bluuebunny/crossref_metadata_2025 huggingface dataset:
P267 Validation of the short inflammatory bowel disease questionnaire as an outcome measure in Crohn’s disease patients
Authors: Reggev S , Goran G , Sarid O , Schwartz D , Sergienko R , Slonim-Nevo V , Friger M , Nemirovsky A , Vinogradov E , Monsonego A , Greenberg D , Odes S
Published: January 2020

Background

Health-related quality-of-life by the self-report, disease-specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is increasingly used as an outcome measure in Crohn`s disease (CD) patients in clinical trials. Higher SIBDQ scores indicate better quality-of-life; the range is 10 to 70. However, the construct validity of SIBDQ and its responsiveness to change of disease status require validation.

Methods

Adult (≥18 years) CD patients (n = 108) with Harvey–Bradshaw Index (HBI) >4 and <16 prospectively filled in the SIBDQ at two time-points (T1, T2) 3 months apart. Medical data at T1 and T2 were collected, and recorded by their physicians in the HBI. Biomarkers of disease activity included Calprotectin and C-reaction protein (CRP), measured at T1 and T2. The construct validity of SIBDQ in relation to biomarkers and HBI was determined by Pearson correlations and group comparisons using Student`s t-test. Statistical significance was taken as p < 0.05. Patients’ medications were prescribed without regard to the study protocol.

Results

Demographic and medical characteristics (median, %) of the cohort were: age 30 years; females 65%, married/partner 48%; higher education 83%; BMI 22; non-smokers/past-smokers 92%; disease duration 5 years; past Crohn’s disease-related surgery 17%; Montreal classification A2 89%, L2+L3 89%, B1+B2 89%, perianal disease 18%; medications: corticosteroids 4%, 5-ASA 5%, immunomodulators 21%, biologicals 43%. HBI and SIBDQ median scores at T1 and T2 were: HBI: 9 and 4 (p < 0.001); SIBDQ: 43 and 49 (p < 0.001). SIBDQ scores correlated inversely with Calprotectin (r = −0.395, p = .002), CRP (r = −0.208, p = .046), and HBI (r = −0.345, p < 0.001). Baseline HBI scores were used to divide the cohort into two groups for comparison: mild disease (5–7) vs. moderate disease (8–16). Mild disease patients reported higher SIBDQ scores than those with moderate disease (42.7 vs. 39.7, t = 1.96, p = 0.05). Regarding sensitivity of SIBDQ to clinical changes between T1 and T2, we found that change in SIBDQ correlated significantly with change in CRP across these two administrations (r = −0.232, p = 0.042). Finally, defining clinical response in CD as a decrease from baseline HBI score by ≥3 points, SIBDQ change scores were significantly larger in treatment responders (n = 51, M = 6.25) than non-responders (n = 30, M = 1.13, t = −3.042, p = 0.003).

Conclusion

The SIBDQ measure is a valid assessment of quality-of-life in CD, correlating with biomarkers and sensitive to change of disease activity, with potential for use as a patient-reported outcome in both clinical practice and as a primary end-point in clinical trials.
P271 Trends in faecal calprotectin levels during pregnancy and post-partum in healthy women
Authors: Doherty J , Moore R , Kivlehan C , Twomey P , McAuliffe F , Cullen G
Published: January 2020

Background

Faecal calprotectin (FCP) is one of the most widely used non-invasive tools for diagnosis and assessment of inflammatory bowel disease (IBD). Numerous factors can influence FCP levels including weight, smoking status and medications. In clinical practise FCP is commonly used to identify flares during pregnancy. For a test that is widely used minimal data exists on the determinants of normal levels and variations in concentrations during pregnancy in healthy individuals. Our aim is to determine normal FCP levels during pregnancy and post-partum and whether levels change during pregnancy and post-partum in healthy individuals.

Methods

We performed a prospective study analysing FCP levels from pregnant women at 16- and 34-weeks’ gestation and 4- and 12-weeks post-partum. Basic demographics were collected including age, parity, medical history, BMI and smoking status. Patients with a history of gastrointestinal disorders were excluded. FCP concentrations were measured with a quantitative ELISA assay.

Results

98 patients were included in our study. 172 stool samples were collected for analysis. Sixty-two stool samples were collected at 16 weeks gestation, 48 samples from 34 weeks gestation, 38 samples from 4weeks post-partum and 24 samples from 12 weeks post-partum. The median age was 33 years (21–44). Forty-one patients had a BMI > 25 (42%). Sixteen patients were ex-smokers (16%) and one patient was actively smoking (1%). The median FCP levels from 16 weeks gestation was 29.5 (10–476), median level from 34 weeks gestation was 25.6 (10–259), from 4 weeks post-partum was 23.4 (10–318) and 12 weeks post-partum was 29.4 (10–216) (Table 1). There was no significant change in median FCP levels over the course of pregnancy and post-partum (p = 0.294). Interestingly median FCP levels were normal at all time points however we saw a slight numerical increase in FCP levels during pregnancy in patients whose BMI was > 25 and this reached statistical significance at 4weeks post-partum (p = 0.01) (Table 1, Graph 1). There was also a significant increase in FCP at 4 weeks post-partum in patients who were ex-smokers (p = 0.004). (Table 1, Graph 1).

