bluuebunny/crossref_metadata_2025_split huggingface dataset:
P176 Patient preferences in steroid resistant ulcerative colitis – a discrete choice experiment survey
Authors: Wickramasekera N , Shackley P , Coates E , Barr A , Lee M , Blackwell S , Bedford H , Dames N , Sebastian S , Probert C , Lobo A 
Published: May 2021

Abstract

Background
Understanding patient preferences in those who are not responding to steroids for ulcerative colitis is important in informing treatment choices. This study aimed to understand the relative importance of treatment characteristics to patients by conducting a discrete choice experiment (DCE).

Methods
Patients completed a two-part online survey. Participants were shown 12 DCE tasks – a series of side by side comparison of competing, hypothetical treatment characteristics describing effectiveness, remission, speed of response, route of administration and safety and asked to select a preferred treatment. Disease control was assessed by the IBD-control-8 questionnaire (poor control &lt; 13). Participants also completed a ranking exercise where patients were asked to rank four commonly used treatments (Adalimumab, Infliximab, Tofacitinib, and Vedolizumab,) in order of preference. Survey responses were analysed using descriptive statistics and regression analyses.

Results
115 patients completed the survey (mean age 45 years; 52% female; median time since diagnosis 10 years). 107 (93%) had previously received steroids; 81 (70%) thiopurines and 81 (70%) biological therapies or tofacitinib. 51 (45%) reported poor control of ulcerative colitis. Figure 1 shows the results of the regression analyses where all treatment characteristics had a significant influence on patients’ treatment choice. Patient preferences were strongest for lower side effects, for example, compared to a treatment that had very common side effects, patients were more likely to take a treatment that had very rare side effects (ß 2.937, p&lt;0.01) even if very rare side effects are usually more severe. Patients preferred a treatment with higher likelihood of induction of response, but they were unable to differentiate between 50% success rate and 60% success rate. Higher levels of remission (ß 0.065, p&lt;0.01) and faster acting treatments were preferred (ß -0.145, p&lt;0.01). Taking a pill daily at home (ß 0.848, p&lt;0.01) or injections at home every 8 weeks (ß0.541, p&lt;0.01) were preferable compared to infusions every 8 weeks. Notably, there was no significant difference between infusion, every 8 weeks at hospital compared to injection, every 2 weeks, at home (ß -0.029, p= 0.85). When asked to rank four commonly used biologics, the most preferred treatment was Infliximab (38%) and Tofacitinib (38%), followed by Vedolizumab (17%) and Adalimumab (6%).

Conclusion
Quantifying preferences through DCEs helps to identify and prioritise treatment characteristics that are important to patients. The results could be used to improve discussions between patients and clinicians when reviewing treatment options.
P181 Patient-led remote intracapillary pharmacokinetic sampling (fingerPRICKS) for therapeutic drug monitoring in patients with Inflammatory Bowel Disease
Authors: Chee D , Nice R , Hamilton B , Jones E , Hawkins S , Redstone C , Cairnes V , Pohl K , Chanchlani N , Lin S , Kennedy N , Ahmad T , Goodhand J , McDonald T 
Published: May 2021

Abstract

Background
Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories.

Methods
We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low-volume intracapillary fingerprick sampling compared to conventional venepuncture. Drug and antidrug antibody levels were measured using standard ELISAs.

Results
Therapeutic drug monitoring requests for adalimumab (96.5 [70.5 - 106] per week to 52 [33.5 - 57.0], p &lt; 0.001) but not infliximab (184.5 [161.2 - 214.2] to 161 [135 - 197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding six months.
Fingerprick sampling was equivalent to conventional venepuncture for adalimumab (Figure 1), infliximab, vedolizumab, and ustekinumab drug and anti-adalimumab and -infliximab antibody levels. The median (IQR) volume of serum obtained using intracapillary sampling was 195µL (130–210). More than 87% (90/103) patients agreed that intracapillary testing was easy and 69% (71/103) preferred it to conventional venepuncture (Figure 2).
In routine care, 75.3% (58/77) patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring.

