bluuebunny/crossref_metadata_2025 huggingface dataset:
P438 The Efficacy and Safety of ustekinumab Therapy in refractory Inflammatory Bowel Disease (IBD) patients with co-morbidities and old age
Authors: Davies B , Lodhia M , Abdalla B , Gupta V
Published: January 2022

Background

Ustekinumab is approved for treatment of active Crohn’s Disease (CD) and Ulcerative Colitis (UC) with a more favourable safety profile to anti-TNF therapy however it is still used with caution in the elderly and those with comorbidities. We present our data on safety and efficacy of Ustekinumab in our IBD population including consideration of age and existing medical conditions.

Methods

Clinical data on all IBD patients treated with Ustekinumab within our population between, 2016 and, 2021 were retrospectively collected from electronic records. This included baseline characteristics, diagnosis, previous medical and surgical history, comorbidities, clinical response, endoscopic response and adverse events (AEs).

Results

120 (M=57, F=63) patients were identified, 98 CD, 17 UC and, 5 IBDU with a median follow up of, 13.9 months (IQR, 3–20.5) The median age of starting Ustekinumab was, 35.5 years (16–81) with, 65% (78/120) previously treated with two or more biologics suggestive of refractory disease. Clinical response was achieved in, 18.0% (16/89) of patients at, 8 weeks, 39.3% (24/61) at, 24 weeks, 42.0% (21/50) at, 1 year and endoscopic response and/or with imaging was seen in, 9/23 (39.1%) at, 24 weeks and, 3/18 (16.7%) at, 1 year.

10% (14/120) were >60 at time of starting Ustekinumab, this group had an average of, 1.4 comorbidities compared to, 0.3 in the <, 60 group (p value -0.00001), 7% (8/, 120) patients had had a prior malignancy (Non-melanoma Skin Ca, 4, Solid organ, 2, melanoma, 1, haematological, 1) and, 5 of these were in the >60 group with a median of, 10 years (IQR, 5–11) since being cured and no episodes of recurrence, with, 1 patient developing a malignancy post Ustekinumab.

Adverse events (AEs) were seen in, 5.8% (7/120) of patients and a serious adverse event (SAE) in, 5% (6/120), this included, 4 patients in the <60 age group requiring admission for Intravenous antibiotics vs, 1 in the >, 60 age group (p value, 0.57).

Conclusion

This study contributes to the real-world data being presented regarding Ustekinumab. The efficacy demonstrated in clinical response is comparable to previous studies, the majority of patients having already been treated with two or more biologics. We have demonstrated a favourable safety profile in the over, 60 age group who had a greater number of comorbidities and a higher rate of previous malignancy. With an ageing IBD population the safety and efficacy of Biologics in the older age groups need to be further examined.
P439 Stability of subcutaneous serum IFX (CTP13) levels between two injections and over two successive cycles in patients with Crohn’s disease
Authors: Roblin X , Bastide L , Veyrard P , Berger A E , Paul S
Published: January 2022

Background

Under IFX sc, we do not know if there is a residual level of IFX. The aim of this work was to investigate this point by analyzing the intra-individual variability of the serum level of IFX sc.

Methods

This was an observational, prospective study that included patients with CD undergoing maintenance treatment with IFX sc (120mg every, 14 days). Patients had IFX determinations (i Track, 10; Theradiag (France) at visit, 1 (day, 4 to, 6 after SC injection), visit, 2 (day, 7 to, 9 after sc injection) and visit, 3 (day, 13 to, 14 after sc injection) on two consecutive cycles. The first determinations were made only after, 8 weeks of switching from IV to SC. All patients at inclusion were in clinical remission (CDAI <, 150) with calprotectin levels <, 250 µg/g stool.

Results

20 patients (mean age:, 36 years, sex ratio M/F:, 1, mean duration of IFX IV:, 16 months) were included, i.e. meaning, 120 determinations., 8 patients were treated in combination with thiopurines. Mean residual levels before switch to sc were, 3.9 +/-1.2 µg/mL. Mean intraindividual levels between the two cycles were comparable (Visit, 1: cycle, 1:, 11.1 +/-, 4.4 µg/mL, cycle, 2:, 11.6 +/-, 4.6 µg/mL; p=0.65; Visit, 2: cycle, 1:, 12.0 +/-, 5.1 µg/mL, cycle, 2:, 11.3 +/-4.9 µg/mL; p=0.25; Visit, 3 cycle, 1:, 11.0 +/-4., 7 µg/mL, cycle, 2:, 10.9 +/-, 4.2 µg/mL; p=0.21. Serum IFX sc levels remained stable over the, 14 days between the two SC injections (p=0.36). Mean IFX levels at any dosing time were comparable in patients with and without thiopurines (IFX sc monotherapy: mean:, 11.5 +/-, 5.5 µg/mL versus IFX sc with thiopurines: mean:, 11.8 +/-, 4.6 µg/mL, p=0.54). Finally, residual IFX IV levels before switch did not influence the results of IFX sc serum concentrations (p=NS).

