bluuebunny/crossref_metadata_2025_split huggingface dataset:
P486 Treatment-emergent COVID-19 infections in ozanimod ulcerative colitis and multiple sclerosis clinical trials
Authors: Ungaro R , Siegel C A , Cree B A C , Selmaj K W , Ahmad H A , Pai A , Ather S , Henry A , Charles L , Petersen A , Cheng C Y , Afsari S , Sheffield J , Vaile J , Colombel J F 
Published: January 2022

Abstract

Background
Ozanimod, a sphingosine 1-phosphate (S1P) receptor S1P1 and S1P5 modulator, is approved in the United States for moderately to severely active ulcerative colitis (UC) and in multiple countries for relapsing multiple sclerosis (MS). We describe COVID-19 outcomes in ozanimod-treated UC or MS patients (pts) in active phase 3 open-label extension (OLE) studies.

Methods
A database search identified COVID-19 infection reports in ozanimod-treated pts with UC in the True North OLE and MS in the DAYBREAK OLE. The analysis period was November 1, 2019 to either August 31, 2021 (UC) or May 10, 2021 (MS). The last COVID-19 event from all pts with ≥1 event was analyzed.

Results
Among 2792 ozanimod-treated pts with UC or MS, 258 developed COVID-19 (confirmed: 215); thus, the incidence in these clinical trial settings was 9.2% during the analysis periods. Most pts with confirmed cases (193/215 [89.8%]) had nonserious infections not requiring hospitalization or meeting other International Conference on Harmonisation criteria for a serious event. Of 611 ozanimod-treated pts with UC, 68 (11.1%) developed COVID-19 (confirmed: 55; Fig 1). A majority of UC pts with confirmed cases (45/55 [81.8%]) had nonserious COVID-19; most (54/55 [98.2%]) recovered (2 with sequalae) and 1 was recovering at data cutoff. One UC pt with confirmed COVID-19 discontinued ozanimod (1.8%), 23 temporarily interrupted it (41.8%), and 31 had no change to treatment (56.4%). No COVID-19‒related deaths were reported in UC pts. Of 2181 ozanimod-treated pts with MS, 190 (8.7%) developed COVID-19 (confirmed: 160; Fig 2). Most MS pts with confirmed COVID-19 (148/160 [92.5%]) had nonserious cases; most (158/160 [98.8%]) recovered (5 with sequelae) (Fig 1). No MS pts with confirmed cases discontinued ozanimod, 61 temporarily interrupted it (38.1%), and 99 had no change to treatment (61.9%). Outcomes in 13 additional UC pts (Fig 1) and 30 additional MS pts (Fig 2) with suspected COVID-19 were similar to those with confirmed cases. There were 3 COVID-19‒related deaths in the MS program. One pt died from a presumed pulmonary embolism; this pt had received high-dose corticosteroids for MS relapse immediately before COVID-19 symptom onset. Another pt died from suspected COVID-19‒related respiratory failure. One tetraplegic, cachectic pt died from a lung abscess following COVID-19 infection.

Conclusion
In the UC and MS OLE studies, most pts with confirmed COVID-19 had nonserious infections, recovered, and did not require ozanimod discontinuation. There were 3 deaths in MS patients (case-fatality rate 1.6% in MS, 1.2% overall).
P501 Vedolizumab is associated with longer drug sustainability compared to infliximab in moderate-to-severe Ulcerative Colitis: a real-world cohort study
Authors: Konikoff T , Yanai H , Banai H , Avni-Biron I , Snir Y , Broitman L , Barkan R , Checholin L , Dotan I , Ollech J 
Published: January 2022

Abstract

Background
Data regarding sustainability of biologics in ulcerative colitis (UC) are limited. We aimed to assess sustainability of intravenous biologics used to treat UC, infliximab (IFX) and vedolizumab (VDZ), in biologic-naïve and biologic-experienced patients, specifically focusing on their sustainability over time.