Conclusion

FCP levels are not affected by physiological changes in pregnancy or post-partum in normal healthy individuals without IBD. This confirms FCP is an effective tool for identifying flares of colitis during pregnancy. However, when using this tool, one should be aware that levels can be slightly altered by a patients’ smoking history and their weight and a detailed clinical history is essential when interpreting results.
P276 Reactivation of Epstein–Barr virus and cytomegalovirus behaves differently in pathophysiology of ulcerative colitis
Authors: Yamada S , Yamamoto S , Honzawa Y , Hayashi Y , Kitamoto H , Okabe M , Seno H
Published: January 2020

Background

Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are members of the herpesvirus family. CMV reactivation is often complicated with ulcerative colitis (UC) and is known as one of exacerbation factors. However, the association between EBV reactivation and pathophysiology of UC is still unclear.

Methods

This study enrolled 116 active UC patients who received colonoscopy between January 2005 and January 2019 in Kyoto University Hospital. 244 biopsy specimens were obtained from inflamed colonic mucosa to assess EVB and CMV reactivation. Viral loads of EBV and CMV in inflamed mucosa were measured by real-time PCR assay. The reactivation of those viruses was defined as DNA quantity more than 10 copies/μg DNA. Clinical severity was assessed by Lichtiger index and defined as follow: 4–8 as mild, 9–12 as moderate, and more than 12 as severe. Endoscopic severity was assessed by Mayo endoscopic score. We examined the correlation between the positivity of each viral reactivation and patients’ characteristics or prognosis of UC.

Results

(1) Median age, Lichtiger score and Mayo endoscopic score at the time to assess the viral reactivations were 36 years-old, 8, and 3, respectively. (2) EBV and CMV reactivation were observed in 127 samples (52.0%) and 73 samples (29.9%), respectively. There was no correlation between EBV and CMV viral load (correlation coefficient 0.19), although a significant correlation between those viral reactivations was observed in active colonic mucosa of UC patients (p = 0.002). (3) The proportion of EBV reactivation was higher in both clinically and endoscopically severe UC patients compared with those with mild activity. On the other hands, there was no association between CMV reactivation and clinical or endoscopic severity. (4) Multivariate analysis indicated risk factors for EBV reactivation as receiving anti-TNF-α antibodies (odds ratio [OR] 4.2) or calcineurin inhibitors (OR 3.5), and CMV reactivation (OR 2.1), respectively. (5) Multivariate analysis also indicated risks for CMV reactivation as steroid-refractory (OR 4.7) and EBV reactivation (OR 2.0). (6) EBV and CMV reactivation did not affect clinical outcomes including the requirement of colectomy or intensification of immunosuppressive treatments and the incidence of colitis-associated cancer, dysplasia and lymphoproliferative disease.

Conclusion

Reactivation of EBV or CMV may behave differently in pathophysiology of UC. Further studies are required to clarify the role of EBV reactivation on colonic inflammation in UC patients.
P277 Ileo-rectal anastomosis vs. ileoanal pouch in ulcerative colitis: clinical outcome in a real-life experience
Authors: Sena G , Neri B , Lolli E , Calabrese E , Sica G , Monteleone G , Biancone L
Published: January 2020

Background

In ulcerative colitis (UC) surgery is required in about 10–20% of patients (patients). Evidence regarding the long-term outcome of Ileo-rectal anastomosis (IRA) vs. the recently proposed ileal pouch (IPAA) are still lacking. In a real-life, retrospective, single-centre study, we aimed to assess the clinical outcome of all UC patients with IRA or IPAA.

Methods

In a retrospective study, clinical records of UC patients with IPAA or IRA in regular follow-up from January 2001 to September2019 were reviewed. Inclusion criteria: (1) UC diagnosis; (2) Age ≥18 years; (3) IPAA or IRA for UC;4)Detailed clinical history; (5) follow up ≥1 year after surgery. The following parameters were reported: demographic and clinical characteristics, hospitalisation, additional surgery, mortality, dysplasia/cancer of the ileum and/or rectum, number of endoscopies and outpatient visits, stool frequency and treatments. The quality of life (QoL) are being evaluated. Data were expressed as median (range), differences among groups assessed by chi-squared test or unpaired T-test.

Results

A total 84(4%) UC patients with IPAA (n = 47) or IRA (n = 37) were detected among 2136 UC patients. Among these 84 UC patients, in a preliminary assessment, clinical outcome was evaluated in 31 patients (16 IPAA,15 IRA) with a median follow up of 72 [12–180] months (mos) and a median time interval from surgery of 63 [1–348] mos. Considering the 16 patients with IPAA (8 M, 9 F) vs. the 15 with IRA (5 M,10 F), the median age at first assessment was 44 [range 30–56] vs. 48 [range 23–82] in patients with IPAA or IRA, respectively (p = 0.2123). The median follow up after surgery was 65 [range 12–132] vs. 79 [range 12–180] mos (p = 0.1955). The median time interval from surgery to first clinical assessment after surgery was 48 [range 1–312] vs. 78 [range 2–348] mos (p = 0.1955). Indication for surgery was refractory UC in 30 patients and endoscopic perforation in 1 pt. During the follow up, the following outcomes after surgery were recorded in patients with IPAA vs. IRA: hospitalised patients (n = 6 vs. n = 6 patients, p = 0.8864); additional intestinal surgery (n = 0 vs. n = 4 patients, p = 0.0269), mortality (n = 0 vs. n = 1 patients,p = 0.2938); occurrence of dysplasia/cancer of the ileum and/or rectum (n = 0 vs. n = 2 patients, p = 0.1310), number endoscopies after surgery (mean: 4 vs. n = 3.75, p = 0.316348), number visits after surgery (mean: 2.4/year vs. n = 1.7/year, p = 0.2429), mean stool frequency (n = 8.08 vs. n = 4.36; (p = 0.0005), need of biologics, n = 5 vs. n = 1 (p = 0.0834).