Conclusion

Measure of IFX levels for IFX SC can be proposed at any time between two injections. No residual levels were found. These data are important for our clinical practice.
P467 Therapeutic drug monitoring of biologics in Inflammatory Bowel Disease: Nordic survey on implementation and barriers in clinical practice
Authors: Bjørlykke K , Jahnsen J , Brynskov J , Molander P , Eberhardson M , Davidsdottir L G , Sipponen T , Hjortswang H , Langholz E , Jørgensen K K , Steenholdt C
Published: January 2022

Background

Therapeutic drug monitoring (TDM) is a useful tool to optimise biologic treatments of patients with inflammatory bowel disease (IBD). Albeit broadly recommended by gastrointestinal societies, it is, however, currently unknown how TDM has been adopted and is being used in everyday clinical practice. The aim of the study was to investigate how TDM has been taken up by physicians including barriers for implementation.

Methods

A web-based survey on TDM was distributed to all gastroenterology consultants in the Nordic countries via national gastroenterology- and IBD societies.

Results

Out of 377 physicians responding, 297 handled IBD patients on biologic therapies and were thus eligible for inclusion (NO 118 (40%), DK 86 (29%), SE 50 (17%), FI 33 (11%), IS 10 (3%)). The vast majority were consultant gastroenterologists (n=252, 85%), 152 (51%) were employed at university hospitals, 136 (46%) at community hospitals, and 9 (3%) in private practice. Overall, 257 (87%) used TDM during biologic therapies; 231 (90%) used reactive TDM and 163 (63%) proactive TDM. Common indications were to improve efficacy (70%), aid treatment decisions (62%), improve safety (36%), and improve cost-effectiveness (32%). Notably, Danish physicians used TDM to a significantly lesser extent than all others (58% vs 98%; odds ratio (OR) 0.03 [95%CI 0.01- 0.09], p<0.001); in particular outside the capital region (OR 0.15 [0.05–0.46], p=0.001). Reactive TDM was applied both at primary (74%) and secondary treatment failure (99%) and predominantly for TNF-inhibitors (90–98%) (vedolizumab 63%, ustekinumab 46%). Proactive TDM was used by 80% during maintenance therapy and 56% during induction, and mostly for TNF-inhibitors (79–97%) (vedolizumab 70%, ustekinumab 54%). Proactive TDM was more commonly used in NO, SE, and FI (p<0.001), and by physicians managing >10 IBD patients per week (OR 2.71 [1.34–5.48], p=0.005), but was not associated with employment at university hospital, size of hospital catchment area, or seniority. Main barriers to the use of TDM were lack of guidelines (51%), long response time from the laboratory (49%), lack of knowledge regarding how to use and interpret test results (42%), costs (38%), and currently available evidence (31%). Among physicians using TDM, only 66% reported awareness of TDM guidelines or recommendations.

Conclusion

TDM, and in particular reactive TDM of TNF-inhibitors, has been broadly adopted into clinical practice in the Nordic countries to improve efficacy and assist treatment decisions. Across the Nordic countries, IBD physicians call for improved test response times and, notably, TDM guidelines detailing indications for TDM and interpretation of test results.
P473 Real world experience with the Crohn’s Disease Exclusion Diet (CDED) in a tertiary IBD clinic
Authors: Fliss Isakov N , Anbar R , Cooperstein A , Helbert G , Hirsch A , Ron Y , Thurm T , Maharshak N
Published: January 2022

Background

The Crohn’s Disease Exclusion Diet (CDED) is a whole-food diet designed to reduce exposure to dietary components, hypothesized to negatively affect the microbiome, intestinal barrier, and immune response. In a clinical study in adults with mild-moderate CD (<5 years duration), an inflammatory phenotype involving the terminal ileum, it induced clinical, biochemical and endoscopic disease remission. We aimed to describe our real-world experience with the CDED, in a clinically diverse CD population.

Methods

A retrospective cohort study of CD patients prescribed with the CDED, between 1.2018 and 11.21. Patients’ medical background, medical therapy, nutritional status and clinical disease activity as well as adherence and clinical outcomes were documented from patients’ medical files.