Methods
This retrospective cohort study was conducted at the Rabin Medical Center (RMC), a tertiary referral center for patients with inflammatory bowel diseases. We included patients ≥ 18 years, treated at the RMC IV infusion center between Dec 1st 2017 and May 1st 2021. An extensive medical chart review was performed. Patients’ data were collected from the first to last documentation of treatment or end of follow-up. Drug sustainability was defined as long as cortico-steroid-free, surgical-free treatment was documented. Data collected, included sex, age at UC diagnosis, age at biologic treatment commencement and the interval UC-diagnosis-first biologic, disease extent (proctitis, left-sided or extensive colitis), previous treatment with biologics, and clinical laboratory data. Concomitant therapy was documented as well, specifically immunomodulatory drugs. Results were adjusted to factors associated with disease severity (based on factors including hemoglobin, hematocrit, neutrophil-to-lymphocyte ratio, albumin, C-reactive protein, and total protein), combination therapy and age.

Results
A total of 217 patients with UC treated with IFX or VDZ were included. Of those, 186 were treatment-(biologic)-naïve. First biologic was IFX in 77 (41.3%) patients and VDZ-in 109 (58.6%). Follow-up continued for up to 300 weeks. Median survival time was 106.5 (82.9–135) weeks for IFX and 265.6 weeks (121.3–273.1) for VDZ (p=0.002, KM survival curve shown in Figure 1).
Median survival time was longer for vedolizumab even when adjusting for factors associated with disease severity, combination therapy and age (HR 0.55 95 CI 0.3–0.98, p=0.042). In treatment-experienced patients, IFX and VDZ sustainability was comparable (p=0.593).

Conclusion
In this -real world, tertiary referral center study, VDZ had significantly longer drug sustainability in treatment-naïve patients with UC compared to IFX. This held true when adjusted for disease severity. Drug sustainability in treatment-experienced patients with UC was comparable. The data support VDZ as the first-line biologic in moderate-to-severe UC.
P502 Different presentation of tuberculosis associated with anti-TNF therapy among patients with Inflammatory Bowel Disease in endemic area: observation from China
Authors: Ye L , Wu L , Tang J , Mao R , Cao Q 
Published: January 2022

Abstract

Background
Anti-tumor necrosis factor (TNF) therapy increased the risk of tuberculosis(TB), and the characteristic clinical feature of western patients with inflammatory bowel disease (IBD) receiving anti-TNF therapy were predominantly extrapulmonary TB. We aimed to analyze the clinical features of patients with IBD who in TB-endemic area (China) that developed active tuberculosis after receiving anti-TNF therapy.

Methods
Patients from 9 hospital in 7 provinces developed active TB after the initial treatment with infliximab. Demographics, interval between the time at the first dose of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis were analyzed in our study. The diagnosis of active TB and LTBI were made based on comprehensive evaluation including TB skin test (TST), interferon gamma releasing assay (IGRA), X-ray test and computed tomography (CT).

Results
Totally 43 patients developed active TB during infliximab therapy. Among 43 patients, 6 patients had a past TB history and 11 patients were confirmed as LTBI before infliximab treatment. Six patients with LTBI received anti-TB prophylaxis as the same time as anti-TNF treatment. The mean time between initiation of infliximab therapy and active tuberculosis diagnosis in patients with LTBI was significantly shorter than patients without LTBI (216.9±83.2 days versus 410.9±220.3 days, p=0.042). Among 43 active TB patients, 29 patients (29/43, 67.4%) had isolated pulmonary tuberculosis and 11 patients (11/43, 25.6%) had pulmonary TB concomitantly with other organ involvement.

Conclusion
IBD patients with LTBI develop TB earlier than those without LTBI during anti-TNF treatment, and history of treatment and anti-TB prophylaxis didn’t fully prevent active TB. The most common disease site is lung in China, most of cases were diagnosed by imaging. Chinese physicians should be aware of the potential for TB development during anti-TNF therapy, especially pulmonary tuberculosis.
P515 Inflammatory bowel disease and malignancy – the outcome of patients with malignancy diagnosed before IBD diagnosis or IBD-targeted therapy
Authors: Shani U , Klang E , Ungar B , Ben-Horin S , Kopylov U 
Published: January 2022

Abstract

Background
The treatment strategy in IBD patients with previous malignancy is not well defined, and the available literature is scarce.The main aim of this study was to describe the outcome of IBD patients with previous malignancy or before exposure to IBD-related treatment.

