bluuebunny/crossref_metadata_2025 huggingface dataset:
P0869 Model-informed dosage de-escalation of infliximab in patients with inflammatory bowel diseases
Authors: Wang Z , De Greef I , Kantasiripitak W , Wicha S G , Tops S , Nigro M , Outtier A , Verstockt B , Sabino J , Thomas D , Vermeire S , Ferrante M , Dreesen E
Published: January 2025

Background

Extending the infliximab (IFX) infusion interval has been attempted in patients with Crohn’s disease (CD) and ulcerative colitis (UC) who maintained response following an earlier interval shortening. We compared therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) for successful de-escalation of infliximab dosage in these patients.

Methods

MODIFI is a monocentric, open-label, historically controlled Phase 4 trial (NCT04982172). Eligible patients with steroid-free clinical (two-item patient-reported outcome [PRO2] ≤1 for UC and ≤8 for CD) and biological remission(C-reactive protein <5 mg/L and faecal calprotectin <250 mg/kg) on accelerated IFX dosing underwent interval extension to every eight weeks. The extension was guided by either TDM (historical control) or MIPD targeting an infliximab trough concentration (Ctrough) of 5 mg/L (prospective intervention). Bayesian forecasting was performed using the TDMx Infliximab module (www.TDMx.eu). Steroid-free clinical and biological remission and IFX concentrations were measured at each study visit over 52 weeks. The primary endpoint was sustained steroid-free clinical and biological remission over one year.

Results

The study enrolled 52 patients: 21 patients (11 CD, 10 UC) in the TDM arm and 31 patients (19 CD, 12 UC) in the MIPD arm (Table 1).

Although the proportion of patients achieving the primary endpoint was numerically higher in the MIPD arm (52%, n=16/31) compared to the TDM arm (29%, n=6/21), this was not significantly different p=0.17; Figure 1A). However, the proportion achieving sustained steroid-free clinical remission over one year was significantly higher in the MIPD arm compared to the TDM arm (81%, n=25/31, vs. 38%, n=8/21, p<0.01), particularly in the UC subpopulation (100% in the MIPD arm, n=12/12, vs. 30% in the MIPD arm, n=3/10, p<0.01; Figure 1D&F). The proportion of patients achieving sustained steroid-free biological remission over one year did not statistically differ between the MIPD and TDM arms, both in the total population and in the subpopulation analyses (p>0.50; Figure 1G–I).

Following a single model-informed dose at baseline, the IFX Ctrough decreased to median 5.9 mg/L [interquartile range IQR 4.4–7.5 mg/L] with 65% of patients having an IFX Ctrough >5 mg/L. The IFX dose per infusion over the one year period was comparable between the TDM arm (7.5 [IQR 7.4–8.2] mg/kg) and the MIPD arm (8.8 [IQR 6.6–10.9] mg/kg).

Conclusion

MIPD-guided IFX dosage de-escalation resulted in numerically higher rates of sustained steroid-free clinical and biological remission compared to dose de-escalation based on TDM. Future confirmatory studies with randomization and larger sample size are needed to validate our findings.
P0875 Predictors for maintained remission at one year following appendectomy in ulcerative colitis: a post-hoc analysis of the ACCURE trial
Authors: Visser E ,   ACCURE study group
Published: January 2025

Background

The ACCURE trial, a randomised controlled trial, demonstrated that appendectomy reduces clinical relapses within one year in patients with ulcerative colitis (UC) in clinical remission without advanced therapies compared to standard medical therapy. We aimed to evaluate predictive baseline characteristics for maintained remission following appendectomy in the ACCURE cohort.

Methods

In this post-hoc analysis, appendectomy patients from the ACCURE trial were included. Patients without endoscopic follow-up or diagnosed with Crohn’s disease were excluded. Maintained remission was defined as the absence of clinical relapse (according to predefined study criteria), with endoscopic confirmation (Mayo subscore ≤1) at one year. Logistic regression was performed to identify baseline characteristics associated with maintained remission at one year, reported as odds ratios (ORs) and 95% confidence intervals (CIs). Associations were also compared to the control group (non-appendectomy patients) to assess differences in baseline predictors for maintained remission between treatment groups and the relative impact of appendectomy on remission.

