bluuebunny/crossref_metadata_2025 huggingface dataset:
P426 In failure of non-optimised adalimumab (ADA) with therapeutic serum levels, a change in biotherapy class is greater than an intensification of ADA dose in IBD patients
Authors: Roblin X , genin C , williet N , veyrard P , boschetti G , berger A E , flourie B , nancey S , Paul S
Published: January 2020

Background

Nearly 40% of patients who failed on ADA have therapeutic residual trough levels (pharmacodynamic failure). It is then recommended to change the therapeutic class to a non-anti-TNF biological. In this situation, however, a quarter of patients respond to an ADA dose optimisation. The purpose of this work was to compare these two strategies and identify predictors of response for each strategy.

Methods

This is a bi-centre, retrospective study based on a clinical and biological database that included patients followed from 2015 to 2016 with an IBD in maintenance treatment with ADA as monotherapy (40 mg/sc/14 days) and in loss of response (CDAI > 220 with faecal calprotectin > 250 µg/g stool for CD and Mayo score > 6 with endoscopic sub-score > 1 for UC). All patients included had residual trough ADA levels > 5 µg/ml. Relapsed patients were treated either with dose optimisation (ADA: 40 mg/sc/7 days) or other biotherapy (ustekinumab or vedolizumab, according to classic regimens and dosages). The primary endpoint was the relapse-free survival rate (defined as clinical and biological or endoscopic activity requiring therapeutic change). The survival curve analysis was performed using the Kaplan–Meier method and the log-rank test.

Results

In total, 125 patients (mean age: 38 years, 75% CD, sex ratio M/F = 57%, previous infliximab = 42%) were included and 50 were treated with another biological (Vedolizumab: 30 patients, Ustekinumab: 20 patients). The characteristics of the two groups were comparable except for significantly higher levels of CRP and faecal calprotectin at inclusion in the biological change arm. The duration without relapse was significantly longer after the class change (p = 0.0005; HR = 0.39[0.23–0.68]). The relapse-free survival rates at 54 weeks were 35% for the optimised arm and 66% for a class change (p = 0.04). In multivariate analysis, the only long-term response predictor was biotherapy class change vs. ADA dose optimisation (p = 0.042; HR = 0.3[0.02–0.95]). Previous use of IFX or type of IBD were not associated with relapse. For the dose optimisation strategy, in multivariate analysis, only age < 40 years was associated with a progression without relapse (p = 0.007; HR = 0.09[0.01–0.52]). Residual ADA levels were not predictive of response to optimisation (p = 0.73) and no ADA quartile was significantly associated with a more favourable clinical response. For the class change strategy, no relapse predictors were isolated in univariate analysis.

Conclusion

In patients on ADA who are losing response despite therapeutic rates, the change of class to non-anti-TNF biotherapy allows a significantly greater lasting response than a dose optimisation strategy for ADA.
P436 Evaluation of targeted vitamin D supplementation regimen in postoperative patients with Crohn’s disease
Authors: LI Y , Zheng L , Yao D , Zhou Z , Liu B , Huang Y , Duan Y
Published: January 2020

Background

Vitamin D with a serum 25(OH)D concentration above 100 nmol/l was associated with disease remission in patients with IBD and suggested that targeted administration may be an anti-inflammatory drug. This study was designed to assess the effectiveness, safety, and predictive measures of a vitamin D regimen in postoperative patients with Crohn’s disease to achieve the above goals.

Methods

In a prospective study, patients with Crohn’s disease and serum 25(OH)D concentrations <75 nmol / L were prescribed an oral vitamin D supplement at a dose of one year, and adjusted 4-weekly to aim for a serum 25(OH)D level of 100–125 nmol/l.

Results

Thirty-two postoperative patients with Crohn’s colitis had an average 25(OH)D concentration of 51.5 (range 25–74 nmol / L). 25 patients reached the target level and six patients reached 90–94 nmol / L. Because of the reoperation, one patient withdrew in 6 months. Patients with BMI <30 kg / m2 could reach the target dose (p = 0.006), and the total dose was negatively correlated with the initial serum 25(OH)D (Spearman r = 0.86, p = 0.002). One patient developed a high level (146 nmol/L) at 2 months and the other had new hypercalciuria. There are no serious adverse events attributable to treatment. Clinical disease activity continued to decline (p = 0.015), but faecal calprotectin (p = 0.264), inflammatory cycle markers (p = 0.513) and Rutgeerts score (p = 0.428) did not decrease.

Conclusion

Specific oral vitamin D regimens can successfully and safely reach or approach target levels, improve symptom-based activity scores, but do not alter objective indicators of intestinal or systemic inflammation. A modified version of this dose-escalation protocol is suitable for randomised placebo-controlled trials, and the further randomised controlled trial was needed.
P438 Real-life effectiveness and safety of ABP501, an adalimumab biosimilar, in inflammatory bowel disease: a multicentre Italian study
Authors: Barberio B , Zingone F , Ferronato A , Buda A , Melatti P , Gubbiotti A , Massimi D , Casadei C , Cingolani L , Savarino E V
Published: January 2020

Background

Recently, various adalimumab (ADA) biosimilars have been approved by the EMA with the same indications of the reference product (Humira), despite the lack of data in terms of efficacy and safety in patients with inflammatory bowel disease (IBD). The aim of our study was to verify the effectiveness and tolerability of ABP501, an ADA Biosimilar, in IBD in the short-term.

