bluuebunny/crossref_metadata_2025_split huggingface dataset:
P760 Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: A final report of effectiveness and safety data
Authors: Matsuoka K , Motoya S , Yamamoto T , Matsuura M , Fujii T , Shinzaki S , Mikami Y , Arai S , Oshima J , Endo Y , Yuasa H , Hoshi M , Sato K , Hisamatsu T 
Published: January 2024

Abstract

Background
Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present the final analysis of a 60-week post-marketing surveillance (PMS) study of tofacitinib in patients (pts) with UC in Japan.

Methods
A final analysis of safety and effectiveness data from a PMS study was conducted (final data as of 30 September 2022). All pts with UC in Japan receiving tofacitinib were registered. All adverse drug reactions (ADRs) during tofacitinib treatment were recorded. Data were excluded for 13 pts from 2 hospitals that did not obtain pt consent and were therefore not permitted for publication. In the risk-management plan, several ADRs were identified as clinically important events or as potential risks, for which all treatment-period data were used to calculate cumulative incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure). Effectiveness was assessed by partial Mayo score as observed.

Results
In total, 2043 pts receiving tofacitinib were enrolled in the PMS study, of whom 1982 and 1969 were included in the final safety and effectiveness analyses, respectively. In total (safety analysis set), 60.5% of pts were male and mean age was 42.5 years, with 2706.4 PY of exposure. ADRs and serious ADRs were observed in 462 (23.3%) and 46 (2.3%) pts, respectively; one death occurred due to an intestinal abscess (not related to study drug per investigator’s assessment). Herpes zoster (HZ; non-serious/serious) was the most commonly reported infection (89 pts [4.5%]). The IRs of malignancy, cardiovascular events and venous thromboembolic events were all &lt;0.5 per 100 PY of exposure (Table). At Week 60, 735 of 870 ongoing pts (84.5%) were in remission (Figure). Overall, 1038/1982 pts (52.4%) discontinued treatment, most commonly due to inadequate clinical response (508/1038 pts [48.9%]).

Conclusion
In this final analysis, the overall safety profile during the treatment period from PMS reports of tofacitinib in pts with UC in Japan was generally comparable with tofacitinib safety data previously reported in PMS reports from Japan and worldwide,1 and in the tofacitinib UC clinical programme.2 However, rates of HZ were higher in this final analysis than in the tofacitinib UC clinical programme.2 Tofacitinib was effective in Japanese pts with UC in a clinical practice setting. The majority of pts with evaluable partial Mayo scores achieved remission during the 60-week observation period, consistent with previously reported data from the tofacitinib UC clinical programme.2
References:
1. Rubin et al. Aliment Pharmacol Ther 2022;55:302–10
2. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–78
Study sponsored by Pfizer. Medical writing support provided by C Duncan, CMC Connect; funded by Pfizer
P772 Comprehensive disease control in patients with Ulcerative Colitis: refinement of a multi-component endpoint using data from the filgotinib SELECTION trial
Authors: Schreiber S W , Feagan B G , Vermeire S , Danese S , Vyncke V , Faes M , Oortwijn A , Peyrin-Biroulet L 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement. We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522).

Methods
CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP &lt;150 µg/g, CDC4-150; CDC4 with FCP &lt;250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP &lt;150 µg/g, CDC5-150; and CDC5 with FCP&lt;250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was visualized in UpSet plots. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components).

Results
At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve pMCS remission compared with 5.0%, 10.1% and 6.0% who did not achieve IBDQ remission, biomarker remission and endoscopic improvement, respectively (Figure). Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions.

Conclusion
CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.
P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease
Authors: Theodoraki E , Papatzelou I , Koutroubakis I 
Published: January 2024

Abstract

Background
ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents.

Methods
This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece.
Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations].

Results
Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively).

