bluuebunny/crossref_metadata_2025 huggingface dataset:
P718 A Phase I Study of Ex Vivo Expanded Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Pediatric Perianal Fistulizing Crohn’s Disease
Authors: Otero Piñeiro A , Lightner A L , Reese J , Ream J , Nachand D , Adams A , VanDenBossche A , Kurowski J
Published: January 2023

Background

Background: Mesenchymal stem cells have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, no studies to date have included pediatric patients.

Objective

To determine safety and efficacy of mesenchymal stem cells for pediatric perianal fistulizing Crohn’s disease.

Methods

Design: Phase I safety trial

Settings

Tertiary inflammatory bowel disease referral center

Patients

Crohn’s patients aged 13-17 with perianal fistulizing disease.

Intervention

75 million mesenchymal stem cells were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved.

Main outcomes measures

Adverse and serious adverse events at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes at the same time points.

Results

Results: A total of 7 pediatric patients were enrolled and treated (6 male; median age of 16.7 years). There were no adverse or serious adverse events reported related to investigational product. At six months, 83% had complete clinical and radiographic healing. The perianal Crohn’s disease activity index, Wexner incontinence score, and VanAssche score had all decreased at six months.

Limitations

Single institution and open label.

Conclusion

Bone marrow derived mesenchymal stem cells offer a safe, and likely effective, alternative treatment approach for pediatric perianal fistulizing Crohn’s disease.
P727 Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies
Authors: Macaluso F S , Ventimiglia M , Orlando A
Published: January 2023

Background

Many observational studies on the use of vedolizumab (VDZ) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) have been published in the last few years. We aimed to comprehensively summarize its effectiveness and safety by pooling data only from observational studies.

Methods

PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalization, loss of response, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes.

Results

Eighty-eight studies comprising 25,678 patients (13,663 with CD and 12,015 with UC) met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC.

Conclusion

Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.
P728 Real world evidence for adalimumab biosimilar, MSB 11022, therapy in inflammatory bowel diseases: Adherence analysis
Authors: Cheung S , Truong D
Published: January 2023

Background

Adherence to medication is crucial for maintaining remission in patients with inflammatory bowel diseases (IBD). Patient-support program (PSP) plays a significant role in education for patients on medication adherence. The objective of this project was to analyze the data collected by Fresenius Kabi PSP (KabiCare) in IBD patients population on their adherence to an adalimumab biosimilar, MSB 11022, in real world practice in Canada.

Methods

Patients with IBD enrolled in KabiCare and received at least one dose of adalimumab biosimilar, MSB 11022, were follow-up from Feb 2021 to Nov 2022 in Canada. Medication initiation date and stop date, disease types (Crohn’s disease [CD], and ulcerative colitis [UC]) and patient treatment (categorized by naïve to biologic, or switched from other biologics) were recorded in the database. The stop date was the date when KabiCare was informed that medication was discontinued. The patients continuing medication were censored at the maximal follow-up date of analysis, November 9, 2022. Log-rank tests were used for KM (Kaplan-Meier) plot comparison to examine if there were differences in medication adherence between CD and UC, and between naïve group vs. switch group by disease.

Results

The study sample consisted of 836 patients, 670 (80.0%) of whom had CD, and 266 (31.8%) were in naïve group. KabiCare followed patients for a median time of 291 days (interquartile range: 190-392 days; maximum: 622 days). At 600 days after starting the medicine, the adherence probability was similar for patients with CD and UC (At day-600: 83.4% vs. 82.2%, P=0.26); however, the adherence probability was higher in the switch group compared to naïve group (At day-600: 87.9% vs. 73.5%, P=0.0001). Among patients with CD, the adherence probability was higher with switch group compared to naïve group (At day-600: 88.8% vs. 71.7%, P=0.0001). Among patients with UC, the adherence probably was similar between switch group compared to naïve group (At day-600: 90.5% vs. 76.5%, P=0.11).

Conclusion

The adherence probability of adalimumab biosimilar, MSB 11022, was over 80% 600-day after initiating therapy, regardless of the type of IBD disease. Compared to patients in naïve group, patients in switch group were more likely to stay on adalimumab therapy. As far as we know, this is the first report of using adalimumab biosimilar, MSB 11022, in real world clinical practice of IBD.
P729 Evaluation of hepatobiliary pathologies using transient elastography in patients with inflammatory bowel disease: What about the effect of drugs?
Authors: Ağargün B F , Şenkal İ V , Rustamzade A , Nuriyev K , İstemihan Z , İmanov Z , Genç S , Çelik B , Şahutoğulları D , Çavuş B , Çifcibaşı Örmeci A , Demir K , Beşışık S F , Kaymakoğlu S , Akyüz F
Published: January 2023

Background

In this study, we evaluated hepatobiliary involvement in inflammatory bowel disease (IBD) with FibroScan® (transient elastography) and examined drug effects on liver fibrosis and steatosis. We particularly focused on the effect of azathioprine (AZT) on spleen stiffness (SS).

