bluuebunny/crossref_metadata_2025_split huggingface dataset:
P579 Real-world comparison of effectiveness between tofacitinib and ustekinumab in patients with ulcerative colitis exposed to at least one anti-TNF agent: results from the TORUS study
Authors: Buisson A , Serrero M , Altwegg R , Guilmoteau T , Bouguen G , Nachury M , Amiot A , Vuitton L , Treton X , Caillo L , Pereira B , Fumery M 
Published: January 2023

Abstract

Background
We aimed to compare the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent.

Methods
In this multicenter study, we retrospectively included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) &gt; 2, having who started tofacitinib or ustekinumab between January 2019 and June 2022.
The primary endpoint was steroid-free clinical remission (pMS ≤ 2) (CFREM) at week 16 (W16).
Secondary endpoints were endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and histological remission (CFREM + MES ≤ 1 + Nancy index ≤ 1).
Comparisons were performed using propensity score analyses adjusted on potential confounders.

Results
Overall, 289 patients were included (tofacitinib = 124 patients, ustekinumab = 165 patients). The groups were comparable (tofacitinib vs vedolizumab) for male gender (50.8% vs 43.3%), mean age (40.7 vs 42.9 years), median UC duration (8.6 vs 9.3 years), concomitant use of 5-ASA (13.7% vs 9.7%), steroids (25.0% vs 29.7%), immunosuppressants (7.3% vs 5.5%), and ≥ 2 prior biologics (85.5% vs 82.4%). Tofacitinib group had more pancolitis (55.6% vs 42.4%, p = 0.026) and UC with pMS &gt; 6 (64.5% vs 50.3%, p = 0.016). In our study, 42.1 % of the patients treated with tofacitinib continued using a dose of 10 mgx2/day until W16 while 47.3% of the patients on ustekinumab required dose escalation to 90 mg/4 weeks before W16.
After propensity score analysis, the rate of CFREM at W16 was 37.8% and 35.6% in the tofacitinib and ustekinumab arms, respectively arm (p=0.75). CFREM at W16 was achieved in 43.3% vs 57.1% (p = 0.48) after failure of one biologic, 20.7% vs 37.9% (p=0.16) two biologics and 46.7% vs 23.2% (p=0.047) or ≥ 3 biologics, in tofacitinib and vedolizumab arms, respectively. After primary failure to at least one biologic, the rate of CFREM at W16 was 46.3% on tofacitinib vs 25.9% on ustekinumab (p = 0.13). CFREM at W16 was similar with tofacitinib and ustekinumab in case of more severe UC such as pMS ≥ 6 (40.6% vs 41.5%) and CRP &gt; 30 (27.2% vs 33.0%).
No predictor of tofacitinib effectiveness has been identified. Factors associated with no CFREM at W16 on ustekinumab were male gender (p=0.035), ≥ 3 prior biologics (p=0.013), prior use of tofacitinib (p=0.03), primary failure to at least one biologic (p=0.013).
Endoscopic remission was achieved in 17.0% vs 11.7% (p =0.47) and histological remission in 4.4% vs 7.8% (p=0.32) of the patients treated with tofacitinib and ustekinumab, respectively.

Conclusion
Tofacitinib and ustekinumab have similar effectiveness in UC after anti-TNF failure.
However, the efficacy of ustekinumab could be more impacted by prior therapeutic failures.
P589 Effectiveness of partial enteral nutrition to treat adults with Crohn's Disease who lost response to biological therapy
Authors: Nardone O M , Calabrese G , Alfonsi L , Rispo A , La Mantia A , Fierro G , Ferrante M , Testa A , Guarino A D , D'Alessandro E , Pasanisi F , Castiglione F 
Published: January 2023

Abstract

Background
Partial enteral nutrition (PEN) is a consolidated treatment in children with active Crohn’s disease (CD). However, the benefit of PEN is not well-established for adults with CD. Based on the assumption that diet could aid in treating active disease, we aimed to assess the effectiveness of PEN in combination with biological therapy on transmural response/remission and selected clinical outcomes in adults with CD who lost response to biologics

Methods
We performed a single-centre retrospective observational study by including patients who received PEN due to loss of response to biologics. The primary endpoint was the rate of transmural response/remission at 6 months. We defined transmural remission as a bowel wall thickness ≤3 mm, while transmural response as a decrease in BWT≥25%. Secondary endpoints included clinical remission, defined as Harvey Bradshaw Index&lt;5, and selected clinical outcomes such as surgery, hospitalisations, and change of therapy, including switch and dose/interval escalation at 6 months. Patients were considered adherent when they completed PEN for 6-8 weeks as required for induction of remission, whereas not adherent when they stopped it or if they did not tolerate.

