Biomarker For Remission Research Articles

P0420 Interim analysis of real-world-data on PROs and biomarker remission collected through the Health Outcome Observatory (H2O) consortium in IBD patients

Abstract Background The Health Outcome Observatory (H2O) project aims to standardize and facilitate the collection of patient reported outcomes (PROs) and clinical outcomes by Core Outcome Sets (COS) in patients with inflammatory bowel disease (IBD).1 The present study describes preliminary data on clinical and biomarker remission as well as quality of life. Methods This is a real-world interim analysis of IBD patients included in the H2O project at the Medical University of Vienna, Austria, and the Hospital Universitari Vall d’Hebron, Barcelona, Spain. The variables analyzed were part of the COS. Clinical remission was defined by PRO-2 (for Crohn’s disease (CD): number of liquid or very soft stools ≤3, abdominal pain score ≤1; for ulcerative colitis (UC): rectal bleeding score=0, stool frequency score ≤1), biomarker remission by faecal calprotectin (<150g/g) and C-reactive protein (<0.5mg/dl), and quality of life by PROMIS_10_Q02 (quality of life answered as very good or excellent). Co-primary endpoints were clinical and biomarker remission and a very good or excellent quality of life. A descriptive analysis was performed. Results 532 patients were included in Austria (221 female [42%]; 298 CD, 178 UC, 6 IBDU, 50 with missing diagnosis) and 30 in Spain (14 female [47%]; 18 CD, 12 UC). 138 of 532 patients in Austria (26%) did not provide PRO data. The majority of patients were on advanced therapies (CD: 221/298; 77%; UC: 118/178; 66%). Among CD patients 175 were in PRO-2 remission in Austria (80%) and 13 in Spain (72%), the corresponding numbers of patients in UC PRO-2 remission were 86 in Austria (62%) and 11 in Spain (92%). Biomarker remission was observed in 128/240 CD patients (53%) and 84/135 UC patients (62%). Detailed results of the PRO-2 and of the biomarker values of the Austrian IBD patients are given in Table 1. Very good or excellent quality of life was reported by 97/224 (43.3%) CD patients and 69/140 (49.2%) UC patients. 77/240 CD patients (32%) and 58/135 UC patients (43%) were in clinical PRO-2 as well as biomarker remission and had a very good or excellent quality or life. Conclusion While a large number of IBD patients in tertiary university centers were in clinical PRO-2 remission a lower number of patients had a very good or excellent quality of life. Biomarker remission was achieved almost equally often as clinical PRO-2 remission in UC patients but less often in CD patients. About one third of the patients were in clinical PRO-2 and biomarker remission and had a very good or excellent quality of life. Despite the frequent use of advanced therapies there is a need for treatment optimizing to reach all treatment goals.

P1138 Curcumin-QingDai combination for patients with active Crohn’s disease: Initial real-world experience from a retrospective multi-center cohort study

Abstract Background A combination of Curcumin and QingDai (CurQD) was shown to exert aryl-hydrocarbon-receptor (AhR) pathway activation and to be effective in ulcerative colitis. However, its benefit in Crohn’s disease (CD) has not been studied Methods A retrospective cohort study of patients with active CD treated with CurQD at three academic centers. Active disease was defined by PRO-2 SF≥2 and AP ≥1. The primary endpoint was the rate of clinical remission at the end-of-induction (weeks 8-12), PRO2 SF≤1 and AP=0. Secondary endpoints included biomarker response (FCP drop ≥50% in a patient with FCP >250mcg/gr at baseline) and remission (FCP drop ≥50% and FCP<250mcg/gr at end-of-induction) and CurQD retention. Public-domain GTEx dataset was explored for mRNA expression of the target AhR in colon versus small intestinal mucosa Results Thirty patients were identified for the safety dataset, of whom 13/30 (43%) were bio-experienced, and 25 were eligible for inclusion in the efficacy analysis,. Clinical PRO2 remission at the end of induction was achieved in 12/25 (48%) of patients and clinical response in 19/25 (76%), with an overall reduction in median PRO2 score from 15 (95%CI 13-19.7) to 4 (95%CI 2-8.7, p<0.001). Biomarker remission and response were observed in 11/20 (55%) and 15/20 (75%), respectively, of patients with baseline FCP>250mcg/gr, with an overall reduction in median FCP from a baseline 639 mcg/gr (95%CI 128-5480) to 138mcg/gr (95%CI 5-1470, p=0.001). Biomarker remission was observed in 8/11 (73%) of patients with colonic-involving L2/L3 disease versus 3/9 (33%) L1 extent (OR 4.5, 95%CI 0.8- 24, p=0.08). After 8-months’ median follow-up (range 2-26 months), 16/19 (84%) of responding patients were still taking CurQD. Three patients experienced headaches and three had abdominal pain/diarrhea. Two of the six stopped CurQD due to these symptoms. One patient had elevated liver transaminases X3/normal, which resolved upon halving CurQD dose. To explore if the signal for a difference in efficacy in patients with or without colonic involvment relates to different expression of the target AhR in colon versus small bowel, an analysis of GTEx dataset was performed, which revealed comparable AhR mRNA expression levels in human colonic and terminal ileum segments. Conclusion In this first-reported real-world experience, the AhR-agonist CurQD was effective in inducing and maintaining clinical and biomarker remission in CD patients, including in biologic-experienced patients

DOP094 Improvement in biomarkers in patients with ulcerative colitis treated with vedolizumab: Results from the continuing VERDICT trial