Results

The CDED was recommended to 218 CD patients. Of these, 62 were excluded from the analysis due to lack of medical information (n=11), prior personal experience with the CDED (n=23), patient’s refusal (n=24), and stoma patients (n=4).

The CDED was initiated in 155 patients (age 37.7±16.3, 66% men, disease duration 7.8±9.6), 35.3% had colonic/ileo-colonic disease, 23.7% and 25% had a stricturing and penetrating disease respectively, 27.5% had a history of intestinal resection, 19.9% had extra-intestinal involvement, and 7.7% had a severe endoscopic disease at diet initiation.

Indications for therapy included patient’s will (44.7%), adjunctive therapy (23.7%), bridge with biologic induction (20.4%), rescue therapy (3.9%), exhaustion/contraindication of other advanced therapy options (1.4%), de-escalation of biologics (0.7%), preparation for surgery (0.7%), and others (3.9%). Upon initiation, 67.3% (n=105) had an active disease [Harvey Bradshaw index (HBI) ≥5 / Calprotectin ≥250 g/l] and 32.7% were in remission.

Physician and dietician follow-up at the end of phase 1 was documented in 89 (57.4%) and 74 (47.7%) of patients with an active disease (mean follow-up period 14.6±9.3 weeks).

Fifty-eight percent of patients with dietary follow-up (n=43) were fairly-fully compliant to the CDED.

Clinical response (drop in HBI>2 points) and remission (HBI<5) at the end of phase 1, were achieved by 58.9% (n=62) and 57.5% (n=60) of patients who were treated for an active disease (n=105). Clinical remission rate at the end of phase 1 was lower among patients with higher baseline HBI score (P for trend=0.028), lower dietary adherence (P for trend<0.001) and a surgical history (P=0.033).

Conclusion

The CDED may have efficacy across different clinical scenarios. Adherence is reasonable, and is associated with higher remission rates among patients treated for an active disease.
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

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

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

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

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

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 <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

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<0.0001) and was correlated with age (r=0.5718; p<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

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

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 <5 in CD and PMS<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<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<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

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 < 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 < 0.00001)]. Similar finding was observed in patients taking ustekinumab [RR= 0.55 (95% CI: 0.43–0.72, p < 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.
P572 Therapy optimisation and intravenous ferric carboxymaltose in active or inactive IBD with iron deficiency: it’s time to make iron deficiency part of tight monitoring to reach T2T? – preliminary results of a prospective study
Authors: Molnár T , Resál T , Bacsur P , Rutka M , Szántó K , Bálint A , Milassin Á , Fábián A , Bor R , Szepes Z , Farkas K
Published: January 2022

Background

Iron deficiency (ID) is often a neglected condition in inflammatory bowel disease (IBD), even though it is one of the most common extraintestinal manifestation. Our questions were the follows: If iron deficiency is part of the T2T management as CRP or fecal calprotectin and requires optimisation of the current therapy, how does this affect the medium-term outcome of the disease and the effectiveness of IV iron replacement? If the disease is active, does optimisation of therapy is sufficient to manage iron deficiency or iv. iron supplementation is also necessary?

Methods

Patients with ID defined by the ECCO guideline (Figure 1.) were randomly included in our prospective one-center, four arms study. Patients were divided into an active (A) and a remission (R) group. Activity was defined by CRP ≥10 mg/l or clinical activity scores CDAI ≥150, pMayo ≥3. Therapy optimisation was performed in the active group, further randomisation was performed into two subgroups: therapy modification alone (A1) or modification with iv. ferric-carboxymaltose (A2). All patients received iron supplementation in the remission group with (R2 – iron T2T group) or without therapy optimisation (R2). Every two months laboratory parameters and clinical activities were assessed until 6 months.

Results

65 patients were included (CD 83.4%). Average follow-up was 3.9 months. Number of patients per group: A1:17, A2:23, R1:16, R2:9. Based on our results, iv. iron supplementation with modification in treatment was more efficient, than therapy optimisation alone, as the difference in increase in haemoglobin (p<0.001), haematocrit (p<0.001) and ferritin (p<0.05) was significant after 2 and 4 months the enrollment. In the remission group iv. iron supplementation with therapy optimisation was more effective, than iv. iron alone, based on transferrin saturation (p<0.05), serum iron (p<0.05) and CRP (p<0.05) during the 2 months period. After that period, no further significant difference was measured. Iv. iron seems to be equally effective both in the active and in the remission group, as no significant difference was measured during the 6-month period. No adverse event was observed.

