bluuebunny/crossref_metadata_2025 huggingface dataset:
P0571 Transmural healing, assessed through the combination of faecal calprotectin and intestinal ultrasound, is associated with a reduced risk of bowel damage progression in patients with Crohn's disease
Authors: Buisson A , Huet J , Dodel M , Coban D , Bazoge M , Mathieu K , Pereira B
Published: January 2025

Background

Faecal calprotectin (Fcal) and intestinal ultrasound (IUS) could be used as non-invasive tools to monitor Crohn's disease (CD).

We evaluated the agreement between Fcal and IUS in detecting active CD and to explore the complementarity of these tools in predicting long-term outcomes in CD.

Methods

In this prospective study, we consecutively included CD patients who underwent both IUS and Fcal testing within 7 days . IUS was performed by an experienced IBD sonographer, blinded from biological results.

Patients were categorized into four groups: transmural healing (both normal), IUS healing (Fcal >100 μg/g but normal IUS), mucosal healing (Fcal <100 μg/g but abnormal IUS), and no healing (both Fcal and IUS abnormal). IUS was considered abnormal if at least one of the following CD-related findings was present: increased bowel wall thickness (>3 mm), abnormal vascular pattern (color Doppler signal >0), loss of intestinal wall layer stratification, mesenteric fat proliferation, enlarged lymph nodes, or CD-related complications (e.g., strictures, fistulas, or abscesses).

Endpoints were the time to bowel damage progression and the time to relapse-related drug discontinuation.

Agreement was expressed as a percentage and quantified using the κ coefficient. Survival analyses were conducted using the log-rank test (univariate) and Cox regression models (multivariate). 10-points acceptability numerical scale were compared using paired tests.

Results

Among 112 included patients, 44.6% (50/112), 12.5% (14/112), 16.1% (18/112), and 26.8% (30/112) achieved transmural healing, IUS healing, mucosal healing, and no healing, respectively. No significant differences were observed among the four groups. At baseline, 42% (47/112) of patients were symptomatic according to PRO-2.

The agreement between IUS and Fcal for detecting active CD was low (71.4%, κ coefficient = 0.41 ± 0.09). Transmural healing was associated with a reduced risk of bowel damage progression compared to no healing (p <0.0001), unlike IUS healing (p = 0.15) or mucosal healing (p = 0.84) (Figure 1).

Transmural healing was also associated with lower risk of relapse-related drug discontinuation compared to mucosal healing (HR = 0.09 [0.02-0.45], p = 0.003), IUS healing (HR = 0.10 [0.02-0.60], p = 0.001), or no healing (HR = 0.09 [0.018-0.04], p = 0.002).

IUS was better accepted than stool collection for Fcal testing (10 points-acceptability numerical scale = 9.6 ± 0.8 vs. 7.9 ± 2.3; p <0.0001).

Conclusion

Transmural healing, assessed through a combination of non-invasive and well-accepted tools such as Fcal and IUS, is associated with improved long-term outcomes and could be used for monitoring patients with CD in daily practice.
P0573 The Burden of Urgency in Ulcerative Colitis: Impact of Disease Duration and Activity
Authors: Singeap PhD A M , Muzica C , Huiban L , Girleanu I , Stafie R , Minea H , Stanciu C , Trifan A
Published: January 2025

Background

Urgency is a prevalent and distressing symptom in ulcerative colitis (UC) that significantly impairs quality of life. In longstanding UC, urgency often persists even during remission. This study aims to assess the burden of urgency in UC according to disease duration, and to disease activity.

Methods

A cross-sectional study was conducted on 96 UC patients in a tertiary care center, divided into two groups based on disease duration: 45 patients with UC for under 5 years and 51 with UC for over 5 years. Additionally, patients were categorized by disease activity, with 48 patients in remission and 48 experiencing active disease. All participants completed a questionnaire evaluating urgency frequency, severity, and its impact on daily life, while quality of life was assessed using validated scales. Statistical analyses compared urgency burden across both duration and activity groups.

Results

Patients with UC duration over 5 years reported significantly higher urgency severity and greater interference with daily activities, social interactions, and work compared to those with a shorter disease duration (p<0.05). Among all patients in remission, urgency persisted in 45%, with 55% of longstanding patients more likely to report urgency as a significant burden, compared to 39% of patients with more recent disease (under 5 years). Comparatively, urgency was more severe in patients with active disease, but a notable portion of those in remission (particularly in the over-5-year group) continued to experience substantial urgency-related impact.

Conclusion

Urgency remains a considerable burden in patients with UC, persisting in 45% of those in remission and affecting quality of life more significantly in longstanding disease. This elevated frequency and impact in patients with prolonged disease may be attributed to cumulative bowel damage, chronic inflammation, or altered bowel sensitivity over time, even when the disease is in remission. Addressing urgency early in the course of the disease is essential to improving quality of life and preventing the chronic sequelae seen in longstanding UC.
P0576 Ultrasound assessment of sarcopenia and body composition in patients with inflammatory bowel disease
Authors: Akchurina O , Mukhametova D , Bodryagina E , Odintsova A , Abdulganieva D
Published: January 2025

Background

Sarcopenia is a progressive pathological condition which can present in inflammatory bowel disease (IBD) together with changes in body composition.

Aim

To provide ultrasound assessment of muscle mass and bioimpedance analysis of body composition in patients with IBD.