Conclusion

In a real-life experience, the need for intestinal surgery was significantly higher in patients with IRA vs. IPAA; the mean daily stool frequency was significantly higher in patients with IPAA vs. IRA.No statistically significant differences were found among the two groups in terms of hospitalisation, mortality, cancer/dysplasia and need for biologics.
P283 Patient-reported symptoms over a period of 14 days reliably predict endoscopic and histological disease activity in ulcerative colitis (UC)
Authors: Kormilitzin A , Walsh A J , Matini L , Kantschuster R , Lepetyukh M , Wilson J , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L
Published: January 2020

Background

Disease activity assessment in UC is most accurately evaluated by endoscopy and biopsy, which often correlates poorly with current symptoms. We investigated whether a machine learning classification algorithm using patient-reported Simple Clinical Colitis Activity Index (SCCAI) over 14 days and signature features could reliably distinguish endoscopic and histopathologic activity from remission.

Methods

The TrueColours ulcerative colitis (UC) monitoring platform was used to collect symptoms (SCCAI, daily) and endoscopic/histopathological activity, as per the UCEIS and Nancy indices (twice in 6 months) in 233 patients. The longitudinal data may be seen as a trajectory. The signature is a collection of statistics which efficiently summarises the trajectory and serves as a non-parametric hierarchical method for longitudinal data representation. Signature features were used as input to the extreme gradient boosting classification algorithm to categorise subjects into remission or active disease groups. Remission: UCEIS ≤1 AND Nancy ≤1; Active disease: UCEIS ≥4 AND Nancy ≥2. The advanced signature-based approach was compared with a baseline model with manually constructed features (mean SCCAI score over 14 days preceding endoscopy). Cross-validation was used to report metrics, Table 1.

Results

Disease activity classification with signature features significantly outperformed mean-SCCAI based approach (AUC 0.87 vs. AUC 0.79 correspondingly, p = 0.011, Figure 1). All other statistical metrics (including sensitivity (0.89), specificity (0.78), PPV (0.82) and NPV) demonstrated the same trend, favouring the signature method. The decision-tree-based ensemble gradient boosting classification algorithm (XGBoost) has the intrinsic ability to rank feature importance. The signature feature of the fourth item within the SCCAI (blood in stool) dominated, followed by cross-correlation between the first (daily bowel frequency) and fourth item.

Conclusion

Gradient boosting classification algorithm with signature features extracted from the longitudinal six-item symptoms of the SCCAI, reliably identified subjects with endoscopic and histopathological disease activity. The developed algorithm may be used with the TrueColours platform as a decision support tool.
P286 Rate of colectomy in ulcerative colitis: Results from a Spanish cohort with 15 years of follow-up
Authors: Rodriguez Gutiérrez C , Elosua Gonzalez A , Prieto Martínez C , Rubio Iturria S , Vicuña M A , Nantes Castillejo Ó
Published: January 2020

Background

Knowing the natural history of ulcerative colitis (UC) is essential to understand the evolution of the disease, assess the impact of different therapeutic strategies, identify poor prognostic factors and provide patients with understandable information who help them in decision making. It has been suggested that biological drugs could modify natural history of UC and therefore decrease the rates of colectomy. In Spain, infliximab is approved for CU since 2005.

Methods

We performed a retrospective study that includes all patients with a definitive diagnosis (DD) of UC or Unclassifiable Colitis (UC) in the Navarra Incident Cohort (which includes all patients diagnosed between 2001 and 2003 in Navarra, Spain). Our objectives were to analyse the Colectomy Incidence Rate (CIR) from diagnosis to the end of follow-up (12-31-2017) and identify predictive factors of colectomy.

Results

We included 174 patients with DD of UC (42.5% E2 - 26.8% E3) and 5 of IC: 44.1 women, median age 39.2 years (7–88), median follow-up of 15.7 years. At the end of the follow-up, 8 patients underwent colectomy (CIR 3 surgeries per 100000patients-year). Timing of colectomy was: 3 at the initial diagnosis (<1 month), 2 in the first 2 years, 2 at 5 years and 1 at 12 years from diagnosis. All had previously received steroids, 5 immunomodulators and 2 biological agents. In 7 (87%) the surgery was urgent and the indication, megacolon in 3 (37.5%), severe outbreak in 3 (37.5%) and failure to medical treatment in 2 (25%). In 5 cases (62.5%), an ileoanal reservoir was made and in 3 definitive ileostomy.

Conclusion

In our cohort, global colectomy rates are lower than those reported in other series and occur mostly in the first 5 years of evolution.
P295 VALIDation of the IBD-Disk instrument for assessing disability in inflammatory bowel diseases in a population-based cohort: The VALIDate study
Authors: Le Berre C , Bourreille A , Flamant M , Bouguen G , Siproudhis L , Dewitte M , Dib N , Cesbron-Metivier E , Goronflot T , Gourraud P A , Kerdreux E , Poinas A , Trang-Poisson C
Published: January 2020

Background

Inflammatory bowel diseases (IBD) are disabling disorders. The IBD-Disability Index (IBD-DI) was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a shortened and visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk in a large cohort of IBD patients and to assess its variability over time.

Methods

From March 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 months intervals (NCT03590639). Validation included concurrent validity, reproducibility, internal consistency, and evaluation of IBD-Disk correlation with IBD activity. Variability was assessed by comparing scores between baseline and follow-up visits.