Methods

All consecutive moderate-to-severe IBD patients who completed induction with ABP501 at three Italian IBD Units (Padua, Santorso, Feltre) were included. We collected data on partial Mayo (p-Mayo) Score, Harvey–Bradshaw Index (HBI), C reactive protein (CRP), faecal calprotectin (FC), concomitant steroid and azathioprine therapy at baseline (T0), after induction (T1) and at six months (T2). Information on the need for optimisation and adverse events (AEs) were also collected. Continuous and categorical variables were expressed as mean with standard deviation and frequency with percentages, respectively. Comparisons between variables were conducted using a t-test and chi-square test. Data were analysed using STATA11.1 software.

Results

Thirty-three IBD patients [17 with ulcerative colitis (CU), 18 with Crohn’s disease (CD)] that completed induction (T1) were considered, with 18 of them who completed at least six months of therapy (T2). Clinical remission was achieved by 14/33 (45.5%) and 8/18 (44.4) patients at T1 and T2, respectively. Steroid-free clinical remission was obtained by 14/33 (42.4%) and 8/18 (44.4) patients at T1 and T2, respectively. After induction FC tended to decrease from baseline to T2, without reaching statistical significance (p = 0.1). However, a significant decrease in CRP levels (p < 0.02) was observed. After induction, AEs occurred in 11 (33.3%) patients: 2 had an infection, 8 reported headache or myalgia or arthralgia, and one experienced a local infusion reaction. Moreover, AEs were observed in 6/18 (33.3%) at T2: 5 had arthralgia and 1 had a local infusion reaction. After induction 4/33 (12.12%) stopped therapy for lack of response, whereas the dropout occurred in 6/12 (33.3%) at six months (4 for loss of response and 2 for adverse events). Finally, 7/33 (21.2%) and 5/18 (27.7%) patients needed therapeutic optimisation at T1 and T2, respectively.

Conclusion

ABP501 seemed to be successful in achieving clinical remission and steroid-free clinical remission, but further data are required. Overall the therapy was well tolerated.
P439 Patient’ recruitment for a Phase 3 inflammatory bowel disease (IBD) programme is significantly increased when accessing the CT-SCOUT™ platform
Authors: Bouhnik Y , Roblin X , Mrad R , Hebuterne X , Laharie D , Tanasa Stefanescu C , Nancey S , Boureille A , Amiot A , Sebbah N , Peyrin Biroulet L
Published: January 2020

Background

The main issue when validating new molecules in the field of IBD is insufficient patient recruitment into clinical trials, resulting in a considerable delay and cost increase. The selection of the best recruiting sites is a long and difficult process, especially since study sponsor has no visibility on the activity of the sites, and the sites have no penalties if the objectives are not achieved. The CT-SCOUT™ platform is a web-based solution to help clinicians to pre-screen potential candidate, facilitating the coordination of the research team and providing sponsor and principal investigator visibility into patient recruitment efforts and status on the site. We aimed to compare the recruitment rate in sites using the application according to Premium or Freemium modalities and in sites not equipped with CT-SCOUT™ for IBD clinical trials.

Methods

We conducted a prospective, multicentre, open-label, observational and comparative study in 25 sites participating in a selected phase 3 IBD clinical trials in France. All sites were proposed to be equipped with CT-SCOUT™, and the recruitment rate was compared according to 3 modalities: a) the Premium mode, giving access to all the functionalities of the application (including specific inclusion/exclusion criteria, possibility of sending notification to the team) in counterpart of which they undertook to use the application; b) the Freemium mode, a basic functionality that only gives the name of the study in the first selection phase; c) sites who were not interested to be equipped. The primary endpoint was the mean number of patients randomised per site per month. Patients screened and those finally randomised were compared in sites equipped (Premium or Freemium) and non-equipped using one-way ANOVA followed by post-hoc Tukey test.

Results

During the recruitment period from 4 to 36 months (mean 24.8 months), 221 and 130 patients were screened and randomised, respectively. The mean number of patients screened and randomised per site per month according to CT-SCOUT™ equipment is reported in the figure below.

Conclusion

This study shows that sites not equipped with CT-SCOUT™ recruit only a few patients. Among the equipped sites, those with Premium access have a significantly higher randomisation rate than those with limited functionality. Sites equipped with digital pre-screening support to facilitate patient recruitment and provide the sponsor visibility are the best candidates for trials.
P440 Polimedication in patients with inflammatory bowel disease: prevalence and outcomes in a retrospective unicentric series
Authors: Mesonero Gismero F , Fernández C , Sánchez-Rodríguez E , García-García de Paredes A , Albillos A , López-Sanromán A
Published: January 2020

Background

Polymedication (PM) can complicate course and management of chronic diseases, and is currently a poorly explored issue in patients with inflammatory bowel disease (IBD).

Our aims were to determine the prevalences of PM, and of inappropriate and high-risk drugs use (APINCH) in a clinical series of IBD patients, describing epidemiological factors associated with PM, and evaluating a possible association of PM with poor disease outcomes.

Methods

A retrospective observational study of a unicentric series, including patients with IBD visited at our Unit (September-October 2018). Prescriptions, demographic data, and clinical features were collected reviewing clinical files and electronic drug prescriptions. PM was defined as the simultaneous use of more than 5 drugs (Gnjidic D, J Clin Epidemiol. 2012). APINCH drugs included insulin, antibiotics, anticoagulants, chemotherapies, narcotics, and potassium supplements (Clinical Excellence Australian Commission 2017). Disease outcomes (flares, hospitalisations, surgeries), non-adherence to treatment and undertreatment were evaluated 12 months after the index visit.