Methods: Material and Method

The study included 102 patients with IBD, 50 (49%) with ulcerative colitis (UC), 52 (51%) with Crohn's disease (CD), 10 persons formed the control group (CG). The average age of patients with IBD was 39,5 [28,5; 50] year, in the CG – 37 [26; 38] years. There were 52 (51%) women in the IBD group and 5 (50%) in CG. Patients underwent an examination with assessment of body mass index (BMI), mid-upper arm circumference (MUAC, cm) and mid-thigh circumference (MTC, cm) of dominant side; bioimpedance analysis of body composition using the ABC-02 “MEDASS” apparatus; ultrasound examination of the muscle thickness (MT) at the following two points of the leading side: ultrasound mid upper arm, ultrasound mid-thigh.

Results

According to BMI, patients were distributed as follows: normal body weight was observed in 57 (55,9%) patients; deficiency – in 12 (11,8%); overweight 25 (24,5%); obesity – 8 (7,8%). The average MUAC values of the dominant hand in women were 28 [24,9; 31] cm, in the CG were 28 [27; 28,5] cm (p>0.05); in men 29,8 [27; 32] cm, in the CG were 33 [31; 34] cm (p<0.05). The average MTC in women with IBD were 54,25 [48,15; 58,1] cm, in the CG were 61,5 [56; 67] cm (p<0.05); in men 48 [46; 51,4] cm, in the CG were 54 [53; 54] cm (p<0.05). The MT in ultrasound mid upper arm in women with IBD was 19,60 [18,23; 22,84] mm, CG 22.49 [20.41; 22.66] (p>0.05); in men with IBD 26,45 [22,87; 29,24] mm, in the CG 21,54 [21,18; 25,13] mm (p>0.05). The MT in ultrasound mid-thigh in women with IBD was 31,05 [23,21; 37,11] mm, CG 41,30 [35,55; 41,74] mm (p<0.05), in men with IBD 30,90 [25,64; 39,99] mm, in the CG 40,67 [39,10; 41,84] (p<0.05). According to the results of bioimpedance, a deficiency of skeletal muscle mass was detected in 31% patients, in 66% patients skeletal muscle mass was normal, excess muscle mass was detected in 3% patients. The MT in ultrasound mid upper arm correlated with MUAC (r=0,557; p<0.05), with BMI (r=0,448; p<0.05), with skeletal muscle mass according to bioimpedancemetry (r=0,666; p<0.05). The MT in ultrasound mid-thigh correlated with MTC (r=0,505; p<0.05), with BMI (r= 0,376; p<0.05), with skeletal muscle mass according to bioimpedancemetry (r=0,373; p<0.05).

Conclusion

In patients with IBD MTC was lower than in CG. The muscle thickness in ultrasound mid-thigh in women and men with IBD was less than in CG, which correlated with MTC, BMI, skeletal muscle mass according to bioimpedancemetry.
P0577 Influence of Pregnancy on Outcomes of Inflammatory Bowel Disease and Medication Adherence
Authors: Ozturk O , Durak M B , Cagir Y , Ergul M , Keskin E T , Atay A , Yuksel I
Published: January 2025

Background

Treatment of inflammatory bowel disease (IBD) is challenging due to the maintenance of remission and associated fetal safety concerns during pregnancy. While existing literature emphasizes the importance of achieving remission prior to conception, optimal management of IBD during pregnancy remains underexplored, especially regarding medication continuation and efficacy.

Methods

This cross-sectional study was performed in pregnant patients with IBD between March 2019 and June 2023. Clinical features, treatment details, disease activation and outcomes were collected and analyzed.

Results

A total of 57 pregnant were included, of those 37 (64.9%) had UC, and 20 (35.1%) had CD. The overall median disease duration was 9.1 (6-12.8) years (8.2 years for UC and 9.9 years for CD). The disease location was 19 (51.4%) left-sided colitis, 15 (40.5%) extensive, and 3 (8.1%) proctitis in UC, while in CD 8 (40%) patients were ileal involvement, 8 (40%) ileocolonic and 4 (20%) colonic. 4 (20%) had stricturing disease and 4 (20%) had penetrating disease in CD. Before pregnancy, medical treatments for UC patients were mesalazine in 29 (78.4%) patients, thiopurine in 20 (54.1%), biologic therapy in 6 (16.2%), while it was 13 (65%) patients biologic therapy and 7 (35%) thiopurine in CD patients. The most prescribed biologic agent was infliximab in both diseases.

During pregnancy, 16 (28.1%) patients [6 (18.8%) with UC and 10 (50%) with CD] had a history of drug withdrawal. 13 (%81) medications were withdrawn by the patient's wish. Disease activation occurred in 25 (43.9%) patients, 10 (50%) with CD, and 15 (40.5%) with UC. 12 (48%) patients required steroids due to activation. There were 54 (94.7%) live births when compared based on whether disease activation developed or not, there was no statistically significant difference in live birth rate 23, 92% vs. 31, 96.9%, p=0.576. There was no statistically significant difference between normal birth and cesarean section rates with activation development. 3 (5%) abortions occurred. Abortion rate was not associated with disease activation (p>0.05). No serious infection occurred during the first month following birth.

Conclusion

In this study, the disease activation was seen in 43.9% of pregnant patients with IBD. Consistent medication management of IBD during pregnancy enhances patient adherence, reduces risks, and promotes positive maternal outcomes. Proactive counseling and careful selection of medications are crucial for disease control and optimizing pregnancy outcomes in IBD patients.
P0578 The relationship between the concentration of D-dimer and interleukin-6 in patients with ulcerative colitis.
Authors: Knyazev O , Kagramanova A V
Published: January 2025

Background

In patients with inflammatory bowel diseases (IBD), there was a more frequent development of thromboembolic complications, which is due to an increased concentration of procoagulants and proinflammatory cytokines.

Aim

to determine the concentration of D-dimer and interleukin-6 (IL-6) in patients with total ulcerative colitis (UC) during the period of exacerbation and remission of the disease and establish a link between them.

