bluuebunny/crossref_metadata_2025_split huggingface dataset:
P616 Prescribing practices of tofacitinib and preferences amongst high-risk patients in the UK
Authors: Bishara M , Clarke M , Smith R , Roberts C , Kennedy N A , Ahmad T , Goodhand J R 
Published: January 2024

Abstract

Background
Tofacitinib was licensed for use in patients with ulcerative colitis in August 2018. Because it is administered orally, has a rapid onset of action and is relatively inexpensive, it was quickly adopted in real-world practice. Safety warnings linking high-dose tofacitinib use to venous thromboembolic events (VTE) and death followed. Further warnings were issued linking its use to an increased risk of malignancy and adverse cardiovascular events in patients: over 65 years, with a history of diabetes, current or past smokers, and those with a history of coronary vascular disease. The most recent Medicines and Healthcare products Regulatory Agency (MHRA) statement advised against the use of all commercially available JAKi in this high-risk cohort unless a suitable alternative is unavailable (MHRA 2023).
We sought to define the number of patients who had, or were, being treated with tofacitinib who were in this high-risk group and the proportion who opted to switch therapy once we had outlined their risk-status and the MHRA advice to them.

Methods
We conducted a retrospective observational cohort study of 131 patients with UC and IBD-U (61% male [80/131]; median age 43 years [range 16-85]; 46% [60/131] patients had previously had at least one biologic agent) treated with tofacitinib from October 2018 to December 2022 in our centre with at least 3 months follow-up. Patients were categorised as high-risk according to the MHRA statement if they had at least one of the criteria above.

Results
Overall, about one-third, 31.3% [41/131] patients that we had treated with tofacitinib were classified in the MHRA high-risk group.
Rates of treatment discontinuation were similar in the high-risk versus no risk group. In the high-risk group ten patients (24.4% [10/41]) had discontinued treatment due to lack of response (4) or an adverse event (6). The most common adverse events were herpes zoster infections (14.6%), malignancy (3.3%) and infections requiring hospitalisation (3.3%). Two patients died while on treatment (one due to complications following cervical spinal surgery and the other due to ischaemic heart disease). There were no incidences of VTE.
We clinically reviewed 29 high risk patients who were being treated with tofacitinib after a median of 2.4 years (range 0.6-4.56) of treatment. 25/29 high-risk patients decided on continuing their treatment in spite of the health care warnings and alternative therapies being available.

Conclusion
About one-third of our tofacitinib-treated patients were classified as at high-risk. The majority of high-risk patients opted to continue therapy even though alternative therapies were available.
P628 Vedolizumab in Indian patients with Inflammatory Bowel Disease: Interim results from a prospective, multicentre, open-label, phase 4 study
Authors: Kabrawala M , Banerjee R , Ahuja V , Anumula K , Bharadwaj V , Dalal A , Ramesh Kumar B , Mukewar S , Sood A , Prasad V M , Arora S , Kirde S , Sharma N 
Published: January 2024

Abstract

Background
Although anti-tumour necrosis factor (TNF)-α agents have revolutionised the management of ulcerative colitis (UC) and Crohn’s disease (CD), they have demonstrated a therapeutic ceiling with numerous safety concerns. Vedolizumab (VDZ) has consistently demonstrated safety and efficacy in patients with UC and CD in pivotal clinical trials, but its efficacy and safety data are very limited in the developing world where infectious diseases predominate.

Methods
This prospective, multicentre, open-label, single-arm, phase 4 study (Clinicaltrial.gov: NCT04804540) included patients (aged 18-65 years [yrs]) with moderate-to-severe active UC and CD who were non-responsive to available conventional therapies and/or anti-TNF agents. Patients received VDZ 300 mg through intravenous infusion for induction (Week [W]0, W2, W6) and maintenance (W14, W22, W30, W38, and W46) treatment phase. This interim analysis included data collected till the last patient completed W14 visit. Safety endpoints including incidence of adverse events (AE), serious AEs (SAE), adverse drug reactions (ADR), and adverse events with special interest (AESI), and efficacy endpoints including clinical response and clinical remission were analysed.

