bluuebunny/crossref_metadata_2025 huggingface dataset:
P0642 Assessment of the real-world effectiveness of upadacitinib in patients with moderate-severe ulcerative colitis in a global real-world setting
Authors: Seidelin J B , Marin-Jimenez I , Dawod F , Lukanova R , Jones W , Morriset P , Sharma D , Siegel C
Published: January 2025

Background

Upadacitinib (UPA), a Janus kinase inhibitor, was approved in 2022 to treat adults with moderate-severe ulcerative colitis (UC). While clinical trials have shown its efficacy, there are limited real-world data on the utilization and effectiveness of UPA in routine clinical practice across different countries. This study aimed to assess the real-world impact of UPA on disease remission and symptom control for optimizing treatment outcomes in patients with UC.

Methods

Data were drawn from the Adelphi Real World UC Disease Specific Programme, a cross-sectional survey with retrospective data collection of gastroenterologists (GIs) in France, Germany, Italy, Spain, the United Kingdom, and the United States of America from February 2023 – October 2024. GIs reported data on their patients with subjectively classified moderate-severe UC at initiation of UPA, including demographics, clinical characteristics (incl. derived partial Mayo score (pMayo)) and symptoms at UPA initiation and at the most recent consultation. Analyses were descriptive, Wilcoxon signed rank and McNemar tests were used to compare severity and symptoms at UPA initiation and at most recent consultation, respectively.

Results

Overall, 215 GIs reported data on 357 patients with moderate-severe UC receiving UPA. Mean (standard deviation; SD) patient age was 39.2 (12.4) years, 65% were male, 43% had pancolitis. Mean (SD) disease duration was 4.5 (5.1) years; 45% were advanced therapy (AT) naïve and 55% AT experienced.

Among those who were receiving UPA for ≥6 months (n=129), 59% were in clinical remission, as defined by pMayo at their most recent consultation. Among all patients on UPA, an increasing proportion of patients in remission, as defined by pMayo, was observed with increasing duration of UPA use (Figure 1A).

GI-reported disease severity significantly reduced from UPA initiation to most recent consultation (p<0.0001; Figure 1B). As duration of UPA use increased, the proportion of patients experiencing key symptoms since UPA initiation to most recent consultation decreased (Figure 2).

Conclusion

In a real-world global setting, UPA demonstrated significant efficacy in reducing disease activity, severity and UC-related symptoms over time. Remission rates and symptom reduction increased with longer treatment duration, with improvements seen as early as four weeks for key symptoms, and continued symptom relief observed through 52 weeks. These findings underscore the effectiveness of UPA treatment for long-term disease management in patients with moderate-severe UC.
P0649 Acceptability and Tolerance of Risankizumab Treatment Administered via On-Body Injector in Patients with Crohn’s Disease: Results of the Nationwide ACCEPT-OBI Study
Authors: Buisson A , Gebara K , Peyrin-Biroulet L , Boschetti G , Gilletta de Saint Joseph C , Brixi H , Juillerat P , Serrero M , Vuitton L , Hébuterne X , Caillo L , Blain A , Laharie D , Pereira B , Fumery M ,   GETAID
Published: January 2025

Background

Risankizumab (RZB) has been available in our country for Crohn’s disease (CD) patients through an early access program and is now administered using an innovative medical device known as an on-body injector (OBI).

We assessed the acceptability and the tolerance of RZB administration via OBI and compare its acceptability with other modalities of CD treatments, and searched for factors associated with the OBI acceptability.

Methods

This was a prospective, multicenter longitudinal study. All CD patients from the early access cohort treated with RZB via OBI starting in February 2024 were assessed at the time of the switch to OBI (week 0 = W0) and at W8, W16, and W24.

The primary endpoint was acceptability, evaluated using a acceptability numerical scale (ANS) ranging from 0 (completely unacceptable) to 10 (perfectly acceptable).

Results

A total of 58 multi-refractory patients were included (mean age : 42.8 ± 13.8 years; 57.9% were women, 17.3% were smokers, 64.7% had a history of intestinal resection, and 78.2% were in PRO2-clinical remission).

Therapeutic education sessions were conducted concurrently for 36.2% (21/58) of patients. OBI was applied to abdomen, thigh, or another site in 43.9%, 52.6%, and 3.5% of patients, respectively.

RZB administration via OBI was well tolerated in 57.4%, with possible mild application-site pain (20.4%, mild in 90% of cases), localized erythema (22.2%), pruritus (16.7%), edema (16.7%). No factors affected the acceptability of risankizumab administration via OBI in more than 15% of patients.

RZB acceptability via OBI was very high (9.5 ± 1.2) at W0, significantly better than RZB subcutaneous injections (6.98 ± 2.57; p < 0.0001). OBI acceptability remained stable over time: 9.6 ± 1.2 at W8, 9.6 ± 1.4 at W16, and 9.6 ± 0.8 at W24 (p = 0.97). OBI acceptability as a medical device was better than other injectable administration modalities for IBD treatments: IV infusions (p < 0.0001), pen injectors (p < 0.001), and syringes (p < 0.001).

Overall, patients preferred OBI (64.0%), followed by oral administration (28.0%), subcutaneous injections (6.0%), and IV infusions (2.0%).

When adjusted for administration frequency, RZB every 8 weeks via OBI was the most preferred method (ANS = 9.2 ± 2.0), compared to long interval subcutaneous injections (every 12, 8, or 4 weeks), more frequent injections (weekly or eow), and IV infusions every 4–8 weeks (p < 0.001 for all comparisons).

