bluuebunny/crossref_metadata_2025 huggingface dataset:
P602 Risankizumab levels but not IL22 are significantly correlated and predictive of clinical and biochemical remission in Crohn's disease
Authors: Roblin X , barrau M , Duru G , Nancey S , Paul S
Published: January 2024

Background

Risankizumab (RZB) is an anti-IL23 monoclonal antibody blocking the p19 subunit, whose recent Phase 3 trial demonstrated its efficacy in CD. Compassionate use has been possible since December 2019. The aim of this study was to investigate whether RZB and IL22 levels correlated with deep remission.

Methods

Any CD patient receiving RZB (compassionate use) was eligible for the study. All patients were treated with a regimen of RZB (600mg W0, W4 and W8) followed by 360 mg/sc every 8 weeks from W12. Patients with other dosing regimens were excluded. Before each infusion or SC injection, fecal calprotectin, CRP, RZB levels (ELISA ; Theradiag) and IL-22 levels (ELLA automated system; Biotechne). Clinical and biochemical remission was defined by a clinical score (CDAI) < 150 with fecal calprotectin < 250 µg/ml and CRP < 5 mg/l.

Results

28 patients on failure to anti TNF, vedolizumab and ustekinumab (mean age: 44 years, sex ratio M/F: 1.3) with 95 RZB maintenance samples (360mg/sc every 8 weeks) were eligible. For 44 RZB samples (46%), patients were in clinical and biochemical remission . Patients with clinical and biochemical remission had higher mean RZB levels than patients without clinical and biochemical remission (21.6 +/-13.3 versus 7.4+/-6.4 µg/ml; p=0.001). Biochemical and clinical remission rates were significantly higher in the highest RZB quartiles (p=0.01) (Figure 1). Area under the curve analysis (AUC: 0.93; p<0.001) isolated a RZB threshold significantly associated with clinical and biochemical remission: 11.5 µg/mL (sensitivity: 81.8%, specificity: 80.3%, PPV: 78.2%, NPV: 83.6%, accuracy: 81%.) . The progression-free survival curves towards loss of clinical and biochemical remission were significantly more favorable in the group of patients with RZB levels > 11.5µg/mL (p=0.03) . In univariate and multivariate analysis, only RZB level was isolated as a factor associated with clinical and biochemical remission: HR: 1.36 (CI95: 1.05-1.35), p=0.001). Conversely, albumin, CRP, albumin and other patient variables were not significantly associated with deep remission. The IL22 levels are not statistically significantly different between clinical and biochemical remission or not (respectively, 10.4 pg/mL (4.2-17.2) vs 8.6 pg/mL (4.3-16.2); p = 0.73)

Conclusion

RZB levels are significantly higher in clinical and biochemical remission CD. A threshold of 11.5µg/mL predicts clinical and biochemical remission in CD and is associated with significantly better progression-free survival. Conversely, IL22 levels are not associated with clinical and biochemical remission. However, these results are in a limited patient population of those receiving compassionate use therapy.
P614 Endoscopic Electroincision Therapy for Children
Authors: Picoraro J , Shen B
Published: January 2024

Background

Anastomotic strictures can be successfully treated by endoscopic balloon dilation (EBD); however, the emerging modality of stricturotomy with electroincision therapy (EIT) and strictureplasty(stricturotomy followed by endoscopic clipping) may achieve superior outcomes. Endoscopic stricturotomy has been shown to have greater efficacy than EBD in adult patients with IBD. While the rate of perforation is lower in EIT as compared to EBD in IBD, stricturotomy has a 4-10% rate of delayed bleeding, with a smaller proportion requiring blood transfusion. EIT can delay the need for surgical intervention and in many circumstances obviate the need indefinitely. This study is to describe the use of EIT for luminal strictures in children.

Methods

Retrospective cohort study of 10 pediatric patients (including 18 procedures) with anastomotic and primary luminal stricture who underwent endoscopic EIT with stricturotomy or strictureplasty. Outcomes and complications were documented.