Conclusion

Our results suggest, that therapy optimisation in addition to iron replacement is more effective in patients with remission and therefore biomarkers of IDA should be involved in the thight monitoring algorhytm to react T2T. However, therapy optimisation has to be associated with iv iron replacement in IBD with IDA and activity without the risk of worsening disease activity. Based on our results, ferric-carboximaltose is an effective and safe therapeutic method in the treatment of IDA associated with active or inactive IBD.
P575 Safety and efficacy of autologous haematopoietic stem cell transplantation for refractory Crohn’s disease after cyclophosphamide-free mobilisation: Preliminary Results
Authors: Giordano A , Rovira M , Barastegui R , Marín P , Martínez N , Fernández-Aviles F , Suárez-Lledó M , Doménech A , Ordás I , Fernández-Clotet A , Caballol B , Gallego M , Vara A , Masamunt M C , Giner A , Corraliza A M , Panés J , Salas A , Ricart E
Published: January 2022

Background

Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with refractory Crohn’s disease [CD]. Although the safety of the procedure has been improved over the last decade, AHSCT is still burdened by high adverse event rate due to chemotherapy toxicity and immunosuppression. The aim of this study was to evaluate the safety and efficacy of AHSCT by using a cyclophosphamide (Cy)-free mobilisation regimen followed by a standard conditioning approach.

Methods

A prospective observational study was conducted at Hospital Clínic of Barcelona in refractory CD patients undergoing AHSCT. Outpatient regimen with G-CSF 12–16 μg/kg/daily for 5 days was used for mobilisation. Patients who failed to achieve >2x106 CD34+ cells received Plerixafor 240 μg/d (1–2 doses). For conditioning, Cy and ATG were administered according to standard protocols. After transplant, patients were followed-up at regular intervals. Colonoscopy and/or magnetic resonance imaging were performed at baseline and at weeks 26, 52, 104 after AHSCT. Crohn’s Disease Activity Index (CDAI) and SES-CD were used for clinical and endoscopic disease assessment.

Results

From June 2017 to October 2021, 14 refractory CD patients were enrolled (9F, median age 40 yr, median CDAI 204, median SES-CD 13); all of them achieved successful mobilisation (median collected CD34+ cells 7.7x106±2.8) and were transplanted. Patients were followed-up during a median of 71.5 months [0–104]. No SAEs or CD worsening were observed during mobilisation. The proportion of patients in clinical remission (CDAI<150) was 70% at 6 months, 43% at 1 yr and 60% at 2 yr. Median SES-CD was 3 at 6 months and 9 at 1 yr. The proportion of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 0% at 6 months, 30% at 1 yr and 40% at 2 yrs. AEs and SAEs during and after conditioning were comparable to previous series, being neutropenic fever the most frequently observed (54%). Colectomy due to refractory severe relapse was needed in one patient at 70 weeks from transplant.

Conclusion

Cy-free mobilisation is feasible and safe in refractory CD patients undergoing AHSCT but early relapse is observed in a significant proportion of patients. While representing an improvement on safety, studies exploring early reintroduction of drugs to decrease relapse rate after transplant are warranted.
P578 Non-medical switch between adalimumab biosimilars and from the originator adalimumab to biosimilars in inflammatory bowel disease patients – a multicentre study on efficacy and drug sustainability
Authors: Lontai L , Gonczi L , Balogh F , Komlodi N , Resal T , Farkas K , Molnar T , Golovics P , Schafer E , Szamosi T , Miheller P , Ilias A , Lakatos P L
Published: January 2022

Background

The use of biosimilar adalimumab (ADA) is effective and safe in inflammatory bowel disease (IBD), although clinical data on switching between ADA biosimilars is still rare. At the end of 2020, a non-medical switch to biosimilar ADA became mandatory in Hungary due to reimbursement policy changes of the National Health Insurance Fund of Hungary (NEAK). The aim of the present study was to evaluate short- and medium term clinical efficacy, drug sustainability and safety comparing non-medical switches from the originator to biosimilar ADA, and between ADA biosimilars.

Methods

246 consecutive patients on maintenance ADA therapy (n=181 Crohn’s disease [CD] and n=65 ulcerative colitis [UC], male/female: 44%/56%, median disease duration: 10years(y) (IQR: 10–16)) were included from 4 IBD centers between September 2019 and December 2020. Data on clinical efficacy, using Crohn’s Disease Activity Index (CDAI) and partial Mayo Score (pMayo), laboratory parameters (C-reactive protein – CRP) and adverse events were collected at 8–12 weeks prior switch, at baseline, and 8–12 weeks, 20–24 weeks after switch. Drug sustainability following the switch was evaluated after a median of 41 weeks (IQR: 35–42) follow-up time.