Abstract Background Treatment targets in ulcerative colitis (UC) include symptomatic remission, endoscopic remission, and histologic remission. The ongoing VERDICT trial (NCT04259138) aims to determine the optimal treatment target in patients with moderately-to-severely active UC.1,2 Patients follow treatment algorithms involving early use of vedolizumab (VDZ). Here we report biomarker changes (fecal calprotectin [FCP] and C-reactive protein [CRP]) from baseline to weeks 8, 16, 32 and 48. Methods VDZ 300 mg was administered intravenously following a treatment algorithm related to baseline UC treatment until assigned treatment target was reached, with an escalation step between week 16, 32 and 48 as indicated. Treatment targets were as follows: Group 1 (corticosteroid-free [CSF] symptomatic remission), Group 2 (CSF symptomatic remission + CSF endoscopic remission), and Group 3 (CSF symptomatic remission + CSF endoscopic remission + CSF histologic remission, also termed disease clearance). CSF symptomatic remission was defined as Mayo rectal bleeding subscore=0, CSF endoscopic remission was defined as Mayo Endoscopic Score [MES]≤1, and CSF histologic remission was defined as Geboes score<2B.0. Biomarker assessments included FCP and CRP at weeks 8, 16, 32, and 48. Biomarker remission was defined as FCP ≤250 mg/kg and CRP ≤5 mg/l. Results As of 1st October 2024, 672 patients were enrolled, with 185, 222, and 265 patients in Groups 1, 2, and 3, respectively. Biomarkers improved from baseline to Week 16 and incrementally through to Week 48 (Table). Mean changes from baseline to Week 48 in FCP in groups 1, 2, and 3 were: -1268.8 mg/kg, -1515.9 mg/kg, and -1230.1 mg/kg (Table). For CRP, mean changes from baseline to Week 48 were -1.5 mg/l (Group 1), -3.4 mg/l (Group 2), and -1.8 mg/l (Group 3). For FCP, mean changes to Week 48 in all 3 groups were greater in bio-exposed than bionaïve patients, whereas mean change in CRP was greater in bio-exposed patients in Group 1 only (Table). In patients who achieved biomarker remission (FCP≤ 250 mg/kg + CRP ≤5 mg/l) at Week 48, the proportions who had met their treatment target were 51.6% (Group 1), 57.1% (Group 2), and 48.6% (Group 3) [Figure]. Higher baseline FCP was associated with lower odds of histologic remission at Week 16, 32, and 48, with corresponding odds ratios (95% CI) for histologic remission per 100 µg/g increase of baseline FCP of 0.89 (0.86, 0.93), 0.89 (0.86, 0.93), and 0.82 (0.76, 0.87). Conclusion Biomarker data from VERDICT shows improvements in FCP and CRP concentrations from baseline to Week 16, with incremental improvements through to Week 48. Almost half or more of all patients who achieved biomarker remission achieved their assigned treatment target.

OP35 Low remission recapture after ustekinumab dose optimization in Crohn’s disease: results of the randomized placebo-controlled double-blind REScUE study.

Abstract Background In Crohn’s disease (CD), an exposure-response relationship exists for ustekinumab, with higher serum levels associated with better outcomes. Although several retrospective and observational studies demonstrate dose-escalation of ustekinumab can be effective in case of secondary loss of response (LOR), prospective placebo-controlled data are lacking. The aim of the REScUE study (NCT04245215) was to investigate the effect of 2 different re-induction regimens with ustekinumab on clinical, endoscopic, biological and pharmacological outcomes in patients with CD. Methods This Belgian multicentre prospective double-blind randomized placebo-controlled trial included adult patients with CD treated with ustekinumab who presented with secondary LOR to ustekinumab after documented primary response. Secondary LOR was defined by PRO-2 (AP> 1 AND SF> 3) and confirmed by either an elevated biomarker (CRP >5 mg/L or faecal calprotectin >250 µg/mg) or endoscopic signs of inflammation. All patients received a single IV re-induction with ustekinumab (≈6mg/kg) and were then randomized 1:1 to blinded maintenance ustekinumab 90 mg SC Q4W (intervention) or 90 mg SC Q8W (control) for 48 weeks. Primary endpoint was proportion of patients with steroid-free clinical remission (definition in fig 1) at week 48, with missing data were handled using non-responder imputation. Results In total, 132 patients were screened, and 108 patients were included: 67% female, median [IQR] age 41 [32-54] year, median disease duration 14 [7-22] years. Prior anti-TNF exposure was reported in 92% of patients, while ustekinumab was the first-line advanced treatment in 7% of patients. The primary endpoint of steroid-free clinical remission at week 48 was achieved by 9/54 (17%) patients in the q4w regimen vs 8/54 (16%) in the q8w regimen (p=0.96) (fig 1). Endoscopic remission (SES-CD <3) was achieved in 5/54 (10%) vs 3/54 (6%) (p=0.52), endoscopic response (≥50% decrease in SES-CD from baseline) was achieved in 11/54 (22%) vs 6/54 (12%) (p=0.23) and 0.52biomarker remission was achieved in 20/54 (38%) vs 13/54 (26%) (p=0.19) in the q4w regimen vs the q8w regimen, respectively. Time to first clinical remission was similar between groups (fig 2). Association with ustekinumab serum levels will be reported. No new safety signals were observed. Conclusion In patients with CD experiencing secondary LOR to ustekinumab, dose optimization with a single IV re-induction followed by intensified maintenance dosing (90 mg SC q4W) was not superior to a single IV re-induction followed by conventional maintenance dosing (90 mg SC q8W) in achieving steroid-free clinical remission. The secondary endpoints were numerically higher but not significant in the intensified regimen.