Results
A total of 42 patients,25 males (59,5%) with mean age of 36,1 ±15,6 yo and a mean duration of disease of 138,0 ±113,1 months were enrolled [Table 1].

Overall, 14 patients completed PEN at 8 weeks, with a rate of adherence of 33,3%. Whilst 16(38.1%) patients stopped the treatment for intolerance and maintained only biological therapy and 12(28.6%) underwent surgery before 6 months follow-up.At 6 months, patients treated with PEN in combination with biologic had a transmural response of 64,9% compared to 25% treated only with biologics (p=0.03). In both groups, no patients achieved transmural remission. Nevertheless, clinical remission was obtained in 9 (64,3%) patients treated with PEN + biologic compared to 4 (25%) with biologic (p=0.03). Overall,3 patients (18.7%) underwent surgery, all of them were intolerant to PEN. Patients who interrupted PEN and maintained biologics had a higher rate 56,2% of dose escalation/interval and 68,7% changed therapy at six months compared to 7,1% and 14,2% respectively treated with PEN+biologic (p&lt;0.05) [Table 2].At multivariate analysis multiple treatment failures were associated with adherence to PEN (OR=1,583; CI=1,06-2,36; p&lt;0.05).

Conclusion
For patients who lost response to biological therapy, the combination with PEN was associated with transmural response and clinical remission. Multiple failures to biologics were associated with adherence to PEN. Hence, the use of PEN dietary should be considered in difficult-to-treat patients
P612 Lack of seroconversion following COVID-19 vaccination, but not treatment, is an independent risk factor for breakthrough SARS-CoV-2 infection in patients with inflammatory bowel disease: data from ESCAPE - an IG-IBD Study
Authors: Macaluso F S , Principi M , Facciotti F , Contaldo A , Todeschini A , Bezzio C , Saibeni S , Castiglione F , Nardone O M , Spagnuolo R , Fantini M C , Riguccio G , Conforti F S , Caprioli F A , Viganò C , Felice C , Fiorino G , Correale C , Bodini G , Milla M , Scardino G , Vernero M , Desideri F , Bossa F , Guerra M , Ventimiglia M , Mannino M , Rizzo G , Orlando A ,   Italian Group for the study of Inflammatory Bowel Disease (IG-IBD)
Published: January 2023

Abstract

Background
As patients with immune conditions were excluded from COVID-19 vaccine clinical trials, it is important to accumulate real-world data in this setting, particularly to identify those who would benefit from repeated doses.

Methods
Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE) is a prospective, multicentre, observational study assessing effectiveness and safety of COVID-19 vaccines in patients with IBD (ClinicalTrials.gov ID: NCT04769258). Here we present data on the rate of breakthrough SARS-CoV-2 infections in the timeframe between 14 days after the second dose and the third dose of COVID-19 vaccine (or a maximum of 9 months from the second dose). The risk factors for SARS-CoV-2 infection, including lack of seroconversion (cut-off for IgG anti-SARS-CoV-2: OD 0.28) and IgG anti-SARS-CoV-2 levels after 8 weeks from the second dose, and treatment for IBD, were assessed.

Results
Out of the 1076 patients with IBD enrolled in the ESCAPE study, data on breakthrough SARS-CoV-2 infection were available in 953 cases. Most of the patients received homologous, double-dose mRNA-based vaccines (BNT162b2 or mRNA-1273: 99.2%). Seroconversion was reported in 92.7% of cases (median OD 1.60 [IQR 0.8-3.6]), while SARS-CoV-2 infection was documented in 95 patients (10.0%), of whom 9 died. At multivariable regression analyses, age (OR 0.97, 95% CI 0.96-0.99; p&lt;0.001) being former smoker (OR 2.23, 95% CI 1.26-3.88; p=0.005), and lack of seroconversion (OR 0.42, 95% CI 0.20-0.99; p=0.034) were independent predictors of SARS-CoV-2 infection. Conversely, none of the treatments for IBD was associated with breakthrough SARS-CoV-2 infection. Notably, all 9 patients who died had reported seroconversion after the second dose.

