safety reports were higher in the second than in the first period. However, the ratio between number of reports and sales was higher in the 2014–2015 period compared with the 2017–2018 period: 3.5 vs. 2.9 reports per 10,000 units sold, respectively. Similar results were obtained when stratifying the described ratios by formulation. The percentages of reports with at least one serious AE were respectively 3.2% in the first period and 2.5% in the second. The two periods appeared to be similar even with respect to the percentages of AEs and serious AEs by SOC and PT, being the AEs under the Gastrointestinal SOC the most frequently reported, as expected.

Conclusion

The analyzed data show that the manufacturing site change had no impact on the safety profile of VSL#3.
P649 Dietary habits in patients with inactive Crohn’s disease: Results of a controlled study
Authors: Ben Mustapha N , Ben Youssef H , Labidi A , Hafi M , Fekih M , Serghini M , Boubaker J
Published: January 2020

Background

The purpose of this study was to compare the dietary habits of patients with Crohn’s disease in remission with a control group.

Methods

This is a comparative cross-sectional descriptive study that took place over a period of one month including 45 patients already managed for Crohn’s disease (CD), who had been in stable clinical remission for at least 6 months at the time of the survey and had the same treatment for at least 6 months compared with a group of 40 healthy volunteers adjusted for age, sex and body mass index (BMI) recruited among health personnel. Questionnaires about dietary habits, patients’ attitudes and beliefs about diet and its impact on their illness, and a dietary history-type food survey were asked and completed for all subjects.

Results

Total energy and macronutrient intakes were comparable in both groups and adapted to the guidelines. Fibre and micronutrient intakes were significantly lower in CD group, as was the consumption of dairy products, legumes, vegetables and fruits, oleaginous fruit. There were multiple dietary restrictions among CD patients including milk and its derivatives, fruits, vegetables, and legumes. In fact, 11% of them continued to strictly follow the same residue-free diet prescribed at the time of flares and others had barely expanded their diet. The reasons were mainly represented by the fear of triggering digestive disorders in 77% of cases. Fifty-six per cent of patients believed that fibre and milk negatively affect their disease and could trigger digestive disorders. Forty-four per cent said that the avoided foods gave them digestive disorders. By stratifying patients by age, sex or disease characteristics (location, treatment, history of surgery), we found no predictive factor for these dietary restrictions. Moreover, in 23% of patients, the diet was totally obscured by the doctor during consultations. In addition, and despite the discussion with the doctor about food, 46% turned to other sources such as the entourage, other patients, media and internet to find information on their diet.

Conclusion

Our study shows that patients with Crohn’s disease in remission suffer from several deficiencies due to multiple dietary exclusions. The results suggest that an unbalanced diet should be identified to avoid the micronutrient deficiency observed and highlights the importance of communication about diet between Doctors and patients.
P650 Outcomes of endoscopic balloon dilation for luminal strictures in Crohn’s disease
Authors: Sarraj R , Martinho M , Bravo F , Benz E , Juillerat P
Published: January 2020

Background

Luminal strictures are common complications of Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is an alternative to surgery for CD strictures. (1–3). The aim of this study was to evaluate the EBD success rate and identify predictive factors in CD patients.

Methods

27 consecutive patients with CD in whom EBD was performed at the outpatient clinic of Bern University Hospital were retrospectively included in this study. Clinical, laboratory and endoscopic data were collected from the patient files. Stricture characteristics, short-term procedure success, procedure-related complications, occurrence of surgery and long-term clinical endpoints were documented. Short-term procedure success was defined by the ability to pass an 11.5-mm-wide endoscope through the stricture after dilatation and the absence of any documented complications during a 1-week follow-up.

Results

The study population consisted of 27 patients with Crohn’s disease. A total of 41 dilations were performed. 61.5% of the patients were on biologic therapy. The short-term dilatation success rate was 60%. 48.1% of the patients required stricture related surgery during the follow-up. There were two procedure-related complications 0.08% (bleeding; asymptomatic perforation discovered during surgery). 33.3% were anastomotic strictures. The median increase in dilatation diameter during a single session was 6 mm (range, 3–12mm). 53.8% of the patients required multiple dilatations during the same endoscopic procedure. In the Kaplan–Meier log-rank analysis, anastomotic strictures (secondary) did show a trend toward a longer surgery-free survival after EBD (p = 0.057) (Figure1)

Conclusion

EBD is successful and safe in treating luminal strictures and in prevention of immediate surgery in a high proportion of CD patients, in particular for anastomotic stricture.