Results
Of 215 patients screened, 150 were eligible (UC, 102 [68.0%], median age: 39 yrs; CD, 48 [32.0%], median age: 31 yrs). Median VDZ treatment duration was 155 days in UC and 143 days in CD groups. Overall, 71 (47.3%) patients (UC, 49 [48.0%]; CD, 22 [45.8%]) experienced ≥1 AE; of these, 40.7% patients had mild AEs (UC, 40.2%; CD, 41.7%). Forty-six (45.1%) patients with UC and 22 (45.8%) patients with CD had ≥1 treatment-emergent AE (TEAE); 5 (4.9%) patients with UC had treatment-related TEAEs. Seven (4.7%) patients (UC, 6 [5.9%]; CD, 1 [2.1%]) had ≥1 SAE (2 [1.3%] were treatment-related), 5 (3.3%) had ≥1 ADR, and 4 (2.7%) had ≥1 AESI. One patient (0.7%) each reported pulmonary tuberculosis and tuberculous pleural effusion as ADR/AESI. Anaemia and small intestinal obstruction were the frequently reported TEAE and SAE, respectively. Most of the AEs were resolved and no AE-related death was reported during study (Table 1). Overall, 90 (60.0%) patients (UC, 56 [54.9%]; CD, 34 [70.8%]) at W14, 37 (63.8%) patients (UC, 29 [61.7%]; CD, 8 [72.7%]) at W30, and 4 (57.1%) patients (UC, 4 [66.7%]) at W46 had the clinical response. Similarly, 62 (41.3%) patients (UC, 40 [39.2%]; CD, 22 [45.8%]) at W14, 23 (39.7%) patients (UC, 19 [40.4%]; CD, 4 [36.4%]) at W30, and 3 (42.9%) patients (UC, 3 [50.0%]) at W46 had the clinical remission (Figure 1).

Conclusion
Treatment with vedolizumab was safe and effective in Indian patients with moderate-to-severe active UC and CD as per this first multicentre prospective study on vedolizumab from India.
P630 Identification of specific cell subsets related to treatment response after anti-tumor necrosis factor use in Korean ulcerative colitis patients using single cell RNA sequencing: a preliminary study
Authors: Shin S R , Jeon S R , Jung Y H , Kim H G , Kim J O , Choi S , Ko B M , Lee W M , Hwang W C 
Published: January 2024

Abstract

Background
The breakdown of the epithelial barrier and mucosal homeostasis plays an important role in the development of ulcerative colitis (UC). Recently, single-cell RNA sequencing (scRNA-seq) has been performed to better understand the gene expression patterns and the characteristics of cells in intestine of UC patients. However, there is a lack of studies focus on Asian UC patients. The aim of this preliminary study was to identify the relevant cellular subsets related to treatment response after anti-tumor necrosis factor (anti-TNF) use in Korean UC patients using scRNA-seq.

Methods
This prospective study was conducted two University hospitals in Korea. We performed scRNA-seq on sigmoid colon tissue samples collected from one healthy control and nine biologic naïve UC patients scheduled to use anti-TNF due to lack of response to conventional therapy. All mucosal biopsies from active moderate to severe UC were collected at baseline (n=9) and at 52 weeks follow-up after anti-TNF use (n=2), at which time treatment response was assessed. Treatment responder was defined as those with sustained clinical remission (a partial Mayo score of ≤2 with no subscore &gt;1 and a rectal bleeding subscore of 0) at 52 weeks.

Results
After processing the scRNA-seq data, 13 clusters were discovered and cell clusters were annotated using colon marker gene. Among nine patients, two patients who underwent response evaluation at 52 weeks after anti-TNF use were treatment responder. The normalized proportion of cluster 1 (stem cell-like cluster) in 52 weeks follow-up tissue samples after anti-TNF use was shown to be decreased significantly (p-value=0.03) from that found in the disease tissue samples. A decrease in the proportion of cell cluster 1 from disease tissue samples’ initial average percentage (30.6%) down to an average of 4.8% in the follow-up tissue samples is quite substantial (p-value=0.03). This decrease signifies a notable change in the composition of this specific cell cluster post-anti-TNF treatment. Moreover, reaching a level close to that of the healthy tissue sample (2.7%) suggests a potential restoration of this cell cluster's proportion towards a healthier state (Figure 1).

Conclusion
In Korean UC patients, this information should be crucial in understanding the impact of anti-TNF treatment on the cellular composition or behavior of this stem cell-like cluster, suggesting a potential effect of anti-TNF treatment on this particular cell population.
P631 Effectiveness of Early Thiopurine Use in Korean Patients with Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) study
Authors: Hyun H K , Kim J W , Lee J , Jeen Y T , Kim T O , Kim J S , Park J J , Hong S , Park D I , Kim H S , Lee Y , Jung E S , Kim Y , Jung S Y , Cheon J H 
Published: January 2024

Abstract

Background
Thiopurines play an important role in the management of steroid-refractory steroid-dependent ulcerative colitis (UC). However, the effectiveness of the early use of thiopurines in UC remains controversial.