Methods

A total of 352 subjects were included in this study, including 298 IBD patients and 54 healthy controls. LSM (liver stiffness measurement), SS, and CAP™ (controlled attenuation parameter) scores were measured by FibroScan®. In addition to disease and patient characteristics; laboratory tests, and effect of the drugs were evaluated and compared within the groups.

Results

The patient and control groups were similar in terms of age and gender. The characteristics of the groups are shown in Table 1. Mean LSM (5.2±3.1kPa vs 4.5±1,1kPa), mean SS (22.69±13,10kPa vs 17.96±7,44kPa), CAP™ score (hepatosteatosis) (233±56dB/m vs 224±47dB/m) were significantly higher in the patients with IBD than in the control group (p<0.05). Liver fibrosis and steatosis grades are shown in Figure 1. A positive correlation was found between CAP™ score and male gender, hypertension, diabetes, BMI, smoking, penetrating disease, GGT, triglyceride, LSM, and SS (p<0.05). LSM (5.7±3,1kPa vs 5.0±3,1kPa) was significantly higher in patients with extraintestinal involvement (p<0.05). In patients with significant liver fibrosis (F2-3-4), the frequency of anti-TNF treatment was lower (44,4% vs 69,5%; p=0,008) (Figure 2). In patients who use alcohol regularly compared to nondrinkers (25.54±14,83kPa vs 21.05±11,24kPa) SS was significantly higher (p<0.05). Additionally, in patients using AZT≥100 mg/day compared to those using AZT<100 mg/day (23.48±14,61kPa vs 19.99±11,84kPa; p<0,05) SS was significantly higher (Figure 3). AZT dose was positively correlated with SS (Spearman analysis; r=0.182 and p=0.013); however, no correlation was found with the duration or cumulative dose of AZT. The mean level of platelets was significantly higher in patients with IBD than in controls (300±104x10³/µL vs 251±52x10³/µL, p=0,001); however, there was no correlation between SS and trombosit level (p>0,05). 83% of patients were in clinical remission (Mayo score≤2/CDAI<150). No positive correlation was found between disease activity and SS in IBD patients. AZT-associated non-cirrhotic portal hypertension was detected in only one patient.

Conclusion

In this study, fatty liver, liver fibrosis, and SS were found to be significantly higher in IBD patients than in healthy controls. Although there is no relationship with the duration of AZT therapy, AZT dose was positively correlated with SS. We recommend that spleen stiffness should be evaluated in patients who use high doses of AZT (≥100 mg/day).
P733 Novelties of COVID-19 vaccination beyond efficacy: Nationwide experiences with trough levels, durability, and disease activity among inflammatory bowel disease patients
Authors: Resál T , Horváth M , Bacsur P , Szántó K , Rutka M , Bálint A , Fábián A , Bor R , Szepes Z , Fekete J , Miheller P , Molnár T
Published: January 2023

Background

The SARS-CoV-2 pandemic has raised issues in the management of inflammatory bowel diseases (IBD). This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-TNF drug levels.

Methods

A prospective, multicentre study of IBD patients was conducted following mRNA and non-mRNA anti-SARS-CoV-2 vaccination. Healthy control (HC) patients were enrolled to reduce bias. Baseline and week 14 samples were obtained following the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured.

Results

This study included 199 IBD (Table 1.; mean age, 40.9 ± 12.72 years) and 77 HC participants. Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (Table 2.; anti-TNF 68.7%). Combined immunomodulation and biological treatment were associated with lower serological response (Figure 1.; p<0.001), and mRNA vaccination promoted better antibody levels (p<0.001). Higher adalimumab levels caused lower serological response (p=0.006). W8 persistence of anti-SARS-CoV-2 level was equal in IBD and HC groups (Figure 2.; p>0.05). Vaccination had no impact on disease activity.

Conclusion

Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although mid-term durability of vaccination is encouraging, more data are needed to expand existing understanding on this issue.
P737 Intensification with intravenous ustekinumab in refractory Crohn′s disease
Authors: Arroyo Argüelles J M , Suárez Ferrer C , Rueda García J L , Martín-Arranz E , Poza Cordón J , Sánchez-Azofra M , García-Ramírez L , Martin-Arranz M D
Published: January 2023

Background

There is little scientific evidence available about the results in terms of clinical and biochemical response after intensification with intravenous (IV) ustekinumab (UST) as a therapeutic strategy to be used in patients with refractory Crohn’s disease (CD) who are receiving subcutaneous (SC) treatment with said drug.

Methods

Patients with CD in stable follow-up at Hospital Universitario La Paz (Madrid), who were undergoing intensified treatment with IV UST, were recruited. The objective of the study was to assess the clinical and analytical response and drug levels 12 weeks after the change from subcutaneous to intravenous UST.

Results

27 patients were retrospectively included, all of them with previous treatment with UST SC. In Table 1 baseline characteristics are collected.

Out of the 27 patients included, 4/27 were under treatment with UST in first line, 10/27 in second line, 9/27 in third line and 4/27 had failed to three biologics.

The reason for intensification with IV UST was the lack of response to treatment in the 27 patients, 7 of them (25.93%) being found in the context of post-surgical recurrence. On the other hand, 10 patients (37.03%) were already under treatment with intensified SC UST, while the remaining 17 patients (62.96%) were under treatment with a standard schedule of SC UST every 8 weeks.