Conclusion
Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.
P193 Assessement of cumulative bowel damage using Lemann index and MaRIA score in surgically naive patients with Crohn’s disease
Authors: Domislović V , Hrabric Sonje K , Brinar M , Cukovic-Cavka S , Turk N , Grgic D , Sjekavica I , Krznaric Z 
Published: May 2021

Abstract

Background
The Lémann index (LI) is a unique tool that measures cumulative bowel damage in Crohn’s disease (CD) using data on surgical procedures and severity and extent of bowel lesions. Magnetic resonance index of activity (MaRIA) is composed of features independently associated with endoscopic disease activity. Primary aim was to investigate differences in factors associated with elevated LI in total population and surgically naive patients. Secondary aim was to compare diagnostic accuracy of gMARIA and LI in determing active disease in surgically naive patients.

Methods
In this cross-sectional study on 251 CD patients LI was calculated evaluating 20 small bowel, 7 large bowel and 3 upper GI segments. For each segment bowel resections, inflammatory, stricturing or penetrating lesions were taken into account. Global MaRIA (gMaRIA) index was calculated using following parameters on 6 bowel segments: bowel wall thickness, ulcers, edema and relative contrast enhancement. Longstanding disease was defined as ≥10 year disease duration. Disease activity was defined as combination of clinical and biochemical disease activity (CRP&gt;5 or HBI≥5).

Results
This study included 251 CD patients [age 35 (25–47), 55.3% males, disease duration 7 (2–15) years]. There were 103 (40%) surgically naïve and 112 (44.6%) patients with longstanding disease. In total population, higher LI values were observed in patients with longstanding disease (10.47 vs 5.41, p&lt;0.001), patients treated with biological therapy (9.6 vs. 6.3, p=0.005) and with prior surgery (11.92 vs. 1.57, p&lt;0.005). There was no difference in LI according to activity (7.53 vs. 7.66, p=0.911) and smoking status (6.9 vs. 7.3, p=0.336). In multivariate analysis adjusted for age, gender and BMI, independent predictors of elevated LI in total population was prior surgery (β=9.26, p&lt;0.001) and disease duration (β=0.20, p&lt;0.003). Independent predictors in surgically naive patients were current or ex smoking status (β=1.69, p&lt;0.001) and gMARIA (β=0.10, p&lt;0.001). Biological therapy, disease duration and clinical and biochemical disease activity were not significant predictors (p&gt;0.05). Diagnostic accuracy of LI in surgically naive patients in defining active disease was lower [AUC 0.75 (95%CI 0.65–0.84)] compared to gMaRIA [AUC 0.82 (95%CI 0.73–0.89)].

Conclusion
Since surgical procedures contribute significantly to the LI, it is important to determine predictors of cumulative bowel damage in surgically naive patients. CD patients should be strongly advised to stop smoking and to regularly monitor disease activity using radiological methods. gMaRIA is superior to LI in detecting active disease in surgically naive patients.
P228 Prehabilitation strategies prior to ileocolonic resection in Crohn’s disease in a prospective cohort study: a missed window of opportunity?
Authors: Ruiterkamp M , Arkenbosch J , van Ruler O , van der Marel S , van Dongen K , Maljaars P W J , Hoentjen F , West R , Jharap B , Dijkstra G , Campmans-Kuijpers M , Jansen S , Romberg-Camps M , Stassen L , van der Woude C J , de Vries A 
Published: May 2021

Abstract

Background
Prehabilitation strategies to improve the postoperative course after intestinal resections in Crohn’s disease (CD) are mostly non-evidence-based. Prehabilitation strategies may include preoperative nutritional, physical and psychological management and optimization of medical treatment prior to surgery. In this study, we explore whether and to what extent prehabilitation strategies are currently used in a real-world prospective cohort.

Methods
In this multicenter prospective cohort study, data were collected in three secondary and two tertiary Dutch hospitals. CD patients (pts) aged ≥ 18 years who underwent ileocecal or ileocolonic (re)resection were included between November 2017 and January 2021. Data were collected on disease severity, IBD medication at time of surgery, preoperative BMI, weight loss within a year prior to resection, assessment of sarcopenia and hand grip strength (HGS), laboratory assessment, including albumin and micronutrients, and preoperative visits to a dietician, physiotherapist and psychologist. In addition, the 30-day postoperative complication rate was recorded.