Results

We included 407 patients (56% males, median age 48 yo, range 17–92, 60.2% Crohn′s disease, 38.8% ulcerative colitis). Chronic comorbidity was present in 54% (29% metabolic, 25.5% cardiovascular, 12.8% psychiatric), and 27% presented multiple comorbidities (≥3). Median patient number of prescriptions was 3 (r 0–15); 14.3% were on more than three drugs, and 15.7% between four and five drugs. Most frequent prescriptions are represented in Figure 1. PM was identified in 18.4% of cases, inappropriate medication in 8.8%, and high-risk drugs in 6.1% (mainly opioids). In multivariate analysis, factors significantly associated with PM were chronic comorbidity (OR 11, CI 2.3-51,2, p˂0.002), multiple comorbidities (OR 4.02, CI 1.93–8.38, p˂0.001), and age >62 years (OR 3.66, CI 1.7–7.7, p˂0.001). In univariate analysis, both undertreatment (54% vs. 16%, p˂0.01) and non-adherence (26% vs. 12%, p˂0.02) were associated with PM after 12 months. No association of PM with poor disease outcomes was found. In multivariate analysis, only undertreatment was significantly associated with PM (OR 5.9, CI 1.4–29.4, p˂0.014).

Conclusion

PM occurs in around one of the five patients with IBD, mainly in the elderly and in those with comorbidity. This scenario could interfere with appropriate IBD treatment and therapeutic success.
P441 Efficacy of biosimilar infliximab CT-P13 among inpatients with severe steroid-refractory colitis
Authors: Ollech J , Normatov I , Dwadasi S , Dalal S , Micic D , Israel A , Labas J , Joel P , Cohen R , Rubin D , Atsushi S
Published: January 2020

Background

The infliximab biosimilar CT-P13 has been reported to have similar clinical effect compared with its originator. In this study, we evaluated the efficacy and safety of CT-P13 in the treatment of inpatients with severe steroid-refractory colitis.

Methods

Adult colitis patients (UC or isolated Crohn’s colitis; Montreal classification E2-3, or L3, respectively) admitted to the University of Chicago IBD inpatient service between January 2018 and December 2018 for management of severe colitis refractory to IV steroids who received CT-P13 were included in the study. Patients diagnosed with active small bowel Crohn’s disease were excluded. CT-P13 was given as a single or several infusions of 5 to 10 mg/kg. For all patients, demographic, clinical, laboratory, and endoscopic data were attained by a comprehensive review of their electronic medical records. The primary endpoint was colectomy-free survival.

Results

Twenty-one patients, 14 with ulcerative colitis and seven with Crohn’s colitis, were included. Fourteen (66%) of patients were female. The median age was 32.2 years (IQR 24.1–43.2). The median disease duration was 4.3 years (IQR 2–10.3), and the median follow-up time was 5.9 months (IQR 1.8–9.1). Patients had a median CRP of 23 (IQR 6–74). All patients had moderate to severe disease on flexible sigmoidoscopy. Three patients (14%) underwent colectomy during their index hospitalisation. Colectomy free survival was 76% at three months and 70% at six months (Figure 1). No severe adverse events were reported in this patient cohort.

Conclusion

A significant proportion of patients with severe colitis failing IV steroids responded to induction therapy with CT-P13. Colectomy free survival rates were similar to previous randomised trials using originator infliximab as induction therapy in severe steroid-refractory colitis. CT-P13 was effective and safe in hospitalised patients with severe steroid-refractory colitis.
P442 Long-term quality of life after surgery for perianal Crohn’s disease
Authors: Angriman I , Tomassi M , Bordignon G , Bardini R , Ruffolo C , Scarpa M
Published: January 2020

Background

Perianal disease is rather common among Crohn’s disease (CD) patients and quality of life is often worsened by disease activity. This study aimed to assess the possible predictors of long-term quality of life after surgery for perineal CD.

Methods

Data of 50 consecutive patients operated on from 2014 to 2018 for perianal fistula or abscess were retrieved. Thirty-three of them had perianal CD while 17 of them had a sporadic perianal fistula and were enrolled as controls. Patients were interviewed with the Cleveland Global Quality of Life (CGQL) and SF-12 quality of life questionnaires. Disease activity was defined as the Harvey–Bradshaw Index (HBI) and Perianal Disease Activity Index (PDAI). Comparisons between CD and sporadic groups were carried out with non-parametric tests and log-rank test and multiple regression models were used to assess predictors of quality of life.

Results

The total CGQL score and that of all its items were significantly lower in CD patients compared with patients with the sporadic perineal disease (p < 0.05) while SF12 sub total did not differ in the two groups. At multivariate analysis, CD diagnosis and perineal disease activity index confirmed to be independent predictors of long-term overall quality of life measured with CGQL. SF-12 mental component (MCS) was predicted by PDAI (p = 0.005) and by HBI (p = 0.03) while SF-12 Physical Component (PCS) was independently predicted by PDAI (p = 0.008), oozing perineal fistulae (p = 0.01) and age at disease onset (p = 0.0003).