At the baseline visit, prior to the change to IV UST, differences in levels were observed between intensified and non-intensified patients (7216 vs 2842, p=0,00005). However, no significant differences were appreciated between these two groups 12 weeks after IV intensification (7949 vs 7937; p=0,99).

In patients with intensified UST SC was observed a decrease in fecal calprotectin 12 weeks after starting IV intensification, going from a mean of 1463 to 751, although the differences were not significant (p=0,14).

In Figure 1 is shown improvement in fecal calprotectin levels and in Figure 2 improvement in UST levels in blood is reflected, both parameters quantified 12 weeks after intravenous intensification of the drug.

In Table 2 data derived from the analysis of the clinical activity and determinations of CRP and calprotectin are collected, before performing the intensification with UST IV and 12 weeks after it.

Conclusion

In our experience, change to intravenous ustekinumab in maintenance led to an improvement in the clinical and biochemical response in patients with Crohn’s disease (even in patients already intensified). Likewise, an increase in drug levels was observed 12 weeks after the change from subcutaneous to intravenous treatment.
P745 Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort
Authors: Gros B , Plevris N , Constantine-Cooke N , Lyons M , O’Hare C , Noble C , Arnott I D , Jones G R , Lees C W , Derikx L A A P
Published: January 2023

Background

Switching from originator to biosimilar infliximab (IFX) is effective and safe. However, data on multiple switching are scarce. The Edinburgh IBD unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety.

Methods

We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, CRP, faecal calprotectin (FC), IFX trough / antibody levels, and drug survival.

Results

297 patients (CD n=196 [66%], UC/IBDU n=101, [34%]) were switched. This was the third, second and first IFX switch for 67 /297 (22.5%), 138 /297 (46.5%) and 92 /297 (31%) of the cohort respectively. Patients who underwent multiple IFX biosimilar switches had longer disease duration (p=0.0001) and IFX duration (p=0.0001) and were less often on combination therapy with an immunomodulator (p=0.0001).

90.6% of patients remained on IFX during a median follow-up of 7.5 months [6.8-8.1] (figure 1). The number of switches was not independently associated with IFX persistence after adjusting for confounders (table 1). Clinical (p=0.77), biochemical (CRP ≤5mg/mL; p=0.75) and faecal biomarker (FC<250µg/g; p=0.63) remission were comparable at baseline, week 12 and week 24 (figure 2).

Conclusion

Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.
P747 The impact of COVID-19 on patients with Inflammatory Bowel Disease: A population-based study using artificial intelligence
Authors: Moralejo Lozano Ó , Beneyto Martín P , Abanades Tercero M , Muñoz Rosas C , Ruano Díaz L , Salmoral Luque R , Gómez Rodríguez R
Published: January 2023

Background

Coronavirus disease 2019 (COVID-19) has been a pandemic that is still very prevalent. Patients with Inflammatory Bowel Disease (IBD) represent a special population considering their already altered immune system and their exposure to several immunosuppressive therapies. We pretend to study the impact of COVID-19 on IBD patients in our community, Castilla-La Mancha (a region in central Spain).

Methods

Retrospective observational study using an artificial intelligence with natural language processing capability, the SAVANA manager, we analyzed data from 1 808 010 patients with Electronic Medical Records (EMR) within the public health system of Castilla-La Mancha from March 1st 2020 to January 1st 2021. Data on demographic characteristics, hospitalization, ICU admission and mortality were collected. We compared COVID outcomes between IBD and non-IBD patients. We compared COVID outcomes in IBD patients according to their treatment (comparing each treatment group to those IBD patients with no treatment); we considered: immunomodulators (azathioprine, mercaptopurine, methotrexate), antiTNF alone or combined with immunomodulator, vedolizumab, ustekinumab and tofacitinib; mesalazine and corticosteroids were not analyzed.

Results

2 243 patients with IBD suffered COVID-19, compared to COVID-19 cases without IBD there were less females, they suffered more arterial hypertension, diabetes mellitus, dyslipidemia, obesity, or tabacco use (TABLE 1). And yet, despite these being proven risk factors for worse outcomes for COVID-19, no differences were appreciated in hospitalization rate, ICU admission, or mortality between those with or without IBD (TABLE 2). COVID-19 was more frequent in IBD patients (32.59 vs 13.28%). Comparing IBD patients with COVID-19 according to their treatments (TABLE 3), vedolizumab is the only treatment with a higher risk for COVID-19 infection, however the hospitalization risk for vedolizumab is lower than for those without it. Immunomodulators do also have a lower hospitalization risk both alone or in combination with antiTNF, no differences were found for antiTNF monotherapy, ustekinumab or tofacitinib. ICU rate and mortality are no different between treatments, except for tofacitinib (0.00% ICU rate, 10.00% mortality), however the small number of patients using this treatment may bias this result.

