bluuebunny/crossref_metadata_2025_split huggingface dataset:
P363 Locally injected allogeneic bone marrow-derived mesenchymal stromal cells for the treatment of refractory proctitis: clinical results of a phase IIa trial
Authors: Ouboter L , Barnhoorn M , van Pel M , Zwaginga J J , Hawinkels L , Maljaars J , Koning F , Verspaget H , van der Meulen - de de Jong A 
Published: May 2021

Abstract

Background
Ulcerative proctitis (UP) can be refractory to treatment, which calls for development of new (local) therapies. Local injection of mesenchymal stromal cells (MSCs) has shown beneficial effects in patients with fistulizing Crohn’s disease and promising results have been obtained when MSCs were locally injected in the bowel of mice with experimental colitis. Our primary aim was to determine the safety, feasibility and tolerability of endoscopically injected allogeneic bone marrow-derived MSCs (bmMSCs) in UP patients.

Methods
UP patients with endoscopic Mayo score (EMS) 2 or 3, who failed on both rectal 5-ASA and corticosteroids for at least 4 weeks, were eligible for inclusion (EudraCT number 2017-003524-75). Rectal therapies were stopped 2 weeks prior to baseline, but other medication was kept stable until at least 6 weeks after MSC injection. MSCs were locally injected in 4 quadrants of the inflamed rectal submucosa if the inflammation was limited to 7 cm. If the length of inflammation was &gt;7 cm, MSCs were injected in another 4 quadrants more proximally as well. Patients in the first cohort (n=7) were treated with 5*106 MSCs/spot and in the second cohort (n=6) with 10*106MSCs/spot. Adverse events, full Mayo score, fecal calprotectin (FCP), histologic activity (Geboes score [GS]) and quality of life (sIBDQ), were assessed at week 0, 2, 6, 12, and 24, and evaluated by non-parametric paired statistical analyses.

Results
All reported adverse events were minor, no patients required interventions and no feasibility issues were reported. Median[interquartile range (IQR)] full Mayo score was 11[9.5-12] at baseline, 9[8-11] at week 2 (p=0.003), 8[6-10] at week 6 (p=0.001), and 4[1.5-7] at week 24 (p&lt;0.001). The FCP improved in 9/13 patients at week 2, in 6/13 patients at week 6 and in 11/13 patients at week 24 compared to baseline. The EMS at baseline was 3 (n=10 patients) and 2 (n=3 patients) and improved in some patients at week 2 and 6 (NS). At week 24 the EMS was 3 (n=2), 2 (n=4), 1 (n=5) and 0 (n=2)(p=0.002). The median[IQR] GS decreased after 6 weeks (7(6.5-12.5);p=0.09) and 24 weeks (4[2-8];p=0.01) compared to baseline (10[6.5-12.5]). Median[IQR] sIBDQ showed improvement during follow-up; week 2 (45[37.5-52];p=0.1), week 6 (47[42.50-55];p=0.02), week 12 (59[39.50-62];p=0.001) and week 24 (56[44.50-63.50];p=0.001) compared to baseline (41[34-49,50]). No dose- response effects were observed in our study when comparing cohort 1 and 2.

Conclusion
Local administration of allogeneic bmMSCs appears safe, tolerable and feasible for the treatment of refractory UP, and shows encouraging indications of clinical efficacy. Further mechanistic and immunological analyses are currently being performed.
P373 Psoriasis and psoriasiform skin lesions in patients with Inflammatory Bowel Disease treated with infliximab: a pharmacokinetic analysis
Authors: Rodrigues I , Damião F , Serrazina J , Fernandes S , Bernardo S , Gonçalves A R , Moura Santos P , Baldaia C , Valente A , Correia L , Tato Marinho R 
Published: May 2021

Abstract

Background
Anti-TNF agents are used to treat a variety of autoimmune conditions, including psoriasis. Paradoxically, new onset of psoriasis or psoriasiform skin lesions (PPSL) can occur in patients treated with these agents. We report a case series of patients featuring PPSL induced by infliximab (IFX) with pharmacokinetic and fecal calprotectin (Fc) correlation.