Methods
The study cohort included IBD patients with at least one malignancy diagnosed before IBD or before initiation of IBD-related treatment (excluding 5-ASA/corticosteroids). All patients were followed at the department of gastroenterology in Sheba medical center between 2010 and 2021. Clinical and demographic data were extracted from the patients’ medical records. The main outcome of interest was a relapse of previous malignancy or the development of a second malignancy.

Results
From our IBD database comprising 3811 patients, we identified 86 patients with malignancy before IBD-related treatment: 38 diagnosed with malignancy 6 years before IBD (median time, IQR=3–12) and 48 - after (15 years (IQR7-22) IBD diagnosis but before exposure to IBD treatment. The most common malignancy preceding IBD was breast cancer found in 9/38 (24%) patients. Other malignancies before IBD diagnosis included: lymphoma 7/38 patients (18%), melanoma in 6 patients (16%), and leukemia in 4 patients (11%). After a diagnosis of IBD, 38/86 (44%) patients were treated with thiopurines, 28/86 (32%) with vedolizumab (VDZ), and 26/86 (30%) with anti-TNFs.
10/86 (9%) patients were further diagnosed with second primary malignancy. The median time from first to second malignancy was 7 years (IQR=16-6); 7/10 patients (70%) were exposed to thiopurines, 6/10 (60%) to anti-TNFs, and 6/10 (60%) to VDZ. The only clinical variable associated with second malignancy was female gender (9/40 (22.5%) vs. 1/46 (2.2%), p=0.005).
20/86 patients (23%) had a recurrence of malignancy (median- 3 years (IQR=3–9). The most common recurrent malignancies were non-melanotic skin cancer (NMSC) In 9 patients (45%) and melanoma in 3 patients (20%). Of patients with recurrence, 11 patients (55%) were exposed to thiopurines, 10 patients (50%) were exposed to anti-TNFs, and 5 patients (25%) were exposed to vedolizumab. Treatment with anti-TNFs was associated with recurrence of NMSC (6/25 (24%) vs. 2/52 (3.7%), p=0.047).

Conclusion
In our retrospective tertiary center cohort, recurrence of malignancies in IBD patients with previous neoplasia was uncommon. However, most recurrent malignancies were solid and hematopoietic malignancies. Female gender was associated with an increased risk of second malignancy, while anti-TNF treatment was associated with an increased risk of NMSC recurrence. Our findings underline the importance of rigorous dermatological follow-up in IBD patients with previous NMSC treated with anti-TNFs
P528 Feasibility, satisfaction and machine learning analysis of factors influencing IBD patients’ trust in the mobile application Care4today IBD
Authors: Costantino A , Vecchi M , Stocco D , Noviello D , Conforti F S , Maregatti M , Caprioli F 
Published: January 2022

Abstract

Background
The use of telemedicine for the management of patients with Inflammatory Bowel Disease (IBD) has developed quickly over the past few years.
In our tertiary referral Centre for IBD we have provided our patients an asynchronous telemedicine service, the App Care4today® IBD (Bepatient, Paris, France). Its main function is the remote monitoring of patients’ symptoms and disease activity (abdominal pain and bowel movements). In addition, it evaluates the quality of life through the EQ-5D-5L questionnaire, it provides information on topics to implement patient education (e.g., smoking), and it allows patients to insert reminders for the therapy.
Decision trees (DT) and random forests (RF) are two machine learning (ML) techniques which have been increasingly utilized in the last few years due to their ability to uncover non-linear relationships between covariates and outputs.