Methods

The study included 38 patients with severe total ulcerative colitis (UC) with exacerbation and 40 patients with total ulcerative colitis in remission. The concentration of D-dimer [N=0.0-0.50 mcg/ml] and the concentration of IL-6 [N=0.0-12.7 pg/ml] were determined in all patients. Correlation analysis of IL-6 concentration and D-dimer concentration in UC patients during remission and during exacerbation was carried out.

Results

The concentration of D-dimer in the group of patients with ulcerative colitis (UC) during remission ranged from 0.04 to 0.08 mcg/ml on average 0.06±0.01 mcg/ml, the concentration of IL-6 ranged from 4.6–21.3 pg/ml, the average value was 11.4 ± 0.2 pg/ml. A moderate correlation was established between the level of D-dimer and the concentration of IL-6 (r = 0.65; p < 0.001) in UC patients during remission of the disease. The concentration of D-dimer in the group of patients with UC during the exacerbation period ranged from 1.0 to 3.8 mcg/ml on average 1.9±0.1 mcg/ml, the concentration of IL-6 ranged from 11.5–34.5 pg/ml, the average value was 18.95 ±0.8 pg/ml, which is significantly higher than during remission UC (p< 0.001). A strong correlation was established between the level of D-dimer and the concentration of IL-6 (r=0.88; p< 0.001) in UC patients during exacerbation.

Conclusion

In patients with UC during exacerbation, the concentration of D-dimer and IL-6 is significantly increased compared to the concentration of D-dimer and IL-6 during remission and has a strong correlation.
P0580 Efficacy and safety results of tulisokibart re-induction treatment in participants with ulcerative colitis in the Phase 2 ARTEMIS-UC clinical trial
Authors: Hoque PhD S S , Sands B E , Feagan B G , Yen M , Dong B , Zhou W , Danese S
Published: January 2025

Background

Tulisokibart is a monoclonal antibody that targets tumor necrosis factor-like cytokine 1A (TL1A), a regulator of inflammation and fibrosis in inflammatory bowel disorders such as ulcerative colitis (UC). The Phase 2 ARTEMIS-UC study demonstrated a significantly higher proportion of tulisokibart vs. placebo participants achieving clinical remission after 12 weeks of treatment1. This analysis evaluates the effects of re-induction treatment in participants who were non-responders during the initial 12-week induction period of the study.

Methods

Participants (≥18 years) of moderate to severe active UC, with conventional or advanced treatment failure, were randomized (1:1 ratio) to placebo or the 12-week induction treatment (intravenous tulisokibart 1000 mg, Day 1 and 500 mg, Weeks 2, 6, and 10). The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in these post-hoc analyses evaluating induction non-responders. Induction non-responders in either the tulisokibart or placebo groups were assigned to an open label 12-week re-induction with aforementioned induction dosing regimen (non-responders are defined as participants who did not achieve reduction of ≥2 points and ≥30% in modified Mayo score from baseline, accompanied by a reduction ≥1 in rectal bleeding sub score or absolute rectal bleeding sub score ≤1 at week 12). Efficacy and safety were assessed following the re-induction treatment at Week 26.

Results

In Cohort 1, 67 and 68 participants were randomized to receive placebo or tulisokibart induction treatment, respectively. At Week 14, 41 (placebo) and 21 (tulisokibart) induction non-responders entered re-induction and received 12-week open label tulisokibart treatment. At Week 26, 48% and 63% of participants who received initial 12-week of tulisokibart treatment (total 24-week tulisokibart treatment) and 63% and 76% of participants who received initial 12-week placebo treatment (total 12-week tulisokibart treatment) achieved symptomatic improvement and symptomatic response, respectively (Table). Re-induction with tulisokibart was well tolerated with no serious AEs or discontinuations due to AEs and no new safety signals (Table).

Conclusion

Re-induction treatment with tulisokibart is effective in participants who did not respond to initial induction treatment. Additionally, up to two tulisokibart induction regimens totaling 24 weeks is well tolerated with no new safety signals identified.

References

1.Sands et al. N Engl J Med 2024; 26;391(12):1119-1129
P0582 Do we need a Structured Transition Programme for patients with IBD? The Irish Experience
Authors: Doherty J , Hurley C , Girod P , Peacock J , Stallard L , Quinn S , Broderick A , Stenke E , Hussey S , Hartery K , Kevans D , O Donnell S , Slattery E , Cullen G , Doherty G , Murphy C , Bourke B , Dunne C
Published: January 2025

Background

The British Society of Gastroenterology recommend the use of structured transition programmes to improve control of chronic GI disease in adolescents. Although research is limited structured transition programmes have been shown to improve disease outcomes in IBD {1}.

Methods

We performed a retrospective multicentre study In collaboration with our National Children’s Hospital. Data was collected on patients prior to transition to adult services and after they transitioned to five adult hospitals across Ireland.

Our aim was to look at the impact of attending a structured transition programme on disease outcomes including need for escalation of medical therapy after transition to adult services, need for steroids, median FCP levels and engagement with services.

Patients were broken up into two groups: patients who attended a structured transition programme and our control patients who were transitioned with a referral letter to the adult gastroenterologist.

Results

In total 282 patients were included in our study. 155 attended a structured transition programme and 127 patients were transitioned with a written referral letter.

No significant differences were seen in basic demographics, median FCP levels or biologic use between either group at the time of transition to adult services. Patients who attended a structured transition programme had significantly lower rates of escalation of medical therapy after transition to adult services compared to our control cohort (38.8% versus 54.4%, p =0.012) (Figure 1). There was no significant difference seen in rates of biologic failure (p = 0.089), need for steroid (p = 0.35) or median FCP levels at 1 (p = 0.09) or 3 years (p = 0.30) between either group after transition to adult services.