Conclusion

In this cohort of refractory patients, the administration of risankizumab via OBI was highly acceptable to CD patients with excellent tolerance, suggesting that this new medical device could promote the use of risankizumab in clinical practice.
P0877 Machine Learning and Mendelian Randomization Analysis for Predicting Endoscopic Restenosis in Patients with Crohn's Disease after Endoscopic Balloon Dilation
Authors: Su T , Wu H , Wu L , Zhi M , Yao J
Published: January 2025

Background

Endoscopic balloon dilation (EBD) is a safe and effective procedure for treating stenosis in patients with Crohn's disease (CD). This study aimed to evaluate factors associated with endoscopic restenosis after EBD and construct a prognostic model.

Methods

We retrospectively collected and analyzed data on patients receiving EBD treatment at the Sixth Affiliated Hospital of Sun Yat-sen University from 2013 to 2024. Seven machine learning (ML) algorithms were used to construct a prognostic model. And explore potential biomarkers of intestinal stricture using Mendelian randomization (MR).

Results

A total of 135 patients were included in the statistical analysis. 53% occurred endoscopic restenosis, with an average restenosis time of 183 days. COX and logistic regression analysis showed that 4 features including ever-use glucocorticoids, stenosis position, technical success, and albumin level were associated with restenosis risk. When comparing different ML models, CoxPH and LASSO models performed better on various evaluation metrics, including C-index which was greater than 0.7 in the train and test set. Based on SHapley Additive exPlanations (SHAP), stenosis position, balloon diameter, and albumin level were identified as the top 3 important features associated with prognosis. Two-sample MR analysis identified 50 potential biomarkers of intestinal stricture. However, two-step MR analysis did not find any mediating effect between CD and intestinal stricture.

Conclusion

ML-based prognostic models have good predictive performance and can accurately assess the risk of endoscopic restenosis after EBD treatment. However, MR analysis did not identify reliable stenosis-related biomarkers in CD.
P0884 Environmental impact and costs of a switching program of intravenous to subcutaneous infliximab in Inflammatory Bowel Disease
Authors: Oliveira R , Roseira J , Araújo N , Cavaco C , André J , Sousa M , Tavares de Sousa H , Cunha M
Published: January 2025

Background

We aimed to compare real-life direct and indirect costs and the environmental impact of switching IBD patients from IV to SC infliximab (IFX).

Methods

Adult IBD outpatients in clinical remission who switched from IV to SC IFX were studied. Data on direct and indirect costs for the hospital (€), and environmental impact (Carbon dioxide equivalents [CO2e]), were evaluated before and after switching. Patients also completed an anonymous pilot questionnaire designed to assess the indirect costs associated with their own drug administration. A consecutive sample of patients was used to calculate costs over 6 months of both therapy regimens.

Results

Twelve patients switched to SC IFX (91.7% were under-optimised IV dosage). Before switching, most missed work (58.3%) or changed shifts for infusions (25%), leading to a median of 4 missed workdays over 6 months, translating to an estimated median loss of 328€ in self-earnings. Patients spent a median of 92.5 min travelling to and 720 min at the hospital. Post-switch, hospital time decreased to 195 min (p=0.005). However, due to pharmacy stock rules requiring frequent hospital visits to collect SC therapy, both travel time (190 min; p=0.009) and travel frequency (4.0 vs 6.0 visits; p=0.004) increased. Estimated travel costs for patients rose from 89.6€ to 196.0€ over 6 months (p=0.007).

Median direct costs were 1321.34€ for IV IFX and 2604€ for SC IFX (p=0.008), while indirect costs dropped as preparation time fell from 140 min for IV to 70 min for SC (p=0.001), corresponding to an estimated cost reduction of 9.59€ (p<0.001). Similarly, nursing staff time significantly reduced from 600 min with IV to 40 min with SC (p=0.002), corresponding to 95.01€ reduction (p<0.001), respectively. Over 6 months, IV IFX had a median carbon footprint of 20.95 kg CO2eq (11.6 kg from infusions; 9.35 kg from patient travel), while SC IFX generated 24.15 kg CO2e (3.6 kg from injections; 20.55 kg from patient travel) per patient (p=0.859).

Conclusion

Our analysis shows SC IFX incurs higher direct costs than IV IFX without reducing the carbon footprint. However, reduced indirect patient costs and improved pharmacy and day hospital efficiency may offset these expenses. To maximise benefits, pharmacies should adjust stock management policies and minimise patient travel. These factors should be evaluated locally in a switching program design.
P0903 Structured yoga practices significantly improve quality of life in patients with Ulcerative Colitis in clinical remission: a randomized controlled trial
Authors: Kalum J D B S , Narang H , Virmani S , Shukla A , Verma M , Madan D , Kumar P , Mathew D , Prasad S , Mubunnu M , Kedia S , Makharia G , Sharma G , Ahuja V
Published: January 2025

Background

Ulcerative colitis (UC) significantly affects quality of life, compromising health-related well-being and life satisfaction, regardless of disease activity. There are anecdotal studies on effect of yoga in patients with ulcerative colitis. We investigated the effect of yoga on health-related quality of life and disease activity in UC patients in remission.

Methods

Patients with UC in remission (SCCAI <3 and fecal calprotectin<150 µg/mg) were randomly assigned to either IBD-specific yoga therapy (45 minutes/day, five days/week) or brisk walking (150 minutes/week), in addition to standard medical treatment, for 6 months. Primary outcome was the effect of yoga on quality of life using the World Health Organization Quality of Life – BREF (WHOQOL-BREF), Hamilton Anxiety Rating Scale (HAM-A), and Perceived Stress Scale (PSS) questionnaires at 6 months. Secondary outcome was relapse rates at 6 months.