Conclusion
IBD patients without seroconversion after COVID-19 vaccines are at increased risk for SARS-CoV-2 infection, while medications for IBD had no impac
P667 USTEkinumAb Double intravenous loading induction therapY at week 0,4 in patients with Crohn’s Disease– results from STEADY study
Authors: Chin A , Jeffrey A , Teh W L , Menon S , So K , Venugopal K , Picardo S 
Published: January 2023

Abstract

Background
Ustekinumab (UST) is a safe and effective therapy for moderate to severe Crohn’s disease (CD). Standard induction therapy involves a single weight-based intravenous dose followed by a subcutaneous dose at week eight. Accelerated or dose intensified induction regimens have been associated with better clinical outcomes for various biologic therapies, however, these have not been investigated in patients commencing UST. UST re-induction has been shown to be effective in recovering response in patients who have previously lost clinical response. We aim to compare clinical outcomes in a group of CD patients who received standard intravenous induction (SII) of UST compared to double intravenous induction (DII).

Methods
A retrospective observational cohort study of all patients that commenced UST, aged ≥ 18 from a single tertiary inflammatory bowel disease (IBD) centre. Patients received either standard IV dosing or double IV dosing (IV dose at week 0 and 4) based on the discretion of the treating physician. Data was collected from a prospectively maintained database between the period October 2015 to October 2022. The primary outcome was clinical remission, defined as Harvey Bradshaw Index (HBI) &lt;5 with scores collected at baseline and at week 52. Patients that discontinued therapy due to a lack or loss of response or progressed to require surgery were considered treatment failures. Two sample t-test was used for comparisons between groups for continuous variable and chi-square for categorical variables.

Results
47 patients were included of which 38 received SII and 9 had DII. There were no significant differences in baseline HBI or previous biologic exposures between groups (Table 1). All 9 patients that received DII were in clinical remission at week 52 compared to 29 out of the 38 that received SII, however, this was not clinically significant (Figure 1; 100% vs 76%, p=0.10). Of the 9 patients, not in clinical remission in the SII group, 5 were due to treatment failures (3 required surgery, 2 switched medical therapy) with the other 4 remaining on UST till week 52 (1 had a clinical response and 3 had no clinical response). There were no safety concerns (serious infections or malignancy) reported in the DII group.

Conclusion
● All Crohn’s patients that commenced double intravenous induction were in clinical remission at week 52.
● A higher proportion of patients that received DII vs SII were in clinical remission at week 52, however this was not statistically significant. Further larger studies and studies with longer duration of follow-up are required to determine a clinical difference.
● Double intravenous induction of UST is a safe and effective option for Crohn’s disease.
P670 “What Matters To You?” – How do patient views compare with a patient experience framework and UK national standards of care?
Authors: Sheldon E , Roman S , Randall K , Rachel H , Winsor G , Wakeman R , Lobo A 
Published: January 2023

Abstract

Background
There is increasing focus on the organisation of services for people with IBD. Patient experience of care is an important consideration in service delivery. The United Kingdom NHS Long Term Plan indicates the importance of support that is more differentiated for individuals, with more personalised care when needed, which starts with the question ‘What matters to you?”. This is particularly important for people with inflammatory bowel disease (IBD).

Methods
The aim was to identify ‘What matters to you?’ for people attending a single UK teaching centre IBD service and to relate it to patient experience and national standards of care. Invitations to take part in the AWARE-IBD quality improvement programme were sent to 4082 patients receiving IBD care at a single UK teaching centre in 2 rounds (October 2021 and May 2022). Invitation letters included an anonymous open-ended questionnaire asking patients “what matters to you?”. Responses were extracted as qualitative data and coded using two frameworks: Patient experience domains (Bull et al) (Communication, Patient-centred Care, Quality, Integration, Involvement, Accessibility, Environment and Facilities, Discomfort) and national IBD UK Standards. Frequencies for each coding strategy were calculated to determine the most important patient experience domains and IBD UK standards.

Results
Responses were received from 408 and 205 patients from each recruitment round (n=613). Figure 1 displays frequencies for each patient experience domain. Accessibility (47.5% and 53.2% respectively), Communication (19.6% and 12.7%) and Patient-Centred Care (15.7% and 11.2%) were expressed most frequently. Sub-themes included access to and contact with IBD nurse specialists, timely and accessible appointments and regular contact with a specialist IBD health care professional (HCP). Responses were coded to IBD UK standards, where possible (Table 1). Responses most frequently coded to statements relating to shared decision making, having a personalised care plan, access to an IBD nurse specialist including helpline and regular clinical review. 77 responses could not be coded to an IBD UK standard.