References
P651 Does ambient temperature alter faecal calprotectin levels?
Authors: Cauchi S , Schembri J , Muscat M , Ellul P
Published: January 2020

Background

Faecal Calprotectin (FCP) is a marker of intestinal inflammation and its measurement is useful in both the diagnosing and the evaluation of disease activity in patients with inflammatory bowel disease (IBD). Limited and conflicting evidence exists on the reliability of FCP as a stable marker at ambient temperature. While an adult publication suggested that FCP can be delivered to the laboratory at ambient temperature with reliable and consistent results, a recent publication in a paediatric cohort demonstrated that samples stored at 4 ˚C were more reliable than those kept at ambient temperature. The aim of the study was to evaluate if there is any variation in FCP levels depending on ambient temperature in patients in clinical remission.

Methods

Patients with IBD (Crohn`s disease {CD}; ulcerative colitis {UC}) who were in clinical, radiological and/or endoscopic remission in the previous 6 months were recruited. The FCP levels taken in between December 2018 and February 2019 (mean daytime temperature – 15.7ºC; range 4 – 19ºC) and those taken July–September 2019 (mean daytime temperature 29ºC; range 21–39ºC) were analysed. No patients had to have any change in IBD medications or any features of relapse during the study period. All recruited patients had to have two samples of FCP taken—one taken in winter and the other in summer.

Results

109 patients were recruited (males: 57 patients; 56% - CD). The mean patient age was 43.9 years (±3.313 SD; range 19–82 years). The mean FCP during the winter months was 135.6 mg/l (±20.9 SD) while that in summer was 121.9 mg/l (±24.1 SD). No statistically significant difference between the winter and summer months (p = 0.41). The mean winter FCP in CD was 122.2 mg/l (±27.5 SD) while that in UC was 147.0 mg/l (±31.4 SD) (p = 0.19). In the same patients, the mean summer FCP in CD was 128.3 mg/l (±31.8 SD) while in UC it was 114.95mg/l (±39.9 SD) (p = 0.73). While numerically, the levels of the FCP in UC were different, this was not statistically significant (p = 0.32). Further FCP analysis for the variables of age and gender did not reveal any significant differences.

Conclusion

These data demonstrate that FCP is a reliable marker of disease activity in routine clinical practice, when submitted to the laboratory at ambient temperatures. The ability of submitting the stool samples to the laboratory with only a few precautions, will undoubtedly ensure patient compliance in submitting stool samples. However further analysis in FCP variation in UC patients needs to be considered.
P653 Efficacy and safety of an additional 8 weeks of tofacitinib induction therapy: Updated results of the OCTAVE Open study for tofacitinib 8-week induction non-responders
Authors: Rubin D T , Dubinsky M C , Danese S , Saad-Hossne R , Ponce de Leon D , Maller E , Lawendy N , Kwok K , Su C
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were demonstrated in three Phase 3, randomised, placebo-controlled trials in patients with moderate to severe UC.1 Patients who received tofacitinib 10 mg twice daily (BID) for 8 weeks (weeks) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951) and did not achieve a clinical response (ie induction non-responders [IndNR]) could enter an ongoing, Phase 3, open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612). We present an update, as of May 2019, of previously published data up to December 2016 from the OLE study for IndNR patients.2

Methods

IndNR patients received tofacitinib 10 mg BID in the OLE study. Patients who were still non-responders after an additional 8 weeks of induction were required to discontinue. Clinical response, remission and mucosal healing were evaluated up to Month (M)36 of the OLE study. Adverse events (AEs) and serious AEs (SAEs) are also presented.