Conclusion

Long-term quality of life after surgery for perineal disease is worse in CD patients than in patients with sporadic perianal disease. Quality of life is predicted by local and systemic disease activity and age at disease onset.
P443 Magnetic resonance imaging after ligation of the intersphincteric fistula tract for high perianal fistulas in Crohn’s disease: a retrospective cohort study
Authors: Van Praag E , van Rijn K , Monraats M , Stoker J , Buskens C
Published: January 2020

Background

Surgical closure of high perianal fistulas using the ligation of the intersphincteric fistula tract (LIFT) procedure is increasingly used in Crohn’s disease. Currently, data on MRI findings after the procedure is lacking, while this is the most important modality to assess deep fistula healing. Therefore, we aimed to evaluate pre- and postoperative fistula characteristics on MRI and the relation with clinical outcomes after LIFT procedure.

Methods

Consecutive Crohn’s patients treated with LIFT between 2007 and 2018 for high perianal fistulas who underwent a baseline and follow-up (FU) MRI were included in this retrospective study. MRI’s were scored by two radiologists according to a composed score based on the original and modified Van Assche scores with the addition of several items (Table 1). Findings at MRI and the relation to clinical healing were described.

Results

A total of 12 patients were included (4 male, median age 34 years (IQR 28–39)). The FU MRI was performed a median 5.5 months (IQR 2.5–6.0) after the LIFT procedure. At this time eight patients (67%) reached clinical healing, which increased to ten patients (83%) during follow-up. None had a recurrence. Three patients (25%) needed a re-intervention after the FU MRI due to inflammatory masses and/or persisting fistula tracts. At baseline, all patients showed a tract predominantly filled with granulation tissue, which changed to predominantly fibrotic in seven patients (58%) (Figure 1). All clinically responding patients showed a decrease in tract volume and/or hyperintensity (i.e. activity) with an absence of hyperintensity on T1 and T2 in four (33%) patients.

Conclusion

Clearly decreased fistula activity can be observed on MRI after LIFT surgery in Crohn’s patients. A large proportion of patients develops a fibrotic tract relatively soon after the procedure and shows no clinical recurrences, suggesting a highly effective therapy and prognostic value of MRI.
P455 Adherence to enteral nutrition therapy by adults with active Crohn’s disease is associated with conscientiousness personality trait
Authors: Wall C , McCombie A , Mulder R , Day A , Gearry R
Published: January 2020

Background

Conscientiousness is a personality trait characterised by the ability to control impulses, delay gratification, set and reach goals, and plan in advance. Conscientious people are more likely to be non-smokers, do physical activity and practice healthy eating behaviours. They are also more likely to be adherent to medication. The aim of this study was to assess whether people with Crohn’s disease who score high on conscientiousness are more likely to be adherent to enteral nutrition (EN) therapy than low scorers.

Methods

Adults aged 16 to 40 years with newly diagnosed Crohn’s disease or having a flare of disease were invited by their gastroenterologist to use nutrition therapy to induce disease remission. Nutrition therapy was either eight weeks of exclusive enteral nutrition (EN) or two weeks of exclusive EN followed by six weeks of partial EN and one meal per day. A convenience control group of healthy participants with no history of gastrointestinal symptoms was also recruited to use exclusive EN for two weeks. Adherence to EN was self-reported fortnightly using a standardised questionnaire. Non-adherence was defined as patients who repeatedly ate foods while using EN or ate more than one meal per day on partial EN. Patients who could not initiate or did not tolerate the EN formula were included in the non-adherent group. Prior to starting nutrition therapy, conscientiousness was measured using the well-validated conscientiousness subset of the Big Five Inventory.

Results

Twenty-three (59%) of the 39 patients recruited with Crohn’s disease completed and adhered to the eight-week treatment. Reasons for non-adherence by the 14 patients who did not complete treatment included: could not initiate EN (n = 4), non-response at week 4 (n = 2), intolerance of EN (n = 7) or repeated eating of food or started eating food again prior to the end of treatment (n = 2). Seventeen (81%) of the 21 healthy controls completed and adhered to 2 weeks of exclusive EN. Reasons for non-adherence were could not initiate EN (n = 3) or intolerance of the formula (n = 1). Adherence and completion of EN therapy were associated with a greater mean conscientiousness score 35.57 (95% CI: 32.88, 38.25) compared with the non-adherence group mean 30.13 (95% CI: 26.53, 33.73), p = 0.014. Mean conscientiousness score of the healthy controls who completed exclusive EN was similar to the Crohn’s disease group (36.65 (95% CI: 33.53, 39.77), p > 0.05).

Conclusion

Conscientiousness was associated with adherence to EN therapy. EN therapy can be a cognitively and emotionally demanding treatment and this personality trait should ideally be considered when determining suitable candidates for EN therapy.
P459 The impact of latent cytomegalovirus infection on the disease behaviour in patients with ulcerative colitis
Authors: Långvall P , Shi C , Karling P
Published: January 2020

Background

Cytomegalovirus (CMV) infection has been associated with steroid-refractory disease and risk for colectomy in patients with Ulcerative Colitis (UC). We aimed to study if patients with latent CMV infection more often needed systemic steroids, immunomodulators, biologics and surgery than patients negative for CMV infection.

Methods

From the national IBD register (SWIBREG) all patients with UC (n = 404) treated at Umeå University Hospital in Sweden, and who were tested for CMV infection were included. A latent CMV infection was defined if a patient had at least one positive serology and/or a positive PCR for CMV. A retrospectively medical chart review between the years 2006 and 2019 was performed to check for medical therapy and surgery due to UC.