Results

Among 18 performed, 14 stricturotomy and 4 strictureplasty, 2 patients did not require further intervention and had no stricture recurrence at time of follow-up. 3 patients required repeat stricture therapy but the time duration between interventions, previously EBD, extended. There were 2 procedural complications, tension pneumoperitoneum managed by needle decompression and microperforation, neither of which required surgical repair or resection. There were no episodes of GI bleeding.

Conclusion

EIT for luminal stricture in children may offer an alternative to EBD or surgical resection and re-anastomosis. The relative risk in children remains to be delineated.
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

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

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

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 >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

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 >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

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

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

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>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<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<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

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.
P656 Plasma Inflammation-related Proteins Predict the Therapeutic Effect of 5-ASA in Patients with Ulcerative Colitis
Authors: Dang Y , Xu X , Zhou M , Xu C , Huang X , Xu F , Wang Z , Wang C , Zhu S , Li P , Zhang S , Shi H
Published: January 2024

Background

5-aminosalicylate acid (5-ASA) is the first line therapy for mild to moderate ulcerative colitis (UC). However, up to 56% of patients on 5-ASA treatment could not achieve mucosal healing, which is the therapeutic target of UC. At present, predictors for patients’ response to 5-ASA are lacking. Our aim was to identify circulating markers to predict the therapeutic effect of 5-ASA in patients with UC.

Methods

Plasma samples were collected from patients with active UC at baseline and analyzed using the OLINK panel (Target 96 Inflammation). Effective therapy was defined as achieving clinical remission within 8 weeks or mucosal healing within 1 year of 5-ASA treatment. Orthogonal Projections to Latent Structures Discriminant Analyses (OPLS-DA) were implemented to correlate patient groups to plasma proteins in linear multivariate models. Machine learning models (ML) were constructed to predict ineffective therapy in UC patients.

Results

Among the 36 UC patients involved (media age 38.5 years old, men 61.6%), 18 patients belonged to the effective group and the ineffective group, respectively. In multivariate analysis, circulating inflammatory protein profiles could distinguish the patients who did not respond well to 5-ASA treatment (Figure 1A). Elevated levels of Axin 1 (p=0.012), sulfotransferase 1A1 (ST1A1) (p=0.032) and interleukin 15 receptor subunit alpha (IL-15RA) (p=0.022), and decreased level of interleukin 2 (IL-2) (p=0.036) were observed in UC patients refractory to 5-ASA therapy (Figure 1B). Receiver operating characteristic curves (ROC) for predicting the therapeutic efficacy of 5-ASA were constructed. The areas under ROC (AUC) of Axin 1, ST1A1, IL-15RA and IL-2 for the prediction of ineffective 5-ASA therapy were 0.744 (p=0.012, sensitivity 83.3%, specificity 72.2%), 0.710 (p=0.031, sensitivity 94.4%, specificity 55.6%), 0.704 (p=0.037, sensitivity 88.9%, specificity 50%) and 0.704 (p=0.037, sensitivity 77.8%, specificity 61.1%), respectively (Figure 1C). Combination of the four protein markers improved the performance of prediction (AUC 0.860 to 1.000, sensitivity 72.2%-100%, specificity 83.3%-100% across all machine learning classifiers) (Figure 1D).

Conclusion

We identified four plasma inflammation-related proteins associated with the therapeutic effect of 5-ASA in UC. The ML models demonstrated excellent performance in predicting the therapeutic effect of 5-ASA, which could help clinicians identify UC patients who are refractory to 5-ASA in the early course of disease and timely initiation of treatment escalation.
P671 Patient perspectives on symptoms and impacts in Crohn’s disease: Results from qualitative research
Authors: Gibble T H , Kosa K , Basnyat B , Martin S , Moses R , Dubinsky M
Published: January 2024

Background

Patients’ perspectives on their Crohn’s disease (CD) symptoms and the impacts of CD on their daily lives can be used to inform clinical care and treatment development. This study aimed to elicit in-depth qualitative information on the symptom burden of CD and to quantify which symptoms patients considered most bothersome and most important to improve.