Results

429 IndNR patients enrolled in the OLE study, 295 of which received tofacitinib 10 mg BID during induction trials (Table). The proportions of patients with prior tumour necrosis factor inhibitor and baseline corticosteroid use were slightly higher in non-responders than responders at M2; other baseline characteristics were generally similar in responders and non-responders. At M2, 59.7%, 25.7% and 16.2% of patients achieved clinical response, mucosal healing and remission, respectively (as observed). Corresponding non-responder imputation and last observation carried forward values were 52.2%, 23.1% and 14.2% (Table). The table shows data up to M36. The proportions of patients with AEs, SAEs and discontinuations due to AEs for IndNR patients censored at M2 (52.2%, 3.7% and 2.4%, respectively) were similar to those for all patients in OCTAVE Induction 1 and 2 (tofacitinib: 55.4%, 3.8% and 3.9%; placebo: 56.4%, 6.0% and 4.3%), with no new safety risks identified (table).

Conclusion

The majority of patients who did not achieve clinical response to tofacitinib 10 mg BID for 8 weeks in the induction studies – and subsequently received an additional 8 weeks of tofacitinib 10 mg BID in the OLE study—achieved clinical response, with a considerable number of patients in remission and/or mucosal healing at M36. No new safety risks were observed in the additional 8 weeks of induction. These data support extended induction with an additional 8 weeks of tofacitinib for non-responders to 8-week induction. Current product labelling recommends 5 mg BID for maintenance in responders.3,4

References
P659 The impact of total colectomy on the course of extraintestinal manifestations in Swiss IBD cohort study patients
Authors: Roth R , Vavrick S , Scharl M , Schreiner P , Greuter T , Zeitz J , Safroneeva E , Schoepfer A , Barry M P , Rogler G , Biedermann L
Published: January 2020

Background

Extraintestinal manifestations (EIM) are reported to occur in a highly variable frequency of between 6% and up to 47% of patient with IBD during the course of disease and may substantially contribute to the overall disease burden. Little is known on the impact of colectomy in UC or CD patients on the course of EIM, neither regarding pre-existing vs. de novo EIM occurring after colectomy nor regarding potential differences between EIM typically known to follow a parallel vs. independent course of activity to disease activity of underlying IBD.

Methods

Using data from the Swiss IBD Cohort Study (SIBDCS) we aimed to analyze the course of EIM in UC and CD patients undergoing colectomy during the prospective SIBDCS follow-up.

Results

Amongst a total of 3620 IBD patients (53.6% CD, 42.8% UC, 3.6% IBD unclassified), 115 IBD patients (33 CD and 82 UC) underwent colectomy. One or more EIM had been present at any time antecedent to colectomy in 35.7% of these patients (27.3% and 39% in CD and UC patients, respectively). Within the 115 IBD patients undergoing colectomy any EIM was present only before colectomy in 21 patients (18.3% of all patients undergoing colectomy), i.e. entirely ceased thereafter in 51.2% of patients with any EIM prior to colectomy. After colectomy, overall 30 out of the 115 patients (26.1%) suffered from any EIM after colectomy. Out of these, two thirds (20 patients) already had any EIM prior to colectomy, while in one third (10 patients) occurrence of EIM represented a de-novo event after colectomy. Overall, amongst all patient with no EIM prior to undergoing colectomy 13.5% of patients developed a de-novo EIM after colectomy. The fraction of patients with complete cessation of EIM after colectomy was numerically higher in patients with UC vs. CD with 56.3% vs. 33.3% of patients with EIM prior to colectomy, respectively (51.2% in IBD patients overall). An overview over the frequency of EIM overall and individual EIM is provided in Figure 1.

Conclusion

In IBD patients with undergoing colectomy, any EIM present prior to surgical intervention will persist in about half of patients. Although our results are based on a limited number of patients our findings indicate, that complete cessation of EIM after colectomy may be less common in CD than in UC patients. Absence of EIM prior to colectomy does not equal freedom from any EIM thereafter as up to one in seven IBD patients may develop de-novo EIM after colectomy.
P662 Efficacy and safety of tofacitinib in patients with moderate-to-severe ulcerative colitis: A real-world retrospective study
Authors: Yoshimura N , Okano Soh , Sako Minako , Takazoe Masakazu
Published: January 2020

Background

Tofacitinib is an orally active, small-molecule Janus kinase inhibitor, recently approved for the treatment of moderate to severe ulcerative colitis (UC) refractory to corticosteroid. However, currently, there is inadequate evidence for efficacy of Tofacitinib in UC patients. Therefore, our objective was to evaluate the efficacy and safety of Tofacitinib for inducing and maintaining remission in UC patients.