Methods
The aims of our study were to evaluate the app use, satisfaction and trust of IBD patients, and to identify the possible determinants influencing its trust through a ML analysis.
From April 26th to May 21st 2021, we have consecutively proposed to all IBD patients (familiar with smartphones and mobile Apps) on biological therapy to download Care4today® IBD. Ease of use, patients’ satisfaction and trust were assessed through a 5 points Likert scale questionnaire adapted on the SUTAQ (Service User Technology Acceptability Questionnaire).
ML tools, DT and RF, were used to identify the determinants of patients’ trust.

Results
Out of 135 enrolled patients (among 151 patients), 87 (64.4%) used the app.
Among the patients who compiled the questionnaire (39/87, 44.8%), 92.4% trusted to use the App, 94.9% showed confidence in the monitoring system. On contrast, disagreement (92.4% giving a score &lt;3/5) was expressed for the statement “the Apps can replace my regular health care”.
The DT showed that the variable which has influenced the most patients’ trust is the conviction that the App is a tool useful for a better monitoring of their disease by physicians, since it represented the root of the tree which explains the final decision. The RF confirmed that this variable influenced the most patients’ trust with a 15% increase in mean squared error (IncMSE) and 7.10 IncNodePurity.

Conclusion
More than half of our patients actively used the Care4today IBD App, and more than four of every five of those who responded to the survey proved to be well disposed to its usage, showing a good level of confidence and trust in it.
The knowledge of patients’ trust determinants (App utility is the most relevant) is the key point in order to implement the use of these new digital monitoring options, which may help to better manage the disease, through tight control and personalized medicine
P549 Oxidative stress and antioxidant capacity biomarkers in adults and children with IBD: current update from OxIBDiet trial
Authors: Quattrini S , Gatti S , Palpacelli A , Mattioli S , Cianfruglia L , Galezzi T , Monachesi C , Quatraccioni C , Catassi G , Di Sario A , Armeni T , Catassi C 
Published: January 2022

Abstract

Background
Oxidative stress takes part in the pathogenesis of inflammatory bowel disease (IBD). The OxIBDiet (NCT04513015) is a multicentre ongoing project designed to evaluate oxidative status of IBD children and adults and to estimate the effects of an antioxidant diet in a subgroup of IBD patients.

Methods
The total antioxidant capacity, measured through the ferric reducing ability of plasma (FRAP, µmol/equivalent FeSO4) and oxygen radical absorbance capacity (ORAC, plasma trolox equivalents), lipid peroxidation, as serum levels of the thiobarbituric acid reactive substances (TBARs, µmol MDA) and the degree of protein oxidation, as advanced Oxidation Protein Products (AOPP, µmol/g protein), were measured. Activities (nmol/min/mg of protein) of the main antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-Transferase (GST) and catalases (CAT) were evaluated in PMNs cells and plasma. Oxidative biomarkers were correlated with clinical parameters.

Results
Twenty-three adults (mean age: 33,7, IQR 20,5 years, 42% male, 63% in remission) and 41 children with IBD (mean age: 12, IQR 4 years, 52% male, 61% in remission) were enrolled and compared respectively to 29 adults and 23 children controls. FRAP was significantly reduced in IBD children compared to adults (202 vs 277 mcmol/eq FeSO4, p&lt;0.0001) and was correlated with age (r=0.5718; p&lt;0.0001). Plasmatic ORAC was significantly higher in IBD children compared to controls and adults with IBD (Figure 1). ORAC in IBD subjects resulted inversely correlated to age (r= -0.4417, p=0.0004) and use of biologics (r= -0.4246, p=0.0006). AOPP were elevated in paediatric IBD versus controls (p=0.0049) and correlated to the diagnosis of Crohn at the multiple regression analysis (r=-0.732; p=0.023). The main antioxidant enzymes plasmatic activities are shown in table 1.