Methods

Individual, web-based interviews were conducted in adults and adolescents (aged 15–17 years) with moderately to severely active CD. Participants were asked open-ended questions to elicit their experiences with CD and CD-related impacts on their daily lives. Participants were then probed about symptom- and impact-related concepts of interest that they did not spontaneously report. Participants were asked which symptoms they considered most bothersome and which symptoms they considered most important to improve. Interview transcripts and field notes were analyzed using a standard thematic analysis approach.

Results

17 adults and 3 adolescents participated between May and July 2023. Participants were 17–60 [mean=38] years old; 70% were female [n=14]; 70% were White [n=14]. Participants had been diagnosed, on average, 10 (range: 0.5–29) years ago. Over half (n=13, 65%) reported moderate CD severity. Nearly all participants reported fatigue (n=19, 95%), bowel urgency (n=18, 90%), diarrhea (n=18, 90%), abdominal pain (n=17, 85%), and frequent bowel movements (n=15, 75%). About a third reported nausea (n=7, 35%), bloating (n=6, 30%), joint pain (n=6, 30%), or blood in their stool (n=6, 30%). In total, nine different most bothersome symptoms or treatment priorities were reported across participants (Figure 1). Participants most commonly reported abdominal pain (n=6, 30%), bowel urgency (n=4, 20%), and diarrhea (n=4, 20%) as their most bothersome symptoms; these were also the symptoms most commonly reported as the most important to improve (abdominal pain: n=7, 35%; bowel urgency: n=5, 25%; diarrhea: n=4, 20%) (Figure 1). All participants reported that CD hinders their daily activities, and nearly all reported that CD affects their mood or emotions (n=19, 95%), social activities or relationships (n=19, 95%), work or school (e.g., loss of productivity) (n=18, 90%), and sleep (n=15, 75%) (Table 1). Participants described "feel[ing] left out", "want[ing] to stay home", and having to cancel or leave activities because of their CD. Several participants indicated that they "plan their day around [their CD]".

Conclusion

Patients with moderately to severely active CD were burdened by a variety of symptoms. Patients commonly considered abdominal pain, bowel urgency, and diarrhea symptoms to be the most bothersome and the most important to improve.
P673 Accelerated intravenous ustekinumab dosing as rescue therapy in Moderate- Severe Ulcerative Colitis
Authors: Muñoz Villafranca M D C , Arreba P , Buendia L , Higuera R O , López M L , Prado N F , Irusta L , Jiménez M A , Aldama M , Santacruz M , Perez A , Rodriguez P , Bilbao A , Ortiz de Zárate J
Published: January 2024

Background

Ustekinumab (UST) is an accepted treatment for patients with moderate- severe Ulcerative Colitis (UC) following failure with corticosteroids and/or anti-TNF. Some studies suggest that intravenous (IV) administration, in an accelerated schedule, could improve outcomes in this difficult-to-manage group with a high risk of colectomy.

Methods

We conducted a retrospective analysis in patients with moderate-severe UC who received UST (IV) as rescue treatment, following failure with corticosteroids and infliximab. UST was administered intravenously, with an initial dose of 6mg/Kg followed by 130mg every four weeks. Clinical activity was determined by the Partial Mayo Score (PMS), and endoscopic activity by the Mayo Score (SM). Clinical Remission (CR) was defined as PMS<2, and Clinical Response (CRp) as a reduction in activity of ≥30%.