Methods
One hundred and thirty-five consecutive patients with Inflammatory Bowel Disease under proactive therapeutic drug monitoring (TDM) with IFX were evaluated for PPSL.

Results
Fifteen patients (11.1%) developed PPSL, 12 females (80%), with median age at diagnosis of 52.0 years (38-63). At the onset of PPSL, 6 patients were on 10 mg/kg every 6 weeks, 5 patients on 5 mg/kg every 8 weeks, 2 patients on 10 mg/kg every 4 weeks, 1 patient on 10 mg/kg every 8 weeks, and 1 patent on 5 mg/kg every 6 weeks. In patients with PPSL, IFX trough levels (IFXTL) significantly increased before and after the advent of PPSL: 6.18 µg/mL (3.28-9.91) vs 9.20 µg/mL (5.89-13.91), P= 0.001. At the time of PPSL, all but 2 patients were in Fc remission (&lt; 250 µg/g), median 41 µg/g (30-103). Seven patients improved with topic therapy and 8 patients (53.3%) discontinued IFX (3 switched to ustekinumab) all of which improved. Compared with the overall cohort, IFXTL were higher in patients with PPSL: 7.27 µg/mL (4.02-10.86) vs 6.26 µg/mL (3.37-9.14), P= 0.023. In multivariate regression analysis, female gender [OR 4.84 95%CI (1.23-19.00), P= 0.024], and any IFXTL≥ 10 µg/mL [OR 5.66 95%CI (1.40-22.87), P= 0.015] were independent predictors of developing PPSL.

Conclusion
Most patients with PPSL presented high IFXTL and low Fc. We hypothesize that high concentrations of IFX in the setting of deep remission may signal aberrant pro-inflammatory pathways potentially responsible for PPSL.
P455 Tofacitinib Therapy is Effective for Arthralgias Associated with Active Inflammatory Bowel Disease
Authors: Silfen A , Cohen N , Traboulsi C , Rodriguez T , Steinberg J , Singer J , Patel S , Cohen R , Dalal S , Micic D , Pekow J , Sakuraba A , Rubin D 
Published: May 2021

Abstract

Background
Tofacitinib is an oral Janus kinase (JAK) inhibitor used to treat ulcerative colitis (UC). It is generally well tolerated and safe with mild to no side effects. Tofacitinib is FDA-approved for use in multiple inflammatory conditions such as rheumatoid arthritis, psoriasis and polyarticular course juvenile idiopathic arthritis as well as for ulcerative colitis (UC). Patients with UC often have extra-intestinal manifestations (EIMs) with up to 20% of patients having arthropathy. There are limited data describing the effect of tofacitinib therapy on EIMs in UC. The aim of this study is to determine whether tofacitinib therapy improves arthralgia in this patient population.

Methods
This retrospective study includes consecutive patients with active UC who initiated tofacitinib at our center since 2014 and remained on the therapy for at least 8 weeks. We reviewed electronic medical records to collect demographic and clinical data. Patients diagnosed with any EIM by the treating physician were included. Improvement in EIM symptoms was determined through patient reports or physician assessment. In the UC patients, a decrease in Simple Clinical Colitis Activity Index (SCCAI) of ≥ 3 was considered response and remission as a score of ≤ 2. In the CD patients, a 3-point reduction in Harvey Bradshaw index (HBI) was considered clinical response and a score of &lt;5 remission.

Results
112 patients were included in this cohort, with 36 (31 UC; 5 CD) having confirmed EIMs (32.1% of total). Basic demographic and clinical data are detailed in Table 1. 35 patients had peripheral arthralgia, 2 patients had primary sclerosing cholangitis (PSC) and 1 had pyoderma gangrenosum. 5 (13.9%) patients discontinued treatment during the induction phase due to lack of response. By 24 weeks, 26 (74.2%) out of 35 patients reported improvement in arthralgias, and 14 (40%) patients reporting resolution of joint symptoms. In terms of gastrointestinal disease activity, at week 24, 17/35 (48.6%) patients achieved clinical response and 11/35(31.4%) patients achieved clinical remission. There was no treatment effect noted on the other EIMs.