P0832 Real-world effectiveness of risankizumab in Crohn’s Disease: The UK Experience

Abstract Background Risankizumab is an IL-23 inhibitor which received approval for Crohn’s disease (CD) by the NICE committee in May 2023. Our aim was to evaluate the real-world outcomes of risankizumab in the United Kingdom (UK). Methods We conducted a retrospective, multicentre, cohort study across twenty health boards in the UK, of patients with CD treated with risankizumab between the 1st of January, 2021 and the 1st of November 2024. Our primary outcome was treatment persistence at 6 months. Our secondary endpoints were treatment persistence, steroid-free clinical remission (Harvey-Bradshaw index <5), biomarker remission (CRP ≤5 mg/L and FCAL <250 µg/g), at 3, 6 and 12 months, and if effectiveness was different between ustekinumab naive and exposed patients. Patients who discontinued therapy for any reason were considered treatment-failure for all indices after the time point they ceased therapy. We recorded adverse events, including hospitalisation, bowel resection, infection, and death. Results We identified 558 patients who commenced risankizumab, of which 526 patients had 3 month outcome data available with a median follow-up time of 28 weeks (IQR, 19-41 weeks). The median number of advanced therapy exposures were 3 (2-4), with 90% (475/526) having failed anti-TNF therapy, and 73% (382/526) having failed ustekinumab (Table 1). Treatment persistence was 97.5%, 94.8% and 89.5% at 3, 6 and 12 months (Figure 1). Unadjusted persistence rates for ustekinumab naïve vs ustekinumab exposed patients were 93.8% vs 95.3% and 93.8 % vs 89.3% at 6 and 12 months respectively (p=0.7). Rates of clinical remission were 59% (211/358), 50% (77/154), and 44% (14/32) at 3, 6 and 12 months. Rates of clinical remission for ustekinumab naive vs exposed were 67% (70/104) vs 55% (141/253) and 60% (21/35) vs 47% (56/119) at 3 and 6 months respectively. CRP remission rates were 57% (266/465), 52% (108/208), and 53% (28/53) at 3, 6 and 12 months. FCAL remission rates were 58% (140/243), 48% (55/114), and 44% (17/38) at 3, 6 and 12 months. There was a significant reduction in median HBI, CRP and FCAL during follow-up (Figure 1). We observed that 12% (62) of patients were hospitalised due to symptomatic CD (58) or an implicated adverse event (4). We observed that 3% (17/526) underwent CD related resectional surgery. Adverse events occurred in 16% (85/526) of the cohort. Serious adverse events occurred in 5% (28/526), of which 25 were hospitalisations. Conclusion Risankizumab was effective in a large, real-world, medically refractory CD cohort with excellent short-term persistence and good clinical and biochemical remission rates. Persistence rates were similar between ustekinumab naive and exposed patients, however clinical remission rates were higher in the naive group.

P0662 Comparative effectiveness and safety of upadacitinib, tofacitinib, and filgotinib in patients with Ulcerative Colitis: analysis of whole and propensity score-matched data

Abstract Background Moderate-to-severe Ulcerative Colitis (UC) often requires advanced treatments. Janus kinase (JAK) inhibitors, upadacitinib, tofacitinib, and filgotinib, have demonstrated efficacy in UC, though real-world comparisons remain limited. This retrospective, single-center study conducted at the Padua Hospital outpatient clinic compares the effectiveness and safety of these agents in patients with UC, analyzing clinical, endoscopic, and biomarker remission rates, adverse events, and therapy discontinuations using both full dataset and propensity score-matched (PSM) analyses. Methods We retrospectively included UC patients which started anti-JAK therapies at Padua Hospital and collected data for a follow up of 12 months. Whole data analysis was conducted first, followed by PSM based on age, sex, and disease location. Outcomes included clinical, biomarker, and endoscopic remission rates at 3 months (T1), 6 months (T2), and 1 year (T3), adverse events and discontinuation rates. Chi-square or Fisher’s exact test were used for categorical data, ANOVA for continuous data. Results Our study included 46 patients with UC patients (16 on upadacitinib, 23 on tofacitinib, 7 on filgotinib) treated at Padua Hospital. In the whole dataset at T3, clinical remission was 5/15 (33.3%) for upadacitinib, 12/20 (60.0%) for tofacitinib, and 3/4 (75.0%) for filgotinib (p=0.18). Endoscopic remission at T3 was 4/15 (26.7%) for upadacitinib, 7/20 (35.0%) for tofacitinib, and 1/4 (25.0%) for filgotinib (p=0.84). Total adverse events were observed in 12/16 (75.0%) of upadacitinib, 18/23 (78.3%) of tofacitinib, and 6/7 (85.7%) of filgotinib patients (p=0.74). Discontinuations were highest for filgotinib, with 4/7 (57.1%) vs. 1/16 (6.2%) for upadacitinib and 4/23 (17.4%) for tofacitinib (p=0.01). After matching, at T3, biomarker remission was 1/5 (20.0%) for upadacitinib, 1/5 (20.0%) for filgotinib, and 1/4 (25.0%) for tofacitinib (p=0.58). endoscopic remission at T3 was achieved by 1/5 (20.0%) for upadacitinib, 2/5 (40.0%) for filgotinib, and 1/4 (25.0%) for tofacitinib (p=0.55).Total adverse events were 3/7 (42.9%) for upadacitinib, 4/7 (57.1%) for filgotinib, and 3/7 (42.9%) for tofacitinib (p=0.67). Discontinuation rates were 2/7 (28.6%) for upadacitinib, 2/7 (28.6%) for filgotinib, and 1/7 (14.3%) for tofacitinib (p=0.81). Conclusion This study suggests variable effectiveness among JAK inhibitors, with tofacitinib showing higher clinical remission trends. Filgotinib showed higher discontinuation in the whole dataset but differences were less pronounced post-matching. Personalized treatment decisions may benefit UC management; larger studies are needed to confirm findings.