Conclusion

COVID-19 in IBD patients is no different in hospitalization, ICU admission or mortality compared to non-IBD population. IBD patients exposed to immunomodulators and vedolizumab have less hospitalization risk than those not exposed, no differences were found for antiTNF alone or ustekinumab. The impact of tofacitinib in COVID outcomes requires further investigation.
P749 Crohn’s disease stricture response and resolution with adalimumab therapy demonstrated with intestinal ultrasound. The STRIDENT randomised trial
Authors: Lovett G , Schulberg J D , Hamilton A L , Wright E K , Sutherland T R , Kamm M A
Published: January 2023

Background

Transmural healing is a treatment goal in the management of Crohn’s disease, and intestinal ultrasound (IUS) is potentially a sensitive, non-invasive and reproducible means to assess the response to treatment.

Methods

The STRIDENT (Stricture Definition and Treatment) study was a randomised controlled trial of standard dose monotherapy adalimumab versus intensive high-dose adalimumab combined with a thiopurine. Crohn’s disease patients with symptomatic intestinal strictures were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) with 40mg fortnightly maintenance plus thiopurine, with possible dose escalation at 4 and 8 months, versus standard dose adalimumab monotherapy. The primary endpoint was clinical response, defined as a reduction in the Obstructive Symptom Score (OSS) of ≥1, at 12 months. IUS was performed at baseline, 4, 8 and 12 months. IUS endpoints included stricture resolution (normalisation of pre-stenotic dilation (<2.5cm); reduced stricture bowel wall thickness (BWT ≥25% reduction); reduced colour doppler blood flow (inflammation, Limberg score ≤1) and normalisation of BWT (≤3mm). Patients with good quality baseline IUS and IUS-visible strictures were included for analysis.

Results

77 patients underwent therapy randomisation. Of 63 patients with IUS-visible strictures 43 (68%) were in the intensive arm. Primary outcome was achieved by 32 (74%) patients in the intensive and 14 (70%) in the standard arms. Stricture resolution was seen in 1/5 non-responders and 18/45 responders. Median BWT reduced from 6.4mm (IQR 5.2-7.3mm) at baseline to 4.9mm (IQR 3-6mm) at 12 months (P<0.001). Clinical responders had significant reduction in median BWT from 6.0mm (IQR 4.5-7.1) at baseline to 4.3mm (IQR 3-5.7) at 12 months (P<0.001). There was no significant reduction in BWT at 4, 8 or 12 months in non-responders (P=0.26, P=0.29, P=0.26 respectively). BWT >3mm at 12 months occurred more often in non-responders than responders (P<0.05). Stricture resolution was seen in 13/36 in the intensive arm and 6/14 standard arm (P=0.75). The intensive arm had significant reduction in median BWT from 6.6mm (IQR 5.5-7.4mm) at baseline to 5.1mm (IQR 3-6.4mm) at 12 months (P<0.001). There was no significant reduction in BWT at 4, 8 or 12 months in the standard arm (P=0.75, P=0.42, P=0.09 respectively). There was no significant difference in BWT>3mm between trial arms at 12 months (P=1).

Conclusion

Stricture resolution and bowel wall thickness normalisation were demonstrated on intestinal ultrasound in stricturing Crohn’s disease patients treated with adalimumab therapy. Adalimumab therapy is associated with clinical improvement, and transmural improvement and healing, in patients with Crohn’s disease strictures.
P758 Impact of co-medication on rates of endoscopic remission: post-hoc analysis of randomised non-inferiority trial of 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis
Authors: Safroneeva E , Laoun R
Published: January 2023

Background

Some studies reported that anti-TNF treatment in biologic-naïve elderly onset inflammatory bowel disease patients may be less effective than in non-elderly onset patients (Amano et al. Scientic Reports. 2022 12:5324). We assessed known factors as well as presence of co-morbidities and polypharmacy associated with endoscopic remission in mild-to-moderate (Mayo clinic score ≥5) adult ulcerative colitis (UC) patients treated with mesalazine.

Methods

In a post-hoc analysis of data from a phase 3 non-inferiority trial ( D’Haens et al. Aliment Pharmacol Ther.2017;46:292–302)we examined the strength of association between number of co-medications and comorbidities by calculating Spearman’s rho. We used multivariable logistic regression modeling to determine the associations between endoscopic remission as outcome (yes vs. no; defined as either Mayo endoscopic subscore of 0 or ≤1 according to blinded central reading) and independent variables (disease duration, Mayo endoscopic score at baseline, leucocyte concentration at baseline, Robarts Histopathologic Index at baseline, age [≤60 vs. >60 years of age], gender, comedications at the time of the trial [none, ≤2, ≥3], comorbidities [none, 1-2, 3-5, >5], body mass index, disease extent prior to the trial, smoking status [current, ex, and never] at week 8 and 38. Collinear variables were examined in separate models. P-value of <0.05 was considered to be statisically significant.