Conclusion
Access to the IBD service when needed matters most to patients with good communication of information and personalised, patient-centred care. Service organisation should therefore reflect these facets of patient experience and defined standards. Patient views that are not currently represented in published standards should be considered in future iterations. This study also highlights personalised written care plans and improved access to the IBD Nurse Advice line.
P671 Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: Results from the UniStar study long-term extension
Authors: Turner D , Rosh J R , Cohen S A , Griffiths A , Hyams J S , Kierkuś J , Adedokun O J , Strauss R , Kim L , Volger S ,   UniStar Investigators
Published: January 2023

Abstract

Background
Ustekinumab (UST) is an approved biologic for the treatment of adults with Crohn’s disease (CD). Through 16 weeks (wks), UST demonstrated high rates of efficacy, low rates of immunogenicity, and safety in paediatric patients (pts) similar to that observed in adults.1 Here, we evaluated UST in paediatric CD pts through 268 wks.

Methods
UniStar was a phase 1, multicentre, double-blind study in paediatric pts (2-18 years old; body weight ≥10kg) with moderately to severely active CD. Pts (n=45) were randomised 1:1 and stratified by body weight (&lt;40kg or ≥40kg) to low (3 mg/kg [&lt;40kg]; 130 mg [≥40kg]) or high (9 mg/kg [&lt;40kg]; 390 mg [≥40kg]) dose intravenous UST. At wk 8, pts received 1 subcutaneous maintenance dose (2 mg/kg [&lt;40kg]; 90 mg [≥40kg]). Pts responding to UST at wk 16 were eligible to enter the long-term extension (LTE) and continued UST maintenance dosing every 8 wks up to wk 268. This study reports efficacy, safety, pharmacokinetics (PK), and immunogenicity evaluated at wks 16, 24, 48, 224, and through 240 wks, as applicable. The primary visit was wk 48, representing outcomes after ~1 year of UST treatment.

Results
Of the 44 pts treated with UST, 34 (77%) responded and entered the LTE; the number of pts receiving treatment at wks 48, 104, 152, and 208 was 26 (77%), 16 (47%), 12 (35%), and 8 (24%), respectively. Among pts in the LTE (n=34), baseline median age (range) was 13.0 (6.0-17.0) years, 62% were female, 47% weighed &lt;40kg, 18% weighed &lt;30kg, and 94% previously failed anti-tumor necrosis factor therapy. At wk 48, 41% (14/34) of pts achieved clinical remission, and 59% (20/34) achieved clinical response. The proportion of pts with abnormal C-reactive protein (CRP) levels at baseline was 71% (24/34), and 59% (16/27) of pts achieved normalization of CRP (&lt;3mg/L) at wk 48. By the final safety visit at wk 240, 91% of pts reported ≥1 adverse event (AE), and 15% discontinued due to AEs, with CD worsening as the most frequent reason. Infections occurred in 74% of pts, and 32% had serious AEs. The majority of serious AEs were gastrointestinal disorders associated with CD. No injection-site reactions, serious infections, malignancies, or deaths were reported. Median serum UST concentrations tended to be lower in pts weighing &lt;40kg compared with pts weighing ≥40kg, but were generally consistent from wks 16 to 268 and remained detectable through wk 200 (Figure). Incidence of UST antibodies was low (1/34; 3%).

Conclusion
In the UniStar LTE, the efficacy, safety, PK, and immunogenicity of UST in paediatric pts with CD was generally consistent with adult pts for as long as 4 years of treatment.
Reference:
1. Rosh JR et al. J Crohns Colitis. 2021;15(11):1931.
P687 Durability of recaptured response to ozanimod during the True North open-label extension
Authors: Dignass A , Regueiro M , Colombel J F , Jain A , Canavan J B , Wu H , Lawlor G , Osterman M T , Vermeire S , Rubin D T 
Published: January 2023

Abstract

Background
Ozanimod is approved in the EU, US, and other countries for treatment of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3 True North (TN) study, ozanimod 0.92 mg once daily demonstrated efficacy and safety for up to 52 weeks in patients (pts) with moderately to severely active UC. This open-label extension (OLE) analysis evaluated the long-term durability of ozanimod based on symptomatic and clinical endpoints in pts who experienced disease relapse while on placebo during the TN maintenance period (MP) and then recaptured response to ozanimod during the OLE.