Conclusion
In our real world experience, treatment refractory IBD patients with peripheral arthralgia on tofacitinib showed significant improvement in joint symptoms, and this often paralleled improvement in gastrointestinal symptoms. This supports that tofacitinib is a suitable treatment for patients with IBD and concomitant peripheral arthralgia.
P476 Effectiveness and safety of ustekinumab in ulcerative colitis: Real-world evidence from the ENEIDA registry
Authors: Chaparro M , Garre A , Iborra M , Sierra M , Barreiro-de Acosta M , Fernández-Clotet A , de Castro L , Boscá-Watts M , Casanova M J , López-García A , Lorente R , Rodríguez C , Carbajo A Y , Arroyo M T , Gutiérrez A , Hinojosa J , Martínez-Pérez T , Villoria A , Bermejo F , Busquets D , Camps B , Cañete F , Manceñido N , Monfort D , Navarro-Llavat M , Pérez-Calle J L , Ramos L , Rivero M , Angueira T , Camo P , Carpio D , García-de-la-Filia I , González-Muñoza C , Hernández L , Huguet J M , Morales V J , Sicilia B , Vega P , Domènech E , Gisbert J P 
Published: May 2021

Abstract

Background
The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice.

Aims
Primary: to evaluate the durability of ustekinumab treatment in UC patients in clinical practice. Secondary: to assess the short-term response (at week 16) and the long-term effectiveness (at maximum follow-up) and to assess the safety of ustekinumab in clinical practice.

Methods
Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) &gt;2] were included. Clinical activity and effectiveness were defined based on PMS.

Results
95 patients were included (table 1).

At week 16, 53% of patients had clinical response (including 35% of patients in remission) (figure 1).

In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with clinical remission. Long-term remission is represented in figure 2.

36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72 (figure 3); primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection.

Conclusion
Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.
P517 One year effectiveness and safety of ustekinumab in Ulcerative Colitis: a multicentre real-world study from Italy
Authors: Chiappetta M F , Viola A , Mastronardi M , Turchini L , Carparellli S , Orlando A , Biscaglia G , Miranda A , Guida L , Costantino G , Scaldaferri F , Bossa F , Renna S , Cappello M , Orlando A , Armuzzi A , Fries W 
Published: May 2021

Abstract

Background
Efficacy and safety of ustekinumab for the treatment of Ulcerative colitis (UC) has been demonstrated in phase III clinical trials, but real world data are scarce. The aim of this study was to assess effectiveness and safety of ustekinumab in an Italian cohort of UC patients.

Methods
Data of patients with UC who started using ustekinumab were collected. Primary endpoint was steroid-free clinical remission at 24 and 52 weeks of therapy. Secondary endpoints were: treatment response, endoscopic remission, treatment persistence at 12 months and safety.

Results
A total of 68 patients (males 63.2 %; mean age (SD) 31 years (14.5)) were included. All patients were biologics experienced. At 24 and 52 weeks, 32 % and 50 % of patients achieved steroid-free clinical remission, 85% and 81% had clinical response, respectively. (Table 1) At the end of follow-up there were a significant reduction of pMS from baseline (p&lt;0.001) and of steroid use (p&lt;0.001) (Figure 1). Of the available endoscopies at 12 months (18/38), 22.2% showed mucosal healing. The probability to persist in therapy with ustekinumab after 12 months of treatment was of 89.7 %. Only one adverse event occurred (diagnosis of an hypophysis adenoma). No patients required colectomy.

Conclusion
Data from our small real-life cohort of treatment-refractory UC patients suggest satisfactory effectiveness of ustekinumab and an excellent safety. More data assessing mucosal healing after one year of treatment are needed
P543 The role of social support on psychological distress and health-related quality of life in adults with mild to moderately active Crohn’s disease
Authors: Regev S , Goren G , Schwartz D , Sergienko R , Friger M , Nemirovsky A , Greenberg D , Monsonego A , Sarid O , Slonim-Nevo V , Odes S 
Published: May 2021

Abstract

Background
Medical and psychological factors contribute to the heightened psychological distress and reduced health-related quality of life in patients with Crohn’s disease. Whether Social Support plays a role in this scenario is unknown. We used the Multidimensional Scale of Perceived Social Support (MSPSS) to investigate whether Social Support associates with psychological distress and quality of life in Crohn’s disease.