Results

A total of 559 patients (73% Crohn’s disease, 27% ulcerative colitis) were included and 389 were followed up (Table 1). There was a good correlation between IBD-Disk and IBD-DI scores (r = 0.75, p < 0.001) (Figure 1). The IBD-Disk was significantly higher in patients with active disease according to Physician/Patient Global Assessment (Figure 2), clinical scores (Figure 3), and biomarkers levels, compared with patients with inactive disease. Reproducibility was excellent (intra-class correlation coefficient = 0.90), as well as internal consistency (Cronbach’s α = 0.89). The IBD-Disk score significantly decreased in patients becoming inactive over time.

Conclusion

This is the first study to validate the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability in clinical practice. Further studies are warranted to assess its correlation with endoscopic activity, to explore its responsiveness to change, and to evaluate the factors associated with disability.
P308 The need for psychological and psychotherapeutic interventions in Austrian patients with inflammatory bowel disease
Authors: Kutschera M , Waldhör T , Gröchenig H P , Haas T , Wenzl H , Steiner P , Koch R , Feichtenschlager T , Eckhardt G , Mayer A , Kirchgatterer A , Ludwiczek O , Platzer R , Papay P , Gartner J , Fuchssteiner H , Peters P G , Reicht G , Moser G , Dejaco C , Primas C , Novacek G , Miehsler W
Published: January 2020

Background

inflammatory bowel diseases (IBD) are lifelong conditions challenging the patient not only with respect to somatic complaints but also affecting psychosocial issues. This may lead to the need for additional psychological care. The present study investigated the patients’ subjective need for additional psychological care and indicators for such a need.

Methods

We performed a cross-sectional multicentre study on Austrian IBD patients who were in routine care at one of the 18 participating IBD centres. The patients were asked to fill in a questionnaire booklet including the ADAPT, a validated questionnaire on the need for psychological care which gives two separate scores (‘ADAPT-IPC’ -need for integrated psychosomatic care, ‘ADAPT-PT’- need for psychotherapy), a validated questionnaire on the use of complementary and alternative medicine (CAM), the SIBDQ, and questions on clinical and sociodemographic data. The primary endpoint was the need for integrated psychosomatic care, psychotherapy or both.

Results

1286 patients returned the questionnaire. In total, 29.7% of all patients expressed a need for additional psychological care, 18.6% expressed a need for ADAPT-IPC and 20.2% expressed a need for ADAPT-PT. The multivariable regression analysis revealed the two dominating factors associated with the need for both types of psychological care were the use of CAM and a low SIBDQ-score ≤ 50 (see Table for details).

Conclusion

About 30% of the Austrian IBD patients expressed a need for integrated psychosomatic therapy a/o psychotherapy. This need was especially associated with reduced quality of life and the use of CAM which may indicate the desire for emphathetic and dedicated care. Further studies will be necessary to clarify if these results can be reproduced in other countries.
P322 Impact of the presence of Epstein–Barr virus in intestinal mucosa of inflammatory bowel disease patients
Authors: NUÑEZ ORTIZ A , Trigo Salado C , De la Cruz Ramírez M D , Márquez Galán J L , Herrera Justiniano J M , Leo Carnerero E
Published: January 2020

Background

To evaluate the importance of positive Epstein–Barr virus (EBV) status in intestinal biopsy in patients with inflammatory bowel disease (IBD), its association with active disease and immunosuppressive (IM) therapy and its influence on the clinical evolution of IBD.

Methods

We retrospectively analysed patients with IBD who were tested for EBV in intestinal mucosa between November 2009 and June 2017. Pathologists decided EBV testing based on the presence of severe histologic activity with/without prominent lymphoplasmacytic infiltrate or refractory disease to various treatments. We analysed phenotypic characteristics, previous treatments, active therapies at the time of EBV testing, EBV status by immunohistochemistry, presence of lymphoma, treatment decision making after EBV testing and subsequent clinical evolution based on hospital admissions and treatment escalation requirement.

Results

We included 56 patients, 28 with Crohn’s disease (CD) and 28 with ulcerative colitis (UC). The predominant phenotype of patients with CD was A2L3C1. Regarding patients with UC, 14 patient had left-sided and 14 extensive colitis.

EBV was positive (EBV+) in 26 cases (46%), one of them associated with a lymphoproliferative disorder. EBV+ status was associated with clinically active disease (53.3% vs. 25%, p = 0.08); severe endoscopic (54.5% vs. 37.5%, p = 0.02) and severe histological activity (72.2% vs. 33.3%, p = 0.007) and the presence of a prominent lymphoplasmacytic infiltrate (68.8% vs. 16.7%, p < 0.0005). In addition, active steroid treatment, but not IM and/or biological therapy, at the time of EBV testing was associated with EBV+ status (61.5% vs. 33.3%, p = 0.03). Only the presence of a prominent lymphoplasmacytic infiltrate showed significant association with EBV+ in the multivariate analysis (p = 0001). IM therapy was de-escalated in 6/26 EBV-positive patients. In EBV- patients, IM treatment was escalated in 10/30. After a mean follow-up of 53.3 months, 17 patients required hospital admission and 26 escalation of therapy. Both risk of admissions and escalation of treatment during follow-up were higher in EBV+ patients (38.5% vs. 23.3%, p = 0.2; and 65.4% vs. 30%, p = 0.008, respectively). Only female sex was associated with a greater possibility of hospital admission and EBV+ with the need for treatment escalation (p = 0.03) in the multivariate analysis. None of the patients developed lymphoma during follow-up.

