bluuebunny/crossref_metadata_2025_split huggingface dataset:
P628 Tofacitinib in pediatric ulcerative colitis: a retrospective multi-center experience from the Paediatric IBD Porto group of ESPGHAN
Authors: Ledder O , Dubinsky M , Dolinger M , Fatima A , Suskind D , Scarlett J , Röeser D , Shouval D , Meyer G , Molle Rios Z , Pujol G , Lozano A , Kolho K L , Rohani P , Hussey S , de Mejj T , Ayers T , Navas López V M , Turner D , Tzivinikos C , Stein R , Savla , S 
Published: January 2023

Abstract

Background
Tofacitinib, a Janus kinase (JAK) inhibitor, has recently been approved for treatment of moderate to severe active ulcerative colitis (UC) in adults. Data on efficacy and safety in pediatrics are limited. In this multicenter study from the Paediatric IBD Porto group of ESPGHAN, we describe the short-term effectiveness and safety of tofacitinib in an international pediatric IBD cohort.

Methods
Retrospective review of children (2-18 years) diagnosed with UC treated with tofacitinib from 15 pediatric centers internationally. Primary outcome was corticosteroid-free clinical remission (PUCAI&lt;10) at week 8, with secondary outcomes including clinical response (≥20 point decrease in PUCAI), colectomy rate and safety. Primary outcome was calculated utilizing non-response imputation (NRI), whereby drug cessation for any reason was considered treatment failure.

Results
78 patients (43 (55%) female, mean age at diagnosis 12.5 (±2.7) years, median disease duration 20 months (IQR 10.3-38.8)), all with previous biologic failure, including 20/78 (26%) with previous failure of three biologic classes.
15/78 (19%) patients achieved corticosteroid-free clinical remission at week 8 with a further 18/78 (23%) demonstrating clinical response. 9/78 (12%) underwent colectomy by week 8, and 21/78 (27%) by week 24. Twelve adverse events were reported including five infective (three of which deemed possibly related to treatment – zoster, HSV-2 cheilitis and septic arthritis), one case of pancreatitis, and abnormal blood test results in 5 children (anemia, lymphopenia, elevated hepatic transaminases and hypercholesterolemia).

Conclusion
In this largest real-life cohort of tofacitinib in pediatric UC to date, tofacitinib seemed effective in at least 19% of highly refractory patients by week 8. Adverse reactions and safety were largely consistent with adult data.
P635 Risankizumab - real world Israeli data in severe refractory IBD patients
Authors: Bar-Gil Shitrit A , Gil Y , Israeli E , Koslowsky B , Mazuz B , Israel I , Goldenberg R , Ben-Bassat O , Weisbrud A , Ledder O , Zinger A , Ben Horin S , Goldin E , Lahat A 
Published: January 2023

Abstract

Background
The landscape of inflammatory bowel disease (IBD) treatment is rapidly expanding with the development of new therapeutic options. Risankizumab (Skyrizi®), a humanised IgG monoclonal antibody that targets the p19 subunit of IL-23, was developed for the treatment of immunological and inflammatory disorders, and recently began to be investigated also in the field of IBD. Most patients who receive Risankizumab do so as part of clinical trials, but there are a number of patients with severe refractory disease who have received it as a compassion treatment and they present preliminary Real-World data for this drug.

Aim
to present the real-world data of patients with severe refractory IBD who received Risankizumab as a compassion treatment.

Methods
Retrospective Israeli multicenter study from 6 tertiary IBD centers (Shaare Zedek medical center, Wolfson, Ichilov, Hadassah , Sheba and Barzilai ) on 21 patients with severe refractory IBD (18 CD, 3 UC) who received Risankizumab (IV 600 mg at 0, 4, 8 weeks; then SC 180 or 360 mg SC every 8 weeks) as compassionate treatment with a median follow up of 30 weeks (4-52 weeks).

Results
Although some of the clinical and laboratory parameters are still being collected, we can present some trends. 21 patients were included in the analysis. 17 /21 were after ustekinumab failure. At week 12, there was a significant reduction in Harvey-Bradshaw index (HBI) for Crohn's disease, in CRP values and Calprotectin as compared with the baseline data (10.13 to 4.82, p=0.03; 4.16 to 1.62, p=0.004; 3758 to 961, p=0.02, Respectively). In addition, there was a reduction in the percentage of steroids dependent patients (0.44 to 0.14, p=0.07). In the margins of the study, it is worth noting that particularly patients with difficult and resistant disease, who were TPN dependent or on the verge of surgery, as a result of treatment were weaned from TPN or were able to avoid surgery.