Results

The study included 17 patients, 8 (47%) women, 9 (52.9%) of whom were hospitalized at baseline, and 11/17 required transfusion or intravenous iron. According to PMS, clinical activity was severe in 16 (94.12%) and moderate in one. Endoscopic activity according to SM was severe in 13 (76.4%). Clinical remission and response were as follows: 1 (5.8%) / 7 (41.1%) patients respectively at week 4; 8 (47%) / 16 (94.1%) patients at week 12; and at week 26, 15 patients had completed the study, 10 (66.6%) in CR, and 12 (80%) in CRp. Ustekinumab was withdrawn in one case due to an infusion reaction, and one patient underwent colectomy. No independent predictors of response to UST were found in this study.

Conclusion

Intravenous ustekinumab in an accelerated dosing schedule is effective in moderate-severe UC, achieving clinical response in more than two-thirds of patients at week 26.
P684 Using a pharmacokinetic simulation model to determine the optimal infliximab intensification strategy to address loss of response in inflammatory bowel disease
Authors: Srinivasan A , Upton R
Published: January 2024

Background

The optimal dose intensification strategy to address loss of response associated with low infliximab levels remains uncertain. Favorable associations between higher infliximab levels and objective endpoints imply that post-intensification trough and treatment targets may have utility. This simulation study aimed to identify intensification strategies capable of achieving post-intensification trough thresholds associated with aspirational treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

A previously published infliximab pharmacokinetic model, applied to 200 simulated patients, identified those with subtherapeutic(<3.00mg/L) trough levels after 30-weeks of standard dosing, and subsequently applied ten dose intensification strategies (Figure 1) over a further 32 weeks. The proportion of simulations achieving infliximab trough thresholds associated with endoscopic remission (CD >9.7mg/L; UC >7.5mg/L) was the primary outcome, with clinical improvement (CD >7.0mg/L; UC >3.7mg/L) and perianal fistula healing (CD >10.1mg/L) representing secondary outcomes. Outcomes were stratified by intensity of dose intensification, with five deemed intensive (>10mg/kg 8-weekly). The impact of pre-intensification antibodies to infliximab (ATI) on post-intensification trough levels was also evaluated.

Results

The median pre-intensification infliximab trough level was 0.91mg/L (IQR 1.31). Intensive intensification strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (UC: 34.76 v 10.56%, CD: 25.80 v 4.92%), clinical improvement (UC: 61.40 v 34.52%, CD: 39.58 v 12.12%) and perianal fistula healing (24.70 v 4.50%, all p<0.01) than standard intensification strategies (Figure 2). When controlling for cumulative (mg/kg) infliximab dose over 32 weeks, strategies that concurrently dose increased and interval shortened achieved the highest trough levels (all p<0.01). Patients simulated to have ATI prior to dose intensification had lower median infliximab trough levels at weeks 30/32 (3.38 mg/L, IQR 5.52 mg/L) compared to those without ATI (3.89 mg/L IQR 6.14 mg/L) across all dose intensification strategies (p=0.015).

Conclusion

This simulation-based analysis highlights the potential of using post-intensification trough level targets to guide dosing strategy and intensity. Combined high-dose, interval-shortened strategies appear to achieve higher infliximab levels, which may be important in the pursuit of stringent endpoints such as endoscopic remission and fistula healing. These findings require validation across real-world cohorts.
P700 The efficacy of adalimumab combined with surgery for rectovaginal fistula in Crohn's disease：a single-center retrospective study
Authors: Yan Y , Liu X , Yi J , Luo D , Gen J , Wang H
Published: January 2024

Background

To assess the efficacy of adalimumab(ADA)combined with surgery in the treatment of Crohn's disease patients with rectovaginal fistulas.

Methods

A single-center retrospective study. The baseline data of patients with Crohn’s rectovaginal fistulas who visited the Anorectal Department of the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to July 2022 and accepted ADA combined with surgery treatment were included. Crohn’s disease Activity Index(CDAI), perianal disease activity index(PDAI) and inflammatory parameters, including Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP), were statistically analyzed at weeks0, 48. Follow-up was performed every 8 weeks. The outcomes included clinical response, clinical remission, fistula response, fistula remission, fistula remission under MRI, endoscopic response and endoscopic remission.