Results

One hundred patients were randomized with 50 in each arm and 5 were lost to follow up. Baseline clinical and demographic characteristics and WHOQOL BREF, PSS and HAM-A scores were similar. At 6 months, patients in yoga group showed significantly lower PSS (16.70±1.44 vs. 17.34±1.5, p=0.03) and anxiety scores (1.51±0.68 vs. 1.89±0.79, p=0.01) compared to walking. Yoga also significantly improved physical (71.29±2.94 vs. 69.65±3.4, p=0.014) and psychological well-being (71.55±4.28 vs. 68.34±4.77, p=0.001), with similar social scores (63.85±6.98 vs 63.47±6.68 p=0.79). One patient in each group had disease relapse.

Conclusion

Yoga showed greater reductions in stress and anxiety, and improved quality of life in both physical and psychological domains, compared to walking. Both groups had similar disease relapse rates. Yoga can be considered an effective ancillary intervention to improve the quality of life in patients with UC in remission.

References

1.Sharma P, Poojary G, Dwivedi SN, Deepak KK. Effect of Yoga-Based Intervention in Patients with Inflammatory Bowel Disease. Int J Yoga Ther. 2015 Jan 1;25(1):101–12.

2.Cramer H, Schäfer M, Schöls M, Köcke J, Elsenbruch S, Lauche R, et al. Randomised clinical trial: yoga vs written self-care advice for ulcerative colitis. Aliment Pharmacol Ther. 2017 Jun;45(11):1379–89.
P0951 The effects of delayed surgery in Inflammatory Bowel Disease – a health economic analysis
Authors: Åberg H , Bengtsson J , Park J , de la Croix H , Hermanson M
Published: January 2025

Background

To manage the COVID 19 pandemic, surgeries that were not immediately life threatening were delayed. Patients with Inflammatory Bowel Disease (IBD) are still affected, which can have effects on patients’ individual physical and mental health as well as on health economics. This includes the risk of complications and possible needs of both acute and planned care during the waiting time for surgery, need for sick leave, prescription of medications and aid; all that could have been diminished with surgery being performed in a timely manner.

Methods

All patients with IBD who either were scheduled for surgery and had a waiting time of 90 days or more (cases) or had elective surgery within 90 days of waiting (controls), between 2017-2023 at Sahlgrenska University Hospital, Gothenburg, Sweden, were included in the study (figure 1). Consumed health care during waiting time for surgery (cases) or after surgery (controls) were registered, as well as drugs prescribed and use of supporting products such as stoma bags. Days of sick leave were registered.

Results

A total of 189 individuals were included, 40 (mean age 43.6 years, 18 women) controls and 149 (mean age 41.6 years, 46 women) cases. Forty-six (24.3%) patients had Crohn’s disease, 140 (74.1%) ulcerative colitis and 3 (1.6%) IBD-unclassified. Number of primary care visits at 24-36 months were 4.9 (CI 3.49-6.45) and 3.6 (CI 1.51-5.83) for the cases and controls respectively. The corresponding number of specialized outpatient visits at 24-36 months was 5.1 (CI 3.66-6.69) and 4.1 (CI 1.12-6.05). The mean direct healthcare cost per person were higher for the control group for the first months, it then shifted to be higher in the cases group (table 1). After 24-36 months the cost for the cases were 8 509 and 5 469 euro for the controls. Mean household income was 36 027 euro (CI 27 310–44 743) for the control group and 28 688 euro (CI 25 844–31 532) for the case group. In total, 90% (n=36) were born in Sweden in the control group vs. 75.2% (n=112) in the case group. There was no difference in terms of sick leave between the groups.

Conclusion

Health care cost for patients with IBD waiting for surgery is similar to patients who have had elective surgery. Since patients waiting for surgery still have the postoperative costs to come, this means that the total cost for the healthcare system and society is a lot higher for this group, compared to patients that have had elective surgery within 90 days. A short period of time between surgical decision and surgical date is therefore advisable.
P0953 Real world effectiveness and safety of filgotinib in Ulcerative Colitis: 1 year follow-up results of the ICC registry
Authors: Naber M , van der Meulen A , Voorneveld P , van Bodegraven A , Duijvestein M , Pierik M , Verleye L , Bodelier A , Bouwknegt D , Visschedijk M , West R , van der Marel S , Mensink P , de Vries A , Römkens T , Oldenburg B , Löwenberg M , van Schaik F ,   The Dutch Initiative on Crohn and Colitis (ICC) Registry
Published: January 2025

Background

Filgotinib is a preferential JAK1-inhibitor approved for the treatment of ulcerative colitis (UC). The ICC registry was developed to evaluate the effectiveness and safety of advanced therapies in inflammatory bowel disease (IBD). Here, we report the one-year follow-up results of filgotinib in patients with UC.

Methods

Fourteen hospitals prospectively enrolled UC patients initiating filgotinib in the Dutch ICC registry. Treatment persistence was assessed by Kaplan-Meier survival analysis. Clinical remission (i.e. Simple Clinical Colitis Activity Index [SCCAI] ≤ 2) and corticosteroid-free clinical remission rates were assessed at 12, 24 and 52 weeks for all patients who were not in remission at baseline, based on SCCAI score, faecal calprotectin and/or endoscopy. Patients lost to follow up were considered as treatment failure. Reasons for treatment discontinuation and adverse events were recorded.