Conclusion
According to real-world data, Risankizumab holds a great therapeutic promise even for patients with particularly serious and resistant diseases.
P636 Real-world clinical effectiveness and safety of vedolizumab and ustekinumab in biologic-naïve patients with Crohn’s disease: Results from the EVOLVE Expansion study
Authors: Ferrante M , Christensen B , Bressler B , Brett N , Bassel M , Kamble P , Adsul S , Gianchetti L , Scharl M 
Published: January 2023

Abstract

Background
This study evaluated real-world clinical effectiveness and safety of vedolizumab (VDZ), a gut-selective α4β7-integrin inhibitor and ustekinumab (UST), an IL-12/23 p40 inhibitor, as first-line biologic treatment (Tx) for patients (pts) with Crohn’s disease (CD).

Methods
The EVOLVE Expansion study (NCT05056441) was a multicenter, observational, retrospective cohort study in biologic-naïve pts with CD (≥18 years old) who initiated VDZ or UST Tx in Australia, Belgium or Switzerland from 2016 to 2021. Data were collected from Tx initiation to initiation of chart abstraction, death or loss to follow-up, whichever came first. The time to event analysis was conducted using the Kaplan-Meier method and cumulative rates of clinical response, remission, mucosal healing and Tx persistence were estimated over 12, 24 and 36 months. Serious adverse events (SAEs), serious infections (SIs), CD exacerbations and CD-related surgeries were also evaluated. Inverse probability of treatment weighing was used to balance demographic and clinical characteristics across treatment groups.

Results
623 biologic-naïve pts with CD (VDZ 347, UST 276) from 31 sites were included. Baseline characteristics are presented in Table 1. Cumulative rates over 36 months were similar between VDZ- and UST-treated pts for clinical response (VDZ 82.0%, UST 84.1%; p=0.87) and clinical remission (VDZ 88.3%, UST 88.5%; p=0.67) (Table 2). Mucosal healing rates were significantly higher in VDZ- versus UST-treated pts (VDZ 91.3%, UST 87.4%, p=0.02), and treatment persistence was higher in UST-treated pts over 36 months (VDZ 70.6%, UST 80.3%; p=0.03). In VDZ cohort, 54 SAEs (including SIs) and 12 SIs occurred in 35/347 (10.1%) and 9/347 (2.6%) pts, respectively, while in UST cohort, 53 SAEs (including SIs) and 5 SIs occurred in 27/276 (9.8%) and 2/276 (0.7%) pts, respectively. There were no significant differences in the risk of CD exacerbations (HR 1.01; 95% CI, 0.68-1.49; p=0.98) and CD-related surgeries (HR 1.80; 95% CI, 0.69-4.73; p=0.23) between VDZ- and UST-treated pts.

Conclusion
In real-world setting, clinical response and clinical remission were similar between VDZ and UST in biologic-naïve pts with CD. However, over 36 months mucosal healing was higher in the VDZ-treated pts, and Tx persistence was higher in UST-treated pts.
P647 Outcomes following the use of vedolizumab first line versus second line in Ulcerative Colitis: a single centre experience
Authors: Almas S , Al-Talib I , Rahman C , Ansari M , Jones J , Slater J , King D , De Silva S 
Published: January 2023

Abstract

Background
With the introduction of an increasing number of biological therapies for Ulcerative Colitis (UC), decisions regarding the sequencing of treatment continues to dominate current management strategies. In this single centre study, we assessed outcomes in patients with UC following first line treatment with the α4β7 integrin blocker vedolizumab (VDZ) therapy vs second line VDZ therapy following anti-Tumour Necrosis Factor (anti-TNF) exposure.

Methods
All patients exposed to VDZ either first line or second line were identified via our Inflammatory Bowel Disease (IBD) registry. Data was collected retrospectively between June 2015 and June 2021. Baseline demographics, disease extent and activity scores, treatment continuation, and colectomy rates were analysed over a 52-week period.