Results

One hundred and thirty-one patients (32%) had at least on one occasion been tested for CMV infection and of these patients, 88 (67%) had evidence of a latent CMV infection. There were no differences in the use of systemic steroids, in the use of immunomodulators/biologics or in colectomy rate between patients with latent CMV infection and patients with no infection (table). There were no differences between patients with latent CMV infection vs. no infection in median faecal calprotectin (FC) levels the first five years after diagnosis (302 vs. 457 µg/g; p = 0.301) or at the last recorded FC test (62 vs. 82 µg/g; p = 0.317).

Conclusion

Patients with latent CMV infection do not differ from CMV negative patients in the use of medical therapy for UC nor in colectomy rate.
P461 Intolerance to 5-aminosalicylate is a risk of poor prognosis in ulcerative colitis patients
Authors: Fujii T , Hibiya S , Maeyashiki C , Saito E , Takenaka K , Motobayashi M , Shimizu H , Nagahori M , Ohtsuka K , Kurosaki M , Yauchi T , Watanabe M
Published: January 2020

Background

5-Aminosalicylates (5-ASA) are the key drugs in induction and maintenance therapy in ulcerative colitis (UC). Some UC patients are involved in 5-ASA intolerance after induction of oral 5-ASA compounds. There is no evidence of the prognosis including the risk of colectomy in 5-ASA intolerant UC patients.

Methods

The aim of this study is to establish the prognosis of 5-ASA intolerant UC patients in a multicenter cohort study. A retrospective review of a prospective multicenter database (2014–2018) of 1,574 UC patients was carried out and a total of 1,286 patients treated with oral 5-ASA compounds were enrolled. We compared the risk of colectomy and biologics induction between patients (i) tolerant to first 5-ASA compound (1079), (ii) intolerant to first 5-ASA compound but tolerant to other 5-ASA compound (107) and (iii) intolerant to 5-ASA compound and withdrawal of 5-ASA (100).

Results

We identified 1,286 patients with UC, of which 40 patients (3.1%) resulted in colectomy and 247 patients (19%) treated with biologics. Colectomy rate in patients (iii) intolerant to 5-ASA and withdrawal of 5-ASA were higher than (i) tolerant to first 5-ASA and (ii) intolerant to first 5-ASA but tolerant to other 5-ASA (9.0%, 2.7%, 1.9%, respectively). (iii) Patients withdrawal of 5-ASA showed higher risk of colectomy compared with (i) tolerant to first 5-ASA (Hazard ratio (HR) 4.71, 95% Confidence interval (CI): 2.04–10.8). The risk of colectomy among (ii) patients intolerant to first 5-ASA but tolerant to other 5-ASA showed no significant difference compared with (i) tolerant to first 5-ASA (HR 0.76, 95% CI: 0.43–1.35). The biologics induction rate in (iii) patients withdrawal of 5-ASA was significantly higher than (i) tolerant to first 5-ASA and (ii) intolerant to first 5-ASA but tolerant to other 5-ASA (37%, 18%, 16%, respectively). Also (iii) patients withdrawal of 5-ASA showed higher risk of induction with biologics compared with (i) tolerant to first 5-ASA (HR 2.35, 95% CI: 1.50–3.68). Those risk among (ii) patients intolerant to first 5-ASA but tolerant to other 5-ASA showed no significant difference compared with (i) tolerant to first 5-ASA (HR 0.76, 95% CI: 0.43–1.35).

Conclusion

Patients with UC who had 5-ASA intolerance and withdrew from 5-ASA showed poor prognosis. We should consider trying other 5-ASA compounds even if the patients had intolerance to one 5-ASA compound.
P463 Induction of endoscopic response: a network meta-analysis of induction studies comparing ontamalimab with other treatments for moderate-to-severe ulcerative colitis
Authors: Vickers A , Nag A , Devine B , Sands B E , Panaccione R , Peyrin-Biroulet L , Danese S , Vermeire S , Gorelick K J , Goetsch M , Hartley L
Published: January 2020

Background

Clinicians, patients, payers and policymakers require relevant, high-quality evidence to support decision-making regarding the treatment of ulcerative colitis (UC). In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all biologics and novel small molecules for which induction study data on endoscopic response were available.

Methods

A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between treatments and placebo in terms of efficacy in inducing endoscopic response. Results were examined by anti-TNF status (naïve vs. experienced).

Results

In total, 15 phase 2 and phase 3 induction studies of the following agents were available and included: adalimumab (160/80mg), etrolizumab (100mg and 300mg), golimumab (200/100mg), infliximab (5mg), ontamalimab (22.5mg and 75mg), ozanimod (0.5mg and 1mg), tofacitinib (10mg) and vedolizumab (300mg). The definition of endoscopic response (improvement) in all trials was a Mayo endoscopic subscore of ≤1. Homogeneity between studies was good, enabling pooling of results. Figure 1 shows odds ratios for induction of endoscopic response with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments performed significantly better than placebo in anti-TNF-naïve patients, with the exception of both doses of etrolizumab and ozanimod 0.5 mg. Significant differences between some treatments were observed; specifically, ontamalimab 22.5 mg (p = 0.0277), tofacitinib 10 mg (p = 0.0233) and infliximab 5 mg (p = 0.0047) were all superior to adalimumab 160/80 mg.