Conclusion

EBV+ status in intestinal mucosa is associated with histological activity. Prominent lymphoplasmacytic infiltrate is the only factor associated with EBV+ status independently of immunosuppression status. EBV+ is associated with subsequent poor clinical evolution and a greater need for escalation of IM therapy.
P329 ECCO grant recipient: preliminary results of the HOT-TOPIC trial (Hyperbaric Oxygen Therapy for the Treatment Of Perianal fistulas In Crohn’s disease)
Authors: Lansdorp C , Gecse K , Buskens C , Löwenberg M , Stoker J , Bemelman W , D’Haens G , van Hulst R
Published: January 2020

Background

Beneficial effects of hyperbaric oxygen (HBO) therapy for perianal fistulising Crohn’s disease (pCD) have been suggested in previous publications. The HOT-TOPIC study was designed to further investigate its feasibility and therapeutic effect in 20 therapy-refractory patients with pCD. Here we present the preliminary results.

Methods

17 patients with pCD refractory to conventional-therapy > 6 months (medical and/or surgical, no patients with deviating stoma) were treated with 40 sessions of HBO therapy (243–253 kPa, 110 min per session throughout 8 weeks). Medical treatment remained stable from screening, seton drain(s) were removed after 30 treatment. Co-primary outcomes were clinical response as measured by the perianal disease activity index (PDAI) and MRI improvement measured by the modified van Assche index. Secondary outcomes were clinical response as assessed by fistula drainage assessment (FDA), biochemical response and patient-reported outcomes. All outcomes were assessed at baseline and 2 months after HBO.

Results

17 patients (6 female, median age 34 years, median duration of disease 13 years) were treated. Median PDAI scores decreased from 8 to 4 (p < 0.001) and MRI scores from 9.4 to 7.3 (p = 0.001). Defined as PDAI of 4 or less, 11 out of 17 patients had inactive perianal disease after treatment, with 3 patients also having a predominantly fibrotic tract on MRI. Of the 45 external openings draining at baseline, 22 were clinically closed after treatment (49%, assessed by FDA). Four patients, three with one external opening and one with five openings at baseline, had no remaining openings after treatment. Median C-Reactive Protein and faecal calprotectin levels decreased from 5.0 and 416 to 2.3 and 31 (p = 0.002 and p = 0.003), respectively. Median scores of the inflammatory bowel disease questionnaire (IBDQ) increased from 169 to 185 (p = 0.001) and VAS scores from the Euroqol-5-dimensions questionnaire increased from 65 to 75 (p = 0.07), higher scores reflecting better quality of life. When asked on a validated decision regret scale if patients regretted their decision to undergo HBO, the mean score was 12.5 (0–100, higher scores indicating higher regret). During follow-up, none of the patients needed new (experimental) medication, re-interventions or stoma. Seven out of 17 patients experienced trouble equalising middle ear pressure during HBO, with four patients showing signs of barotrauma after otoscopy. Three patients needed tympanostomy tubes. No other clinically relevant adverse events occurred, and no adverse events led to discontinuation of the treatment.

Conclusion

Based on preliminary data, HBO treatment is associated with significant improvement in pCD, as measured by clinical and MRI endpoints.
P332 Mindfulness-based stress reduction and cognitive intervention improve the health-related quality-of-life and ability to work in Crohn’s disease patients: A randomised controlled trial
Authors: Schwartz D , Sergienko R , Goren G , Reggev S , Friger M , Nemirovsky A , Monsonego A , Greenberg D , Sarid O , Slonim-Nevo V , Odes S
Published: January 2020

Background

Crohn’s disease (CD) patients have reduced quality-of-life (QoL) in physical, emotional and social domains, and diminished work and leisure activities. We examined whether Mindfulness-Based Stress Reduction and Cognitive Intervention (‘Intervention’) can improve QoL and ability to work.

Methods

Patients (≥18 years), Harvey–Bradshaw Index (HBI) >4 and <16, were randomised to Intervention or Control groups. Intervention was taught in 8 weekly sessions by social workers via SKYPETM with twice-daily practice and back-report required. Medications were not controlled. HBI was completed at entry (T1) and 12 weeks (T2), and these questionnaires: (1) Short inflammatory bowel disease questionnaire (SIBDQ), disease-specific HRQoL measure. (2) Short-Form 12 (SF-12) questionnaire, generic HRQoL measure of physical health (PH) and mental health (MH). (3) EQ-5D-3L HRQoL questionnaire. (4) Work Productivity and Activity Impairment (WPAI) questionnaire, measuring absenteeism, presenteeism (reduced productivity), work impairment (composite of absenteeism and presenteeism), and leisure activity impairment. Statistics: Pearson Chi-squared, Wilcoxon signed-rank test.

Results

There were 39 Intervention and 43 Control patients. Demographic and medical characteristics (median, %) were: age 30 y; women 65%, married/partner 48%; higher education 83%; BMI 22; non- or past-smokers 92%; disease duration 5 y; HBI 8 (range 5–15); past surgery 17%; Montreal A2 89%, L2+L3 89%, B1+B2 89%, perianal disease 18%; drugs: corticosteroids 4%, 5-ASA 5%, immunomodulators 21%, biologics 43%; (p = ns between groups). Socio-economic status was higher in Intervention (87% = good/very good) than Control (58%, p = 0.016). HBI, SIBDQ and SF PH improved in both groups, but SF MH, EQ-5D-3L and all WPAI measures improved only in Intervention group (Table). Non-significance of WPAI indices between groups resulted from small sample size.

