bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;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

Abstract

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

Abstract

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 (&lt;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&lt;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&lt;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 &gt;3mm at 12 months occurred more often in non-responders than responders (P&lt;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&lt;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&gt;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

Abstract

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. &gt;60 years of age], gender, comedications at the time of the trial [none, ≤2, ≥3], comorbidities [none, 1-2, 3-5, &gt;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 &lt;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 &lt; 0.001; week 38: Spearman rho=0.512, P-value &lt; 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

Abstract

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&gt;5 for CD e p-Mayo&gt;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

Abstract

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&lt;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&lt;0.01), and BE (50.5% versus 22% p&lt;0.01). In the PBE patients with surgical intervention for IBD had higher rates of BID than those without surgery (81% vs 58%, p&lt;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&lt;0.01). This association persisted with time with BE patients with BID also having higher rates of QoL impairment (85% vs 45% p&lt;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

Abstract

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 &gt; 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&lt;.001), CRP (3.85 mg/L (0.4-181) vs 3.15 (0.88-10.3); p&lt;.001) and calprotectin (1040 (13-6000) vs 300 (3.8-2980); p&lt;.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

Abstract

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.