Conclusion

This study suggests that ontamalimab, infliximab and tofacitinib could be superior to adalimumab in inducing endoscopic healing, although it was conducted before any large-scale head-to-head trials of these drugs. Furthermore, large variances due to differing endpoint timings, the combination of phase 2 and phase 3 data, and lack of control for placebo response rates preclude firm conclusions being drawn.
P464 Vedolizumab concentrations in colonic mucosal tissue of ulcerative colitis patients inversely correlate with the severity of inflammation
Authors: Van den Berghe N , Verstockt B , Gils A , Ferrante M , Vermeire S , Thomas D
Published: January 2020

Background

Multiple studies have reported the association between vedolizumab serum concentrations and endoscopic outcomes in patients with ulcerative colitis (UC). However, little is known about drug consumption in tissue and the relationship with mucosal inflammation. This study aimed to investigate vedolizumab concentrations in the tissue of UC patients and the correlation with their inflammatory state and serum levels.

Methods

A paired serum sample and colonic mucosal biopsy were collected in 36 UC patients at week 14 of vedolizumab treatment. In non-responders, defined as a Mayo endoscopic subscore of ≥2, inflamed colonic biopsies were taken in the sigmoid around 20–30 cm from the anal verge. In responders, defined as a Mayo endoscopic subscore ≤ 1, a biopsy was taken in a macroscopically uninflamed area at the same location. Biopsies were lysed by the addition of 10 μl lysis buffer (50 mM Tris, 0.1% Triton X-100 and 100 mM NaCl) per mg tissue and vortexed every 5 min during 1 h. Total protein content was measured and normalised to 3 mg/ml before analysis of the vedolizumab concentration using an in-house developed ELISA. Results are expressed as µg vedolizumab/mg total protein content.

Results

A positive correlation was observed between vedolizumab concentrations in tissue and serum (Spearman r = 0.8447, p < 0.0001), both in inflamed (r = 0.8609, p <0.0001, n = 16) and uninflamed tissue (r = 0.7925, p <0.0001, n = 20). The median tissue vedolizumab concentration in patients with Mayo endoscopic subscore 0, 1, 2 and 3 were 0.120, 0.074, 0.062 and 0.064 μg/mg, respectively (p < 0.01, see figure), indicating that tissue drug levels inversely correlate with the severity of inflammation. Vedolizumab tissue concentrations were significantly lower in non-responders compared with responders (0.064 vs. 0.112 μg/mg, p <0.05). Moreover, patients achieving Mayo endoscopic subscore 0 had significantly higher vedolizumab levels in colonic tissue compared with patients not achieving this outcome (0.120 vs. 0.065 μg/mg, p <0.02). Interestingly, a trend was observed towards higher serum-to-tissue ratios of vedolizumab in non-responders compared with responders (p = 0.0523). This finding suggests that if two patients have the same serum vedolizumab concentration, the patient with mucosal inflammation is more likely to have lower tissue levels than the patient with no or limited inflammation.

Conclusion

Vedolizumab concentrations in colonic mucosal tissue of UC patients inversely correlate with the severity of inflammation. As the serum-to-tissue ratio of vedolizumab is numerically higher in non-responders compared with responders, the relative distribution of vedolizumab in serum and tissue might be more important than the drug concentration alone.
P465 Therapeutic drug monitoring in Crohn’s disease patients, a comparison between homogeneous mobility shift assay and point of care method
Authors: Bodini G , Demarzo M G , Djahandideh A , Baldissarro I , Savarino E , Savarino V , Jain A , Risso P M , Giannini E G
Published: January 2020

Background

Therapeutic Drug Monitoring (TDM) is a useful tool to help physicians managing patients with Inflammatory Bowel Disease treated with anti-tumour necrosis factor (TNF) drugs. Different techniques are available to evaluate serum drug concentration (TL), However, these techniques are time-consuming. A point-of-care (POC) method has been proposed to evaluate drug TL and overcome the limitations inherent to other methodologies. Our aim was to evaluate the capability of POC to discriminate between IBD relapse and remission and to evaluate the concordance of drug TL measured with POC and HMSA

Methods

We analysed with Quantum BlueÒ (Buhlmann Laboratories AG, Schonenbuch, Switzerland) (POC) 200 Adalimumab (ADA) and 200 Infliximab serum samples of 46 Crohn’s disease (CD) patients previously assessed with HMSA. Blood samples were drawn at standardised time points during anti-TNF treatment (2, 6, and every 8 weeks), before anti-TNF administration. Disease activity was assessed by the Harvey–Bradshaw Index (HBI, remission defined by HBI<5).

Results

We evaluated 46 CD patients responders to anti-TNF induction with ADA (n = 25, 54.3%) and IFX (n = 21, 45.6%) with a median follow-up of 83 weeks (range 16–144 weeks). At week 16, median ADA TL of patients in remission were significantly higher as compared with patients in disease relapse using both HMSA [12.7 μg/ml (range, 8.9–23.6 μg/ml) vs. 6.6 μg/ml (range, 0.7–9.6 μg/ml), p = 0.0001] and POC [17.8 μg/ml (range 7.6–35.0 μg/ml) vs. 9.8 μg/ml (range 5.8–11.4 μg/ml), p = 0.0003]. The concordance between the two different techniques has been assessed as 0.76 by Choen Kappa. Considering IFX TL, patients in remission had higher serum drug concentration using both HMSA [7.0 μg/ml (range, 0.0–21.8 μg/ml)] and POC [6.2 μg/ml (range 0.4–14.3 μg/ml)] as compared with patients who experienced disease relapse [HMSA, 0.1 μg/ml (range, 0.0–4.1 μg/ml), p = 0.019; POC, 0.45 μg/ml (range 0.4–3.3 μg/ml), p = 0.0072]. The concordance between the two different test for IFX TL was 0.81. We obtained similar results at the end of follow-up: median ADA TL was higher in remission than in disease relapse patients using both HMSA and POC [p = 0.001 and p = 0.0012] with a concordance of 0.75. Median IFX TL was higher in remission than in disease relapse patients using both HMSA and POC (p = 0.13 and p = 0.25) with a concordance of 0.70.