Patients who took part in a structured transition programme did have significantly better engagement with adult IBD services with significantly lower rates of non-attendance at outpatient clinics in the 1st year after transition (11.6% versus 27.2%, p = 0.04) and significantly lower rates of disengagement with services (4.2% versus 13.1%, p = 0.015) (Figure 2).

Conclusion

Structured transition programmes in IBD improve disease outcome for patients and overall improve engagement with IBD services. More research and funding is required in the field of transition services in IBD to improve outcomes for patients long-term.

References

1.Brooks AJ, Smith PJ, Cohen R, Collins P, Douds A, Forbes V, et al. UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care. Gut [Internet]. 2017;66(6):988–1000. Available from: http://dx.doi.org/10.1136/gutjnl-2016-313000
P0583 The Effects of a Dual-Strain Probiotic Versus Placebo on Cytokine Levels in Patients with Ulcerative Colitis
Authors: Carroll A , Meagher S , Walker C , Magdeldin H , McNamara D , Ryan B , O'Donnell S , Breslin N , Corr S , O'Connor A
Published: January 2025

Background

Ulcerative colitis (UC) is a form of Inflammatory Bowel Disease (IBD) characterised by chronic mucosal inflammation of the colon. It has been shown that fatigue in patients with ulcerative colitis is a particularly burdensome symptom[1]. Studies have shown that patients with IBD have higher fatigue scores than non-IBD control groups[1]. In UC, activation and dysregulation of the adaptive immune response at the epithelial level results in the abnormal response to antigens leading to an inflammatory cascade resulting in a production of multiple different pro-inflammatory cytokines including IL10, IL23 and TNF-α amongst others[2]. The aim of this study therefore is to evaluate the effects of a dual-strain probiotic versus placebo on cytokines in relation to UC and fatigue.

Methods

This is a single centre double-blind randomised placebo-controlled trial in Tallaght University Hospital, Dublin. Participants are between the ages of 18 to 65 and have a confirmed diagnosis of ulcerative colitis. After randomisation, participants were enrolled on either a 3 month probiotic or placebo arm. Participants had blood tests and a faecal calprotectin at baseline and at conclusion of the study. The probiotic is a dual strain Bifidobacterium longum 35624® combined with B. longum 1714®.

Results

10 controls and 59 participants meeting eligibility criteria were successfully recruited. After double-blind randomisation, 30 participants were on the active dual-probiotic arm with 29 participants on the placebo arm (table 1). In our cytokine analysis the mean concentrations for IFN-α, IFN-γ, IL-10, IL-12p70, IL-6, IL-8, IP-10 and MCP-1 increased post the probiotic. SAA and IL-17A remained relatively unchanged post the probiotic, and an improvement was seen in IL-1β and TNF-α. Contrasted with the placebo arm of the study where mean concentrations in IFN-γ, IL-17A, IL-6, IP-10 and MCP-1 increased post the placebo. SAA and IL-8 remained relatively unchanged post the placebo. There was an improvement seen in IFN-α, IL-10, IL-12p70, IL-1β and TNF-α (table 2). Results could be due to low detection rates.

Conclusion

This study found probiotics may not always be beneficial for patients with UC and may worsen some pro-inflammatory cytokine levels.

References

1.Römkens TEH, van Vugt-van Pinxteren MWJ, Nagengast FM, van Oijen MGH, de Jong DJ. High prevalence of fatigue in inflammatory bowel disease: A case control study. Journal of Crohn's and Colitis. 2011;5(4):332-7.

2.Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19.
P0585 A treat to target approach in IBD: contemporary real-world perspectives from an international survey
Authors: Sharip M T , Brezina B , La Revilla Negro J , Subramanian S , Parkes M , Raine T , Noor N M
Published: January 2025

Background

The management of Inflammatory Bowel Disease (IBD) varies due to differences in healthcare systems, treatment costs, access to diagnostics, and diverse clinical practices between specialists. Despite the frequent advocacy of a treat-to-target (T2T) approach, there is insufficient clarity on how clinicians implement T2T in real-world settings. We aimed to conduct a large, global survey among IBD experts to identify current practices in management.

Methods

A prospective, cross-sectional study was conducted using a 16-item survey divided into two sections — for Ulcerative Colitis (UC) and Crohn’s Disease (CD) — and distributed to practicing IBD clinicians. A hyperlink to the survey was widely circulated among attendees to the ECCO annual congress 2024 as well as ECCO members using the ECCO online platform, ECCO newsletter, and the ECCO electronic app. The survey was active from 17/01/2024 until 31/03/2024. Completion of the anonymous survey was deemed to imply consent for data analysis.

Results

A total of 261 respondents from 88 countries participated in the survey, with the majority (253/261) being physicians and 8 IBD nurse specialists. Despite global guidance, only a quarter of respondents routinely performed an endoscopy to assess response after starting an advanced therapy (28.4% in UC vs 23.5% in CD). Moreover, despite an increasing academic focus on intestinal ultrasound (IUS), 171 (66%) of respondents in UC and 132 (51%) in CD reported that they did not routinely undertake IUS to guide treatment decisions. Faecal calprotectin for monitoring treatment response was routinely used by 87% (90% in UC and 84% in CD) of respondents. Forty-five percent reported use of therapeutic drug monitoring (TDM) both proactively and reactively and 35% reported only using TDM reactively.