Methods

In a single-centre retrospective setting, 71 consecutive patients with UC who had failed to respond to corticosteroid or biologics were included. All patients had received 10mg Tofacitinib orally twice daily for at least 8 weeks as remission induction therapy and then, the responders received 5mg twice daily as maintenance therapy for up to 26 weeks. The clinical response and adverse events were evaluated at weeks 8 (induction) and 26 (maintenance). UC activity was assessed by the partial Mayo score. Clinical remission was defined as p-Mayo score ≤1 and the bleeding subscore = 0. Clinical response was defined as p-Mayo score ≤4 and a decrease of ≥3 points relative to baseline. Furthermore, the cumulative remission rates up to 26 weeks were determined by the Kaplan–Meier survival analysis.

Results

At week 8, 24 of 71 patients (33.8%) achieved clinical remission and 20 (28.2%) achieved response level. The mean p-Mayo score fell from 5.8 ± 1.1 at entry to 3.5 ± 2.3 at week 2 (p < 0.01) and 2.3 ± 1.9 at week 8 (P<0.01). The average total cholesterol increased from 180.8 ± 36.0 mg/dl at entry to 206.8±39.3 mg/dl (p < 0.01). In anti-tumour necrosis factor (TNF)-α or vedolizumab (VDZ) naïve subgroup (n = 14), 8 patients (57.1%) achieved response level, while in biologic failure subgroup (n = 57), 36 patients (63.2%) achieved response level. In single biologic failure subgroup (n = 27), 19 patients (70.4%), in double biologics failure subgroup, 14 of 24 patients (58.3%), and in 3 biologics failure subgroup, 3 of 6 patients (50.0%) achieved response level, showing a decrease in the efficacy of Tofacitinib in patients who had failed more than one biologic. Furthermore, of the 25 patients followed for 26 weeks, 23 (92.0%) sustained remission at week 16 and 19 (76.0%) at week 26. Herpes virus infection occurred in 4 patients. The increase in total cholesterol was observed in 68.8% of the patients.

Conclusion

Our retrospective efficacy assessment indicated that Tofacitinib was effective and safe for inducing and maintaining remission in corticosteroid refractory UC patients, regardless of biologic naïve or failure background. The efficacy of 10mg twice daily was rapid and observed within 2 weeks of starting the treatment.
P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies
Authors: Rutka M , Farkas K , Pigniczki D , Szántó K , Anita B , Bor R , Fábián A , Szepes Z , Nagy F , Molnár T
Published: January 2020

Background

Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab.

Methods

In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8.

Results

Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up.

Conclusion

After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.
P674 Monitoring posologic change in adalimumab intensification dosing regimen from 40 mg every week to 80 mg every other week
Authors: Diz Lois Palomares M T , Porta Sánchez Á , Elberdin Pazos L , González Conde B , Outeda Macías M , Vázquez Rey M T , Guerrero Montañés A , Estévez Prieto E
Published: January 2020

Background

The previous usual adalimumab (ADA) intensification regimen was 40 mg every week (ew)). Recently the original laboratory commercialised the 80 mg injection pen, with pharmacokinetic studies indicating an alternative intensification dose of 80 mg every other week (eow) similar to 40 mg ew, even though interchangeability has not been assessed in clinical practice. In the biosimilars era, this pen was sold to many Hospitals at the same price as the 40mg pen. For this fact and for patient comfort, we proposed our stable-intensificated-ADA IDB patients on a 40 mg ew regimen, to change the dose to 80 mg eow (clinical practice).

Methods

In this setting, we designed an observational study to monitor clinical, analytical and pharmacokinetic outcomes through this posologic change, for patients who signed the Informed Consent. Clinical (Harvey–Bradshaw index (HBI), partial Mayo score), analytic parameters and ADA trough levels were prospectively obtained at baseline, 4 and 8 months after posologic change. We describe the evolution of this cohort and calculate savings.