P1064 Association of subcutaneous infliximab CT-P13 serum levels and therapeutic outcomes in patients affected by Inflammatory Bowel Disease: A retrospective international multicentric study

Abstract Background The association between therapeutic outcomes and serum levels associated with the use of subcutaneous (SC) IFX CT-P13 in patients with inflammatory bowel disease [IBD] has been poorly studied. We aimed to define SC-IFX thresholds associated with therapeutic outcomes. Methods Patients receiving SC-IFX who had at least one therapeutic drug monitoring [TDM] were enrolled. Therapeutic outcomes were assessed as follows: clinical remission [HBI <5, SCCAI ≤2]; fecal calprotectin [FCAL] remission [<250 mg/g]; C-reactive protein [CRP] remission [CRP <5 mg/L]; deep remission [clinical + biomarker remission]. Chi-squared test for trend was used to analyze serum levels quartile data. Results 177 patients [54% male; 67% Crohn’s disease; Weight ≥ 80 kg 51%; 7% active smoker; 39% on immunosuppressants [IMM]; 9% on steroids; 26% with previous biologic exposure] from 4 centres had a total of 263 TDM measurements. Of these, were available 242 concurrent clinical measurement, 244 CRP and 152 FCAL.Median duration of SC treatment at time of TDM was 24 months (4-135). Proportion of patients achieving outcomes is described in table 1. The median IFX serum level was significantly higher in patients with clinical remission as well as in those with clinical and CRP remission (Figure 1), compared with patients who did not reach these targets. Conversely, there was no significant difference for the FCAL, clinical and FCAL, clinical and CRP and FCAL outcomes. In univariate analysis of factors associated with clinical remission (p<0.1) were sex, concomitant IMM, concomitant steroids, and previous biologic exposure and were included in a multivariate analysis in which only concomitant IMM showed remained significant [OR 0,1796 CI 95% 0,028-0,633]. Quartile analysis showed better outcome on higher drug levels for clinical remission, but not for other outcomes. Based on the ROC analysis and the Youden index, the cut-off levels for the therapeutic outcomes were respectively: clinical remission 12.85 mg/ml [sensitivity 0.85, specificity 0.5]; FCAL remission 11.8 mg/ml [sensitivity 0.82, specificity 0.32]; clinical and CRP remission 14.55 mg/ml [sensitivity 0.77, specificity 0.44]; clinical and FCAL remission 12.05 mg/ml [sensitivity 0.85, specificity 0.35]; clinical, CRP and FCAL remission12.05 mg/ml [sensitivity 0.85, specificity 0.33]. Conclusion An association between drug levels and clinical outcomes was identified in patients with IBD treated with SC IFX. Clinical remission was associated with a level of 12.8 mg/ml but the association between higher drug levels and deeper remission that has been described previously was not seen. References Roblin X, Nancey S, Papamichael K, et al. Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(5):679-685. doi:10.1093/ecco-jcc/jjad188 Iborra M, Caballol B, Garrido A, et al. Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry. J Crohns Colitis. Published online August 22, 2024. doi:10.1093/ecco-jcc/jjae127

P0536 Clinical profile and treatment outcomes in patients receiving advanced therapies for ulcerative colitis – the READ-UC real-world study

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that requires effective treatment with the main goal of inducing and maintaining remission. This study aimed to characterize UC patients receiving advanced therapies (AT), by describing their demographic and clinical characteristics and remission outcomes. Methods Cross-sectional and retrospective study in 5 IBD referral centres. Eligible subjects (≥18 years-old with UC diagnosis and receiving AT for ≥16 weeks) were consecutively enrolled at a standard of care appointment (study appointment). The primary endpoints were the proportion of patients achieving remission, defined as both symptomatic [Mayo subscores stool frequency of 0 or 1 and rectal bleeding of 0] and faecal biomarker remission [faecal calprotectin <150 µg/g]. Data on patients’ demographic and clinical characteristics, including extraintestinal manifestations (EIMs), comorbidities and treatment patterns, and on healthcare resource utilization were also collected. Results The study included 219 patients (50.9% female, median [P25;P75] age 46 [36;58] years) presenting a median disease duration of 9 [5;14] years. History or current evidence of EIMs and comorbidities were reported in 13.7% and 43.8% of patients, respectively. At diagnosis, 17.0% of patients had ulcerative proctitis, 38.1% had left-sided UC, and 44.8% had extensive UC. Over half (58.4%) were diagnosed with moderate or severe UC. Most patients (57.1%) were on their first AT, mostly on infliximab (47.5%) and vedolizumab (37.4%), while a minority received ustekinumab (5.9%), adalimumab (5.5%), tofacitinib (2.3%), and golimumab (1.4%). After treatment (26 [14; 47] months), symptomatic and faecal biomarker remission was achieved in 35.2% of patients, while 83.9% presented symptomatic remission and 46.1% of patients attained faecal biomarker remission (). There were no significant differences between patients who achieved symptomatic and faecal biomarker remission and those who did not (Table 1). Patients were prescribed concomitant specific therapies [5-ASA derivatives (78.0%), immunosuppressants (34.7%), and steroids (6.4%)]. Steroid-free remission was achieved in 34.9% of patients (Figure 1), who were off this medication for a median of 26 [15;45] months. Since AT initiation, 20.6% of patients relapsed, 11.9% were hospitalized, and 27.4% visited an emergency department. Conclusion The READ-UC study provides a detailed real-world characterization of UC patients on AT. The high proportion of patients not achieving symptomatic and faecal biomarker remission or steroid-free remission, highlights the urgent need for implementing strategies that improve UC management and outcomes of these patients.