Conclusion

Our study shows considerable variation in IBD management across different countries, and interpretation of the T2T approach. This highlights the need for standardised and pragmatic guidelines to help improve outcomes for patients with IBD globally.
P0589 High treatment persistence following infliximab dose escalation in Inflammatory Bowel Disease: A real world study
Authors: Salehi O , Gondal F , Terlato M , Pillay L , Macrae F , Rentsch C , Dimkovski S , Segal J P
Published: January 2025

Background

Biologic dose escalation is frequently employed in inflammatory bowel disease (IBD) patients who lose response to standard dosing regimens. Infliximab (IFX), the most commonly used biologic in IBD, has a well-established role in inducing and maintaining remission in IBD, particularly in fistulising Crohn's disease (CD).¹ Secondary loss of response to IFX can occur due to low serum drug levels, primarily from immunogenicity.² We investigated the effectiveness and treatment persistence of IFX dose escalation in IBD patients with inadequate response to standard dosing after initial clinical response.

Methods

We conducted a retrospective analysis of IBD patients who underwent IFX dose escalation between 2020-2024 at a tertiary IBD centre. Dose escalation was defined as increase in dose (>5mg/kg) and/or frequency [>every 8 weekly (Q8W)]. Primary outcomes included clinical disease activity scores (Simple Clinical Colitis Activity/SCCAI Index for UC, Harvey-Bradshaw Index/HBI for CD), biochemical markers (CRP, faecal calprotectin) and treatment persistence, evaluated at 3-12 months, 12 months, and annually up to 36 months post-escalation.

Results

The cohort included 47 patients (mean age 29 years, 52% female), comprising 33 CD (70%) and 14 UC (30%) patients. Primary indication for dose escalation was low drug levels (76%), followed by loss of response despite adequate levels (24%). Dose escalation led to significant improvements in disease activity scores (HBI: p=0.01; SCCAI: p=0.04) and CRP (p=0.02) at 3-12 months. These improvements were sustained at 12 months for CRP (p=0.04) but not for clinical scores. Treatment persistence at 36 months was notably high at 100% for biologic-naïve patients and 92% for biologic-exposed patients. Mild adverse events occurred in 5 patients (11%) including psoriasiform rash (n=3), transient liver enzyme derangement (n=1) and shingles (n=1). No serious adverse events occurred.

Conclusion

IFX dose escalation demonstrates significant improvements in clinical and biochemical parameters in the short term, with high treatment persistence up to 36 months. While both groups showed excellent outcomes, biologic-naïve patients achieved superior persistence (100% vs 92%). These findings support dose escalation as a viable therapeutic option for maintaining response in IBD patients, with an acceptable safety profile. Prospective studies are needed to identify predictive factors for successful dose escalation and optimal timing of intervention.

References

1.Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541-1549.2. Rahman MU, Strusberg I, Geusens P, et al. Double-blinded infliximab dose escalation in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66(9):1233-1238.
P0597 Clinical and biochemical correlates of infliximab pharmacokinetics in adult patients with Inflammatory Bowel Disease
Authors: Pool I A , Volkerink I , Stavast M , Kosterink J G W , Dijkstra G , Mian P , Bourgonje A R
Published: January 2025

Background

Antibodies against tumor necrosis factor-alpha (TNF-α) such as infliximab (IFX) are important in the treatment of patients with inflammatory bowel disease (IBD), but many patients lose drug response over time or do not respond at all. Loss-of-response and non-response can at least be partially attributed to suboptimal dosing due to individual differences in pharmacokinetics (PK)1. In this real-world study, we aimed to identify clinical, biochemical and endoscopic variables influencing IFX PK in patients with IBD.

Methods

Patients diagnosed with IBD aged ≥18 years who were treated with IFX were included based on available IFX trough levels from a hospital-based pharmacy registry. Information on endoscopic, clinical, and biochemical parameters was collected. Univariable and multivariable linear mixed-effects models were used to model associations between individual IFX trough level trajectories and identified factors to examine their relative contributions to IFX PK. In addition, a systematic literature study on IFX PK in adults with IBD and other immune-mediated inflammatory diseases was performed to better contextualize the obtained findings.

Results

A total of 200 patients were included (Crohn’s disease [CD] (n=163) and ulcerative colitis [UC] (n=37)) with 452 IFX trough levels available for analysis (Figure 1). Patients with antibodies (ATI) to IFX (unstandardized β=4.35, p<0.001) and those treated with longer dosing intervals (β=-1.89, p=<0.001) exhibited lower trough levels (Figure 2). Higher levels of aspartate aminotransferase (AST) (β=0.04, p=0.027), hemoglobin (β=0.76, p=0.022) and albumin (β=0.15, p=0.029) were positively associated with IFX trough levels. Among clinical factors, Simple Clinical Colitis Activity Index (SCCAI) scores in patients with UC, both as continuous (β=3.31, p=0.03) and as categorical variable (β=13.25, p=0.033), were positively associated with higher IFX trough levels. The presence of endoscopic inflammation, regardless of its severity, was also positively correlated with IFX trough levels (β=2.60, p=0.045).

Conclusion

This data demonstrates a role of AST, albumin, hemoglobin, SCCAI, and endoscopic inflammation as covariates potentially relevant to IFX PK in IBD. Findings of albumin, endoscopic inflammation, dosage interval and ATI were supported by our systematic review confirming them as previously identified covariates. AST, hemoglobin, and SCCAI were newly identified covariates. These covariates could optimize treatment strategies and should therefore be considered for integration in population-PK/PD models and PK dashboards in order to make patient-specific prediction models for IFX treatment.

References

1.Hemperly, A & Vande Casteele, N. Clin Pharmacokinet. 2018 doi: 10.1007/s40262-017-0627-0.

Figure 1. Snippets of tables 1 and 2.