Results

12 from 18 patients initially evaluated for new dose regimen were finally changed. All of them agreed to participate in the study. Eighty-three per cent were CD patients, 58% males, median age 51 years old (intecuartil range (IQR) 42–55). Median age at IBD diagnosis was 34 years (IQR 24–44). In 9 patients ADA was the first-line biologic. Median IBD duration before starting ADA was 6 years (IQR 5–8). Median time from ADA initiation to intensification was 31 months (IQR 14–55). The median time of ADA intensification was 37 months (IQR 30–66). Seventy per cent of patients were on immunosuppressors (IS) at the start of the study. Table 1 shows the results of clinical, analytical variables and ADA trough levels at baseline, 4 and 8 months. No differences were found. At 4 months, all patients maintained ADA 80 mg eow. Two patients referred mild worsening, (HBI from 3–4 to 5–6) without significant changes in CRP, calprotectin or ADA levels. They recovered after restoring the previous regimen (ADA 40mg ew). At 8 months, ADA was stopped in one patient in remission with undetectable ADA levels and positive ATI. Total savings in the first 8 months were 59022 €.

Conclusion

in IBD patients with stable response to ADA intensification regimen of 40 mg ew, changing to 80mg eow seems to maintain response and similar trough levels, although some patients may perceive mild symptoms. Economic savings are 50% per patient.
P675 CT-Scout platform, the digital solution to boost patient recruitment in inflammatory bowel disease clinical trials: A multicentre prospective observational comparative study
Authors: Bouhnik Y , Hebuterne X , Raith M , Amiot A , Tanasa Stefanescu C , Laharie D , Roblin X , Bourreille A , Nancey S , Sabbah N , Peyrin Biroulet L
Published: January 2020

Background

The main issue to validating new molecules in the field of IBD is insufficient patient enrollment into clinical trials, resulting in premature trials termination and cost increase. CT-SCOUT™ platform is a web-based solution to help clinicians to pre-screen potential candidates and facilitating the coordination of the research team. Our aim was to compare the number of patients enrolled in IBD clinical trials in sites equipped or not with CT-SCOUT™.

Methods

We conducted a prospective, multicenter, open-label, observational study in sites participating to phase 3 trials evaluating the efficacy and safety of etrolizumab in ulcerative colitis (UC, Hickory) and in Crohn’s disease (CD, Bergamot). Recruitment figures were provided by the sponsor, and we considered the 21 French sites equipped with CTscout and 134 sites in other countries not equipped with CT-SCOUT™. The primary endpoint was the mean number of patients randomised per site in both trials. Secondary endpoints included a mean number of patients randomised in each study. Patients screened and those finally randomised were compared in sites equipped and non-equipped using one-way ANOVA followed by post-hoc Tukey test and Mann–Whitney test.

Results

During the observational period of 40 months (September 2015–December 2018), 644 and 289 patients were screened and randomised in Hickory and/or Gardenia, respectively. There were 307 and 149 patients in 78 sites for Hickory, and 337 and 140 patients for Bergamot in 102 sites. The mean numbers of screened and randomised patients in CT-SCOUT™ equipped sites vs. non-equipped are given in the table.

The mean number of patients randomised in Hickory in CT-SCOUT™ sites increased by 4.0 folds as compared with non-equipped sites (p < 0.001). The mean number of patients randomised in Bergamot in CT-SCOUT™ equipped sites has been increased by 1.9-folds as compared with non-equipped sites (p = 0.009).

Conclusion

This multicentric study demonstrated a significant increase in patient recruitment in IBD clinical trials. Randomisation rates were twice to four times higher in equipped sites compared with non-equipped ones. CT-SCOUT™ appears to be a promising digital solution to the global issue of patient enrollment in clinical trials.
P683 Infliximab, adalimumab and vedolizumab levels are not altered by pregnancy progression in IBD patients and neonatal vedolizumab levels are lower than in mothers: Results from the PICCOLO study
Authors: Flanagan E , GIbson P R , Rosella O , Ross A , Bell S J
Published: January 2020

Background

Optimal timing for the last intrapartum dose of biologic agents is controversial. We established that cord blood levels of anti-TNF agents in exposed infants are greater than maternal levels,1 and another study with limited observations suggested maternal infliximab (IFX) levels increased in pregnancy but adalimumab (ADA) levels did not.2 The effect of pregnancy on vedolizumab (VDZ) levels, and placental transfer and time to clearance of VDZ in exposed infants remain undefined.