Conclusion

Both POC and HMSA are TL tests able to differentiate relapse and remission in IBD patients. The association between anti-TNF TL and disease status (remission/relapse) was better in ADA-treated patients rather than patients treated with IFX. Finally, we demonstrated a good concordance between HMSA and POC. Anti-drug antibody concentrations while available on HMSA were not available on POC
P468 Switching from adalimumab originator to ABP 501 biosimilar: a multicentre North Italian study
Authors: Barberio B , Melatti P , Zingone F , Bertani L , Ferronato A , GUBBIOTTI A , Massimi D , D’Incà R , Savarino E V
Published: January 2020

Background

In late 2018, adalimumab (ADA) biosimilars have been approved by the EMA with the same indications of the reference product (RP), that is Humira. However, while their efficacy and safety have been proven in patients with rheumatoid arthritis and psoriasis showing no differences compared with the RP, data on inflammatory bowel disease (IBD) is lacking. The primary aim of this study was to verify the ability of ABP501 to maintain the clinical response induced by the RP after switching to the biosimilar.

Methods

We retrospectively enrolled all consecutive patients who switched to ABP501 by ADA Originator at the IBD Units of Veneto Region (Padua, Santorso) from December 2018 to November 2019. We collected data on partial Mayo (p-Mayo) Score, Harvey–Bradshaw Index (HBI), C Reactive Protein (CRP), faecal calprotectin (FC), concomitant steroid and azathioprine therapy at the time of the switch (T0) and after six months. Continuous and categorical variables were expressed as mean with standard deviation (SD) and frequency with percentages respectively. Comparisons among variables were conducted using one-way ANOVA and chi-square. Data were analysed using STATA11 software.

Results

Forty IBD patients switched to biosimilar [7 with ulcerative colitis (UC) and 33 with Crohn’s disease (CD)] were included in the study. All switched patients were in remission or in mild clinical activity at the time of the switch. We observed a clinical worsening and clinical improvement in 8 and 2 patients, respectively (p = 0.001) from T0 to T1. FC value increases at T1 compared with T0 (from a mean value of 98.32 to 137.9 μg/g) but without significant difference. Seven patients needed to add steroids at T1 (p = 0.04) and five (12.5%) needed therapeutic optimisation. Finally, 8 (20%) patients stopped therapy: 7 for loss of response and 1 for an adverse event.

Conclusion

Our data show that after switching, one out of three of the patients may experience disease relapse, requiring treatment optimisation (i.e. addiction of steroids or increasing the dose to once a week) or treatment discontinuation. Thus, patients should be strictly observed in order to prevent or, at least, early manage such clinical relapses. Larger and longer studies are mandatory to understand the clinical implications of these findings.
P469 Stay in class or switch out of class after anti-TNF failure in inflammatory bowel disease (IBD). Real-world data from a large district general hospital
Authors: Johnson H , Vythilingam S , McLaughlin S
Published: January 2020

Background

Biosimilar infliximab (IFX) and adalimumab (ADA) are well-proven cost-effective anti-TNF drugs in IBD; in our practice, the majority of patients with IBD receive IFX or ADA first line. Since the introduction of Vedolizumab (VED) and Ustekinumab (UST) some have recommended switching out of class after failing a single anti-TNF. This practice has significant cost implications. To establish the outcome of treatment response in patients treated with a second anti-TNF agent after anti-TNF failure compared with the outcome of patients treated with VED and UST after anti-TNF failure.

Methods

We maintain a prospective IBD database. We searched our database for the outcomes of patients who failed their first anti-TNF drug but were in a clinical remission 6 months after changing to a second or third biologic drug. Disease type, age, gender and response to their second and third biologic drug were recorded. Clinical remission was defined as off steroids with calprotectin <250 and no symptoms of active IBD.

Results

Two hundred and eighty-seven patients were identified. One hundred and forty (48.8%) were male. Mean age was 43.2 (range 18–94). Disease type was 75 (26%) UC, 210 (73.2%) CD, 2 (0.7%) IBD-U. One hundred and ninety-three patients received IFX 1st line, 118 (40%) failed. Of these 84 (72%) received ADA, 28 (24%) VED and 6 (5%) UST second line. Remission with second-line treatment was achieved in 58 (69%); ADA, 18 (64%); VED, 6 (100%); UST. Remission with third line treatment; was achieved in 6 (100%); VED; 5 (100%); UST. Ninety-four patients received ADA 1st line, 33 (35%) failed. Of these 11 (33%) received IFX, 10 (30%) VED and 8 (24%) UST second line. Remission with second-line treatment was achieved in 6 (55%); IFX, 10 (100%); VED and 8 (100%); UST. Remission with third line treatment; was achieved in 1 (100%); VED, 4 (100%); UST.