Results

We analyzed data on 774 patients (330 female, 43.5±14.3 [SD] years of age, median disease duration of 3.00 years [IQR 0.56; 7.88], 175 and 92 persons with 1-2 and ≥3 comedications, respectively) and 679 patients (289 female, 43.7±14.5 [SD] years of age, median disease duration of 2.99 years [0.57; 7.62]; 150 and 85 persons with 1-2 and ≥3 comedications, respectively) that had colonoscopy/sigmoidoscopy at 8 weeks of double-blind induction and 38 weeks open-label maintenance phases of the study, respectively. We observed a moderate association between number of comorbidities and comedications (week 8: Spearman rho=0.545, P-value of < 0.001; week 38: Spearman rho=0.512, P-value < 0.001). Patients with baseline Mayo clinic endoscopic score of 3 and increased baseline leucocyte concentration, were less likely to be in endoscopic remission irrespective of endoscopic remission definition and time post treatment (Table 1). In addition, patients with ≥3 co-medications were less likely to be in endoscopic remission of 1 at week 8 and 38 and in endoscopic remission of ≤1 at week 38 (Table 1).

Conclusion

The increased number of co-medications rather than the actual age may be responsible for decreased effectiveness of medications, including mesalazine, in elderly UC patients highlighting the importance of healthy aging.
P760 Adalimumab biosimilars versus Azathioprine: indirect comparison of efficacy, safety and persistence in treatment
Authors: Saladino M , Celsa C , Amato L M , Di Giorgio F M , Muscarella S , Melatti P , Brinch D , Cappello M
Published: January 2023

Background

The advent of low-cost adalimumab (ADA) biosimilars is expected to increase access to biologics. Whether ADA biosimilars influence the use of conventional immunomodulators, especially azathioprine (AZA), which should be the alternative in steroid-dependant IBD, has not been investigated and comparative data on efficacy and safety are scanty. The aim of this study is to compare ADA biosimilars and Azathioprine (AZA) in patients with IBD naive to biologics and/or immunosuppressive agents.

Methods

A retrospective-prospective observational study was conducted on 55 consecutive IBD-patients (30 CD, 25 UC), in follow up in our tertiary referral center, who started ADA biosimilars or AZA between 11/2018 and 11/2021. Drug choice was upon clinical judgement. Primary outcomes, clinical response and steroid-free clinical remission, were evaluated at 12 and 84 weeks, using HBI for CD and p-Mayo score for UC. Active disease was defined HBI>5 for CD e p-Mayo>2 for UC. Secondary outcomes were persistence and retention rate.

Results

The two treatment groups showed similar baseline characteristics regarding age, sex, familial predisposition, smoking, type of IBD and previous surgery, except the use of systemic steroids (42,85% of patients treated with ADA and 18,5% of patients with AZA; p= 0,029) and presence of active disease (60,71 % of ADA and 37,03% of AZA; p=0,082). At week 12 clinical response was obtained in 22/28 (78,6%) treated with ADA and in 22/27 (81,5%) with AZA (p=0.789), at week 84 response rate was obtained in 10/10 (100%) of ADA e 10/13 (76,9%) of AZA (p= 0,155). Clinical remission at week 12 was achieved by 19/28 (67,9%) of ADA patients and by 24/27 (88,9%) AZA (p=0,061), at week 84 by 10/10 (100%) of ADA and by 12/13 (92,3%) of AZA (p=0,380). No adverse events were registered in the ADA group, 5 AE leading to discontinuation occurred in the AZA group (0% VS 18,52% , p=0,018). The retention rate was 85,7% for ADA and 74,1% and AZA (p= 0,285). According to IBD type, treatment persistence of ADA was higher in patients with CD (Log-rank test p=0,004); in CD the persistence rate is significantly better for ADA as compared to AZA. (Log-rank test p=0,008), in UC the difference was not significant (p=0,41).

Conclusion

Our results suggest that ADA biosimilars are an effective therapy in steroid-dependent IBD, with a better safety profile compared to AZA, thus resulting in a higher probability of treament persistence especially in CD. The use of AZA is expected to decline in the next years.
P761 Negative Body Image in Inflammatory Bowel Disease persists despite Modern IBD care
Authors: Madigan S , Prichard I , Smart C , Prosser R , Mountifield R
Published: January 2023

Background

Body image dissatisfaction (BID) is prevalent in patients with Inflammatory Bowel Disease (IBD). Historically female sex, previous IBD surgery, impaired QoL have been associated with negative body image. The introduction of biologic therapies and modern IBD care in Australia in 2007 has improved disease control and endoscopic outcomes, but it is unclear if body image has improved in parallel with this. We aimed to determine whether body image and QoL have improved amongst IBD patients with modern IBD car

Methods

Tertiary IBD service patients were offered inclusion in the study in 2006 by postal survey (pre-biologic era), and in 2021 by electronic survey (biologic era). Surveys included demographics and history of IBD surgery. In the pre-biologic era (PBE) body image dissatisfaction (BID) and QoL were assessed using a patient reported yes/no question, followed by an open question about how IBD or treatment has changed the way they view their body’s appearance. In the biologic era (BE) the validated modified Body Image Scale and Short Inflammatory Bowel Disease Questionnaire were used.