Results

Eighty-three UC patients (47% females) were enrolled between January 2022 and October 2023. Mean age and disease duration at baseline were 41 [sd ± 16] and 12 years [sd ± 9], respectively. A total of 49 (59%) patients had used up to two advanced therapies and 34 (41%) patients had used three or more. At baseline, 75 patients (90%) had active disease of whom 24 (32%) used oral corticosteroids. After one year of follow-up, 58.8% of patients still used filgotinib (Figure 1). At week 12, 24 and 52, corticosteroid-free clinical remission rates were 57.1%, 32.7% and 34.6% respectively (Figure 2). Reasons for treatment discontinuation were primary non-response (n=17), secondary loss of response (n=13), side effects (n=3) or other reasons (n=4). Fifty-seven adverse events were recorded (19 infections). Ten infections required treatment with antibiotics or antiviral therapy, none of them led to hospitalization or therapy discontinuation. No thromboembolic events were reported.

Conclusion

The results of this real world study show that, even in a therapy-refractory UC population with an average disease duration of 12 years, more than half of the patients still used filgotinib and one third of patients was in corticosteroid-free clinical remission after one year of follow-up. No new safety signals were found.
P0958 Curcumin-QingDai combination for active ulcerative colitis: A cost-effectiveness analysis
Authors: Yanai H , Choi D , Ben-Horin S , Salomon N , Loebstein R , Leshno M , Rubin D T
Published: January 2025

Background

A combination of two herbal compounds, curcumin and QingDai (CurQD), was recently proposed as an effective treatment for patients with active ulcerative colitis (UC) based on randomized controlled and real-world evidence, but no cost-effectiveness analysis for this nutraceutical is currently available

Methods

A Markov model was generated to simulate the progression of patients with moderate-to-severe UC, by separate analysis for a cohort of advanced therapy-naïve and advanced therapy-experienced patients. Medications costs were derived from published average wholesale price (AWP) in the US. Efficacy data was modeled by synthesis of efficacy reports of randomized placebo-controlled trials and real-world cohort studies of all FDA-approved drugs for UC, and each compared with CurQD. The model used a time horizon of 54 weeks. The threshold of 50,000$/quality adjusted life-year (QALY) was chosen, and a one-way sensitivity analysis was performed for testing analysis robustness.

Results

The comparison of CurQD with the FDA approved advanced therapies for UC yielded an estimated incremental cost-effectiveness ratio (ICER) of over 200,000$/QALY for all comparisons. Differences ranged from -0.05 to a slight gain of 0.07 QALY in bio-experienced patients and from -0.1 to 0.04 QALY in bio-naïve patients. The one- way sensitivity analysis proved the robustness of the analysis.

Conclusion

The present analysis suggests that the markedly reduced cost and demonstrated efficacy of CurQD provides a significant cost-effectiveness benefit over advanced therapies for active UC, including over anti-TNF biosimilars.

References

1.Yanai, H., et al., Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study. Aliment Pharmacol Ther, 2023. 58(2): p. 175-181.

2.Ben-Horin, S., et al., Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Gastroenterol Hepatol, 2024. 22(2): p. 347-356 e6.

3.Ben-Horin, S., et al., Letter: Change in bowel urgency in active ulcerative colitis patients treated with Curcumin-QingDai (CurQD): A post-hoc analysis of a randomized placebo-controlled trial. J Crohns Colitis, 2024.
P0969 Treat to Target strategy in IBD: A real world multicentre experience
Authors: Tan Y Y , Tey T T , Thia T J K , Yan Z H , Qiu T Y , Leong W H J , Chowdhury S , Liew I Y , Lin H , Tan T K M , Lim C T T , Tay S W , Salazar E
Published: January 2025

Background

Suboptimal control of inflammatory bowel disease (IBD) can lead to clinical relapse and disease progression. The STRIDE-II consensus in 2021 encompasses recommendations for short term, intermediate, and long-term targets involving clinical, biochemical and endoscopic remission respectively in a ‘Treat to Target’ strategy to improve IBD-related clinical outcome . We aim to assess the rates of biochemical and endoscopy assessments in our cohort.

Methods

This was a multi-center retrospective study involving four hospitals in Singapore. Between 1 January 2021 to 1 June 2022, we included patients who were initiated on or had a change in advanced therapies and followed up for up to 18 months. Clinical remission was defined as per STRIDE-II treatment targets for Patient Reported Outcomes 2. Biochemical remission defined as CRP <5mg/L or fecal calprotectin (FC) levels <250μg/g. Complications were defined as IBD-related hospitalisation or surgery.

Results

A total of 107 patients were included. The median age was 37 years, 75 (69.4%) were male and 69 (64.4%) had Crohn’s disease (CD). Seventy-three (68.2%) patients had a history of steroid use and 62 (57.9%) were on immunomodulators (Table 1). Eighty-seven (81.3%) were biologics naïve. Ninety-one (85.1%) required new initiation and 16 (14.9%) required a switch of advanced therapy. Eighty-three (76.6%) were started/switched to anti-TNF.

During study period, CRP, FC and endoscopic evaluation was done in 64 (59.8%), 79 (73.9%) and 67 (62.6%) patients respectively. By end of follow up, 100 (93.4%) patients had at least one assessment done. The median time to CRP evaluation was 51 (24-126) days, 92 (49-197) days for FC, 363 days (218-463) for endoscopy. Eighty-one patients (75.7%) were in clinical remission at the end of follow up.