Figure 2.
P0601 Is advanced combination therapy effective in patients with refractory Inflammatory Bowel Disease?
Authors: Rodríguez Gallardo M , Valdés Delgado T , Maldonado Pérez B , Belvis Jiménez M , Aguado Paredes A , Castro Laria L , Argüelles Arias F
Published: January 2025

Background

Advanced combination therapy (ACT) involves combining two biological therapies or a biological drug with a small molecule, in order to complement their mechanisms of action inhibiting multiple inflammatory cascades. The primary aim of our study was to evaluate the effectiveness of combination therapies in Inflammatory Bowel Disease (IBD)

Methods

A prospective, single-centre observational study was conducted, including all patients diagnosed with ulcerative colitis (UC) or Crohn´s disease (CD) starting treatment with ACT from March to August 2024. Clinical and biological response and remission were assessed at week 16 and the last available visit. Clinical response was defined as a decrease ≥3 points from baseline Harvey-Bradshaw Index (HBI) in CD or baseline Partial Mayo Score (pMS) in UC. Clinical remission was considered as a HBI score ≤4 or pMs of 0-1. Biological response was determined as a ≥50% decrease from baseline C-reactive protein (CRP) and faecal calprotectin (FC) and remission as a CRP<5 and FC<250

Results

A total of 20 patients were included, 70% (14/20) diagnosed with UC (Figure 1A). The most frequent combination was vedolizumab (VEDO) with upadactitinib (UPA) (Figure 1B)

The median baseline HBI was 10.5 [IQR 6-15] decreasing to 6.5 at week 16 [IQR 3-11] and to 5.5 [IQR 2-10] at the last follow-up (p<0.001)(Figure 2A). The median baseline pMS was 7 [IQR 5-8] decreasing to 4 [IQR 2-4] at week 16 and to 2 [IQR 1-3] at the last visit (p<0.005) (Figure 2B)

The median baseline FC was 1994 [IQR 805-3238], decreasing to 635 [IQR 183-222] at week 16 and to 387 [IQR 93-1115] at the last follow-up (p=0.047) (Figure 2C). Regarding CRP, the median baseline was 5.3 [IQR 1-31], decreasing to 2.4 [IQR 1-5] at week 16 and to 1.2 [IQR 1-4] at the end of follow-up (p=0.014) (Figure 2D)

65% of patients achieved clinical response and 20% reached clinical remission at week 16. At the end of follow-up, 80% achieved clinical response and 65% clinical remission (Figure 2E)

At week 16, 45% and 20% of patients achieved biological response and remission, respectively. At the end of follow-up, 65% were in biological response and 45% in biological remission (Figure 2F)

Treatment was discontinued in 3 patients, in 2 of them due to improvement and in the reimaining one due to lack of response. Treatment intensification was required in 7 patients. A total of 8 mild adverse effects were recorded, none of which led to discontinuation of the ACT

Conclusion

These results demonstrate adequate clinical and biological response in patients treated with ACT. Clinical and biological remission was achieved in 65% and 45% of patients at the end of follow-up, with good safety profile. Nevertheless, to confirm this results futher large prospective studies are needed
P0602 Long-term effectiveness and safety of ustekinumab dose escalation in patients with refractory ulcerative colitis: a multicenter retrospective cohort study
Authors: Van Lierop L , Albino L , Rosentreter R , Thomas P W A , Lu C , Siffledeen J , Kroeker K I , Ma C , Peerani F , Halloran B P , Baumgart D C , Dieleman L A , Du L , Hoentjen F , Wong K
Published: January 2025

Background

Ustekinumab dose escalation (DE) may be an effective strategy to recapture clinical response in patients with ulcerative colitis (UC). The aim of this study was to assess the real-world long-term effectiveness and safety of ustekinumab DE in patients with refractory UC.

Methods

This multicenter retrospective cohort study included patients with refractory UC who received at least one IV induction ustekinumab dose between January 2016 and November 2021. We compared ustekinumab DE to no DE, examining clinical, biochemical, and endoscopic disease outcomes. The primary endpoint was corticosteroid-free clinical remission (partial Mayo score ≤ 2 without systemic corticosteroids) at the end of follow-up. Cox-proportional hazards regression analysis was performed for factors associated with time to DE, and a Kaplan-Meier plot was created for visualizing drug persistence probabilities.

Results

We enrolled 121 patients. Eighty-one patients (67%) underwent DE during a median follow-up of 141 weeks. Corticosteroid-free clinical remission at the end of follow-up was achieved for 53.2% (DE group) and 59.0% (non-DE group). In the DE group, 53% discontinued ustekinumab, mainly due to a lack of effectiveness. At the end of follow-up, 47% of DE patients remained on ustekinumab, compared to 55% in the non-DE group. Ustekinumab persistence probability after 2 years was 40% (DE group) versus 79% (non-DE group). Only 2 patients discontinued ustekinumab for adverse events.

Conclusion

Our results indicate that DE is a common method for optimizing ustekinumab treatment in refractory UC. While DE appears safe, effectiveness and drug persistence of DE beyond 2 years are limited.
P0603 The real-world use of intravenous and subcutaneous Vedolizumab in IBD across Australia and New Zealand, Crohn’s Colitis Cure Data Insight’s Program
Authors: Su W K , Wilson W , Wark G , Ghaly S , Lynch K , Lawrance I , Walker G , Forbes A , Brett L , An Y K , Connor S J , Andrews J M
Published: January 2025

Background

Vedolizumab, an established therapy for inflammatory bowel disease (IBD), has been proven to be effective in both intravenous (IV) and subcutaneous (SC) formulations. This study aims to understand the patterns of use of both formulations in real world clinical care.