Methods

We performed a prospective observational study of maternal anti-TNF and VDZ levels pre-conception, in each trimester of pregnancy, at delivery and post-partum where possible. Women with IBD on IFX, ADA or VDZ who were pregnant or planning pregnancy were recruited. Serum trough IFX and ADA levels were measured by ELISA (Q-INFLIXI and Q-ADA (Matriks Biotek, Turkey) or Promonitor (Grifols, Spain)) and VDZ levels by ELISA (Theradiag, France). Infant VDZ levels were measured from the umbilical cord at delivery and at around 6–8 weeks and 3 months to assess time to clearance.

Results

Forty-nine patients (24 IFX, 14 ADA, 11 VDZ) with at least two observations on stable dosing were included. The median number of levels per patient was 3 (range 2–5). Infliximab cohort (n = 24): Median IFX levels were stable (Figure 1). IFX was administered 6–8 weekly at doses of 5 mg/kg (n = 21) or 10 mg/kg (n = 2) except for one patient on 4-weekly dosing. The last dose was given at a median 32 weeks; 3 remain pregnant. Adalimumab cohort (n = 14): Median ADA levels were stable (Figure 1). Twelve were on ADA fortnightly and 2 on weekly. Eleven continued ADA throughout pregnancy and 3 stopped at 30–33 weeks; 2 remain pregnant. Three patients were induced in pregnancy at least 12 weeks before the earliest ADA level. Vedolizumab cohort (n = 11): Trough VDZ levels were stable (Figure 2). Eight patients were on 8-weekly dosing and three were on 4-weekly. The last dose was given at a median 30 weeks; 4 remain pregnant (Patients H-K). Vedolizumab in infants (n = 8): The median VDZ cord blood level was 4.95 (1–19) μg/ml with a median infant:maternal ratio of 0.6 (0.4–0.9). VDZ was cleared at 8 weeks of age in three infants and by 15 weeks in two infants.

Conclusion

The stability of maternal levels of IFX, ADA and VDZ during pregnancy indicate that intrapartum dosing adjustment and routine therapeutic drug monitoring for patients in remission are not needed. Unlike anti-TNF, infant VDZ levels were lower in cord blood than in mothers and were cleared by 15 weeks.

References
P684 The effect of tofacitinib on serum lipids and cardiovascular safety in patients with ulcerative colitis: updated results from the tofacitinib ulcerative colitis clinical programme
Authors: Sands B E , Taub P R , Feagan B G , Armuzzi A , Damião A O , Lawendy N , Solano G , Kwok K , Woolcott J , Salese L , Su C
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In the tofacitinib UC clinical programme, the majority of patients did not have cardiovascular (CV) risk factors at baseline (BL), and increases in lipid levels occurred primarily during induction and remained elevated to Week 61 during maintenance; lipid ratios were relatively unchanged.1 Here, we present updated results of lipid levels in the ongoing, open-label, long-term extension (OLE) study (NCT01470612) and major adverse CV events (MACE) in the Phase 3/OLE tofacitinib UC clinical programme.

Methods

Lipid levels were assessed at multiple time points, and changes from OLE study BL to Month 48 in the OLE study were evaluated. Lipid-lowering agent (LLA) use (proportion of patients) and adjudicated MACE (proportion of patients and incidence rate [IR; unique patients with events per 100 patient-years] with 95% confidence interval [CI]) were reported in patients with UC in two Phase 3, 8-week, placebo-controlled induction studies (OCTAVE Induction 1 and 2; NCT01465763, NCT01458951), a Phase 3, 52-week, placebo-controlled maintenance study (OCTAVE Sustain; NCT01458574) and the OLE study (data as of May 2019; database not locked).