P0667 Therapeutic Optimization of Biologic Therapy in Ulcerative Colitis: A Retrospective Analysis of Endoscopic and Biomarker Outcomes

Abstract Background Biologic therapies have transformed the management of ulcerative colitis (UC), offering effective options for achieving remission. However, some patients require therapy optimization, guided by clinical and endoscopic assessments, to enhance outcomes. Despite their routine use, real-world comparisons of optimization strategies for different biologics remain limited. This study evaluates the impact of endoscopy-guided optimization on remission rates and safety profiles in a UC cohort. Methods This retrospective study included consecutive patients at the Humanitas outpatient clinic from 2021 to 2023 who underwent endoscopy-guided therapy optimization. All patients had minimal clinical activity (pMayo score <2) and underwent colonoscopy to assess biologic therapy response. Statistical analyses included the Student’s t-test or Mann-Whitney U test for continuous variables, and chi-square or Fisher’s exact test for categorical variables. Propensity score matching (PSM) was used to balance baseline characteristics, including bio-experienced status. Results A cohort of 176 UC patients was included. Among them, therapy optimization with anti-TNFs was used in 41.2% for infliximab, 19.9% for adalimumab, and 4.6% for golimumab, while 14.4% received ustekinumab and 17.1% vedolizumab. Multivariate logistic regression analysis identified key predictors for outcomes: patients who were biologic-experienced at baseline had significantly reduced odds of achieving endoscopic remission at 12 months following optimization (odds ratio [OR] = 0.223, 95% CI: 0.070–0.711, p = 0.011). Other variables, including age at diagnosis, disease extent, and specific biologic therapy (anti-TNF vs. ustekinumab vs. vedolizumab), were not statistically significant predictors of remission. In the PSM-adjusted dataset, endoscopic remission rates were 61.5% for anti-TNFs, 33.3% for ustekinumab, and 60.0% for vedolizumab (p = 0.666, chi-square test). Biochemical remission was also highest in the anti-TNF group (61.8%), significantly greater than in ustekinumab (26.7%) and vedolizumab (53.3%) (p = 0.042, chi-square test). Adverse events were least frequent in the ustekinumab and vedolizumab groups, with only 3.5% reported for anti-TNFs (p = 0.293, Fisher’s exact test). Adverse events remained low across all groups, with a tendency toward fewer events in the ustekinumab and vedolizumab groups compared to anti-TNFs, though these differences were not statistically significant (p = 0.324, Fisher’s exact test). Conclusion The optimization of Anti-TNFs showed superior endoscopic healing and biomarker remission rates compared to ustekinumab and vedolizumab, with all groups exhibiting low adverse event rates.

N11 Switching from intravenous to subcutaneous infliximab enhances trough levels and can facilitate de-escalation of concomitant immunomodulation, irrespective of the HLA DQA1*05 status: a prospective real-world study

Abstract Background There is emerging data on the continued efficacy of infliximab when switched from intravenous (IV) to subcutaneous (SC) route in Inflammatory bowel disease (IBD). The impact of cessation of concomitant immunomodulators (IMMs) following switch on trough levels or development of anti-drug antibodies (ADAs) is not evaluated in real world practice. We aimed to study the impact of cessation of IMMs following switch of infliximab from IV to SC route and determine relationship with HLA- DQA1 *05 status. Methods Consecutive patients who participated in a planned switch programme were prospectively included. Clinical, biomarker and pharmacokinetic data were collected pre-switch, and at 8 weekly intervals post switch for 6 months. Trough levels and remission status in patients who discontinued or reduced the dose of IMMs were compared with those who remained or continued same dose on IMMs. All patients had HLA-DQA1*05 status determined at initiation of Infliximab and we evaluated the impact of HLA status on development of anti-Infliximab antibodies post switch. Results One hundred and fifteen patients (M: F=1.4:1, Median age 44 years (13-76), UC/CD (48/67) who completed 6 month follow up were included. All patients were in clinical and biomarker remission prior to the switch. 72 patients (62.6%) were on concomitant IMMs and 46 (40.86%) was HLADQA1*05 positive. The mean infliximab trough level prior to switch was 5.54 µg/mL which increased 8 weeks post switch to 12.52 µg/mL (p=0.006). The enhancement of levels persisted at 16 weeks (Mean 16.28) and at week 24 (17.25). 36 patients (32%) were positive for ADAs before switch; in 8 patients (22%) the ADAs disappeared at 8 weeks and in further 4 (total 33%) by 6 months. In total antibody titre reduced or become negative in 17 patients (48.6%), static in 14 patients (40%) but increased in 5 patients (14%) without significant lowering of trough levels. 18 of the 72 patients (25%) had IMMs discontinued, and dose reduced in further 21 patients. The total de-escalation rate was 54% and none of these patients developed ADAs at 6 months irrespective of the HLADQA1*05 status (HR = 0.76, 95% = 0.64 to 1.73, p 0.12). One patient switched back to IV due to personal preference. At 6 months none of the patients discontinued SC infliximab or were switched within or out of class. Conclusion Switch from IV to SC infliximab is effective in maintaining and enhancing trough levels with positive impact on reducing ADAs. It is feasible to de-escalate concomitant IMMs in a considerable proportion of patients following switch. Economic analysis of switch should be incorporated in the feasibility of IMMs withdrawal.