Methods
In this multicenter prospective cohort study, we divided patients with UC into those who underwent early (within 6 months of diagnosis) and late (6 months after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score &gt;2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes.

Results
Overall, 333 patients with moderate-to-severe UC were included in the MOSAIK study. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.96% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3–2.0), and the median maintenance dose was 1.1 mg/kg (0.3–2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis during a 3–year period (p = 0.712). Multivariate analysis showed that the presence of extraintestinal manifestations (hazard ratio [HR]: 4.674, 95% CI: 1.210–18.061, p = 0.025) independently predicted an increased risk of clinical relapse.

Conclusion
Patients with UC who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.
P634 Durability of a second-line anti-TNFɑ agent compared to a different mechanism of action after first anti-TNFɑ failure in ulcerative colitis: CambiaCU Study
Authors: López-Vico M , Hernández-Martínez Á , Soto-Escribano P , Rojas-Feria M , Cornejo-Jiménez A , Caballero-Mateos A M , Trapero-Martínez A M , Sánchez-Capilla A D , Cabello-Tapia M J , Martín-Rodríguez M D M 
Published: January 2024

Abstract

Background
After first anti-TNFɑ (aTNF) failure in ulcerative colitis (UC), switching to a different mechanism of action (MoA) could decrease the rates of failure and discontinuation compared to a second aTNF and with a better safety profile.

Methods
We performed a multicenter and retrospective study (6 Andalusian sites) in which patients diagnosed of UC who had failed a first biological therapy with an aTNF and started a second-line biological therapy with another aTNF or a different MoA such as ustekinumab (UST), vedolizumab (VDZ), tofacitinib and filgobinib (JAK) were included. The aim of our study was to evaluate the long-term durability of a different MoA compared to a second aTNF after a first-line therapy failure with aTNF.

Results
185 patients with UC were included. There were no significant differences between both groups in term of age, sex, extension of disease, extraintestinal manifestations or IMIDs, smoking habit or HLA-DQA1*05. The only significant difference was disease duration (9 years MoA vs 12 years in second aTNF, p=0.02). 80 patients received a different MoA (37 VDZ, 24 UST, 7 JAK) and 105 a second aTNF (34 IFX, 60 ADA, 11 golimumab). Duration of first aTNF, although non-significant (p=0.06), tended to be shorter in the MoA group (7 months vs 12 months in aTNF group). The most frequent cause of suspension of first aTNF in the MoA group was primary failure (46% vs 31%, p= 0.02) and in the second aTNF group was secondary failure (51% vs 35%, p=0.02). The follow-up mean was 22.4 months in the group of a different MoA and 23.3 months in the second aTNF group. 60% of patients discontinued the second-line biological treatment, 64% with aTNF vs 35% with a different MoA. Durability of therapies in the group of different MoA was significatively longer compared with second aTNF (50% vs 31.4%, p=0.036) (figure 1). JAK showed the best durability (63.2%), followed by UST (66.7%), IFX (52.9%), VDZ (32.4%), ADA (21.7%) and golimumab (18.2%), with significant differences (p=0.03). Reasons for discontinuation were primary failure in 29.7% (63.6% second aTNF vs 36.4% different MoA), secondary failure in 25.9% (64.5% second aTNF vs 35.5% different MoA) and intolerance or adverse events in 6.4% (66.6% second aTNF vs 34.4% different MoA). Adverse events were reported in 12 patients, 8 with aTNF a 4 with other MoA (2 vs 0 infusion reactions, 1 vs 1 mild infections, 2 vs 1 respiratory adverse effects, 1 vs 1 cutaneous reactions, 1 vs 0 musculoskeletal effects, 1 vs 1 neoplasia).