Conclusion

Our data suggest that treatment with ADA after IFX failure is an effective treatment option whereas IFX treatment after ADA failure is less effective. It is interesting that the majority of those who failed the anti-integrin treatment second line responded to third line ADA. These data are consistent with earlier anti-TNF studies including GAIN (Gauging Adalimumab efficacy in Infliximab Non-responders) and SWITCH (Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial) which demonstrated that anti-TNF failure is not a class effect. We recommend prescribing a second anti-TNF after anti-TNF failure in preference to using an anti-integrin second line. This practice will lead to significant cost savings for the health care economy.
P470 The concept of illness identity in inflammatory bowel disease
Authors: Knödler L L , Thomann A , Ebert M P , Lis S , Reindl W
Published: January 2020

Background

Chronic diseases like inflammatory bowel diseases (IBD) can pose challenges to the self-concept of a patient. Illness identity (IID) describes a patient′s way to integrate a chronic illness into the self-concept distinguishing the dimensions rejection, engulfment, acceptance and enrichment. Associations between IID and psychological and physiological functioning have been shown in other chronic diseases, but haven’t been investigated in IBD. In this study, we focus on associations between IID and (i) psychosomatic well-being and (ii) response to biological therapy in patients with IBD.

Methods

Eighty-four patients with active IBD answered questionnaires assessing IID, anxiety, depression, childhood trauma, quality of life (QOL), fatigue and visceral sensitivity (VS.) before the beginning of treatment with biologicals. Response to therapy (n = 73) and changes in the reported outcomes (n = 46) were assessed 3–6 months later. Associations between IID types and QOL, anxiety, depression, childhood trauma, fatigue and VS were examined using Pearson′s correlation. Response to therapy was defined as i) reduction of Harvey Bradshaw-Index (HBI) of >/ = 3 points/Partial Mayo-Score (PMS) of 0–1 points (if HBI >5/PMS >1 at baseline) OR ii) decline of faecal calprotectin or CRP of at least 50% OR iii) confirmation of a significant decline of inflammation in endoscopy/ sonography/MRI. Logistic regression was conducted to examine associations between IID and response to therapy.

Results

IID-rejection was positively associated with anxiety (r = 0.23, p < 0.05), depression (r = 0.28, p < 0.01) and VS. (r = 0.43, p < 0.01). IID-engulfment was associated with lower QOL (r = -0.61, p < 0.01) and more fatigue (r = 0.45, p < 0.01), anxiety (r = 0.66, p < 0.01), depression (r = 0.63, p < 0.01) and VS. (r = 0.74 p < 0.01). In contrast, IID-acceptance was associated with higher QOL (r = 0.34, p < 0.01) and lower levels of fatigue (r = -0.34, p < 0.01), anxiety (r = -0.45, p < 0.01), depression (r = -0.33, p < 0.01), childhood trauma (r = -0.31, p < 0.01) and VS. (r = -0.52, p < 0.01). IID-enrichment was negatively associated with depression (r = -0.3, p < 0.01). Logistic regression indicated no association between IID and response to therapy.

Conclusion

This study is the first to examine the concept of IID in IBD patients. It supports previous findings regarding its association to QOL and psychological well-being in patients with chronic disorders. Contrary to our expectation, IID was not shown to influence treatment response in this cohort, which might be owed to the modest sample size. However, given the strong association between IID and QOL, future studies should investigate the potential of IID as a targetable characteristic in personalised holistic therapy.
P474 Efficacy and safety of GCAP therapy for UC with PSC
Authors: Ito A , Murasugi S , Omori T , Yonezawa M , Tokushige K
Published: January 2020

Background

Primary sclerosing cholangitis (PSC) is a disease with poor prognosis that progresses to cirrhosis due to chronic inflammation of unknown cause. PSC is a progressive disease, and it is essential to control infection such as recurrent cholangitis, so treatment for UC with PSC is desirable because it does not suppress the immune mechanism. Among certain UC treatments, granulocyte adsorption therapy (GCAP) has been reported as a highly safe treatment method with almost no drug load. To clarify the efficacy and safety of GCAP for ulcerative colon associated with PSC. We examined for the purpose.

Methods

We examined patients with PCAP with UC (n = 35) who were in our hospital from April 2000 to July 2019 (n = 9) who were treated with GCAP. Items to be considered Background factors, the presence/absence of steroid combination (0.5 mg/kg or more), 2. Remission induction rate (remission rate after 5 GCAP treatments: remission is defined as CAI is 4 or less), 3. Safety (adverse events caused by GCAP, GCAP We compared the liver function before and after the treatment.

Results

1. Gender (M/F: 4/5), age (age) 45.2 ± 24.3, Affected range (all colitis/right-sided/rectitis 9/0/0), clinical score before GCAP treatment (Lichtiger score: CAI) 7.4 ± 2.0, Alb (g/dl) 3.0 ± 0.9, T-bil (mg/dl) 0.7 ± 0.3, ALP (U/l) 653 ± 390, γ-GTP (U/l) 63.4 ± 27.7, endoscopic score (Mayo 1.5 ± 0.7, UCEIS 2.8 ± 1.5), steroid combination rate was 22.2% 2. Remission induction rate was 77.7% 3. Safety harmful to GCAP the events were only fever (n = 1) and poor return (n = 1). Hepatic function did not deteriorate before and after GCAP.

Conclusion

GCAP was performed in mild to moderate cases, with a high remission rate of 77.7% and fewer steroid combinations. For UC with PSC, GCAP is an effective and safe treatment for induction of remission, suggesting that it may be an option in the future.