Results

The BE included 135 patients, 59% female, mean age 45.9. The PBE included 215 patients, 66% female and mean age 35.5. PBE had 40% reporting IBD surgery vs 36% in BE (P=0.489). BID was observed in 67% vs 39% of the PBE and BE respectively (p<0.01). In the PBE free text responses elicited themes of dissatisfaction with medication or steroid-related appearance changes (41%), bloating (30%), weight gain (28%), weight loss (12%), and specific appearance changes. The link between body image and QoL was mentioned by 33% of patients, with 8% specifically mentioning its impact on their mental health. Females were affected to a greater extent in both PBE (75% vs 52% p<0.01), and BE (50.5% versus 22% p<0.01). In the PBE patients with surgical intervention for IBD had higher rates of BID than those without surgery (81% vs 58%, p<0.01). This association between surgery and BID was not observed in the BE (47% vs 34.9%, p=0.168). In the PBE those with BID were significantly more likely to report impaired QoL(97% vs 71%, p<0.01). This association persisted with time with BE patients with BID also having higher rates of QoL impairment (85% vs 45% p<0.01).

Conclusion

Whilst the rate of BID has decreased with modern IBD treatment; it remains highly prevalent and is associated with impaired QoL. Whilst females remain disproportionately affected, the historically observed association between IBD surgery and impaired body image was not demonstrated in the BE. This may reflect improved surgical techniques and biologic down staging prior to surgery. However, body image remains an important Patient Reported Outcome in IBD and warrants further attention.
P782 Ustekinumab in Ulcerative colitis: a real-life effectiveness study across multiple Belgian centers (SULTAN)
Authors: Holvoet T , Truyens M , Reenaers C , Baert F , Vandenbranden S , Cremer A , Pouillon L , Dewint P , Van Moerkercke W , Rahier J F , Vandermeulen L , Van Dongen J , Peeters H , Lambrecht G , Vijverman A , Lobaton T ,   BIRD
Published: January 2023

Background

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon.1 Ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 has shown in the UNIFI trials to be effective and safe in patients with moderate-to-severe UC.2 Real-life data are still limited.3

The aim of this study was to assess the real-world effectiveness and safety of UST in patients with UC across Belgian hospitals.

Methods

In this multicentric, retrospective observational study, patients with UC who received UST from September 2020 onwards were included. Clinical and biochemical response was assessed at baseline, week 8, 16 and 52. The primary endpoint was steroid-free remission defined as partial Mayo score of ≤ 2 with no subscore > 1 at week 16. Secondary endpoints included clinical and biochemical response (defined respectively as a decrease in partial Mayo score ≥ 3 points and ≥ 3 plus a decrease in rectal bleeding score ≥ 1 or an absolute rectal bleeding score ≤ 1 and a decline of 50% or more in CRP and/or fecal calprotectin).

Results

107 patients with moderate-severe UC (86% patients with ≥ S2 severity) were included across 16 participating centers. Median disease duration was 10 years (1-73y) and 69 (64%) of patients had previously failed 2 or more biologicals. At week 16, 35 patients reached the primary endpoint of steroid-free clinical remission (33%), while 67 had a clinical response (62.6%) (Fig 1). There was a statistically significant decline in partial mayo score (median at baseline 6.0 range (1-9); W16 2.0 (0-9, p<.001), CRP (3.85 mg/L (0.4-181) vs 3.15 (0.88-10.3); p<.001) and calprotectin (1040 (13-6000) vs 300 (3.8-2980); p<.001) (Fig 2 and 3). Biochemical response was seen in 41 patients (38%). No predictors for steroid-free remission could be identified.

At the end of follow-up at week 52, 75 patients were still treated with UST (70%). Reasons for discontinuation were primary non-response (N=18 (17%), loss of response (N=8 (7.5%) and adverse events (N=2 (1.9%)). No predictor for UST failure could be identified. Eight patients needed to be referred for colectomy (7.5%). In 7 patients dose optimization via IV reinduction occurred. No difference in occurrence of extra-intestinal manifestations was noted during treatment, severe infections occurred in 1 patient (0.9%). No other new safety signals were observed.

Conclusion

In this multi-centric, real-life cohort with highly refractory UC patients, UST was associated with a clinical response rate of 63% at 16 weeks while steroid-free remission was achieved in 33% of patients. No important new safety signals were observed.
P783 Symptom Improvement of ulceRative colitis after an Injection dose of Ustekinumab in Japanese clinical practice, measured using patient-reported outcomes (SIRIUS) study, Interim Analysis
Authors: Matsuoka K , Katsumasa N , Murata Y , Hisamatsu T ,   SIRIUS study group
Published: January 2023

Background

Ustekinumab (UST) is treated to moderate to severe adult ulcerative colitis (UC) patients. We conducted the SIRIUS study (Symptom Improvement of ulceRative colitis after an Injection dose of UStekinumab in Japanese clinical practice, measured using patient-reported outcomes (PRO)) to record daily symptoms for 8 weeks after the introduction of intravenous ustekinumab in moderate to severe UC patients, which aimed to reveal early response patterns of symptoms during the induction of remission period with ustekinumab, and to explore symptoms suitable for monitoring and predicting treatment effect. This interim analysis focuses on stool frequency (SF) and rectal bleeding (RB) scores in the PRO-2 during the 8-week induction period.