Assessment of CRP within 90 days of treatment change was associated with CRP <5mg/L (p=0.037) but not clinical remission or complication rates. Assessment of FC within 90 days was also associated with clinical remission (p=0.02) only.

Sub-analysis of UC patients demonstrated association of timely CRP and FC assessment with biochemical remission (p=0.02) and reduction in complications (p=0.05). Sub-analysis of CD patients did not show any significant associations.

Conclusion

Around 60% of patients had biochemical and endoscopic assessment within the first 18 months from change in therapy. Timely biochemical assessments within 90 days was associated with clinical remission.
P0973 Early infliximab use is associated with less disease progression in luminal Crohn’s disease: a real-world tertiary centre experience
Authors: Gordon H , Pakpoor J , Radia C , FurtadoOMahony L , Sanford J , Azzu H , Valentine C , Al-Allawee M , Gupta T , Brain O
Published: January 2025

Background

The PROFILE study demonstrated clear benefits of early advanced therapy in luminal Crohn’s disease (CD) in the trial setting. We retrospectively evaluated the relationship between timing of onset of infliximab as first advanced therapy and disease outcomes in a real-world single centre cohort at Oxford University Hospitals NHS Trust.

Methods

A pharmacy database was searched to identify patients who received infliximab as first advanced therapy in CD. Electronic patient records (Cerner) were searched to capture the following: demographics, Montreal classification, timing of onset of infliximab, biochemical, endoscopic and radiological parameters. The primary outcome was persistence on therapy. Secondary outcomes were survival without surgery or hospitalisation, progression of disease phenotype and steroid use. Data was analysed using GraphPad Prism.

Results

247 patients prescribed infliximab as first advanced therapy were identified (F:M = 112:135). Median duration (IQR) from diagnoses to first infliximab dose was 2.83 (0.25 – 10.02) years. 117 patients had inflammatory luminal disease at therapy onset (Montreal B1P0), with median first therapy from diagnosis of 2.67 (0.25 – 9.91) years.

When reviewing all cases, and those with exclusively inflammatory luminal disease, persistence on therapy, survival without surgery and survival without hospitalisation did not vary with time to first advanced therapy (p>0.05 all comparisons, figure 1). However, in patients with luminal inflammatory CD who started therapy within 2 years of disease onset there was less disease progression, defined as extension in location, behaviour or new perianal disease (2/52 vs 10/65 chi sq 4.18 p=0.04), and a trend towards less systemic corticosteroid use (4/52 vs 13/65 chi sq 3.53 p=0.06).

Conclusion

Early infliximab therapy in luminal CD is associated with less disease progression and less use of systemic corticosteroids. The lack of variation in other outcomes may be due to historical case selection for advanced therapies.

References

Noor NM et al. PROFILE. Gastro Lancet Hep 2024

Figure 1: Persistence on therapy, surgery and hospitalisation free survival, categorised by duration from diagnosis until first infliximab dose. *luminal = Montreal B1P0
P1007 Influence of pharmacokinetic-pharmacodynamic failure mechanisms on outcomes in biologic therapy sequencing in inflammatory bowel disease
Authors: Steenholdt C , Lorentsen R D , Henneberg J , Petersen P , Brynskov J
Published: January 2025

Background

Increasing therapeutic options for inflammatory bowel disease (IBD) calls for tools to aid choice of sequencing. We investigated if pharmacokinetic (PK) and pharmacodynamic (PD) failure mechanisms prompting therapy change influenced subsequent outcomes when switching to a different biologic drug class.

Methods

Retrospective cohort study at a tertiary, Danish IBD center including all patients treated with first TNF-inhibitors, followed by vedolizumab, and then ustekinumab, as defined by national treatment regulations at time of study. Clinical and objective disease remission were defined by validated indices (HBI, SCCAI, Mayo, SES-CD). Treatment failure was defined by the treating physician and supported by clinical disease activity scorings and objective disease activity evaluations. Drug trough levels and anti-drug antibodies were measured at manifest treatment failure in routinely collected biobanked samples. PK-PD failure was defined according to maintenance drug concentrations: infliximab 8.0 µg/mL, adalimumab 12.0, golimumab 1.4, vedolizumab 15. Primary treatment failure despite dose intensification was ascribed to PD. Primary endpoints were steroid-free treatment persistence and one-year remission.

Results

The study included 112 patients switching from TNF-inhibitors to vedolizumab (infliximab n=61, adalimumab n=32, golimumab n=16, certolizumab pegol n=3) and 31 subsequently to ustekinumab. Treatment persistence on vedolizumab did not differ between patients discontinuing TNF-inhibitors due to PK (n=28, 31%) or PD (n=63, 69%) (mean 989 days [554-1,424] vs. 951 [659-1,242], p=0.93). One-year steroid-free clinical and objective remission rates on VDZ were also comparable between PK-PD groups (29% vs 35%, p=0.63 and 35% vs. 43%, p=0.48, respectively). Furthermore, treatment persistence on ustekinumab was neither different between patients having initially discontinued TNF-inhibitors due to PK or PD (1,553 [997-2,110], n=11) vs. 1,200 [762-1,639], n=14; p=0.42), nor later discontinued vedolizumab due to PK or PD (1,305 [832-1,778], n=11 vs. 1,323 [785-1,862], n=15; p=0.43). Clinical and objective remission on ustekinumab was also similar between these groups. Sensitivity analysis using other thresholds to define PK or PD failure were congruent to the above findings. Sensitivity analyses with exclusion of primary non-responders and multivariate analyses correcting for potential confounders also supported the findings.