Results
A total of 100 patients were included in the study, age (median [IQR]) 52 [37-64] years; 52% male 48% female). VDZ as first line biologic included 38 patients, age (median [IQR]) 51 [34-65] years; 50% male and 50% female). The VDZ as second line (Ant-TNF exposed) group included 62 patients, age (median [IQR]) 52 [38-61] years; 53% male and 47% female). The Anti-TNF exposed group included infliximab 26 (43.3%), adalimumab 22 (35.5%), golimumab 12 (19.2%) and both infliximab and adalimumab 2 (3%).
Disease extent (Montreal classification: E1:proctitis, E2: left-sided or E3: extensive disease) in the VDZ first line group (E1 (13.1%), E2 (61.6%) and E3 (26.3%)) versus VDZ second line (E1 (11.3%), E2 (61.3%) and E3 (27.4%)).
In the VDZ first line group (38 cases), the outcomes at 52 weeks were: Treatment continuation 24 (63%), colectomy 2 (5%) and treatment switch in 12 (32%) to infliximab (4), Adalimumab (3), Ustekinumab (4) and Tofacitinib (1).
In comparison, the Anti-TNF exposed group (62 cases) outcomes at 52 weeks were: Treatment continuation 46 (74%), colectomy 5 (8%) and treatment switch in 11 (18%) to Adalimumab (2), Ustekinumab (4) and Tofacitinib (5).
A total of 7 of patients underwent colectomy during the 52 week follow up period. By 52 weeks, 94.8% (36/38) were colectomy free in the VDZ first line group versus 92% (57/62) in the anti-TNF exposed group, which was not statistically significant (odds ratio (OR) of having a colectomy in the VDZ1st line group vs the VDZ 2nd line group was 0.61(p=0.58)).

Conclusion
Our study evaluated real-world treatment continuation and colectomy-free outcomes for VDZ as first and second line biologic therapy (Anti-TNF exposed) in patients with ulcerative colitis and confirmed its effectiveness in both treatment groups.
P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?
Authors: Carbery I , Lin S , Chanchlani N , Janjua M , Nice R , McDonald T J , Bewshea C , Kennedy N A , Ahmad T , Goodhand J R , Selinger C P 
Published: January 2023

Abstract

Background
Lower serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio has been linked to non-response to treatment in a range of diseases, including in biologic-treated patients with IBD. We sought to assess whether baseline serum fT3/fT4 ratio predicted primary non-response (PNR) and non-remission to infliximab and adalimumab in patients with Crohn’s disease.

Methods
We included 997 adult participants from the Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS). Thyroid function tests, using the Roche Elecsys TSH immunoassay and T3 and T4 electrochemiluminescence assays, were measured on stored baseline samples (prior to biologic treatment). PNR, assessed at week 14, was defined as treatment failure (including IBD-related surgery), ongoing corticosteroid use, or both CRP failing to fall to ≤3 mg/L, or by 50% from baseline, and HBI failing to fall to ≤4, or by 3 points. Non-remission, assessed at week 54, was defined as either CRP of &gt; 3mg/L or HBI of &gt;4 points, ongoing corticosteroid therapy, or exit for treatment failure.

Results
Serum fT3, fT4 and TSH concentrations were similar in infliximab (n=549) and adalimumab treated (n=448) patients. Baseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27 - 0.34] vs 0.32 [0.28 - 0.36], p&lt;0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25 - 0.33] vs 0.32 [0.29 - 0.36], p&lt;0.001).
Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (OR 0.51, 95% CI 0.31 – 0.85, p = 0.009), however when stratified by drug and adjusted for variables known to be associated with PNR, low fT3/fT4 ratio remained associated with PNR for adalimumab, but not infliximab. After excluding patients treated with corticosteroids at baseline, there was no difference in fT3/fT4 ratio in those who experienced PNR compared to those who did not (PNR: [128/630] 0.31 [0.28 – 0.35] vs no PNR: [502/630] 0.32 [0.29 – 0.36], p = 0.095). The optimal threshold to determine PNR was 0.31 (AUC 0.57 [95% CI 0.54 - 0.61] sensitivity 0.62 [95% CI 0.41 - 0.74], specificity 0.53 [95% CI 0.42 - 0.73]).
No association was seen for baseline fT3/fT4 ratio and non-remission or changes in faecal calprotectin concentrations at week 54.