Conclusion
The antioxidant system and therefore the antioxidant capacity is significantly different in IBD compared to controls and evolve from paediatric to adult age, maybe as an effort to compensate the persistent redox imbalance and inflammation. Involvement of antioxidant cascade in IBD pathogenesis and role in therapeutic approach will be better outlined by the final results.
P551 Safety and effectiveness of vedolizumab for the treatment of paediatric patients with Inflammatory Bowel Diseases
Authors: Fabiszewska S , Derda E , Szymańska E , Osiecki M , Kierkuś J 
Published: January 2022

Abstract

Background
Vedolizumab is effective in induction and maintenance of remission in adults with inflammatory bowel diseases (IBD). Paediatric data are still limited. The aim of this study was to assess safety and efficacy of vedolizumab in paediatric patients with IBD.

Methods
Fifty one patients with paediatric IBD (24 female, 27 male), both Crohn’s Disease (CD) and Ulcerative colitis (UC) were included into this retrospective study. There were 8 patients with CD and 43 patients with UC.
At weeks 0, 2, 6 vedolizumab was administered intravenously in a dose of 300 mg as induction therapy followed by a maintenance phase, infusions every 8 weeks.
At 1st dose week, 4th dose week and 10th dose week of treatment clinical activity scores (PUCAI, PCDAI), nutritional and laboratory parameters were collected.
Primary outcome was clinical response after induction therapy after 3 doses of vedolizumab (4th dose week). Secondary outcome was clinical remission after induction phase (4th dose week) and maintenance phase after 9 doses of vedolizumab (10th dose week).

Results
Patients’ age at the time of diagnosis was 6 – 16,6 y.o. (median 12,4 y.o.), age at week 0 was 8,2 – 17,9 y.o. (median 16,1 y.o.).
There was 1/51 patient (2%) anti-TNF naive, 50/51 patients (98%) had failed at least one anti-TNF alfa agent, 12/51 patients (23,5%) had failed at least two anti-TNF alfa agents. Systemic steroid therapy had been used previously in 47/51 patients (92,2%). Previous budesonide MMX, 5-ASA, Azathioprine or Cyclosporine therapy were also commonly used in our patients.
Vedolizumab treatment is still continued in 28/51 patients (54,9%), 11 of these patients (21,6%) received at least 10 doses of the drug.
Twenty three out of 51 patients (45.1%) were disqualified from further treatment due to: allergic reactions, non-response, loss of response or others causes.
Clinical response at 4th dose week was observed in 43/51 patients (84,3%). Clinical remission at 4th dose week was achieved in 32/51 (62,7%). Mean baseline (1st dose week) PUCAI score was 50,6; decreased to 7,8 after induction therapy with vedolizumab (4th dose week) and to 5,5 after maintenance phase (10th dose week). Mean baseline PCDAI score was 46,4, decreased to 22,9 after induction therapy and to 13,8 after maintenance phase.
No serious adverse events were reported.

Conclusion
Vedolizumab was safe and effective in the treatment of paediatric patients with IBD.
P552 Higher Serum Ustekinumab Levels Correlate With Higher Rates Of Steroid-Free Deep Remission And Endoscopic Healing In Patients With Inflammatory Bowel Diseases
Authors: Yarur A , Ungaro R , Jain A , Nunex L , Spencer E , Bruss A , Berens B , Beniwal-Patel P , Dervieux T , Dubinsky M 
Published: January 2022

Abstract

Background
Ustekinumab (UST) is currently approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). However, a significant number of patients either partially respond or do not benefit at all. With other biologics, this non-response has partially been explained by sub-optimal pharmacokinetics. The aim of this study was to assess the association between UST trough levels (UTL), antibodies to UST (ATU) and clinical/endoscopic disease activity.

Methods
In this prospective cross-sectional study, we enrolled patients with CD or UC on maintenance doses of UST (≥6 months). We collected clinical data, UTL and ATU titers using a drug-tolerant assay, biomarker levels (c-reactive protein [CRP] and fecal calprotectin [FC]), Harvey Bradshaw Index (HBI) and simple endoscopic score (SES-CD) in CD, partial and endoscopic Mayo score (PMS and EMS) in UC. The primary outcome was deep steroid-free remission (SFDR) defined as HBI &lt;5 in CD and PMS&lt;2 in UC and a normal CRP/FC while off corticosteroids (prednisone or budesonide). The secondary outcome was endoscopic healing defined as an EMS≤1 in UC or SES-CD≤2.