Methods

Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in Australia (AUS) and New Zealand (NZ). Data feed into a de-identified clinical quality registry (CQR), which was interrogated in August 2024. We examined the real-world use of Vedolizumab in people with IBD under usual ambulatory care. People with Crohn’s Disease (CD) or Ulcerative colitis (UC) with a clinical assessment ever recorded were included.

Results

Of 8,724 eligible people with IBD, 13.6% (n=1,187) have ever received Vedolizumab, 734 (61.8%) of whom have UC and 453 (38.2%) have CD. The median age was 42 years (IQR 31 – 56), and the median disease duration was 11.1 years (IQR 5.6 – 19.1). There was an even gender distribution with 50.0% (n=593) male. The majority of people resided in AUS (n=1,117, 94.1%) with 5.9% (n=70) in NZ.

A higher proportion of people with UC have received vedolizumab compared to those with CD (19.5% vs 9.1%, p<0.001). In those where residential location was documented, Vedolizumab was more frequently used in people residing in a metropolitan compared to a non-metropolitan area (n=875, 15.2% vs n=177, 10.7%, p<0.001). In those currently receiving Vedolizumab (n=541), there was no difference in the formulation used across metropolitan and non-metropolitan areas (72.9% IV vs 71.3% IV, p=0.75).

Of those who ever received maintenance IV Vedolizumab (n=1,015), only 59 people (5.8%) have switched to SC Vedolizumab. The median duration on IV before switching was 97 weeks (IQR 59.5 – 217.8). There was no difference in the rate of IV to SC switching in CD compared to UC (4.9% vs 6.4%, p=0.34). Of those who ever received maintenance IV Vedolizumab, 161 (15.9%) were on dose escalated (DE) therapy. The proportion of people on DE Vedolizumab did not differ between CD and UC (13.2% vs 17.5%, p=0.07).

Conclusion

In this large, real-world data of people with IBD, Vedolizumab has been used in 13.6% of the cohort, more often in people with UC compared to CD. The majority of people receiving Vedolizumab remain on IV formulation with only a small subset of people changing to, or established on, SC route. SC formulations have the potential to reduce the patient’s burden of disease by reducing travel costs and time out of role, promoting autonomy and empowering people living with IBD. However, in the absence of economic incentive or policy change, there will remain inertia to change to SC formulation.
P0608 Safety of guselkumab in Inflammatory Bowel Disease up to 1 year: Integrated safety analysis of phase 2 and 3 studies in Crohn’s Disease and Ulcerative Colitis
Authors: Sands B E , Panaccione R , Danese S , Panés J , Hisamatsu T , D’Haens G , Van Rampelbergh R , Olurinde M , Yee J , Baker T , Yarandi S , Germinaro M , Vetter M L , Li H , Rosas Ballina M , Allegretti J , Afzali A , Rubin D T
Published: January 2025

Background

Guselkumab (GUS), a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), is currently approved in the United States for treatment of ulcerative colitis (UC) and worldwide for the treatment of plaque psoriasis and psoriatic arthritis. While GUS has been shown to be safe in Crohn’s disease (CD) and UC, safety results have only been reported in individual trials to date. To characterize the overall safety profile of GUS in inflammatory bowel disease (IBD), we evaluated pooled safety data from Phase 2/3 clinical trials of GUS in CD and UC.

Methods

Participants (pts) with moderately to severely active CD (n=1492; GALAXI 1, 2, and 3, and GRAVITI) or UC (n=1514; QUASAR Induction Study 1, Induction Study 2, and Maintenance Study and VEGA-GUS monotherapy arm only) were assigned to GUS 200 mg intravenous (IV) or 400 mg subcutaneous (SC) induction (GRAVITI only) at Weeks 0, 4, and 8, followed by GUS 100 mg SC every 8 weeks or 200 mg SC every 4 weeks; or placebo (PBO). SC maintenance treatment continued through approximately 1 year. GUS studies were pooled for the induction period (GALAXI, GRAVITI, and QUASAR; IV and SC, Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, and VEGA). In this pooled analysis, safety events were normalized to 100 pt-years (PY) of follow-up with corresponding confidence intervals.

Results

Through Week 12, 1703 pts were treated with GUS with 399.9 PY of follow-up. Rates of adverse events (AEs) were similar between pts treated with GUS (200 mg IV or 400 mg SC) and PBO (Figure 1A). AEs occurred at a rate of 202.82/100 PYs and 223.26/100 PY, serious AEs at 11.75/100 PY and 28.56/100 PY, AEs leading to study agent discontinuation at 5.50/100 PY and 16.32/100 PY, and serious infections at 1.50/100 PY and 1.17/100 PY, for GUS and PBO, respectively.

Through 1 year, 2057 pts were treated with GUS, with 1752.1 PY of follow-up. Rates of AEs, SAEs, AEs leading to discontinuation, and serious infections, were no higher in GUS-treated than PBO-treated pts (Figure 1B). Through 1 year, no anaphylactic or serum sickness reactions were reported, and rates of malignancy, opportunistic infection, major adverse cardiovascular events, and clinically important hepatic disorders were low (Table 1). In GUS-treated pts, one pt (from an endemic region) reported active tuberculosis, and 2 deaths (acute myocardial infarction in a pt with pre-existing cardiovascular risk factors and non-suicidal gunshot wound, respectively) occurred.

Conclusion

Through 1 year of treatment, GUS demonstrated a favorable safety profile comparable to placebo in patients with CD and UC. No new safety concerns were identified.
P0611 Effectiveness comparisons between tofacitinib, filgotinib and upadacitinib in ulcerative colitis: results from the JAKARTA real-world evidence multicenter study
Authors: Buisson A , Treton X , Nachury M , Uzzan M , Bouguen G , Banana Hamadidi A , Amiot A , Serrero M , Fumery M , Caillo L , Hupé M , Pereira B , Altwegg R
Published: January 2025

Background

As no direct comparisons exist, we compared the effectiveness of tofacitinib (TOFA), filgotinib (FILGO) and upadacitinib (UPA) in patients with Ulcerative Colitis (UC).