Methods

This single-arm prospective observational study conducted in 23 centers in Japan aimed to recruit 140 patients with moderate-to-severe UC between July 2021 and July 2022. RB score, SF score, abdominal pain, nocturnal diarrhea, tenesmus, and patient perception of improvement were recorded daily using a smartphone app. To be eligible for the study, participants must have a documented diagnosis of UC, be ≥16 years of age, have UC (partial Mayo score of 5~9), have had an inadequate response or intolerance to prior UC therapies, and be able to understand and complete PRO instruments using a smartphone. Patients who had prior exposure to UST, history of extensive colectomy, or were hospitalized when UST was started were excluded.

Results

In this analysis,137 patients were included. Seventy-four (54.4%) patients were male and the median age was 35 years. Seventy-six (55.9%) patients were Bio-naïve. This high proportion of Bio-naïve patients reflects the fact that UST can be used for Bio-naive patients without restrictions in the Japanese health insurance. At weeks 2 and 4, 56 (41.2%) and 57 (41.9%) patients attended outpatient clinics, respectively. The data collection rate of the PROs was 95%. Mean SF and RB scores were demonstrated stratified by prior treatment with Bio (Figure 1&3). Significant decreases in mean SF and RB scores were observed within 1 week in both Bio-naïve and -experienced patients. the time-course change in SF was similar between Bio-naïve and -experienced patients, but the decrease in RB scores was greater in the Bio-naïve patients than the Bio-experienced patients.

Conclusion

A daily PRO-based analysis was conducted in the Sirius study to monitor symptoms during the first 8 weeks after the introduction of UST in patients with moderate-to-severe UC. This interim analysis revealed that SF and RB scores started to decrease within 1 week, demonstrating a rapid symptomatic response to UST. The analysis of the other PROs and predictors of efficacy will be performed in further studies.
P784 Real-world use and 6-month effectiveness of vedolizumab subcutaneous in IBD patients: results of the VEDO-IBD study
Authors: Plachta-Danielzik S , Bokemeyer B , Efken P , Mohl W , Hoffstadt M , Krause T , Schweitzer A , Schnoy E , Ehehalt R , Trentmann L , Teich N , Atreya R , Franzenburg S , Hartmann P , Wenske T , Schreiber S
Published: January 2023

Background

Since April 2020, vedolizumab (VEDO) has been available for use in IBD in intravenous (iv) and subcutaneous (sc) formulations. Due to limited data on real-world use and effectiveness, the objectives of this real-world evidence (RWE), observational, prospective study are to observe (1) the time point of conversion to VEDO sc, (2) the 6-month remission rate with VEDO sc. using data from the VEDOIBD study.

Methods

Between 2017-2020, 1200 consecutively enrolled patients with ulcerative colitis (UC) and Crohn’s disease (CD) were prospectively included in the VEDOIBD study from 45 IBD-experienced centers across Germany. Additionally, 74 VEDO-naïve patients were included with the goal of conversion to VEDO sc after an iv-induction period with VEDO (VEDO iv week 0, 2, 6). Effectiveness was measured by clinical remission (HBI ≤ 4) at month 6.

Results

A total of 180 IBD patients with a running VEDO iv therapy were converted to VEDO sc during the entire study, with at least one 6-month visit from 119 patients (UC: n=67; CD: n=52). Characteristics are shown in Table 1. 87 IBD patients (73.1%) were still receiving VEDO sc after 6 months. 32 IBD patients (26.9%) stopped VEDO sc therapy within the first 6 months. The majority of patients returned to treatment with VEDO iv (37.9%) and the others switched to other biologics: 24.1% ustekinumab, 34.5% anti-TNF (Figure 1). At the time of conversion to sc, 92 patients (77.3%) were in remission (UC: 75%; CD: 84.6%). Of those, 88% remained in remission at 6 months (UC: 89.6%; CD: 86.4%). 45.8% of patients not in remission at the time of conversion to VEDO sc were in remission at 6 months (UC: 50%; CD: 37.5%). Of the 74 patients with planned conversion to VEDO sc, 52 patients (70.3%) received VEDO sc as planned previously: 11.5% within the first 2 weeks, 42.3% after week 6, 19.2% after week 14, and 26.8% after six months or later.

Conclusion

IBD patients with a conversion from VEDO iv to VEDO sc show high effectiveness after 6 months; conversion usually was carried out between 6 and 14 weeks. Based on these data, VEDO sc is shown to be an effective alternative to VEDO iv in RWE and should therefore be considered an important option in treatment planning and discussion with patients.
P785 A retrospective cohort study on vedolizumab trough levels in Crohn’s disease patients
Authors: Pokryszka J , Stadlmann M , Primas C , Gerold N , Reinisch S , Novacek G , Reinisch W
Published: January 2023

Background

Background: Vedolizumab (VDZ), an α47-integrin inhibitor, is approved for the treatment of moderate to severe Crohn’s disease (CD). Exposure-response relationship for VDZ is less evident in CD. Here, we are exploring associations between serum VDZ serum concentrations and clinical/biomarker-defined endpoints from a single center, real-world cohort.