Results
136 patients were included; 123 (90%) had CD, mean age was 43 years (SD:17), and 73 (54% were women). The median time on UST was 40 weeks (IQR: 32–78). Median UTL were 5.5 µg/mL (IQR: 3–8.8 µg/mL) and no patients had detectable ATU. There was a positive correlation between UTL and albumin (rho:0.35 [p&lt;0.01]) and a negative correlation between UTL with body mass and CRP (rho:-0.32 [p=0.005] and rho: -0.32 [0.0002], respectively). Among the study population, 48/136 (35.2%) was in SFDR and 26 (42%) were in endoscopic remission. Patients in SFDR and in endoscopic remission had significantly higher UTL vs. that did not (6.4 µg/mL [4.6–11.7] vs. 4.8 µg/mL [2.5–7.6]; p&lt;0.01 and 6.4 µg/mL [5–15] vs. 4.4 µg/mL [2.2–7.1], p=0.03 respectively) – Figure 1 and 2. There were no differences in UTL between those patients on monotherapy and those on combination therapy with a thiopurine or methotrexate (5.8 µg/mL [3.4–9.3] vs. 4.5 µg/mL [2.3–7.9], p=0.07). Patients with a UST ≥5.45 µg/mL had a two-fold higher chance of being in steroid-free deep remission vs. those that did not (OR:2.2 [95%CI:1.1–4.5], p=0.031). When adjusting for albumin (a surrogate marker of drug clearance), higher UTL were associated with higher rates of SFDR (OR per 1 µg/mL: 1.12 [95%CI: 1.01–1.26], p=0.034).

Conclusion
Among patients with CD and UC, higher UTL were associated with better clinical and endoscopic outcomes. No patients in the cohort had developed immunogenicity. Dose-escalation, interventional studies looking into how a higher exposure-response to UST may improve rates of non-response are warranted.
P568 Impact of Biologics and Small Molecules for Inflammatory Bowel Disease on COVID-19 Related Hospitalization: A Systematic Review and Meta-analysis
Authors: Alrashed F , Alasfour H , Shehab M 
Published: January 2022

Abstract

Background
The use of biological therapies and small molecules have been a concern for patients with inflammatory bowel disease (IBD) during COVID-19 pandemic. We aim to assess the association between risk of COVID-19 related hospitalization and these agents.

Methods
A systematic review and meta-analysis of all published studies from December 2019 to September 2021 was performed to identify studies that reported COVID-19 related hospitalization in IBD patients receiving biological therapies or tofacitinib. The risk ratio (RR) was calculated to compare the relative risk of COVID-19 related hospitalization in patients receiving these medications to those who were not, at the time of the study.

Results
18 studies were included. The relative risk of hospitalization was significantly lower in patients with IBD and COVID-19 who were receiving biologic therapy with RR of 0.47 (95% CI: 0.42–0.52, p &lt; 0.00001). The RR was lower in patients receiving anti-TNFs compared to those who did not [RR= 0.48 (95% CI: 0.41–0.55, p &lt; 0.00001)]. Similar finding was observed in patients taking ustekinumab [RR= 0.55 (95% CI: 0.43–0.72, p &lt; 0.00001)]. Combination therapy of anti-TNF and an immunomodulator did not lower the risk of COVID-19 related hospitalization [RR= 0.98 (95% CI: 0.82–1.18, p =0.84]. The use of vedolizumab [RR= 1.13 (95% CI: 0.75–1.73, p =0.56] and tofacitinib [RR= 0.81 (95% CI: 0.49–1.33, p =0.40] was not associated with lower risk of COVID-19 related hospitalization.

Conclusion
Regarding COVID-19 related hospitalization in IBD, anti-TNFs and ustekinumab were associated with decreased risk of hospitalization. In addition, vedolizumab and tofacitinib were not associated with COVID-19 related hospitalization.