Conclusion

Mindfulness-Based Stress Reduction and Cognitive Intervention led to increased QoL and less work and activity impairment. If confirmed in a large cohort the intervention may be offered to all CD patients.
P334 Impact of disease duration on tofacitinib efficacy in patients with ulcerative colitis
Authors: Travis S , Dotan I , Danese S , Chiorean M , Yamamoto-Furusho J , Ponce de Leon D , Su C , Paulissen J , Maller E , Modesto I , Colombel J F
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib in patients with UC were evaluated in two Phase 3 induction studies (OCTAVE Induction 1 and 2; NCT01465763, NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574) [1], and an ongoing, open-label, long-term extension study (NCT01470612) [2]. We evaluated the impact of disease duration on tofacitinib efficacy in the OCTAVE trials.

Methods

Patients received tofacitinib 10 mg twice daily (BID) or placebo in OCTAVE Induction 1 and 2, and responders at Week 8 were eligible to receive tofacitinib 5 or 10 mg BID or placebo during OCTAVE Sustain (final efficacy assessment at Week 52). Non-responders from OCTAVE Induction 1 and 2 and completers/treatment failures from OCTAVE Sustain could enter the OLE study. In the OLE study, patients who did not show clinical response to 8 weeks of tofacitinib 10 mg BID in OCTAVE Induction 1 and 2 (induction non-responders [IndNR]) received an additional 8 weeks of tofacitinib 10 mg BID; all patients underwent endoscopy at Month 2 (data as of Sep 2018). Patients were stratified by UC disease duration (<3, 3–6 and >6 years) at OCTAVE Induction 1 and 2 baseline (ie prior to study treatment). Associations between disease duration category and efficacy endpoints were assessed using the Cochran-Mantel–Haenszel Chi-square test.

Results

Among patients who received tofacitinib 10 mg BID in OCTAVE Induction 1 and 2, remission and mucosal healing rates at Week 8 were numerically higher in those with shorter disease duration than those with longer disease duration, but associations were not statistically significant (Table). Clinical response rates were similar across disease duration categories. At Week 52 of OCTAVE sustain, remission and mucosal healing rates were highest in patients with the shortest disease duration (<3 years; Table). Among IndNR, the proportions of patients achieving efficacy endpoints at Month 2 of the OLE study were lowest in those with disease duration <3 years, but associations were not statistically significant (Table).

Conclusion

In general, disease duration did not impact tofacitinib efficacy. Patients diagnosed with UC <3 years prior to starting tofacitinib treatment were numerically more likely to achieve remission and mucosal healing in induction and maintenance trials than those with longer disease duration, but the associations were not statistically significant. These analyses are post hoc and limited by the small sample size, and further data are needed to understand whether disease duration may have an impact on the response to tofacitinib treatment.

References
P352 Infliximab-therapy intensification based on endoscopic activity suppresses treatment interruption among patients with Crohn’s disease
Authors: Komaki Y , Kanmura S , Yutsudo K , Kosuke K , Komaki F , Tanaka A , Nishimata N , Sameshima Y , Sasaki F , Ooi H , Tokushige K , Sameshima Y , Ido A
Published: January 2020

Background

Although biologics have improved the therapeutic goals for Crohn’s disease, the problem of diminishing efficacy exists. With recent advances, it is possible to administer double doses or shortening the dosing interval of infliximab (IFX); however, its effectiveness and right timing of strengthening remain unclear. In this study, we examined the treatment outcomes in patients with Crohn’s disease who received IFX-therapy intensification for the reduction of IFX effects at multiple centres.

Methods

Of the 243 patients with Crohn’s disease who were seen at our hospital and related facilities from July 2002 to July 2018, a total of 46 patients who could be observed for more than 1 year after IFX-therapy intensification for diminished effect of IFX were included in this study. The relationship between patient background and continuation of therapy intensification was retrospectively examined using logistic regression analysis. Furthermore, the relationship between therapy intensification and the treatment discontinuation rates for each of double doses and shortening the dosing interval was also evaluated.

Results

Of the 46 patients (30 men and 16 women), 67.4% (31 cases) were able to continue therapy intensification for 12 months. In univariate analysis of the relationship between patient background and continuation of therapy intensification, therapy intensification due to the remaining endoscopic findings contributed to the decrease in therapy intensification interruption rate. However, multivariate analysis did not reveal any significant contributing factors. Next, treatment discontinuation rates were compared between the group in which therapy intensification was performed due to the remaining endoscopic findings (n = 14) or clinical symptoms (abdominal pain, diarrhoea, and subjective general condition) (n = 32). The rate of treatment discontinuation 12 months after treatment strengthening was significantly lower in the therapy intensification group due to the remaining endoscopic findings than in that due to clinical symptoms (7.1% vs. 43.8%, p = 0.015). The rates of treatment discontinuation between the group of double doses (n = 34) and the group of shortening the dosing interval (n = 12) were also compared, but there was no significant difference after 6 or 12 months of treatment strengthening.

Conclusion

Treatment interruption would less likely occur among patients with Crohn’s disease receiving IFX if IFX-treatment intensification is triggered by the remaining endoscopic findings and not by clinical symptoms.
P356 Infectious events in patients with inflammatory bowel disease: The impact of immunomodulators and tumour necrosis factor antagonist therapy
Authors: Andersson P , Karling P
Published: January 2020

Background

Immunomodulators (IM) and tumour necrosis factor antagonist therapy (anti-TNF) are effective treatments for inflammatory bowel disease (IBD) but has been associated with an increased risk for infectious diseases. We investigated the frequency of infectious events in patients with IBD and the association of infectious events with concomitant treatment with IM and anti-TNF therapy.

Methods

We performed a retrospective medical chart review of patients with IBD, 18 to 65 years of age, included in the Swedish Registry of IBD (SWIBREG) and treated in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period January 1, 2006, to January 31, 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection.