Tofacitinib versus Vedolizumab Among Bio-naïve Patients with Ulcerative Colitis: A Real-World Propensity-Weighted Comparison.

Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic-naïve patients. We aimed to compare the persistence, effectiveness and safety of tofacitinib and vedolizumab as the first advanced treatment for patients with UC. Patients who received either tofacitinib or vedolizumab as their first advanced therapy for UC in NHS Lothian were included. We used inverse probability of treatment weighting (IPTW). The probability of treatment assignment was calculated via logistic regression using age, sex, UC duration, Montreal extent, CRP, concomitant corticosteroids, and partial Mayo score at drug commencement. We included n=158 patients, of whom n=81 (51.3%) received vedolizumab and n=77 (48.7%) tofacitinib. Median follow-up for vedolizumab patients was 3.1 years (IQR 1.6-4.8) and for tofacitinib patients 1.5 years (IQR 0.3-2.3). The cohort was 59.5% male with a median age of 41.1 years (IQR 31.5-51.8). At two years, vedolizumab persistence was superior to tofacitinib (p=0.005). At week 12 and week 52 clinical, biochemical and fecal biomarker steroid free remission were comparable between groups. Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. Frequency of adverse events was comparable (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629). We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bio-naïve UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy.

Treat-to-Target in Inflammatory Bowel Disease: An Updated Survey of Treatment Strategies among Portuguese Gastroenterologists

Background: In 2018, the authors surveyed the clinical practices among Portuguese gastroenterologists (PGEs) regarding treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC). Since then, new evidence has emerged supporting additional targets, such as transmural remission and histological remission. This study provides an updated assessment of treatment practices among PGE with special emphasis on these new targets. Methods: Using the Portuguese Inflammatory bowel disease Study Group (GEDII) physician database, we invited PGE to participate in an anonymous online survey. Results: Fifty-six physicians agreed to participate in the study. Deep remission, steroid-free clinical remission, endoscopic remission, and biomarker remission were ranked among the most important treatment targets in CD (89%, 80%, 89%, and 84%, respectively) and UC (82%, 84%, 79%, and 84%, respectively). In CD, transmural remission was considered a target by 70% of participants, with 48% agreeing to intensify treatment to achieve it. In UC, histological remission was aimed by only 45% of PGE with most (88%) being unwilling to intensify treatment to achieve this goal. Physicians were more likely to seek endoscopic remission in CD and UC in younger and healthier patients, compared to older patients with comorbidities. Conclusion: PGEs are increasingly pursuing tougher treatment targets such as transmural remission in CD and, to a lesser extent, histological remission in UC. Physicians are more willing to escalate treatment to achieve endoscopic remission in younger patients.

Evaluación de la sensibilidad y especificidad de la sigmoidoscopia en comparación con la colonoscopia en la detección de actividad inflamatoria intestinal en el seguimiento de pacientes con colitis ulcerosa

IntroductionUlcerative colitis (UC) is a chronic disease characterized by periods of inflammatory activity and remission, which vary from the rectum to the proximal colon. Currently, mucosal healing is a long-term goal in the management of inflammatory bowel disease, with colonoscopy and sigmoidoscopy being the recommended tools for evaluation. ObjectiveTo assess the effectiveness of both examinations in determining the presence of inflammatory activity in the follow-up of patients with UC. MethodsRetrospective observational study analyzing colonoscopies performed as part of the follow-up of UC patients between January 2021 and July 2023 by gastroenterologists from the Inflammatory Bowel Disease Program at the Clínica Universidad de los Andes. The study compared endoscopic and histological activity observed in the rectosigmoid region with that found in the rest of the colon. Sensitivity and specificity were determined using concordance and correlations tests. ResultsA very good concordance and correlation were observed regarding endoscopic findings, with a Kappa index of 0.97 and a Spearman coefficient of 0.97. The Positive Predictive Value (PPV) of sigmoidoscopy for endoscopic activity was 1, and the Negative Predictive Value (NPV) was 0.96. In relation to histological activity, the concordance had a Kappa index of 0.93 and a Spearman coefficient of 0.93, with a PPV of sigmoidoscopy for histological activity being 1 and an NPV of 0.91. ConclusionThis cohort suggests that sigmoidoscopy is a cost-effective option for evaluating mucosal healing in UC patients in symptomatic and biomarker remission. However, complete colonoscopy should be considered in cases of discrepancies with the clinical picture or in colorectal cancer surveillance.

Real-world effectiveness of upadacitinib in Crohn’s disease: a UK multicentre retrospective cohort study

BackgroundUpadacitinib is a Janus kinase inhibitor, which has recently been approved for treating Crohn’s disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn’s disease.ObjectiveOur aim was...

Real-World Outcomes of Dual Advanced Therapy in Children and Young Adults with Inflammatory Bowel Disease.