Results

A total of 43 RVF patients were included, 53.4% (23/43) patients were treated with Seton,44.1% (19/43) patients were treated with Advancement flap and 2.3%(1/43) patient was treated with Fecal diversion, with a median follow-up of 11.0 (2.5-15.0) months. After 48 weeks of treatment, CDAI[325(262,397)vs.197(134,396)], PDAI[8(6,9) vs. 5(3,6)], ESR[31(8,50) mm/h vs. 10(4,28)mm/h]and CRP[4.62(0.85, 14.45)mg/L vs.0.5(0.5,2.14)mg/L] were significantly lower than 0 week (Table 1) . CDAI, PDAI, ESR and CRP at the 48th week of treatment were significantly lower than those before treatment (p<0.05). At the last follow-up, 62.7%(27/43) patients achieved clinical response, 30.2%(13/43) achieved clinical remission. Meanwhile 69.7%(30/43) of patients achieved fistula response,32.5%(14/43) achieved fistula remission(Table 2),and 25.5%(11/43) achieved fistula remission under MRI; A total of 37 patients completed endoscopic re-examination, including 54.0% (20/37) of patients with endoscopic response and 24.3%(9/37) with endoscopic remission.

Conclusion

ADA combined with surgery is effective in the treatment of patients with Crohn’s rectovaginal fistulas.
P711 Outcomes of Outpatient Biologic Exposed Patients Hospitalized with Severe Ulcerative Colitis
Authors: Al-Bawardy B , Al Sulais E , Mukhtar M , Hart A , Raine T
Published: January 2024

Background

Up to 20% of patients with ulcerative colitis (UC) will require hospitalization for an acute severe flare. It is unclear whether outpatient exposure to biologics alters the outcomes of inpatient severe UC. We aimed to assess the outcomes of hospitalized severe UC patients exposed to biologics in the outpatient setting.

Methods

This was a multicenter, retrospective study of adult patients hospitalized with severe UC at University of Cambridge, Cambridge, St. Mark’s Hospital, London and Yale University, Connecticut (from 1/1/2012-11/1/2021). We included adult patients (age ≥ 18 years) who were hospitalized for a severe UC flare as determined by the treating clinician. The primary outcome was need for colectomy among outpatient biologic exposed vs biologic naïve patients. Secondary outcomes stratified by outpatient biologic exposure included length of hospitalization and need for rescue medical therapy.

Results

A total of 382 patients (53.2% male) with a median age of 35 years [interquartile range (IQR) 25-53] were reviewed. Outpatient biologic exposure was noted in 23.2% (n=86, 52 exposed to infliximab) while 76.8% (n=284) were naïve to biologics. Median disease duration was longer in the biologic exposed group at 6 years (IQR 2-11) compared to 2 years (IQR 1-8) in the biologic naïve group (p < 0.001). Biologic exposed group was more likely to have pancolitis (70.2% vs. 54.7%; p=0.04). The C-reactive protein (CRP) to albumin ratio was higher in the biologic naïve group was higher at 12.8 (IQR: 3.2-35) vs. 8 (IQR: 1-21.5) (p=0.004).

The biologic exposed group was more likely to undergo colectomy at 25% (n=21) vs. 9.3% (n=26) in the biologic naïve group (p<0.001). The median hospital length of stay was 6 days (IQR: 4-9) in both groups (p=0.96). Need for rescue medical therapy 37.7% (n=107) in the biologic naïve group vs. 41.9% (n=36) in the biologic exposed group (p=0.49).