Methods
Consecutive adult patients with Crohn’s disease, presenting at specialist gastroenterology services or recruited by advertising, with mild to moderate disease activity by the Harvey-Bradshaw Index (HBI), were enrolled into the study. Patients completed the 12-item MSPSS questionnaire that measures psychological support in three categories: Family, Friends and Significant Other, and provides individual category scores and a total score (range of all scores 1–7; a higher score indicates more social support). Patients also completed the following questionnaires: psychological distress (Brief Symptom Inventory, with Global Severity Index, GSI), quality of life (Short Inflammatory Bowel Disease Questionnaire, SIBDQ), satisfaction with life (SWLS), family stress (Family Assessment Device, FAD), coping strategies (Brief-COPE), and presenteeism and work activity (WPAI). Statistics: Spearman rho. *p&lt;0.05, **p&lt;0.01.

Results
The cohort comprised 126 patients, mean (SD) age 33.7 (10.6) years, females 79%, HBI 8.4 (2.5), CRP 1.2 (2.3), calprotectin 394 (674). MSPSS scores were as follows: Total score 5.72 (1.14), Friends 5.36 (1.34), Family 5.73 (1.14), and Significant Other 6.07 (1.15); Cronbach’s α ≥ .877. MSPSS scores correlated negatively with family stress measure FAD: Friends -.258**, Family -.732**, Significant Other -.401**; and with GSI psychological stress measure: Friends -305**, Family -.352**, Significant Other -.245**. MSPSS correlated positively with SIBDQ quality of life: Friends .300**, Family .188*, Significant Other .200*; and with satisfaction with life SWLS: Friends .379**, Family .333**, Significant Other .245**. MSPSS correlations with emotion-focused coping were: Friends -.337**, Family -.263**, Significant Other -.329**. MSPSS Family score correlated negatively with WPAI presenteeism -.270*, and WPAI work activity -.294**.

Conclusion
In mild to moderate Crohn’s disease, strong social support was associated with better quality of life, more satisfaction with life, and better performance in the work arena. Social support was associated with reduced psychological distress, reduced family stress, and less use of emotion-focused coping. This research shows the importance of social support in improving the psychological condition of patients with Crohn’s disease.
P576 Ustekinumab levels correlate with induction fecal calprotectin drop-slope and discriminate the need for intensification at week 52 in Crohn’s Disease patients
Authors: Mateos B , Sáez-González E , Iborra M , Moret I , Cañada A , Tortosa L , Bastida G , Aguas M , Cerrillo E , Nos P , Beltrán B 
Published: May 2021

Abstract

Background
Ustekinumab (UST) intensification during Crohn’s Disease (CD) treatment is becoming common in clinical practice. Little is known about early intensification maintenance regimens and their drug levels utility in discriminating CD-response and the need for further intensification. We aim to analyze UST levels’ evolution in an intensified maintenance regimen, their capacity to discriminate response according to inflammatory parameters and indicate the need for further intensification.

Methods
This is a retrospective study with 43 moderate/severe active CD patients (Harvey-Bradshaw Index [HBI] ≥4 and Fecal Calprotectin [FC] &gt;250 µg/g) who received UST induction treatment (induction dose of 6mg/kg IV, plus dose of 90mg SC at week 8). Patients received maintenance treatment (90mg SC/8 weeks) and were followed for 52 weeks. They were classified according to the response obtained at the first year in responders (R), HBI &lt;3 and FC &lt;200µg/g; non-responders (NR), HBI ≥4 and FC &gt;250µg/g; and intensification group (IG), partially responders that needed UST intensification to every 4 weeks. HBI, FC, C-Reactive Protein (CRP), and UST levels data were collected at baseline (w0), week 8 (w8), week 16 (w16), and 52 weeks (w52) of maintenance. IG was followed 12–26 weeks after intensification (aI).