Results

Among the 593 included patients (397 patients with UC and 195 patients with CD), 1398 events occurred. The proportion of events that occurred on treatment with corticosteroids, IM, anti-TNF, combination therapy (IM + anti-TNF) and without any immunosuppressive treatments was 8.3%, 35.8%, 17.7%, 10.0% and 47.4%. Of all patients, 60.4% had at least one infectious event, and 29.3% had >0.3 events per year. Compared with patients not receiving immunosuppressive therapy, an event rate of >0.3 per year was more common among those receiving immunomodulator monotherapy or combination therapy (Table), and was more common in patients with Crohn’s disease than ulcerative colitis (35.0% vs. 26.1%, p = 0.022). There were no significant differences in infectious events between patients who had received immunomodulator monotherapy and patients who had received combination therapy.

Conclusion

We found an increased frequency of infection associated with the use of combination therapy and immunomodulator monotherapy, but no difference between the two treatments.
P357 Importance of stool drug monitoring in anti-TNF-treated patients
Authors: Bacsur P , Szántó K , Madácsy T , Kata D , Ferenci T , Rutka M , Bálint A , Bor R , Fábián A , Milassin Á , Elekes G , Szepes Z , Nagy F , Földesi I , Maléth J , Farkas K , Molnár T
Published: January 2020

Background

Anti-tumour necrosis factor (TNF) therapy has dramatically changed the treatment of inflammatory bowel disease (IBD). The relationship between clinical outcomes and serum anti-TNF levels is controversial. This study aimed to perform simultaneous analyses of the serum, mucosal and faecal infliximab and adalimumab levels to determine the mucosal expression of TNF-α and assess the relationship of the anti-TNF-α levels in these biological samples with the endoscopic and clinical activities and body composition in IBD patients.

Methods

Consecutive IBD patients who received maintenance anti-TNF-α therapy and underwent colonoscopy were enrolled. We assessed the clinical disease activity, collected the blood, faecal and biopsy samples. The number of TNF-α positive cells in the mucosa was detected using immunofluorescent labelling. Serum, mucosal and faecal anti-TNF-α levels, anti-drug antibody level in the serum and faecal calprotectin were determined using ELISA. Each patient underwent body composition analysis.

Results

Fifty consecutive patients have been analysed in the study. The number TNF-α positive cells was significantly higher in the inflamed than in the un-inflamed part of the colon (p = 0.01); however, such a difference was not detected in case of tissue drug levels. Tissue drug level did not correlate with the serum drug level. Nevertheless, tissue drug levels of the samples obtained from the un-inflamed part of the colon were significantly higher in patients who were in remission (p = 0.03467). The presence of the drug in the faeces was significantly different according to disease activity (p = 0.0022). Drug levels in the biological samples did not show any association with the presence of anti-drug antibodies. Body composition parameters had no significant impact on the serum and tissue drug levels. Faecal calprotectin showed significant correlation with faecal drug concentration (p = 0.0162) and clinical and endoscopic activity (p < 0.001).

Conclusion

To the best our knowledge, this is the first study to measure drug concentrations in all the relevant biological samples. Our findings highlight the importance of faecal drug monitoring because active disease may be present in spite of normal serum anti-TNF levels. Simultaneous determination of faecal drug concentration and faecal calprotectin may be more accurate for evaluating therapeutic responses in the future.
P360 Safety and clinical efficacy of double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicentre study
Authors: Mazza S , Fascì A , Casini V , Ricci C , Munari F , Pirola L , Girelli C , Lupinacci G , Pastorelli L , Cavallaro F , Piazza O’Sed N , Ferraris L , Colucci A , Amato A , Maurizio V , Fiorino G , Caprioli F
Published: January 2020

Background

Since infliximab (IFX) patent expiry in 2015, several IFX biosimilars have been licensed in EU for all indications, including inflammatory bowel diseases (IBD). IFX biosimilars currently available in Italy include CT-P13 and SB2, both of which demonstrated comparable efficacy, safety and immunogenicity with IFX originator in IBD patients. Safety and clinical efficacy of single switch from originator IFX to CT-P13 have also been confirmed in a prospective clinical trial. On the contrary, data regarding multiple therapeutic switching of IFX originator with CT-P13 and SB2 are currently lacking.

Methods

This study was aimed to evaluate the safety and efficacy of double switch from IFX originator to CT-P13 and subsequently to SB2 in patients with IBD. From November 2018 to May 2019, patients undergoing IFX double switch in 8 Centres in Lombardy were retrospectively analysed. The overall rate of IFX discontinuation, incidence and type of adverse events (AE) and proportion of patients on clinical remission over time were recorded. Data were compared with a control group of 66 IBD patients single switched from IFX originator to CT-P13.

Results

Fifty-two double-switched IBD patients were enrolled (63% M, mean age 41 years, 75% Crohn’s disease, 25% ulcerative colitis). Main indications for IFX therapy were moderate to severe disease (50%) and steroid-dependent disease (25%). The overall 24- and 48-week IFX discontinuation rates following second switch (CTP13->SB2) were 2% (95% CI 0–6%) and 14% (95% CI 3–25%), respectively. During a median follow-up of 40 weeks (18–48), 4 patients (12%) experienced a total of 6 AE (2 cutaneous, 2 infectious, 1 articular and 1 immunological), leading to IFX discontinuation in 3 cases (6%). No infusion reactions were observed. At week 24 following second switch, 49 (94%) patients were in clinical remission, the remaining 3 patients not being in remission already at the time of second switch. Only one patient lost response after week 24, 48 (92%) of patients being in clinical remission at the end of follow-up. No differences in IFX discontinuation, AE and clinical remission rates were found between double-switched and single-switched patients. No clinical parameters were found to predict safety and efficacy outcomes.