Conclusion
Lower baseline serum fT3/fT4 ratio was independently associated with female sex, higher inflammatory burden at baseline, and baseline corticosteroid use, and predicted PNR to anti-TNF therapy at week 14, but not non-remission or change in faecal calprotectin concentrations at week 54. Overall, however, the diagnostic accuracy of baseline fT3/fT4 ratio to predict PNR to anti-TNF treatment was modest, limiting its clinical utility.
P658 Comparative Efficacy and Safety of Upadacitinib Versus Tofacitinib as Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: A Matching-Adjusted Indirect Comparison
Authors: Reinisch W , Tran J , Patel K , Borruel N , Melmed G Y , Wegrzyn L , Levy G , Ilo D , Sanchez Gonzalez Y , Panaccione R 
Published: January 2023

Abstract

Background
Upadacitinib (UPA) and tofacitinib (TOFA) are Janus kinase (JAK) inhibitors approved for the treatment of patients (pts) with moderately to severely active ulcerative colitis (UC), but evidence on their comparative efficacy and safety is limited. This study conducted a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) of efficacy and safety induction outcomes between UPA and TOFA.

Methods
Pts received oral UPA 45 mg once daily or PBO for 8 weeks in the phase 3 induction studies U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026), and oral TOFA 10 mg twice daily or PBO for 8 weeks in phase 3 OCTAVE 1 and 2 Induction trials (NCT01458951, NCT01465763). MAIC of efficacy outcomes was conducted for bio-naïve and bio-failure pts. These included clinical remission per full Mayo score (FMS; FMS ≤2 with no subscore &gt;1), clinical response per FMS (decrease from baseline in FMS ≥3 points and ≥30%, with a decrease in rectal bleeding score [RBS] of ≥1 or an absolute RBS of 0 or 1), and endoscopic improvement (EI; endoscopic subscore [ES] 0 or 1). The overall population was used to assess endoscopic remission (ER; ES of 0) and safety outcomes including any adverse events (AEs), serious AEs (SAEs) and discontinuation (DC) due to AEs. Baseline characteristics of age, gender, extent and duration of disease, FMS, and corticosteroid use from UPA trials were weighted to match reported OCTAVE pts for primary efficacy outcomes, plus weight, C-reactive protein, and haemoglobin for ER and safety outcomes. Numbers needed to treat/harm (NNT/NNH) were calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes between UPA and TOFA.

Results
The MAIC used data from 961 and 977 UPA pts for primary efficacy and ER/safety outcomes, respectively, and 1,139 TOFA pts. A greater proportion of pts receiving UPA vs TOFA in bio-naïve and bio-failure groups achieved clinical remission, clinical response, and EI (p &lt;0.05, Table 1). PBO-adjusted differences between UPA vs TOFA for clinical remission, clinical response, and EI were 14.6%, 23.0%, and 25.1%, respectively, for bio-naïve pts and 8.5%, 27.7%, and 14.3% for bio-failed pts. ER was also higher in UPA vs TOFA (8.6% difference, p &lt; 0.001). AEs and SAEs were not statistically different between UPA and TOFA pts, but proportion of DC due to AEs were lower in UPA vs TOFA (p &lt; 0.05, Table 2). NNT/NNH analysis showed a favorable benefit-risk profile of UPA vs TOFA.

Conclusion
Pts with moderately to severely active UC achieved greater clinical efficacy and similar safety during induction treatment with UPA compared to TOFA based on MAIC, suggesting a favorable benefit-risk profile of UPA in the JAK class.
P669 Improving Crohn’s disease stricture dilation outcome: Effect of repeated dilation, needle knife stricturotomy, and ongoing active inflammation
Authors: Schulberg J D , Hamilton A L , Wright E K , Holt B , Sutherland T , Ross A L , Vogrin S , Kamm M A 
Published: January 2023

Abstract

Background
Traditionally Crohn’s disease strictures have been treated by a single endoscopic balloon dilation (EBD), repeated only for obstructive symptom recurrence. We postulated that scheduled repeated EBD may result in greater dilation effect than a single EBD; and that needle-knife stricturotomy (NKSt) may be a valuable salvage intervention in patients with strictures.

Methods
In this prospective observational study, patients with endoscopically accessible and short (&lt;5cm), symptomatic Crohn’s disease stricture were assessed clinically (using an Obstructive Symptom Score [OSS]) and by imaging (colonoscopy, MRI and IUS). All patients had drug treatment optimized to decrease inflammation. Patients were treated with 3 serial balloon dilatations each 3 weeks apart, single EBD, or needle-knife stricture incision. The primary endpoint was improved OSS at 6m. Secondary outcomes; ability to endoscopically pass the stricture, treatment failure / surgery, stricture morphology on imaging, and safety.