Results

No major changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, LDL-c:HDL-c and TC:HDL-c from OLE study BL were observed at Month 48 of the OLE study (Table). In the Phase 3/OLE programme (n = 1124), 7.7% of patients had a new LLA added and 1.9% of patients had their LLA dose increased. Seven MACE were reported (IR 0.26; 95% CI 0.11, 0.54; 2654.66 patient-years); the IR has remained stable since Dec 2016 (IR 0.24; 95% CI 0.07, 0.62).1 Reported MACE was one each of myocardial infarction, acute myocardial infarction, acute coronary syndrome, cerebrovascular accident, haemorrhagic stroke, cerebellar haemorrhage and aortic dissection. Both myocardial infarction events and the acute coronary syndrome event led to temporary tofacitinib discontinuation; the haemorrhagic stroke, cerebrovascular accident and cerebellar haemorrhage led to permanent tofacitinib discontinuation; and the aortic dissection resulted in death. Of the seven patients with MACE, five had CV risk factors at BL.

Conclusion

At Month 48 of the OLE study, lipid levels and ratios remained generally unchanged from OLE study BL following tofacitinib treatment. MACE were infrequent, with the IR remaining stable since the previous report.1 Limitations include low patient numbers and short tofacitinib exposure duration. Longer-term observation studies will further assess risk.

Reference
P686 Expression of CD39 ectonucleotidase on regulatory T cells and on T helper 17 cells in children with IBD receiving anti-TNF therapy
Authors: Petrichuk S V , Radygina Т , Illarionov A , Kuptsova D , Potapov A , Fisenko A P
Published: January 2020

Background

CD39, CD73 ectonucleotidases convert extracellular ATP (eATF) to adenosine. eATF is known to have pro-inflammatory activity, and adenosine has anti-inflammatory activity. It was shown decreasement CD39 expression on regulatory T lymphocytes (Treg) during exacerbation in adult patients with IBD. The aim of this study was to evaluate the expression of CD39 on Treg and Th17 lymphocytes (Th17) in children with inflammatory bowel diseases (IBD) with different responses to anti-TNF therapy.

Methods

The study included 68 children with IBD (CD 35 patients, UC 33 patients) aged 4–18 years with duration of the disease from 6 months till 15 years. All patients were treated with anti-TNF (infliximab, adalimumab) during 11–86 weeks. Clinical response was evaluated according to PUCAI (UC) and PCDAI (CD) scores. Group 1 (n = 35) included patients with exacerbation during anti-TNF therapy, in Group 2 (n = 25) patients with sustained remission. The expression of CD39 on Treg (CD3CD4CD25CD127low) and Th17 cells (CD3CD4CD161) was determined by flow cytometry (NovoCyte Acea Biosciences, Inc.). Statistical analysis was performed using nonparametric Mann–Whitney test and ROC analysis (SPSS Statistics 20).

Results

It were observed inflammatory activity increasement according to PUCAI (Med 40 [30–65], p = 0.8 × 10–5) and PCDIA scores (Med 28.8 [15–55], p = 1.2 × 10–5) in Group 1 in comparison with Group 2. The amount of Treg expressing CD39 (Treg CD39) was 6–58% from Treg (6–80 cl/μl), and the amount of Th17 with the CD39 marker (Th17CD39) was 0.5–57% (2–49 cl/μl). A direct correlation was revealed between TregCD39 and Th17CD39 (r=0.55 p = 1 × 10–6). It was shown that the number of TregCD39 and Th17CD39 does not depend on the age of the child. However, with an increase in the duration of the disease, a decrease in the absolute amount of Th17CD39 is observed (r = −0.3, p = 0.016). In patients Group 1 there was a significant reduction of CD39 expression on Treg (p = 0.00002) and on Th17 (p = 0.0009) compared with a Group 2 in both diseases. The dependence of TregCD39 on PUCAI (r = −0.5 p = 0.013) and PCDAI (r = −0.43 p = 0.03) was revealed. ROC analysis showed that the cut-off level for groups 1 and 2 is 31.7% for TregCD39 (AUC=0.77; Se 69%, Sp 68%) and 37 cl/μl (AUC=0.907; Se 88%, Sp 88%). Cut-off level for the absolute amount of Th17CD39 was 21 cl/μl (AUC=0.888; Se 79%, Sp 81%).

Conclusion

The decreasement in the amount of TregCD39 below 31 cl/μl and Th17CD39 below 21 cl/μl is associated with an exacerbation of the disease. The expression level of ectonucleotidase CD39 on Treg and Th17 in children with IBD receiving anti-TNF therapy is independent of age and allows to differentiate the state of remission and exacerbation.