Conclusion
Our study shows that after a first aTNF failure in UC, a switch to a biological therapy with a different MoA achieves longer survival compared to switching to a second aTNF, with less primary and secondary failure.
P637 Ozanimod efficacy with or without concomitant corticosteroids in 5-ASA–exposed, advanced therapy–naive, immunomodulator-naive patients with ulcerative colitis: a post hoc analysis of True North
Authors: Horst S , Fischer M , Kinnucan J A , Sauk J S , Wu H , Jain A , Ahmad H A , Osterman M T , Rosen M , Sands B E 
Published: January 2024

Abstract

Background
Long-term corticosteroid (CS) use is not recommended for patients (pts) with ulcerative colitis (UC). Receiving early advanced therapy (AT) may help limit CS overuse, but there is a need to identify pt populations who may benefit most from receiving early AT as monotherapy. Previous post hoc analyses of the phase 3 True North (TN) study (NCT02435992) demonstrated ozanimod (OZA) efficacy in 5-aminosalicylate (5-ASA)–exposed, AT-naive, immunomodulator (IMM)–naive pts. This analysis further assessed the efficacy of OZA induction therapy with and without concomitant CS in this pt population by baseline (BL) endoscopic disease severity.

Methods
In TN, pts in Cohort 1 (C1) were randomised to OZA or placebo (PBO); pts in Cohort 2 (C2) received open-label OZA through Week (W) 10. Pts were on stable doses of oral 5-ASA and/or CS for ≥2 wk before screening and continuing through W10. 5-ASA–exposed, AT-naive, IMM-naive pts were grouped as moderate (Mayo endoscopy subscore [MES]=2 at BL) or severe (MES=3 at BL). Data were analysed in all moderate and severe pts and by concomitant CS use. Clinical remission, clinical response, endoscopic improvement, mucosal healing, and histologic remission were assessed at W10.

Results
Of the 464 5-ASA–exposed, AT-naive, IMM-naive pts, 237 had moderate (PBO, n=47; OZA C1, n=108; OZA C2], n=82) and 227 had severe (PBO, n=54; OZA C1, n=97; OZA C2, n=76) BL endoscopic disease. BL pt characteristics were generally similar between moderate and severe pts with or without concomitant CS use. Overall, OZA was significantly more effective in moderate pts and numerically more effective in severe pts vs PBO in C1, with numerically greater treatment differences in moderate vs severe pts (Figure 1A). The moderate and severe groups each had 51 pts (~22%) on concomitant CS. In moderate pts, numerically greater OZA vs PBO C1 treatment differences were observed in those without concomitant CS use vs those with concomitant CS use for clinical remission and clinical response; treatment differences were significant for all endpoints in pts without concomitant CS use (Figure 1B). In contrast, severe pts with concomitant CS use demonstrated greater OZA vs PBO C1 treatment differences vs those without concomitant CS use for all endpoints (Figure 1C). Results in OZA C2 were generally similar to OZA C1.

Conclusion
OZA treatment was efficacious in 5-ASA–exposed, AT-naive, IMM-naive pts with UC, with numerically greater efficacy in moderate pts than severe pts. Additionally, the results suggest that concomitant CS may not provide additional benefit over OZA monotherapy in moderate pts. These findings support OZA positioning after 5-ASA, but before CS, in pts with moderate UC.
P638 Efficacy of Induction upadacitinib Therapy in Chinese Patients with Moderately to Severely Active Crohn’s Disease
Authors: Chen M , Gao X , Cao Q , Zhang X , Chen Y , Hou X , Zhong J , Sun Y , Phaleng X 
Published: January 2024

Abstract

Background
Upadacitinib (UPA) is the 1st oral, reversible, selective Janus kinase inhibitor that approved in China for moderately to severely active Crohn’s disease (CD) treatment. UPA demonstrated significantly greater efficacy compared with placebo (PBO) in phase 3 global multicenter, double-blind, PBO-controlled induction U-EXCEL and U-EXCEED studies. This analysis reports the efficacy and safety results on a sub-analysis of Chinese from the combined 2 induction studies.

Methods
Eligible patients with an average daily very soft/liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2, plus a Simple Endoscopic Score for CD (excluding the narrowing component) ≥6 (≥4 for isolated ileal disease) were randomized (2:1) to UPA 45 mg or PBO for 12 weeks. Patients receiving corticosteroid at baseline began a steroid taper at week 4 per protocol. This analysis included Chinese subjects from global population. The 2 induction studies were combined for each analysis set. Clinical remission per PROs was defined as average daily very soft or liquid SF ≤ 2.8 and average daily AP score ≤1.0 and both not greater than baseline. Endoscopic response was defined as decrease in SES-CD&gt;50% from baseline (or for subjects with an SES-CD of 4 at baseline, at least a 2-point reduction), as scored by central reviewer.