Conclusion
About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.
P781 Mirikizumab administration experience from Ulcerative Colitis patients and healthcare providers: Survey data from the LUCENT clinical program
Authors: Clemow D , Radawski C , Milata J , Alaka K , Hunter Gibble T , Schaum A , Ezennia O , Martinez N , Szaloki T , Ito Y , Rodriguez D , Kirk K 
Published: January 2024

Abstract

Background
Mirikizumab (MIRI) is an anti-IL-p19 antibody approved for moderately-to-severely active ulcerative colitis (UC). The recommended dose regimen has 2 parts: MIRI administration begins with intravenous (IV) infusion every 4 weeks (Q4W; 3 total) followed by subcutaneous (SC) injections (2 injections per dose) Q4W (Figure 1). Self-injection of SC MIRI is allowed after patient training. This study explored differences between healthcare provider (HCP) perspectives of UC patients’ experiences and patients’ actual experiences regarding MIRI administration during the LUCENT program. It also assessed HCPs’ own experiences with MIRI administration.

Methods
The study involved two cross-sectional, 30-min, web-based surveys including one for patients and one for HCPs. Patients were eligible if they were enrolled in LUCENT-3 having entered from LUCENT-1 or -2 phase 3 studies or AMAC phase 2 study. HCPs from LUCENT-3 sites were eligible if they administered or oversaw MIRI IV infusions or SC injections during LUCENT-1, -2, -3, or AMAC. Survey questions had responses based on 5-point Likert scales. Outcomes included satisfaction with and acceptability of MIRI administration (Table 1). The survey was completed during LUCENT-3; MIRI SC injection experience at the time of survey varied from &gt;2 to ≥3 yrs.

Results
The surveys were completed by 93 patients from 11 countries and 42 HCPs (gastroenterologist/physician 31.0%, nurse 40.5%, other [coordinator] 28.6%) from 9 countries. Most patients were satisfied or very satisfied with IV infusions (82.8%) and SC injections (91.4%), which was lower than HCPs’ perspectives of patients’ experiences (IV, 92.9%; SC, 100%), but generally similar to HCPs’ own experiences (IV, 81.0%; SC, 95.2%). Consistent with patients’ actual experiences (SC Q4W, 97.8%; two injections, 96.8%), most HCPs thought that patients felt that receiving SC injections Q4W (100%) and receiving 2 SC injections for each dose (92.9%) were somewhat or completely acceptable. Patients (97.8%) were satisfied or very satisfied with MIRI administration overall and 90.3% agreed or strongly agreed that treatment benefits outweighed any administration dissatisfaction. These patient perspectives were similar to both HCP perspectives of UC patients’ experiences (95.2%; 88.1%) and HCPs’ own experiences (97.6%; 95.2%).

Conclusion
Most patients and HCPs were satisfied or very satisfied and acceptable or completely acceptable of MIRI IV and SC administration. Patients’ experiences were similar to HCPs’ perspectives of patients’ experiences as well as HCPs’ own experiences, although there was a tendency for HCPs to perceive patients’ satisfaction to be very satisfied at a higher rate than patients’ actual responses.
P793 Efficacy and safety of probiotics in inflammatory bowel disease: an umbrella review and updated meta-analysis of randomized controlled trials
Authors: Estevinho M M , Rodriguez-Lago I , Dias C C , Barreiro-de Acosta M , Magro F 
Published: January 2024

Abstract

Background
Probiotics hold potential in IBD, yet knowledge gaps persist. We aimed to perform an umbrella review of systematic reviews and updated metanalysis of all RCT assessing the effect of probiotics in on Crohn’s disease (CD) and ulcerative colitis (UC).

Methods
We searched MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials until September 2023 for systematic reviews and randomized controlled trials (RCT). Primary outcomes were clinical response and remission; secondary outcomes included endoscopic response, remission, and side effects. We calculated odds ratios using a random-effects model in R. Quality was assessed using the AMSTAR-2 (systematic reviews) and Jadad scale (RCTs), the Cochrane Collaboration tool was used to grade trials’ risk of bias.