Data are limited on the safety and efficacy of combining advanced therapies for refractory patients with IBD. To evaluate the real-world efficacy and safety of dual advanced therapy (DAT), combining 2 biologics or a biologic with a small molecule, in children and young adults with refractory IBD. Primary outcome of this single IBD center cohort was DAT remission (clinical and biomarker remission) at first assessment (T1). Secondary outcomes included remission at T2, if DAT de-intensification (De-I) occurred and T3, if T2 DAT re-intensification (Re-I) occurred. Efficacy and safety outcomes were described. Of the 30 patients [43% female, 30% CD, median age of 18.3 [15.1-19.8] years], all 11 UST + TOFA achieved T1 remission; 6/10 De-I failed at T2; and 4/4 Re-I achieved T3 remission. Of 9 VDZ + TOFA, 6 achieved T1 remission; 5/6 De-I failed at T2; and 1/1 failed T3 Re-I. Of 4 UST + VDZ, 3 achieved T1 remission; 2/3 De-I failed at T2; and 0 had Re-I. Of 5 UST + UPA, 4 achieved T1 remission; 1/5 De-I failed at T2 but recaptured T3 remission post-Re-I. One VDZ + OZA achieved T1 remission and maintained T2 remission post-De-I to OZA monotherapy. At last follow-up, 43% were on original DAT, 17% on one of original DAT, and 40% neither. One UST + TOFA patient developed mild leukopenia and another developed septic arthritis and venous thromboembolism on VDZ + TOFA and prednisone. Most children and young adults treated with DAT achieved remission with minimal safety events; however, de-intensification had limited success.

P772 Comprehensive disease control in patients with Ulcerative Colitis: refinement of a multi-component endpoint using data from the filgotinib SELECTION trial

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 <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<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.

P484 Intestinal Ultrasound Can Detect Active Inflammation In Inflammatory Bowel Disease Patients Despite Combined Clinical And Biomarker Remission

Abstract Background Intestinal ultrasound (IUS) has only recently been implemented in the USA for inflammatory bowel disease (IBD) monitoring. Colonoscopy is considered the gold standard for evaluation of inflammation but may not be feasible for every assessment due to cost, time, and accessibility. Clinical activity scores and biomarkers are used instead as adjunct measures of disease. Since IUS incurs low cost and time with easy accessibility, our study aimed to demonstrate the utility of incorporating IUS into IBD practice by evaluating the sensitivity and specificity of these adjunct measures of inflammation and the impact of decisions made based on IUS. Methods This retrospective cohort analysis evaluated patients with IBD at our institution who underwent IUS from July 2020 to May 2021. The patients were reviewed for repeat IUS visits until July 2022. Patients received IUS regardless of clinical or biomarker remission, and/or if they were able to receive a colonoscopy. Clinical remission was defined as UCAI ≤ 5 and partial Mayo ≤ 2 or HBI ≤ 5. Biomarker remission was defined as ESR ≤ 40 mm/hour; CRP ≤ 8 mg/L; FCP ≤ 125 mg/mg; and fecal lactoferrin ≤ 30 mcg/mL. Combined remission was defined as both clinical and biomarker remission. The sensitivity and specificity of these groups was evaluated based on IUS. Treatment plans were decided based on IUS findings. Patients with normal IUS maintained therapy while those with positive findings required a change/escalation of therapy. These patients had repeat IUS to ensure the changes resulted in reduction of inflammation. Results In 148 total patients receiving IUS, 62% (N=92) had active disease. Clinical remission (figure 1) was 41% sensitive and 75% specific while biomarker remission was 49% sensitive and 58% specific to IUS findings. When combined (clinical + biomarker remission), sensitivity increased to 62% and specificity decreased to 52% (figure 2). There was a total of 39 repeat ultrasounds. Inflammation was improved at repeat IUS, measured by a decrease in overall bowel wall thickness in 77% (30/39) patients for a mean of 0.121 cm. Vascular flow improved in 79% (15/19) of patients with abnormal Doppler at initial IUS by a mean of 0.65, and mural stratification improved in 80% (20/25) of patients with mural disruption at initial IUS. Conclusion Our study showed that even when combining biomarker results and clinical scores, the sensitivity for detecting inflammation was 62%. Additionally, as demonstrated by the improvement in inflammation at IUS follow up, clinical decisions based on IUS results effectively reduced inflammation in IBD patients. As such, IUS is necessary in the management of IBD to effectively identify and treat patients with masked inflammation.

P858 Real World Outcomes of Dual Advanced Therapy in Inflammatory Bowel Disease in Children and Young Adults

Abstract Background There is mounting interest in dual advanced therapy (DAT), combining 2 biologics or biologics with small molecules, in patients with refractory disease or partial responders. We evaluated the real-world efficacy and safety of DAT in pediatric and young adults with IBD. Methods Single-center, cross-sectional cohort study, conducted between 2018-2023. Primary outcome was DAT remission (clinical (Harvey Bradshaw Index ≤ 4 or partial Mayo Score ≤ 2) and biomarker (C-reactive protein ≤ 5 mg/L and/or fecal calprotectin ≤ 250 ug/g) at first efficacy assessment (T1). Secondary outcomes included remission at T2 if intensification or de-intensification occurred at T1 and T3 remission if re-intensification performed at T2. Failures defined those not achieving remission. Adverse events, surgical and therapy outcomes as of last follow up were evaluated. Descriptive statistics summarized the data. Results 30 patients were included [43% female, 57% CD, median age of 18.3 [15.1-19.8] years, 46% <18 years, and median IBD duration of 5.2 [4.0-6.9] years at DAT start] (Table 1). Of 11 (37%) treated with TOFA + UST, 100% achieved T1 remission. Of the 10 de-intensified at T1, 6 failed at T2, and all 4/6 that re-intensified achieved T3 DAT remission. Of 9 (30%) TOFA + VDZ patients, 6 (67%) achieved T1 remission and of the 3 T1 failures, 1 had colectomy, and 1 of 2 attempting VDZ intensification achieved T2 remission. All 6 with T1 remission de-intensified, but 5 (83%) failed and only 1/5 attempted re-intensification and failed. Of 4 (13%) VDZ + UST patients, 3 (75%) achieved T1 remission and the 1 T1 failure achieved T2 remission after VDZ intensification. The 2/4 de-intensified failed at T2 and none were re-intensified. Of 5 (17%) UPA + UST patients, 4 (80%) achieved T1 DAT remission and the 1 failure achieved T2 remission after UPA intensification. The 1 who de-intensified failed at T2 but in T3 remission post re-intensification. One (3%) VDZ + OZA patient achieved T1 remission and successfully de-intensified to monotherapy OZA at T2. One TOFA + UST patient developed mild leukopenia and responded to TOFA de-intensification, and 1 developed septic arthritis on TOFA +VDZ on prednisone and resumed TOFA once resolved. At last follow-up, 14/30 (47%) patients were on DAT, 11 (37%) changed therapy, 1 of which underwent colectomy and 5 (17%) were on monotherapy (Figure 1). Conclusion The majority of IBD patients treated with DAT achieved clinical and biomarker remission with minimal safety events; however, de-intensification to monotherapy has limited success and supports continuing DAT in more refractory patients. Future studies are needed to guide management.