Results
Of the 1021 patients enrolled in the 2 induction studies, 120 from China were included in the analysis. Baseline demographic and characteristics were mostly similar with a few exceptions. A significantly higher percentage of Chinese patients who received UPA 45mg QD than those received PBO had clinical remission per PROs at week 12 (70.9% vs 22.0%, p&lt;0.0001). At week 4, clinical remission per PROs was achieved by a numerically greater proportion of patients receiving UPA (51.9%) than PBO (17.1%). At week 12, in patients taking corticosteroids for CD at baseline, a numerically greater proportion of patients receiving UPA (72%) discontinued corticosteroid use and achieved clinical remission per PROs than did patients receiving PBO (30%). A significantly higher percentage of Chinese patients who received UPA than those received PBO had endoscopic response at week 12 (64.6% vs 12.2%, p&lt;0.0001). The rate of adverse events (AEs) in the UPA group was comparable to PBO group. There were no treatment-emergent deaths in either group. In the Chinese population, AEs of special interest occurred at similar rates between PBO and UPA group. No malignancies, adjudicated major cardiovascular events, or venous thromboembolic events were reported.

Conclusion
Similar to global population, Chinese patients treated with UPA 45mg achieved clinical and endoscopic outcomes at higher rates than did patients receiving PBO, with a tolerable safety profile.
P640 Role of vedolizumab trough levels in predicting clinical response in Inflammatory Bowel Disease: a multicentre prospective study
Authors: Falzone M H , Ribaldone D G , Saracco G M , Bertani L , Ceccarelli L , Costa F , Bottari A , Fornaroli G , Cusato J , D'Avolio A , Palermiti A , Antonucci M 
Published: January 2024

Abstract

Background
Medical treatment of Inflammatory Bowel Diseases (IBD) has developed aiming at a target-therapy using molecular-targeted drugs, such as vedolizumab (VDZ), recommended in moderate to severe forms of IBD refractory to conventional therapy. Considering the low rate of clinical remission after 12 months of treatment (about 30%) and its cost, it is important to identify predictors of clinical efficacy: therapeutic drug monitoring (TDM) based on measuring VDZ trough levels (TL) and circulating neutralizing antibodies could be useful in this setting.
This prospective study aims at evaluating the association between VDZ TLs at week 24 and clinical and biochemical disease activity at the same timepoint and at week 52, in order to identify if these levels can predict 12-months clinical remission

Methods
The study has included patients who started VDZ treatment from 2016 to 2022 at two IBD centres (Turin and Pisa). Patients were monitored through clinical scores (HBI and PMS) and laboratory tests (haemoglobin, CRP, faecal calprotectin) at the beginning of treatment, at 6, at 12-months; TDM has been performed at month 6; response to the treatment and clinical remission have been defined according to IOIBD criteria after 6 and 12 months

Results
All of 40 patients included (16 CD, 24 UC) have undergone a follow-up at month 6, while only 35 have been to an annual evaluation. At the beginning of treatment the clinical disease activity was moderate (HBI mean 7.5; PMS mean 4.9), it became mild at the second timepoint (HBI mean 3.5; PMS mean 2.5) and was found to be mild or in remission after a year (HBI mean 3.6; PMS mean 1.5). The response rate (77%) and clinical remission rate (63%) at 6 and 12-months have been steady over time. TDM has found a mean of VDZ TLs of 79.3 μg/ml (SD 51.3) and no anti-VDZ antibodies. 12-months clinical remission has been tested through logistic regression in order to identify predictive factors: it was inversely proportional to PMS (OR 0.47; p 0.02) and abnormal CRP levels (OR 0.24; p 0.04) at 6-months and directly associated with haemoglobin concentration at 0 (OR 2.14; p 0.04) and 6-months (OR 1.86; p 0.02). As to TDM, VDZ TLs at the second timepoint were positive predictors of symptoms remission at the next timepoint (OR 1.02; p 0.03): higher concentrations at 43.1 μg/ml were associated with clinical remission (AUC 0.69; p 0.03) and were positively correlated with laboratory tests, such as haemoglobin (r 0.36; p 0.03)

Conclusion
Response to VDZ at the end of the year can be predicted after the first 6 months with clinical evaluation and laboratory tests, as well as TDM: lower PMS, higher haemoglobin, quiescent inflammatory biomarkers together with higher VDZ TLs allow to identify who will achieve clinical remission.