Conclusion

Our study does not show evidence for inferior outcomes during subsequent sequencing to biologics with different modes of action in patients switching due to PK failures as compared to those with PD failure. Choice of sequencing may thus take into account other aspects such as efficacy, safety and costs.
P1024 Switching to subcutaneous infliximab in week 6 – the effect on mucosal healing and treatment persistence
Authors: Brinar M , Zlopasa L , Kodvanj I , Jelakovic M , Turk N , Grgic D , Cukovic Cavka S , Kunovic A , Krznaric Z
Published: January 2025

Background

Infliximab remains a cornerstone in managing inflammatory bowel disease (IBD) patients. The recent introduction of subcutaneous (SC) infliximab offers a potential alternative to intravenous (IV) administration. However, the optimal timing of the switch is still unclear. We aimed to investigate the difference in mucosal healing rates and therapy persistence in patients switched to SC infliximab at week 6 as opposed to those maintained on IV therapy.

Methods

All patients starting infliximab treatment from January 2023 to April 2024 were included. Patients with primary non-response to IV infliximab and those starting treatment for prophylaxis of postoperative disease recurrence were excluded from the analysis. At week 6, patients were stratified into two groups: SC (n = 48) and IV (n = 77). The primary outcomes included mucosal healing and persistence on therapy. Mucosal healing was defined as a Mayo endoscopic score of 0 or 1 for ulcerative colitis patients, a simple endoscopic score for Crohn’s disease (SES-CD) ≤ 3, or a modified Rutgeerts score ≤ i2a. Drug concentrations were measured, and odds ratios were calculated for comparative efficacy. Statistical analyses were performed using R version 4.3.1

Results

A total of 125 IBD patients starting infliximab for active disease with were included (71 with Crohn’s disease, 54 with ulcerative colitis). No significant differences in gender, age at diagnosis, age at infliximab initiation and concomitant immunomodulator use were found between the IV and SC treatment groups. Patients in the IV group had a significantly shorter disease duration compared to SC group (median 2, interquartile range (IQR) [1-11] years vs median 7, IQR [3-14] years; p=0.009). In 86% of the cohort, infliximab was the first-line biologic. No significant difference in mucosal healing rates was found between the IV and SC treatment groups (p = 0.06). Therapy discontinuation rates were similar between groups: 24% (18/77) for IV versus 22% (11/48) for SC. Median infliximab concentrations measured at week 14 were significantly higher in the SC group (median 12.0, IQR [10,9-12] µg/mL) compared to the IV group (median 6.2, IQR [4,1-9,3] µg/mL; p = 0.004). No therapy optimization was observed in the SC group, whereas 32% (n = 23) of patients in the IV group required dose optimization.

Conclusion

Switching to subcutaneous infliximab at week 6 is equally effective, with similar treatment persistence compared to IV maintenance therapy. Furthermore, SC application is preferred by patients and is cost-effective, with significant proportion of patients on iv maintenance therapy requiring treatment optimization during follow-up. These findings support SC infliximab as a viable alternative in IBD management.
P1026 Rectal stump surveillance in the IBD population
Authors: Clark J , de Silva S , King D
Published: January 2025

Background

Patients with inflammatory bowel disease (IBD) may require surgical resection, including subtotal colectomy, to manage symptoms and improve quality of life. However, there remains a risk of colorectal cancer (CRC) within the retained rectal stump. Although robust national and international guidelines exist for CRC surveillance in IBD patients with an intact colon, there is a significant gap in guidance for those with a retained rectal stump. We examined the current surveillance practices for the rectal stump in IBD patients, aiming to clarify current practice and optimise long-term surveillance strategies.

Methods

We performed a single centre, retrospective observational study. Patients with IBD undergoing surgical resection were identified using the local surgical IBD database, between January 2012 and September 2023. Cases without a rectal stump were excluded. Data was collected regarding age, sex, date of IBD diagnosis, date of surgery, frequency of surveillance, endoscopic appearance at surveillance, histology at surveillance and histological appearance at resection – this was used to assess initial risk. The British Society of Gastroenterology (BSG) guidelines for surveillance frequency of IBD were used as a comparator.

Results

Of the 53 patients (median age = 52 (IQR = 32), 34% female, 66% male) included, 30.2% underwent surveillance following the BSG guidelines, according to their risk at formation of the rectal stump, determined by BSG guidelines. 39.6% of patients underwent surveillance but not in accordance with the BSG guidelines and 30.2% had no surveillance documented. 51.4% of patients had their risk reclassified at first surveillance, 48.6% had no change to their risk. No patients developed colorectal cancer on surveillance. 85% of patients underwent subtotal colectomy within 10 years of diagnosis.

Conclusion

Conclusion IBD patients with a retained rectal stump are susceptible to adjustment of their risk based on histological and endoscopic appearance at surveillance, when using risk at initial resection as a baseline. This implies close monitoring is required, to ensure any dysplasia or CRC is adequately identified. Surveillance was inconsistent, and many patients had no surveillance documented. This study highlights the need for surveillance guidelines for patients with IBD with a retained rectal stump. The BSG guidelines suggest a screening colonoscopy 10 years post-diagnosis, yet most patients underwent initial resection before this could take place. This raises the question whether patients should undergo surveillance 10-years post-resection, or if this would be required earlier, dependant on risk following resection. The answer to this requires further research, to ensure uniformity in practice.
P1102 Albumin predicts post-operative complications in Acute Severe Ulcerative Colitis
Authors: Hodges P , Phillips J , King H , Creamer J , Kitchin A , Carter O , Tyrrell-Price J ,   Severn and Peninsula Research in Gastroenterology Trainee Network (SPRinG)
Published: January 2025

Background

Acute severe ulcerative colitis (ASUC), defined by the modified Truelove and Witts criteria, is a potentially life-threatening condition. Randall et al showed over a decade ago that prolonged medical therapy prior to surgery was associated with a higher rate of major post-operative complications.(1) We undertook a retrospective cohort study with the aim of identifying other clinical parameters that could predict adverse outcomes following colectomy in the setting of ASUC.