Methods
Responders to ozanimod 10-week induction therapy were rerandomised 1:1 to ozanimod (n=230) or placebo (n=227); this OLE interim analysis (data cutoff: January 10, 2022, at which point the OLE Week 94 disposition was available for pts) included all pts who relapsed on placebo during the MP and reinitiated ozanimod in the OLE. Endpoints included symptomatic response and remission, clinical response and clinical remission (which include endoscopy subscores), and corticosteroid (CS)-free remission (clinical remission while off CS for ≥12 weeks) evaluated using observed case (OC) and nonresponder imputation (NRI) analyses, and mean total Mayo score over time.

Results
A total of 77/227 pts (34%) rerandomised to placebo during MP experienced a relapse after a median of 12.7 weeks and all entered the OLE. Symptomatic response was achieved by 46/73 (63%) pts 5 weeks after restarting ozanimod in the OLE (NRI analysis: 60% at OLE Week 5) and in 32/33 (97%) by OLE Week 94 in the OC analysis. Symptomatic remission was also achieved by OLE Week 5 by 24/73 (33%) pts. Sustained efficacy of ozanimod reinitiation was also demonstrated comparing OLE Weeks 46 and 94 across clinical endpoints by OC analysis (clinical response, 76% and 86%; clinical remission, 44% and 59%; CS-free remission, 37% and 52%) and NRI analysis (clinical response, 42% and 31%; clinical remission, 25% and 22%; CS-free remission, 21% and 20%) (Figure 1). In addition, 56.3%, 52.6%, and 50% of pts who experienced clinical response, clinical remission, and CS-free remission, respectively, at OLE Week 46 continued to sustain these endpoints at OLE Week 94. Reductions in mean total Mayo score at OLE Week 46 were also sustained through OLE Week 94 (Figure 2).

Conclusion
Response to ozanimod was regained after temporary therapy discontinuation for most pts, and this response was durable for up to 2 years as demonstrated by both symptomatic and clinical endpoints in this interim analysis from the TN OLE study. These results suggest that pts who experienced disease relapse after temporarily holding ozanimod in clinical practice may benefit from resumption of ozanimod.
P694 Long-term monitoring of post-surgical recurrence in Crohn’s disease using a strategy based on the periodic determination of fecal calprotectin in patients without early postoperative recurrence
Authors: Mañosa Ciria M , Oller B , Garcia-Planella E , Guardiola J , Cañete F , Gonzalez Muñoza C , Camps B , Calafat M , Domènech E 
Published: January 2023

Abstract

Background
Current guidelines recommend to perform an ileocolonoscopy 6-12 months after surgery in patients with Crohn’s disease (CD) and ileo-cecal resection with ileocolic anastomosis to assess the occurrence of endoscopic post-operative recurrence (PORe) and escalate therapy if necessary. However, it is not established whether and/or when endoscopic monitoring is advised in patients who do not present early PORe

Objective
To evaluate the usefulness of a strategy based on the periodic determination of faecal calprotectin (FC) to decide whether to carry out a new endoscopic control in patients without PORe (iR&lt;2) in the last endoscopic assessment performed

Methods
Pilot, prospective, multicentre and open study. Inclusion criteria: 1) CD with intestinal resection and ileo-colic anastomosis; 2) last ileocolonoscopy after surgery with a Rutgeerts score i0 or i1; 3) No suspicion of clinical POR. Patients with an ostomy or chronic use of NSAIDs or omeprazole were excluded. Centralized FC determinations were performed every 4 months for 2 years and an ileocolonoscopy at the end of follow-up was performed. In the case of FC&gt;250μg/g in 2 consecutive determinations, ileocolonoscopy was advanced and the patient was withdrawn from the study. The main variable of interest was the rate of advanced PORe (as defined by Rutgeerts score &gt;i2) at the final ileocolonoscopy.

Results
55 patients were included, 13% perianal disease, 24% smokers and 27% surgery prior to the index surgery. 47% followed prevention with thiopurines and 14% with anti-TNF. During follow-up, 7 patients had FC&gt;250μg/g in two consecutive determinations; advanced PORe was identified in 5 of these patients, PORe i2 in one and intestinal adenocarcinoma in another one. Among the patients who completed the 2-year follow-up, none had advanced PORe at the final ileocolonoscopy although intermediate PORe (i2) was found in 12. The rate of advanced PORe was 71% in those who finished the study before 2 years and 0% in those who were not advanced to endoscopy. The AUC for FC to detect advanced PORe was 0.98 (p=0.002). The cut-off point of FC&gt;250μg/g obtained a sensitivity of 100% and specificity of 60% to detect advanced PORe.

Conclusion
The serial determination of FC is a suitable long-term monitoring tool to decide whether to perform ileocolonoscopy in patients without early PORe.