Results
Out of 2613 search results, 67 studies (22 systematic reviews and 45 RCTs) met eligibility criteria. In the updated meta-analysis, the OR for clinical remission was 1.88 (95%CI 1.20-2.93, I2=60% - Figure 1). However, the positive effect was statistically significant only for UC (OR 2.00, 95% CI 1.28-3.11, I2=57%) but not for CD. Likewise, probiotics significantly decreased the odds of clinical recurrence in UC patients (OR 0.65, 95%CI 0.42-1.01, I2=52%) and in relapsing pouchitis (OR 0.03, 95%CI 0.00-0.25, I2=64%), but not in CD. The De Simone formulation consistently outperformed other probiotics in achieving remission and preventing recurrence in UC. On the other hand, the use of probiotics was not associated with better endoscopic outcomes. The occurrence of both mild and severe adverse events was comparable to control group.

Conclusion
Our results support the use of probiotics for patients with UC, both for the induction of clinical remission and for the prevention of relapse, as well for patients with previous diagnosis of pouchitis, and reinforces their good safety profile.
P794 Relationship between Ustekinumab Trough Concentrations and Clinical, Biochemical and Endoscopic Outcomes in Crohn’s Disease; A Multi-Center Nationwide Study (TARGET STUDY)
Authors: Shehab M , Alrashed F , Abdullah I , Alfadhli A 
Published: January 2024

Abstract

Background
Ustekinumab (UST) has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn’s disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real life settings

Methods
We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6mg/kg intravenous induction followed by 90 mg every 4 or 8 weeks during maintenance were included. Clinical, biochemical, and endoscopic outcomes, trough concentrations of ustekinumab that was taken from week 42 to week 52 were included. Primary outcome was to assess if ustekinumab trough concentrations were associated with clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes

Results
A total of 137 patients with CD. mean age of 34.1 years and 83 (60.6%) males. The mean serum levels of ustekinumab was 7.2 (SD 4.5). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and SES-CD score (r = -0.464, p &lt; 0.001. Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by HBI score (r = -0.582, p &lt; 0.001), C-Reactive Protein(CRP) levels (r = -0.598, p &lt; 0.001) and fecal calprotectin (FCAL) levels (r = -0.529, p &lt; 0.001). A multivariate analysis adjusted for age, sex and BMI showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/ml was associated with 24% increase in the likelihood of having an SES-CD score less than 3 (OR 1.24, CI 1.12-1.37, P&lt;0.001), 44% more likely to achieve HBI score less than 5 (OR 1.44, CI 1.26-1.65, P&lt;0.001), 52% higher likelihood of CRP less than 10 (OR 1.52, CI 1.31-1.77, p &lt; 0.001), and 42% increased likelihood of FCAL less than 250 (OR 1.42, CI 1.24-1.62, p &lt; 0.001).

Conclusion
Ustekinumab trough concentrations above 4.5 mcg/ml was associated with clinical, biochemical and endoscopic remission in Crohn’s disease. Prospective data is warranted to confirm these findings
P803 iGenoMed-MTT: A prospective multiomic study of response to molecularly targeted therapies in IBD
Authors: Battat R , Boucher G , Thompson Legault J , Mercier V , Bitton A , Rioux J 
Published: January 2024

Abstract

Background
No tools exist to individualize treatment selection in Inflammatory bowel disease (IBD) to optimize outcomes. We prospectively recruited patients prior to initiation of molecularly targeted (advanced) therapy (MTT) to identify predictive biomarkers of response and define pathways impacted by successful treatment.

Methods
Serum was collected before initiation of treatment in all patients, and at visit 1 (V1~16 wks) for a subset of patients. Serum samples were analyzed for &gt;140 protein biomarkers (OLINK) and &gt;1200 lipid metabolites. Whole exome sequencing and GWAS data was generated for all participants. Initial data outline proteomic data.