Results
To date, 90 pts were included (38% male, median age 35.6 years) (Table 1). The main indications for ileocolonic resection were stenosis (55 (61%)), therapy refractory inflammation (15 (17%)) and penetrating disease (14 (18.9%)). At time of surgery, 60 pts (67%) were on IBD medication (immunomodulator n=16; biological n=22; combination therapy n=11, corticosteroids n=19). Median preoperative BMI was 23.7 kg/m2 (IQR 20.9–27.2). Sarcopenia and HGS were not assessed. Preoperative weight within a year prior to resection was recorded in only 31/90 (34%) pts. During the preoperative period, 32/90 pts (36%) visited a dietician, of whom 25/32 (78%) received a nutritional intervention (enteral support 16 (64%), parenteral support 0, exclusive enteral nutrition (EEN) 7 (28%), total parenteral nutrition (TPN) 2 (8%)). 4/90 pts (4%) visited a physiotherapist and 6/90 (7%) a psychologist. Albumin was assessed in 52/90 (58%) pts (median 38 (IQR 32–45); ferritin, vitamin B12 and D in 9/90 (10%), 10/90 (11%), 6/90 (7%) patients. Postoperative complication occurred in 32/90 (36%) pts, most often infections (68%) (Table 2). Four pts underwent a re-intervention for abdominal infection (2/4), anastomotic leakage (1/4) or ileus (1/4). Five pts (16%) were readmitted for anastomotic leakage (2/5), ileus (1/5), abdominal pain (1/5) and infection (1/5).

Conclusion
Prehabilitation strategies are not routinely applied in CD patients scheduled for ileocolonic resection and, since postoperative complications occur in more than a third of patients, further research into the yield of implementing multimodal prehabilitation is indicated.
P272 Tofacitinib as salvage therapy for patients hospitalized with refractory severe active ulcerative colitis: a GETAID multicenter prospective/retrospective cohort
Authors: Uzzan M , Bresteau C , Laharie D , Stefanescu C , Carbonnel F , Serrero M , Viennot S , Nachury M , Amiot A , Altwegg R , Picon L , Nahon S , Vuitton L , Ah Soune P , Kirchgesner J , Peyrin-Biroulet L , Bouhnik Y 
Published: May 2021

Abstract

Background
Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In UC patients admitted who have already experienced multiple drug failures, including steroids and anti-TNF agents, new quick-acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid mechanism of action. It could be considered in this setting.
We aimed to evaluate the efficacy and safety of tofacitinib in patients hospitalized for an acute UC flare.

Methods
We conducted an observational and multicenter study with both retrospective and prospective collections in 14 GETAID tertiary IBD centers. The primary objective was to assess the survival without colectomy following tofacitinib initiation. We determined rates of clinical response, clinical remission, and clinical steroid-free remission at week 6 and week 14 and safety.

Results
Fifty-eight patients were included. All but one patient with active lupus were exposed to antiTNF. 50 (86.2%) patients have received infliximab and 18 (31%) to ciclosporin. Patients were previously exposed to a median of 2.5 lines of biologic treatment before tofacitinib.Median Lichtiger at inclusion was 11.5 (interquartile range IQR[9 - 13]), median CRP was 17 mg/l (IQR[6.5 - 67]) and total Mayo score was 10 (IQR[9.3 - 11]). Deep ulcerations were observed in 10 patients (17.2%).With a median follow-up of 6.5 months (IQR [2.9-12.4]), colectomy-free survival rates were estimated at 80.1% (95CI [70.1-91.4]) at 3 months and at 75.1% (95CI[64.1-88.1]) at 6 months. Rates of clinical response, clinical remission and clinical steroid-free remission were 60.3%, 46.6% and 37.9% at week 6 an, 48.1%, 37% and 35.2% at week 14, respectively. At the end of follow-up, 29 patients (50%) were still treated with tofacitinib. The survival without tofacitinib discontinuation was estimated at 82.8% (95CI[73.6-93.1), 67.8% (95CI[56.6-81.4]) and 46.2% (95CI[34.2-62.4]) at 1, 3, and 6 months (Figure 3).Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zosters occurred in patients aged over 60 years old. No thrombotic event occurred.