DOP17 Tofacitinib versus Vedolizumab Among Bio-naïve Patients With Ulcerative Colitis: A Real-World Propensity-Weighted Comparison

Abstract Background Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic naïve patients. There are sparse data comparing biologics with small molecules for IBD. We aimed to compare the efficacy, safety and persistence of tofacitinib and vedolizumab as the first advanced treatment for patients with UC. Methods Patients who received tofacitinib or vedolizumab as first advanced therapy for UC in NHS Lothian were included. We capped the upper age limit at 65 years to take into account regulatory guidelines for the use of JAKi as first line therapies across IMIDs. To allow treatment effect to be assessed outside of a randomized trial, we used inverse probability of treatment weighting (IPTW). This approach takes the probability of treatment assignment into account without potentially drastically reducing the analysable cohort size. The probability of treatment assignment was calculated via logistic regression using age, gender, IBD duration, Montreal extent, CRP, concomitant corticosteroids and partial Mayo score at drug commencement. Missing data for these variables were imputed using multivariate imputation by chained equations. Confounder-adjusted survival curves were created using Kaplan-Meier estimates weighted via IPTW. The Pepe and Fleming test was used to compare survival curves from drug commencement to day 1000 of treatment. Results We included 158 patients of whom 81 (51.2%) received vedolizumab and 77 (48.7%) tofacitinib. Median follow-up for patients on vedolizumab was 3.1 (1.6-4.8) years and for tofacitinib 1.5 (0.34-2.3) years. Baseline demographics were comparable except for disease extent (Table 1). At drug commencement there were no differences in steroid prescription (60.5% vedolizumab versus 57.1% tofacitinib), partial Mayo score, CRP or faecal calprotectin. At week 12, steroid free clinical remission was more frequent in the vedolizumab group (69% vs 51.4%, p=0.030) Figure 1B. Vedolizumab persistence was superior to tofacitinib (p=0.005) Figure 1A. Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. There were no differences in the frequency of adverse events (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629). However, adverse events resulting in temporary discontinuation of the drug occurred in 1 (1.2%) vedolizumab versus 11 (14.3%) tofacitinib, p=0.013. Conclusion We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bionaive UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy in UC.

P823 Real-world effectiveness of upadacitinib in Crohn's disease; a UK multicentre retrospective cohort study

Abstract Background Upadacitinib is a Janus kinase inhibitor which has recently been approved for the treatment of Crohn’s disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn’s disease. Our aim was to evaluate the outcomes of upadacitinib in a real-world cohort. Methods We conducted a retrospective, multicentre, cohort study. Our primary outcome was treatment persistence at week 24. Our secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index ≤4), and biomarker remission (CRP ≤5 mg/L and FCAL <250 µg/g). We measured outcomes at 12 weeks, 24 weeks and at last observation. We recorded adverse events. Results We included 74 patients who commenced upadacitinib over a two-year period for analysis, with a median follow-up time of 23 weeks (IQR, 15-39 weeks). All patients had failed anti-TNF therapy, with 78% and 58% additionally failing prior IL12/23 and vedolizumab (Table 1). Treatment persistence was 83.6% at week 12, and 76.6% at week 24 (Figure 1). Reasons for treatment cessation included primary non-response 15% (11/74), secondary loss of response 1% (1/74), and adverse events 12% (9/74). Rates of clinical remission were 58% (32/55) at week 12, 43% (16/37) at week 24, and 52% (35/67) at last observation. CRP remission rates were 45% (27/60) at week 12, 35% (12/34) at week 24, and 44% (30/69) at last observation. FCAL remission rates were 40% (17/42) at week 12, 31% (9/29) at week 24, and 36% (19/53), at last observation. There was a significant reduction in HBI, CRP and FCAL during follow-up (Figure 1). During the maintenance period, 11% (7/61) of the cohort who continued therapy were prescribed corticosteroids. Ten patients (19%) had a hospitalisation due to a Crohn’s flare. Five patients (7%) underwent Crohn’s disease related resectional surgery during the study period. Two were emergency surgeries (3%), and three (4%) were elective surgeries for symptomatic fibrotic strictures, which were present prior to commencing upadacitinib. Thirty-four adverse events were recorded across 29 patients (39%). Serious adverse events occurred in 9 patients (12%), three of which (4%) led to hospitalisation. Conclusion Upadacitinib was effective in a real-world, medically refractory, moderate to severe Crohn’s disease cohort with good persistence.