Methods

Methods: Electronic health data records of CD patients during their first year of treatment with VDZ from January 2014 – July 2022 at our tertiary care center were obtained. Serum drug levels (TDL) and their correlation with outcomes were assessed at specified timepoints – weeks 12 (± 2), 26 (± 4) and 52 (± 6). Clinical remission was assessed by patient reported outcomes as suggested in STRIDE II guidelines (stool frequency ≤ 3 and abdominal pain ≤ 1). Fecal calprotectin (fCP) values ≤ 150 µg/g marked biomarker remission. Vedolizumab drug levels were measured with IDKmonitor Vedolizumab drug level ELISA kit (Immundiagnostik AG, Germany), In case of missing data patients were categorized as non-responders. For association modelling, multivariable fractional polynomials and generalised additive models were used (R statistical software, v4.1.2; R Core Team).

Results

Results: In total, 58 patients (females = 55.2%) with at least two available data points were included (Table 1). Sixteen individuals (16/58, 27.6%) were naive for biologics therapies. 98.3% (57/58) reached week 12 (± 2). Both at weeks 26 and 52 91.4% (53/58) subjects still were on drug. Clinical remission was achieved in 51.7% (30/58), 49.1% (26/53) and 45.2% (24/53) cases at weeks 12, 26 and 52, respectively, with biomarker remission rates of 24.1% (14/58), 35.8% (19/53) and 27.6% (16/53) patients reached biomarker remission. TDLs differed only between clinical remitters and non-remitters at week 26 (Mann-Whitney-U-test, p = 0.04). Also, there was no significant association between clinical and biomarker remission at defined timepoints and corresponding TDLs (for all p > 0.05). TDLs at week 2 and 6 were correlated with fCP values at the same time (rho: -0.327, p = 0.03 at week 2 and rho: -0.356, p = 0.02 at week 6). When TDLs at week 2 and week 6 were taken into consideration and associated separately with therapy outcomes in a univariate regression, only association between serum levels at week 6 and biomarker remission at weeks 26 and 52 was found (p = 0.02 and p = 0.03, respectively).

Conclusion

Conclusion: The only association between serum drug levels and remission was found between TDLs at week 6 and biomarker remission at weeks 26 and 52 suggesting a complex exposure-response relation for vedolizumab in CD patients.
P787 Subcutaneous infliximab in IBD patients with previous immunogenic failure of intravenous infliximab
Authors: Husman J , Matthes K , Gilger M , Arsova M , Schmidt A , Hampe J , Zeißig S , Schmelz R
Published: January 2023

Background

The immunogenicity of infliximab (IFX) is a major reason for secondary loss of response to intravenous (IV) IFX treatment. A lower incidence of anti-drug antibodies (ADA) with subcutaneous (SC) IFX treatment compared to IFX IV has been described1,2. Furthermore, data on four patients with immunogenic failure or allergic reactions to IFX IV documented safety of exposure to IFX SC3. Here, we analyzed the efficacy and safety of IFX SC in IBD patients with previous immunogenic/allergic failure to IFX IV in a monocentric analysis conducted at the Dresden University Hospital.

Methods

Immunogenic failure was defined as presence of ADA and low/undetectable IFX trough levels during IFX IV therapy. Patients received IFX SC 120 mg every other week (EOW). HBI and partial Mayo, IFX trough levels, free ADA, and fecal calprotectin (FCP) were determined at wk 0 and wk 12. Clinical remission was defined as HBI<5 or partial Mayo≤1. FCP<250ug/g was considered biochemical remission.

Results

Ten patients (7/10 with active IBD and 3/10 in remission) were included. All patients had previously developed ADA during IFX IV treatment. Two patients had suffered an IFX infusion-related allergic reaction. Baseline demographic parameters are shown in table 1. Patients were extensively pretreated (5/10 had previous treatment with ≥3 biologics). 5/10 patients were switched from ongoing IV application to IFX SC, while 5/10 were started on IFX SC without IFX IV induction. During follow up, 6/10 patients did not reach IFX trough levels≥3ug/ml, of whom four patients showed detectable ADA. 2/10 patients developed mild injection site reactions. No severe immediate hypersensitivity reactions were observed. Treatment persistence across wk 12 was 70% (7/10), while 3/10 patients discontinued IFX SC due to lack of efficacy. In the active IBD group, clinical remission at wk 12 was achieved in 1/7 patients. 2/7 patients showed a decrease in FCP from baseline to wk 12. Among the three patients who entered the study in remission, all maintained clinical and biochemical remission until wk 12 (3/3).

Conclusion

In this cohort, exposure of patients with previous immunogenic/allergic failure of IFX IV was well tolerated and safe. However, only a minority of patients established significant IFX through levels with EOW IFX SC therapy and clinical responses were heterogeneous. Further studies are required to assess the safety and efficacy of IFX SC in patients with previous immunogenic IFX failure and to investigate the value of dose intensification and/or interval shortening of IFX SC in this patient population.

References:

1 Smith et al, J Crohn Colitis, 2022

2 Schreiber et al, Gastroenterol, 2021

3 Caron et al, Aliment Pharmacol Ther, 2022