Methods

We identified patients who had undergone colectomy for ASUC across 5 UK hospitals forming part of a trainee research network (the South West and Peninsula Research in Gastroenterology (SPRinG) network) over a 10-year period. We undertook a notes review for all these patients and compared pre-operative biomarkers (CRP, albumin) as well as length of stay prior to surgery in those who had a post-operative complication with those who did not.

Results

We identified 126 patients who had undergone colectomy for ASUC. 57% were male and 43% female. Median age was 44. 47% patients (n=59) received rescue therapy (ciclosporin n=17, infliximab n=40, Ustekinumab n=1, unclear from documentation n=1), 37% did not receive rescue therapy (n=46) and documentation was not found in 16% (n=21). Pre-operative albumin level was significantly lower in those who developed a post-operative complication up to 30 days (p=0.04, 95% CI 0.13, 4.68) (Figure1). It was not possible to identify a specific albumin level below which the risk of post-operative complications increases. There was no difference in length of stay prior to surgery, number of days of intravenous corticosteroid treatment, or pre-operative CRP between those who developed post-operative complications up to 30 days and those who did not. Of those who had complications within 30 days (66/126), the most common complications were abscess or wound infection (n=14) and ileus (n=12). Death occurred in 2 patients within 30 days.

Conclusion

We have shown that pre-operative albumin is associated with post-operative complications in ASUC. Our findings do not support the previous observation that prolonged medical therapy (either measured by length of stay or by number of days of intravenous corticosteroid treatment) prior to surgery increases the risk of post-operative complications.

References

1.Randall J, Singh B, Warren BF, Travis SP, Mortensen NJ, George BD. Delayed surgery for acute severe colitis is associated with increased risk of postoperative complications. Br J Surg. 2010;97(3):404-9.

Table 1 Comparison of clinical parameters between patients with and without complications up to 30 days

Figure 1 Pre-operative albumin in those with and without complications up to 30 days
P1105 Reswitching Anti-TNF’s as Third-Line Biologic Therapy After Second-Line Failures: Factors Influencing Outcomes
Authors: Akpınar A , Gur M B , Bakkaloglu O K , Vatansever H , Eskazan T , Hatemi A I , Erzin Y Z , Celik A F
Published: January 2025

Background

Anti-TNF agents may show different response profiles when reintroduced after discontinuation due to nonresponse or allergy. This study aims to evaluate and compare the efficacy and side effect profiles of anti-TNF agents in patients who underwent a re-switch.

Methods

A retrospective cohort of 53 patients (41 treated with infliximab [IFX], 12 with Adalimumab [ADA]) was analysed between 2005 and 2024. All patients had previously discontinued anti-TNF therapy, which was later re-switch. Premedication was administered during re-switch for patients receiving infliximab treatment to reduce the risk of allergic reactions.

Results

Of the 53 patients, 47 (89%) had Crohn’s disease (CD), and 33 (62%) were male, with a mean age of 28 ± 12.6 years. Patient characteristics, doses used before re-switch, doses at reintroduction, and maximum doses achieved are summarized in Table 1a. Treatment discontinuation due to lack of response occurred in 73% of patients during the initial use of the drug. Approximately half of the patients, (54% with IFX and 50% with ADA), switched medications without dose escalation. The summary of the reasons why patients discontinued their initial anti-TNF treatment is presented in Table-2b. Of the 53 patients who underwent re-switch, 22 (42%) continue treatment. Among the 17 patients receiving IFX, 6 achieved radiological fistula closure (5 on 10 mg/kg/4w, 1 on 10 mg/kg/8w), and 11 achieved endoscopic remission (2 on 5 mg/kg/8w, 2 on 10 mg/kg/8w, 7 on 10 mg/kg/ 4w). Among the 5 patients receiving ADA, 1 achieved radiological fistula closure with 80 mg/7 days, and 3 achieved endoscopic remission (2 on 80 mg/7 days, 1 on 40 mg/7days). In 31 patients (58%), treatment was discontinued or changed after re-switch due to allergic-like adverse effects, lack of response, or the patient being lost to follow-up. Details are provided in Table 2a. In the IFX re-switch group, 23 patients (56%) reinitiated treatment with the standard dose, while in the ADA group, 4 patients (33%) started with the standard dose. In the total reswitch group, median CRP at initial treatment was 11 (23) and 13 (20) before medication change, with no significant difference (p: 0.386). The CRP course of patients who underwent reswitch is presented in Table-1b.