Colectomy was associated with outpatient biologic exposure (44.7% vs. 19.9%, p=0.0002), Mayo UC endoscopic sub-score of 3 (81.6% vs. 55.1%, p=0.002), higher median CRP [70.6 (IQR:26.8-126.3) vs. 38.8 mg/dL (IQR: 9.7-94.7), p=0.04], lower median albumin [3 (IQR: 2.7-3.6) vs. 3.5 (IQR: 3-4) g/dL, p=0.0002], and female sex (61.2% vs. 44.8%, p=0.03). On multivariable analysis, only low albumin was independently associated with risk of colectomy (odds ratio: 3.31, 95% confidence interval 1.59-6.87, p=0.0005)

Conclusion

In our multicenter cohort, outpatient biologic exposure was associated with increased risk of colectomy among hospitalized patients with severe UC but on multivariable analysis only low albumin was independently associated with risk of colectomy. Further study of larger cohorts is warranted.
P715 Multiparametric assessment of IBD and SpA-IBD patients to explore disease biomarkers and response predictors
Authors: Privitera G , Parisio L , Perniola S , Varca S , Alivernini S , Tolusso B , Petito V , Napolitano D , Schiavoni E , Scaldaferri F , Gasbarrini A , Armuzzi A , Gremese E , Guidi L , Pugliese D
Published: January 2024

Background

Immune-mediated inflammatory diseases (IMID) are an emerging problem in Western world. Despite being traditionally considered nosologically distinct entities, two or more IMID can coexist within the same patient and their pathogenesis overlap to a certain extent. Two IMID, inflammatory bowel disease (IBD) and spondylarthritis (SpA), often associate, but their pathogenesis remains unknown and disease biomarkers are not fully characterized. This project aims to investigate pathogenic and predictor markers of response

Methods

A collaborative study, enrolling IMID patients (pts) starting a target therapy, was performed. We focused on 2 cohorts: IBD and IBD-SpA. At baseline, serum (to measure CRP, IL17A, TNFα, and TREM1), intestinal biopsy and stools were collected. Clinical response was assessed at 4 months. The exploratory outcome of this preliminary analysis was to investigate whether serum, immunohistochemical and microbiological markers correlate with each other and with response to therapy

Results

We enrolled 60 pts (36 IBD, 24 IBD-SpA): 61.7% were female, median age was 46 years (IQR 30-57.3). At 4 months, 52.8% and 41.7% of the IBD and IBD-SpA cohorts showed clinical response. A nearly significant correlation between increased intestinal CD68+ cell infiltrate and higher baseline CRP levels (R=0.52, p=0.06), and between increased CD21+ cell infiltrate and CRP drop at 4 months (R=0.47, p=0.09) was observed. Lower baseline TNFα levels correlated with CRP drop at 4 months (R=0.35, p=0.02); higher baseline TNFα levels correlated with a reduced intestinal infiltrate of CD20+ and CD21+ cells (R=0.67, p=0.04; R=0.69, p=0.04). In the IBD-SpA cohort, a trend towards higher mean TREM1 levels was observed in non-responders vs responders (389.0 pg/mL vs 276.4 pg/mL, p=0.09); ROC curve identified a cut-off of 361.0 pg/mL to predict nonresponse (sensitivity 66.6%, specificity 75.0%, p=0.09). IBD patients had a reduced α-diversity compared to healthy controls (HC) and SpA patients; IBD and SpA patients had an increased β-diversity compared to HC. IBD pts had increased Proteobacteria and decreased Bacteroidetes compared to HC. Agathobacteria, Bacteroides, Faecalibacteria and Prevotella genera were significantly decreased in IBD vs HC, whereas Streptococci and Escherichia-Shigella were significantly increased

Conclusion

Baseline TNFα may correlate with specific immune signatures of the intestinal infiltrate. Baseline TREM1 may help predicting response in the specific setting of concomitant IBD and SpA. Gut microbiome composition is altered in IBD pts compared to HC, comprising more pathogenic and fewer protective bacteria. Further analyses will be needed to confirm such observations and explore additional features and predictive biomarkers