Conclusion

The study supports both safety and efficacy of the double switch from IFX originator to CT-P13 and SB2 in patients with IBD, and demonstrates its non-inferiority to a single switch strategy, with potential cost implications.
P372 Effects of filgotinib on anaemia, thrombocytopenia and leukopenia: Phase 3 study results in patients with active rheumatoid arthritis and prior inadequate response/intolerance to biological DMARDs
Authors: Besuyen R , Genovese M , de Vlam K , Gottenberg J E , Kalunian K , Bartok B , Tan Y , Guo Y , Tasset C , Sundy J , Walker D , Takeuchi T
Published: January 2020

Background

Anaemia, thrombocytopenia and leukopenia in rheumatoid arthritis (RA) patients treated with non-Janus Kinase 1 (JAK1) selective inhibitors may be due to inhibition of haematopoietic growth factors signalling through JAK2. Therefore, we investigated anaemia, thrombocytopenia and leukopenia in patients with active RA with prior inadequate response/intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARDs) treated with filgotinib (FIL), a selective JAK1 inhibitor (FINCH-2; NCT02873936).

Methods

In the randomised, double-blind, placebo-controlled Phase 3 FINCH-2 trial, patients were randomised 1:1:1 to oral FIL 200 mg, 100 mg, or placebo (PBO) once daily plus conventional synthetic DMARDs for 24 weeks. In this subgroup analysis, we assessed shifts from baseline (BL) in haemoglobin (hgb), platelets (plt), neutrophils and lymphocytes.

Results

A total of 448 patients were treated; FIL 200 mg, n = 147; FIL 100 mg, n = 153; PBO, n = 148. Hgb, plt, lymphocyte and neutrophil counts remained consistent throughout the study. At BL, 28.8%, 0.9%, 2.2% and 5.8% patients had mild–moderate low hgb, plt, neutrophil and lymphocyte, respectively, and 1.1% had severely low lymphocyte levels. Of patients with mild–moderate hgb levels at BL, 13.1% with FIL 200 mg, 9.5% FIL 100 mg, and 7.6% PBO achieved normal hgb at Week 24, respectively (Table). Of those with normal BL hgb, only 6–9.8% had mild low levels at Week 24. Patients with BL mild-moderate low plts and neutrophils had normal levels at Week 24, except one with mild neutropenia on FIL 100 mg. Of patients with normal plt and neutrophil levels at BL, >94% maintained these at Week 24 in all treatment groups. By Week 24, 3.2%, 5.2% and 2.2% of patients treated with FIL 200 mg, FIL 100 mg and PBO, respectively, in the mild–moderate subgroup and 1.7% in the severe subgroup treated with FIL 100 mg had normal lymphocyte counts.

Conclusion

In this subgroup analysis, most patients with normal hgb, plt, lymphocyte and neutrophil at BL maintained them over 24 weeks of FIL treatment. Of the patients with mild–moderately low hgb at BL, >9% shifted towards normalisation. Similar patterns of improvement were observed for plt, lymphocyte and neutrophil counts. These results suggest that FIL does not increase the incidence of anaemia, thrombocytopenia or leukopenia in patients who entered the study with active RA despite prior bDMARDs.
P373 Telemedicine and inflammatory bowel disease: Results of the IBD assistant pilot project
Authors: Malickova K , Pesinova V , Bortlik M , Duricova D , Machkova N , Hruba V , Lukas M , Mitrova K , Vasatko M , Kostrejova M , Kolar M , Lukas M
Published: January 2020

Background

Telemedicine enables proper and immediate monitoring of the patient’s current health state, followed by well-timed and customised treatment. The aim of our study was to assess feasibility and safety of telemonitoring in Czech patients with inflammatory bowel disease (IBD). Furthermore, we wanted to evaluate the impact of telemonitoring on the number of outpatient′s visits and direct health-care cost.

Methods

We performed randomised controlled study including patients with IBD in stable remission on conventional therapy who were randomised either to telemonitoring (IBDA) or control (CTRL) group and were followed-up for 12 months. All IBDA patients had access to a specific web application which contained a set of questioners assessing disease activity and complications which were filled-in at least every 3 months. Evaluation of clinical activity was accompanied by measurement of faecal calprotectin (FC) at home using CalproSmart test. Individuals in the CTRL group were followed under the standard conditions as other outpatients.

Results

A total of 131 were included (42% males; 47% with Crohn′s disease) and randomised to IBDA (n = 94) or control group (n = 37). HBI/pMayo activity indexes were not significantly different at baseline (p = 0.636 and p = 0.853) and end of study (p = 0.517 and p = 0.890) in the two groups. Similarly, no significant difference in inflammatory markers (C-reactive protein, FC) was observed in either group (p>0.05). The occurrence of intercurrent infections (0.93 vs. 0.81 cases of infection/patient-year, p = 0.87) or the need for hospitalisations (1 vs. 0) was similar between the groups. The number of outpatient visits was significantly lower in the IBDA than in the CTRL group (median number in IBDA group 0, in the CTRL group 4.2 visits, respectively, p < 0.0001). Telemedicine led to a reduction in the direct annual health-care cost of patient follow-up by ~25% compared with the standard care.

Conclusion

Results of the first Czech IBD telemedicine study confirm the effectiveness and safety of the telemedicine approach, which led to a reduction in outpatient visits and savings in health-care costs while maintaining a high standard of health care.

Acknowledgements: Supported by the IBD-Comfort Endowment Fund.