Conclusion

This study demonstrates that re-switching anti-TNF therapy can lead to significant clinical improvements, particularly in terms of CRP reduction, particularly in patients who could not be given optimum dose adjustment previously. Approximately 42% of patients continued treatment after re-switch, showing notable radiological and endoscopic improvements. These findings highlight re-switching as a viable option and the importance of proper dose adjustment before concluding treatment failure.
P1114 Engineering and Development of a Novel Bispecific Antibody Targeting IL-23 and TL1A
Authors: Huang J , Ran H , Zhang X , Li S , Su C , Dong L , Chen C , He Y , Liu D , Xu X , Chen X , Wang Y , Fei K , Tian J , Tian L , Peng J , Zhu Z
Published: January 2025

Background

Both IL23 and TL1A are clinically validated targets with genetical linkage to various human autoimmune diseases. Here we engineered and produced HXN-1003, a bispecific antibody (bsAb) simultaneously targeting both IL23 and TL1A, with the aim to further enhance clinical efficacy, and to overcome refractory and resistance associated with single-target based therapies.

Methods

The binding and blocking efficacy of HXN-1003 for each target were assessed using various in vitro assays, including IL23 reporter and mouse splenocyte activation assays for IL23, and TF-1 apoptosis and DR3-NFκB-Luc reporter assays for TL1A. The synergistic effect of dual targeting was measured by IL22 secretion in mouse splenocytes co-stimulated with IL23 and TL1A. In vivo efficacy was evaluated in hIL23/hTL1A transgenic mice with DSS-induced colitis and IMQ-induced psoriasis models, as well as in SD rats with subcutaneous injections of hTL1A and hIL23 to induce dermatitis.

Results

HXN-1003 features a tetravalent structure, with the anti-IL23 arm specifically binds to the p19 subunit of IL23, demonstrating superior affinity and blocking activity compared to benchmark Risankizumab. For TL1A, HXN-1003 binds to both the TL1A trimer and monomer with sub-nanomolar affinity, exhibiting similar blocking activity to its parent antibody HXN-1001 and RVT-3101. In the mouse splenocyte activation assay induced by IL23 and TL1A, HXN-1003 showed greater activity than each individual antibody and was equally active to their combination. In animal models, HXN-1003 significantly alleviated symptoms of DSS-induced colitis, and demonstrated superior therapeutic effects in the IMQ-induced psoriasis model compared to the IL23 monoclonal antibody. Additionally, in the dermatitis model induced by hTL1A and hIL23, the bsAb outperformed each individual antibody and their combination.

Conclusion

HXN-1003 simultaneously blocks IL23 and TL1A, with each arm exhibiting activity comparable to the parent monoclonal antibodies. It has demonstrated synergistic/additive therapeutic effects in both in vitro and in vivo experiments, highlighting its potential to enhance clinical efficacy and benefit autoimmune patients in multiple clinical settings.
P1117 A 24-year, single-centre perianal fistulizing Crohn’s disease cohort: documentation of demographics and factors influencing clinical and radiological remission
Authors: Bayar M , Bakkaloglu O K , Sirolu S , Sari E , Hamid R , Tutar O , Eskazan T , Hatemi A I , Erzin Y Z , Celik A F
Published: January 2025

Background

Radiological remission (RR), is the ultimate treatment goal in treatment of complex perianal fistula (cPAF) in Crohn’s disease (CD). In this study, we analysed cPAF disease characteristics and RR-related factors in a CD cohort.

Methods

Patients with CD (1999–2023) and MRI-confirmed cPAF (per AGA 2003 criteria, reviewed by 4 radiologists) were analyzed. Clinical remission (CR) was defined as no drainage under compression for ≥3 months, and RR as fibrotic fistula closure.

Results

Among 1688 CD patients, PAF prevalence was 24.7% (n=417), with 19% (n=79) classified as simple fistulas. Detailed analysis included 223 cPAF patients with sufficient follow-up. Male predominance was noted (65.5%), with a median CD diagnosis age of 28(IQR: 20) years and cPAF onset at 8(53) months. Median follow-up was 58(79) months. Isolated PAF occurred in 8.5%. Patients had a median of 2 fistulas, with ≥1 fistula in 51.6%. Common cPAF types were ISF (77%) and TSF (46%), with branching formation evident in 38.6%. Immunomodulator (IM) use was 94%, Anti-TNF+IM combination 87%, and multiple Anti-TNF exposure 35%. IFX was given to 31.8% at 5mg/8w and 51.9% at higher doses (up to 15mg/kg/4w).

CR was achieved in 71% and RR in 43.5% of patients following a stepwise treatment approach including antibiotics, IM, Anti-TNF dose escalation, and diverting stoma (Figure 1). In the RR group, cPAF onset after CD diagnosis, non-mucosal (B2-B3) involvement, and abscess-related low fistulas were more frequent, while multiple cPAF, branching formation, and TSF were more common in the non-RR group (Table 1). Time-dependent analyses showed better RR associated with cPAF onset after CD diagnosis (log-rank <0.001), fewer fistulas (LR=0.035), abscess-related low fistulas (LR<0.001), and early Anti-TNF initiation (<0.008). Poor RR was linked to branched fistulas (LR=0.003), TSF (LR=0.042), and multiple Anti-TNF exposure (LR=0.017). The development of cPAF after CD diagnosis during follow-up, fistulas other than TSF, the absence multiple Anti-TNF exposure, and early initiation of Anti-TNF treatment were independently associated with better RR rates in multivariate analyses.

Conclusion

With a appropriate stepwise approach, including dose adjustments and stoma, RR can be achieved in 43.5% of cPAF patients. TSF-type fistulas are associated with poorer outcomes, while low perianal fistulas complicated by abscesses show better prognosis. Multiple Anti-TNF exposure predicts a poor response, whereas cPAF onset during follow-up and early Anti-TNF initiation are strongly associated with achieving RR.