Results
Twenty-one consecutive patients were included in the analysis. Of these 17 (81%) were receiving treatment with a biologic therapy. Median stricture length at baseline was 20mm (IQR 20mm) and median estimated stricture diameter was 8mm (IQR 3mm). 18 (86%) had visible ulceration. Of the 21 patients 11 (52%) underwent more than one EBD, 5 (24%) had ≥1 NKSt and 5 (21%) underwent a single EBD. Four of the 21 patients (19%) strictures were passable before endoscopic treatment. All procedures were technically successful. 14/21 (67%) had improvement in OSS at 6m, including 8/11 (73%) with 3 serial EBD, 4/5 (80%) with NKSt and 2/5 (40%) patients undergoing a single EBD. Two patients required surgery. At 6m, 3/8 (38%) who had repeat dilations, 4/5 (80%) who had NKSt, and 2/5 (40%) having a single EBD had a passable stricture. All 4 patients with highly elevated stricture inflammation (stricture magnetic resonance index of activity [MaRIA] score ≥20) at the 6m MRI had a non-passable stricture at study endpoint, whilst 9/12 (75%) were passable when stricture MARIA was &lt;20 (P=0.019). No major complications occurred.

Conclusion
Endoscopic stricture treatment was safe and technically successful in all patients with accessible Crohn’s disease strictures and was associated with symptom improvement in most. Progression to surgery in this symptomatic and advanced disease was low at 6m. The highest rates of symptom improvement were seen in patients who had NKSt. Lesser stricture inflammation on MRI was associated with a better outcome, suggesting that controlling inflammation is important in preventing stricture recurrence after dilation. NKSt should be considered when balloon dilation is not possible or has failed, as a salvage treatment alternative to surgery.
P672 Switching out of class or to another anti-TNF agent is the most effective strategy in IBD patients with immunogenicity against anti-TNF antibodies
Authors: Anjie S , Hanžel J , Gecse K B , D'Haens G R , Brandse J F 
Published: January 2023

Abstract

Background
Immunogenicity to anti-TNF agents is associated with loss of response in inflammatory bowel disease (IBD). However, the efficacy of different strategies to restore favourable pharmacokinetics and/or clinical response upon the detection of anti-drug antibodies (ADA) has not been widely studied. We evaluated the success of different strategies leading to clinical remission with ADA disappearance (in patients continuing the same anti-TNF), in patients with IBD.

Methods
IBD patients with ADA to infliximab or adalimumab were identified through an electronic database search at a single tertiary centre between 2004 and 2021. ADA were measured using a drug-sensitive assay at Sanquin laboratories. Data concerning clinical, biochemical and endoscopic activity, medication and surgery were retrospectively and systematically collected by reviewing clinical records. Criteria for success of a strategy were clinical remission 1 year after ADA detection without further change in strategy combined with disappearance of ADA (in patients continuing the same anti-TNF).

Results
Two-hundred-and-fifty-five IBD patients (206 Crohn’s disease, 46 ulcerative colitis, 3 IBD-unclassified, 149 female) were included, 129 patients were diagnosed to have ADA against infliximab and 126 against adalimumab. At baseline, median ADA titer was 77 AU/ml (IQR 25-350), 50.2% of patients were in clinical remission. Groups were as follows: 1) 81/255 (32%) conservative management, 2) 102/255 (40%) optimization of the same anti-TNF, 3) 72/255 (28%) switch to another anti-TNF or biological class. Switch to another anti-TNF or out of class was the most successful strategy in terms of improvement of clinical remission (from 19.4% at ADA detection to 69.4% at 1 year, p&lt;0.001). Patients that continued with the same dose anti-TNF or discontinued all biological therapy after ADA detection were often in clinical remission at baseline, but deteriorated significantly in the following year (22.7%, P=0.004). Anti-TNF dose intensification with concomitant addition/optimisation of immunomodulators was the fastest (median 3 months (IQR 2-4.5), p=0.004) and most effective (in 73% of these patients, p=0.007) strategy to suppress ADA to undetectable levels compared to anti-TNF dose intensification or immunomodulator optimization alone.

Conclusion
Switching to another anti-TNF or out of class switch is the most successful strategy to regain and maintain clinical remission upon detection of ADA. Intensification of anti-TNF dosing with concomitant optimisation of immunomodulatory therapy is the fastest strategy to suppress ADA.