Results

A total of 246 IBD patients (n=153 patients [115CD/38UC, median age: 38y(IQR: 27–45)] and n=93 patients [66CD/27UC, 32y(IQR: 26–40.5)] underwent a non-medical switch from the originator to a biosimilar, and biosimilar to biosimilar. Clinical disease activity based on CDAI and pMayo scores are presented in Figures 1 and 2. No significant difference was found in the proportion of patients in clinical remission at week 8–12 prior switch / switch / week 8–12 and week 20–24 in either patients switched from originator to biosimilar (86.8% / 88.2% / 86.0% / 85.0%; p=0.87 among groups) or biosimilar to biosimilar (72.0% / 77.4% / 84.9% / 77.6%; p=0.21). 89.2% and 83.1% of patients who were in clinical remission at switch/baseline sustained clinical remission up to week 20–24 in the first and second cohorts. Mean CRP levels were also unchanged during follow-up in both cohorts (p=0.71 and p=0.94). Drug survival was similar between originator to biosimilar and biosimilar to biosimilar switch cohorts, with a probability of 90.6% (SE: 2.4) and 85.8% (SE:3.7) to stay on drug after 40 weeks (log-rank: p=0.271). Figure 3. Two cases of skin reactions were registered as adverse events, one leading to treatment discontinuation.

Conclusion

Clinical remission was sustained following non-medical switch from originator or biosimilar adalimumab to a biosimilar in IBD patients. Medium-term drug sustainability following the switch was high, and comparable between patients with an originator to biosimilar and a biosimilar to biosimilar switch.
P582 Association between serum ustekinumab concentrations and endoscopic disease activity in Crohn’s disease
Authors: Yanofsky R , Abduallah Y , Golovics P , Lakatos P L , Bitton A , Wild G , Afif W , Bessissow T
Published: January 2022

Background

Therapeutic drug monitoring, the measurement of serum biologic concentrations and immunogenicity, has become an important method in guiding the management of biologic therapy in patients with Crohn’s disease (CD). Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an approved therapy for patients with CD. However, few studies have explored the relationship between serum ustekinumab drug levels and outcomes in CD. Thus, the utility of serum ustekinumab drug levels in the management of CD remains unknown. The primary objective of the study was to evaluate the association between serum ustekinumab drug levels and endoscopic remission (ER) in CD. Secondary outcomes included evaluating the association between serum ustekinumab drug levels and clinical (CR), biochemical, and histological remission (HR).

Methods

Adult patients with CD maintained on ustekinumab were prospectively recruited at the time of routine colonoscopy from 2019 to 2021 at the Montreal University Health Centre, Montreal, Quebec. Clinical and demographic information was obtained from chart and patient review. CD symptom severity was assessed by the Harvey-Bradshaw Index (HBI), with clinical remission defined as an HBI score less than 5. Blood samples were drawn for measurement of serum ustekinumab drug level and C-reactive protein. Stool samples for fecal calprotectin were also collected. Elevated C-reactive protein and fecal calprotectin were defined as a value greater than 5 mg/L and 200 ug/g, respectively. Endoscopic remission was evaluated by the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), with ER defined by an SES-CD score less than 3. If biopsies were taken, histological outcomes were recorded. HR was defined as inactive colitis.

Results

53 patients were included in the study, of which 22 (41.5%) were in ER. Median [interquartile range] ustekinumab drug levels were not associated with ER (Figure 1. ER = 5.4 mg/L [2.6–9.4 mg/L], no ER = 4.3 mg/L [2.3–9.4 mg/L]; P=0.843). There was also no association between quartiles of ustekinumab drug levels and ER (P=0.772). In addition, there was no association observed between median ustekinumab drug level and CR (CR = 4.7 mg/L [2.7–8.3 mg/L], no CR = 3.8 mg/L [2.1–9.6 mg/L]; P=0.993) or HR (HR = 6.4 mg/L [3.5–9.5 mg/L], no HR = 3.7 mg/L [2.2–8.0 mg/L]); P=0.168). There was no association observed between median ustekinumab drug level and C-reactive protein or fecal calprotectin as well (P=0.158 and 0.923, respectively).

Conclusion

There was no association observed between serum ustekinumab drug levels and endoscopic remission. Further studies are required to validate our findings.