Results
Half of the patients (48.8%) were male. Most of them (97.7%) have received previous anti-TNF-α treatment (53.49% ≥2 anti-TNF-α). Patients’ median age at the moment of starting UST was 51 (37.5, 58.5) years. Median disease duration was 11 (7.5, 23) years. Location of disease was ileal in 30% of patients and ileocolic in 53%. One-third of patients suffered perianal disease, and 41 % were smokers. The only demographic factor associated with non-response was ileocolic location.
Table 1 shows the evolution of inflammatory parameters and UST levels according to the response. A Pearson correlation (r=0.62) between higher FC drop (baseline-w16) and higher drug levels at w16 was observed. The evolution of biological markers discriminates NR during induction; however, neither biological markers nor UST level can distinguish between R and those who will need intensification. R shows higher UST levels at w52 compared to IG. IG showed a significant increase of UST levels (mean of 5.39 points) and a substantial drop of FC and HBI (mean of 115.62 and 2.27 points, respectively) after intensification. Those patients reported clinical improvement; however, they could not reach a FC &lt;250µg/g, which could need a more extended period to decrease.

Conclusion
FC drop-slope is associated with higher levels of UST at the end of induction. UST levels at w52 are useful for discriminating patients who will benefit from UST intensification every 4 weeks.
P610 Fear of COVID-19 among persons with Inflammatory Bowel Disease according to employment status, educational background and residential setting, as compared to persons with other gastrointestinal conditions
Authors: Lo B Z S , Mokrowiecka A , Mikocka-Walus A , Bernstein C N , Trindade I A , Burisch J , Barreiro-de Acosta M , Ferreira N , Gearry R B , Knowles S R 
Published: May 2021

Abstract

Background
Although several studies have reported the impact of fears relating to COVID-19 on several chronic illness populations, there are few studies focused on gastrointestinal (GI) conditions. The aim was to compare how fear of COVID-19 is manifested in people living with Inflammatory Bowel Disease (IBD) compared to other GI conditions; and, how fear of COVID-19 is manifested across different demographic backgrounds (employment status, education level and country of residence) among IBD respondents using a large international sample.

Methods
Participants with a GI condition (≥18years of age) were recruited from 22 countries through a web-based questionnaire. Demographic, clinical, and psychosocial information was collected in relation to the COVID-19 pandemic. An adaptation of the scale developed for IBD by Trindade & Ferreira (2020) measuring fear of COVID-19 (FoC; original items 1–9) and GI specific fear of COVID-19 (GI-FoC; new items 10–14) was used.

Results
In 831 participants (312 IBD), there were no significant differences in FoC between IBD and other GI conditions; whilst significant increases in GI-FoC were found in IBD respondents (mean [SD]: 13.5 [5.5] vs. 10.9 [5.0], p&lt;0.01). The greatest fears of IBD respondents were: their condition would get worse; impact on access to medical support;
being at increased risk of getting COVID-19; and being at increased risk of death if they got COVID-19.
Among IBD respondents, persons on sick leave had significantly more general FoC than those who were employed, and significantly more GI-FoC compared to the employed or respondents outside of the labour market (Figures 1a and 1b). Persons living in a rural setting had significantly more general FoC and GI-FoC (Figures 2a and 2b). These persons were fearful of contracting COVID-19, having contact with someone with respiratory symptoms, having contact with healthcare professionals, going outside, meeting people, having contact with someone who was in contact with an infected person, having contact with someone infected with COVID-19, and that their IBD means being at increased risk of death if they got COVID-19.
There were no differences in general FoC and GI-FoC according to educational background. However, respondents with higher education were less afraid of dying from COVID-19.

Conclusion
Respondents with IBD are more afraid of the consequences of COVID-19 due to their disease compared to other GI diseases; especially, persons on sick leave or persons living in a rural setting. Persons with higher education were less afraid of dying from COVID-19. These findings should be taken into consideration to personalise the support health-care providers can offer in mitigating fear related to COVID-19 in IBD patients.