Results
Of the first 166 IBD patients analyzed, therapies initiated included TNF antagonists (n=85), ustekinumab (n=43), vedolizumab (n=28) and janus kinase inhibitors (n=10). Bio-naïve (n=96) and patients using baseline corticosteroids (n=77) were included. Sixty-three patients achieved remission.
In TNF-antagonist initiations, serum TNF concentrations increased between baseline and V1 (p=4E-3), while it decreased for other MTTs (p=0.07). In bio-naïve patients, serum TNF concentration had a strong correlation with CXCL10 (r=0.58, P=3E-10). From the Principal Component Analysis of analytes correlated to TNF in bio-naïve patients, we built a proxy for the level of active TNF.
At baseline, compared to TNF antagonist naïve patients, significantly higher serum TNF concentrations existed in patients with prior TNF-antagonist exposure &gt;1-month post-cessation and a markedly high TNF concentration with cessation &lt;1 month prior to baseline (p&lt; 2E-16). In patients with prior TNF-antagonist exposure, serum TNF concentrations did not correlate with other cytokines (incl. CXCL10). In these patients, elevated serum TNF were found at V1, suggesting accumulation of inactive (complexed) TNF with treatment. A similar pattern was observed for IL-12 after ustekinumab treatment (elevated serum IL-12 with recent ustekinumab (p= 8E-13), large increase in IL-12 after ustekinumab (p=9E-5)). Reduced IL-12 concentrations existed in current corticosteroid users, compared to previous users and those who never used (p=4E-8). In baseline samples in bio-naive patients prior to therapy initiation, serum concentrations of six analytes provided a discriminant model of corticosteroid use, whith an area under (AUC) the receiver operation characteristic (ROC) curve showed excellent discrimination (AUC=0.91).

Conclusion
These data uniquely characterize proteomic data in patients with various advanced therapies and will enable development of predictive panels. Unique availability of multiple therapies linked to longitudinal proteomic data may allow personalized panels for treatment selection.
P804 Does Crohn's disease extent and behavior have an impact on ustekinumab effectiveness? A real-world multicenter retrospective study
Authors: Samarentsis N , Kapizioni C , Georgakopoulou N , Michalopoulos G , Striki A , Karoumpalis I , Kartsoli S , Mellos A , Vrakas S , Vougadiotis I , Neonaki A , Karatzas P , Tsiamperas N , Kourikou A , Siakavellas S , Polymeros D , Manolakopoulos S , Papatheodoridis G , Triantafyllou K 
Published: January 2024

Abstract

Background
Crohn's disease (CD) presents heterogeneity in clinical phenotypes. Progression of disease and response to therapy have been associated, among other factors, with the extent and behavior of the disease. Real-world data on long term effectiveness of ustekinumab (UST) in CD based on disease characteristics are limited and conflicting1,2. The aim of this study is to describe real-world UST persistence according to disease distribution and perianal involvement in patients with CD.

Methods
This was a retrospective multicenter study involving adult patients with CD who received, at least, one dose of UST until August 2023, at 5 major hospitals in Athens, Greece. UST effectiveness based on treatment persistence was evaluated using Kaplan Meier curves for survival free of treatment discontinuation among patients with different disease extent and behavior. Log-rank test was used for statistical significance.

Results
A total of 147 adult CD patients who received biological treatment with UST for a median of 34 months (IQR 17-48) were included in the study. Patient baseline characteristics are shown in Table 1. UST treatment persistence rates were 93% (95% CI: 89-98) at 12 months and 87% (95% CI: 81-94) at 36 months. The persistence rate of UST differed significantly between patients with or without perianal disease (p=0.036) (Figure 1), while there was no significant difference based on disease extent (p=0.59) or behavior (p=0.31).

Conclusion
Our study showed that UST treatment persistence is similar in adult patients with CD, regardless of disease localization or behavior. Nonetheless, perianal disease involvement is associated with reduced treatment persistence.
References
1. Liefferinckx C, Verstockt B, Gils A, et al. Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn's Disease Who Failed Biologic Therapies: A National Cohort Study. J Crohns Colitis. 2019;13(11):1401-1409. doi:10.1093/ecco-jcc/jjz080
2. Iborra M, Beltrán B, Fernández-Clotet A, et al. Real-world long-term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry. Aliment Pharmacol Ther. 2020;52(6):1017-1030. doi:10.1111/apt.15958