Conclusion
Tofacitinib appears as a promising option in patients hospitalized with a severe UC flare that needs further validation in prospective and controlled trials.
P273 The duration of clinical remission in patients with Crohn’s disease depends on the frequency of administration of mesenchymal stromal cells of the bone marrow
Authors: Knyazev O , Kagramanova A V , Lishchinskaya A , Li I , Shkurko T , Veselov A , Fadeeva N , Zhulina E , Parfenov A 
Published: May 2021

Abstract

Background
Anti-cytokine therapy with anti-TNF-α drugs contributes to the achievement of persistent remission of Crohn’s disease (CD). Allogeneic mesenchymal stromal cells (MSC) of the bone marrow are also used for the treatment of CD.

Objective
to evaluate the duration of remission of CD in the context of mesenchymal stromal cells (MSC) therapy of the bone marrow, depending on the frequency of MSC administration.

Methods
76 patients with CD with luminal form of CD (terminal ileitis, colitis, and ileocolitis) were divided into two groups. The first group of patients aged 19 to 58 years (Me-29) (n=34) received culture of MCS according to the scheme: 0-1-2-12-26-52 weeks, then annually 2 times a year. The second group of patients with CD (n=42) aged 20 to 62 years (Me-28) received culture of MCS according to the scheme: 0-1-2-12-26-52 weeks to achieve remission within one year. The effectiveness of therapy was evaluated 12, 24, 36, 48 and 60 months after the start of therapy using the Harvey-Bradshaw index.

Results
During 12 months of follow-up, 4/34 patients (11.76%) relapsed among patients in 1-st group. In 2-nd group, relapse occurred in 5/42 (11.9%) (HR-0.63; 95% CI 0.288-3.397; p=0.84).
After 24 months, 6/34 patients (17.6%) relapsed in 1-st group. In the 2-nd group of patients, the disease relapsed in 11/42 (26.2%) (HR-0.674; 95% CI 0.278-1.634; p=0.37).
After 36 months, the disease relapsed in 7/34 patients in 1-st group (20.6%). In the 2-nd group, relapse was in 18/42 (42.8%) (HR-0.48; 95% CI 0.228-1.014; p=0.038).
After 48 months, in the 1-st group receiving MSCS, a relapse occurred in 9/34 (26.5%). In the 2-nd group, relapse occurred in 22/42 (52.4%) (HR-0.5; 95% CI 0.269-0.949; p=0.021).
After 60 months, 10/34 (29.4%) relapsed in 1-st group. In the 2-nd group, relapse occurred in 24/42 (57.1%) (HR-0.463; 95% CI 0.250-0.860; p=0.007).

Conclusion
The duration of clinical remission in patients with luminal Crohn’s disease depends on the frequency of administration of mesenchymal stromal cells.
P294 AMT-101, a gut selective oral IL-10 fusion: results from a Phase 1b study in patients with active Ulcerative Colitis
Authors: Posch M , Tanase R , Maisaia K , Jucov A , Geier C , Hotson D , Hamdy O , Whitney J A , Garovoy M , Kanwar B , Schreiber S 
Published: May 2021

Abstract

Background
IL-10 is a pleiotropic anti-inflammatory cytokine that restores mucosal homeostasis. Genetic deficiencies in IL-10 cause intestinal inflammation in mice and are associated with early onset IBD in humans. In mice, this can be reversed by addition of exogenous IL-10. Subcutaneous use of recombinant human IL-10 treatment in patients with Crohn’s Disease led to symptomatic and endoscopic improvement, but dose limiting systemic toxicity including anemia and thrombocytopenia was observed and appeared to be mediated by induction of gamma-interferon. AMT-101 is an oral, gut selective, fusion protein of IL-10 and a carrier protein that mediates transcytosis through intestinal enterocytes into the lamina propria (LP). Pre-clinical studies demonstrated that AMT-101 efficiently transits the epithelial cell barrier, targets mucosal immune cells in the LP, and results in improved colitis disease severity without systemic exposure.

Methods
A multiple ascending dose Ph1b POC trial was conducted in 16 patients with active UC where patients were randomized 3:1 to receive AMT-101 at doses of 1, 3, 10, or 30 mg or PBO, orally, once daily for 14 days. Primary and secondary outcome measures included safety and PK. Exploratory endpoints included changes in fecal calprotectin, histology, and stool microbiome.