Methods

In this retrospective multicenter study, we included all consecutive patients with UC ≥18 years-old, partial Mayo score > 2 who had started TOFA, FILGO or UPA after receiving ≥ 1 biologic.

Following regimen were applied : TOFA (10mg b.i.d --> at W8: 5mg or 10 mg b.i.d according to physician’s judgement), FILGO (200mg q.d) and for UPA (45mg q.d --> at W8: 45mg, 30 mg or 15 mg q.d according to physician’s judgement).

The primary endpoint was symptomatic remission (partial Mayo score ≤ 2) without corticosteroids (CFREM) at W16. Secondary endpoints were clinical-endoscopic remission (CFREM + endoscopic Mayo score ≤ 1), histological-endoscopic mucosal improvement (HEMI) (= clinical-endoscopic and histological remission (Nancy index ≤ 1)), drug retention and secondary loss of response.

Comparisons were performed using propensity scores adjustment (IPTW).

Results

Overall 290 UC patients were included: TOFA=150, FILGO=79, UPA=61. The 3 groups were comparable except for higher proportion of patients with partial Mayo score > 6 or prior exposure > 3 biologics in UPA group (p < 0.001).

Recommended maintenance dose (TOFA 5mg b.i.d/UPA 30 mg/FILGO 200 mg) from W8 after response to induction was applied in 41.3% (62/150), 65.8 % (52/79), and 59.0% (36/61), in TOFA, FILGO and UPA groups, respectively, and failed (need for dose re-escalation/drug discontinuation/no clinical remission at last follow-up) in 58.1% (36/62), 42.3% (22/52), 30.5% (11/36), in TOFA, FILGO and UPA groups, respectively, (p <0.001).

After IPTW, CFREM at W16 was higher in UPA (60.1%) compared to TOFA (38.9%) or FILGO groups (36.8%) (p < 0.001 for both). No predictor of efficacy/ failure was identified with these 3 JAK inhibitors. We failed to show any significant difference regarding clinical-endoscopic remission (UPA:16.5%, TOFA:16.5%, FILGO:12.8%) or HEMI (UPA:11.9%, TOFA: 4.4, FILGO: 12.7%).

Among patients achieving CFREM at W16 (regardless of the dose), secondary loss of response (clinical relapse) was similar across the groups (TOFA:12.8%, FILGO: 19.2% and UPA: 10.3%; p = ns after IPTW).

After adjustment, drug retention was longer for UPA compared to TOFA and FILGO groups (HR = 0.42 [0.21-0.85], p = 0.016) and shorter in FILGO than in TOFA group (HR = 1.60 [1.07-2.38], p = 0.021). No difference was demonstrated in terms of time to hospitalization or surgery between the 3 groups.

Conclusion

In this real-world evidence study, UPA was the most effective JAK inhibitor in UC at short and long-term but the large use of off-label maintenance doses in current practice needs further safety investigations.
P0616 ViT-based deep learning and unsupervised clustering analysis in Crohn’s Disease based on body composition to identify distinct phenogroups and predict the effectiveness of anti-TNF therapy
Authors: Wang Y , Ding Z , Zhang M , Li Y
Published: January 2025

Background

Anti-TNF therapy is considered as a crucial treatment in Crohn’s disease (CD). However, it has a primary nonresponse rate in up to 30% of patients and secondary loss of response rate of about 5% per patient-year with unknown reason. Herein, we aimed to establish an artificial intelligence algorithm to identify patients with beneficial response and predict the effectiveness of anti-TNF theray based on body composition.

Methods

Between July 2020 and August 2023, 105 CD patients who underwent anti-TNF therapy from Shanghai Ninth people’s Hospital were enrolled in this study. An unsupervised clustering analysis (K-means clustering) was utilized to classify subjects into distinct groups based on body composition parameters before anti-TNF therapy. We analyzed the relationship between different phenogroups and the response to anti-TNF therapy. Besides, radiomics features were extracted from subcutaneous fat (SF), visceral fat (VF), and skeletal muscle (SM) at the level of L3/L4 based on CTE. A deep learning model based on Vision Transformer (ViT) was established to predict the response of anti-TNF therapy.

Results

Our analysis identified three phenogroups: Cluster 1 (PhAhigh/BCMhigh/BMChigh/SMIhigh/BMIhigh/proteinhigh/IWhigh/EWhigh), Cluster 2 (PhAlow/BCMlow/BMClow/SMIlow/VFAhigh/BFPhigh/proteinlow/IWlow/EWlow) and Cluster 3 (VFAlow/BMIlow/BFPlow). Patients in Cluster 1 showed best response of anti-TNF thrapy (p = 0.023). Among patients in Cluster 3, those with high nutritional risks showed significantly earlier loss of response than those with low nutritional risks (p = 0.041). The prediction model achieved satisfactory accuracy in predicting the effectiveness of anti-TNF therapy (SF: AUC = 0.700; VF: AUC = 0.745; SM: AUC = 0.785) in the validation cohort.

Conclusion

Patients with good nutritional status have a better response to anti-TNF therapy in CD. Earlier loss of response occurred in patients with high nutritional risks, which may be improved by nutritional support. Subcutaneous fat, visceral fat, and skeletal muscle at the level of L3/L4 showed a satisfactory performance in predicting the response to anti-TNF therapy.