Results
AMT-101 was safe and well tolerated; all AEs were mild to moderate and self limiting. No systemic toxicities associated with prior administration of IL-10 (e.g.anemia or thrombocytopenia) were observed. Systemic levels of AMT-101 were below limit of quantitation, given the GI restricted design. 1 mg and 3 mg AMT-101 led to placebo-adjusted mean reductions of FCP of 44% and 27%, respectively, in patients with baseline FCP&gt;150 μg/g. Paired biopsy samples were centrally read in a blinded manner using the Geboes scoring system. Improvements were observed in 60% (6/10) of patients on AMT-101, compared with 0% (0/2) patients treated with placebo. Microbiome analyses revealed changes in phyla abundance in the 1mg and 3mg treatment cohorts (Bacteroidetes: 28.3% ± 31.4 to 51.3% ± 21.6; Firmicutes: 21.8% ± 12.7 to 30% ± 7.3), including Roseburia hominis and Faecalibacterium prausnitzii species.

Conclusion
The results of this Phase 1b study confirm that once daily, oral AMT-101 was safe and well tolerated without SAEs previously observed with systemic IL-10 and without systemic exposure, by design. Doses at 10 mg or less suggest potential clinical efficacy paired with an enhancement of favorable enteric commensal bacteria after only 14 days of treatment. These findings support AMT-101 as actively exerting an immunomodulatory effect in the intestinal lamina propria and support ongoing Ph2 trials of AMT-101.
P298 Budesonide MMX versus Prednisolone for Ulcerative Colitis: Comparative outcomes from a British retrospective multi-centre study
Authors: Rosiou K , Ong Ming San E , Kumar A , Esquivel K , Almas S , Stokes D , Ng T , Jayasooriya N , Ranasinghe I , Pollok R , Brookes M , Selinger C P 
Published: May 2021

Abstract

Background
Budesonide MMX (Cortiment) is superior to placebo for mild to moderate UC flares and has a favourable side effect profile. However, no head-to-head data with Prednisolone exist. During the COVID-19 pandemic many IBD units chose Cortiment as first line treatment for outpatients’ flares of UC. The aim of this retrospective study was to compare outcomes of Cortiment vs Prednisolone treatment for UC.

Methods
Hospital based prescriptions from of 3 UK IBD units were extracted from computerized pharmacy records for the time periods between 1/3/2019 – 30/6/2019 and 1/3/2020 – 30/6/2020. All adult outpatients treated with oral steroids for a flare of UC were included.
Baseline data included age, sex, phenotype, IBD medications, symptoms and changes to medication at time of steroid prescription. Follow up data included need for hospital admission for acute severe ulcerative colitis, symptoms at 4 weeks and end of treatment, need for rescue Prednisolone (Cortiment group only). Primary outcome was symptomatic improvement at 4 weeks.

Results
The 2019 (94 patients) and 2020 (127 patients) cohorts did not differ significantly with regards to age, sex, phenotype and baseline characteristics. The proportion of Cortiment prescriptions rose significantly from 24.5% in 2019 to 70.1% in 2020 (p&lt;0.001). At week 4 of treatment there were statistically significant differences in mean bowel frequency (3.49 in 2019 vs 5.85 in 2020, p=0.001), rectal bleeding &lt;50% (89.7% of patients in 2019 vs 73.1% in 2020, p=0.039) and physician global assessment (39.2% of patients in remission in 2019 compared to 19.8% in 2020, p=0.045).There was no significant difference in hospital admissions, rectal bleeding and physician global assessment at end of treatment.
Patients prescribed Cortiment in 2019 had similar baseline characteristics to those prescribed Cortiment in 2020. Mean bowel frequency at four weeks was significantly higher in 2020 (6.18) compared to 2019 (3.69, p=0.034), but rectal bleeding (p=0.388) and physician global assessment at week four did not differ between 2019 and 2020 (p=0.422). Rescue Prednisolone was required in 10% of Cortiment patients in 2019 vs 31.3% in 2020 (p=0.058).

Conclusion
Cortiment was used as the main first line steroid for UC during the pandemic to reduce the risk of adverse COVID-19 outcomes. This change in treatment was, however, associated with worse UC outcomes at 4 weeks and 31% needed rescue Prednisolone. As active IBD is associated with worse COVID-19 outcomes clinicians should carefully evaluate the choice of steroid to achieve optimal disease control and COVID-19 risk minimization.