Results

Of 82 included appendectomy patients, 51 (62.2%) maintained clinical remission up to one year. Baseline characteristics are shown in Table 1. Several numerical trends were observed: patients who maintained remission were younger (40±11 vs 46±14 years), had less previous exacerbations (median 3.5 [IQR, 1.8-5.0] vs 6 [IQR, 4-10]), shorter disease duration (4.7 [IQR, 1.4-12.1] vs 5.5 [2.6-13.2] years), more often proctitis (39.2% vs 32.3%), endoscopic Mayo score of 0 at baseline (52.9% vs 29.0%), and less immunomodulators therapy (3.9% vs 12.9%) when compared to patients who failed maintaining remission. Age (per 10-years: OR 0.68, 95% CI 0.47-0.98, p=0.04) was associated with reduced odds of maintained remission (Figure 1A). This association contrasted significantly with the control group, where older age was associated with greater odds of maintained remission (age per 10-years: OR 1.61, 95% CI 1.10-2.36; Figure 1B), indicating an inverse relationship between age and remission outcomes across treatment groups.

Conclusion

In this post-hoc ACCURE analysis, younger age was significantly associated with higher odds of maintained remission up to one year following appendectomy in UC, contrasting with older age predicting better remission outcomes in the control group. Interestingly, these results align with previous epidemiological studies suggesting appendectomy as a protective factor for the development of UC in younger individuals. Age may therefore serve as an predictor for maintained remission, offering a potential basis for refining patient selection criteria for appendectomy in UC management.
P0881 Effectiveness and Safety of Tofacitinib in Biologic-Naïve Elderly Patients with Ulcerative Colitis
Authors: Singh D.M. A , Midha V , Bhardwaj A , Sharma R , Singh D , Mahajan R , Sood A
Published: January 2025

Background

The prevalence of ulcerative colitis (UC) is increasing in elderly populations, yet real-world data on the efficacy and safety of tofacitinib in this demographic remains limited. This study aimed to evaluate the real-world effectiveness and safety of tofacitinib in elderly patients (≥60 years) with moderate-to-severe UC treated at a tertiary care center in North India.

Methods

This cohort study was conducted at Dayanand Medical College and Hospital, Ludhiana, from July 2022 to June 2024. Elderly patients (aged ≥60 years) with moderate-to-severe UC refractory to conventional therapies were included. Patients received tofacitinib at a dose of 10 mg twice daily for induction, followed by 5 mg twice daily for maintenance, and were assessed at weeks 8 and 52. The primary outcome was steroid-free remission at both weeks 8 and 52. Secondary outcomes included clinical remission (partial Mayo score ≤1), clinical response (≥3-point reduction in partial Mayo score), and steroid-free remission at individual time points. Adverse events were systematically recorded.

Results

A total of 35 patients (median age: 64 years, 40% male) were analyzed. Most patients (80%, n=28) had left-sided colitis. The primary outcome of steroid-free clinical remission at both weeks 8 and 52 was achieved in 9 patients (25.71%). At week 8, clinical remission, steroid-free remission, and clinical response were observed in 18 (51.42%), 15 (42.85%), and 22 (62.85%) patients, respectively. At week 52, clinical remission and steroid-free remission were each achieved in 22 (62.85%) patients, while 27 (77.14%) patients demonstrated a clinical response. The most common adverse events included hair loss (17.14%, n=6), sadness of mood (11.42%, n=4), and dyslipidemia (8.57%, n=3). Three patients developed self-limiting herpes zoster infection, and one patient reported bilateral retinal vein occlusion.

Conclusion

Tofacitinib demonstrated favorable efficacy and safety in biologic-naïve elderly patients with moderate-to-severe UC. These findings highlight its potential as a viable treatment option for this growing and often underrepresented patient population.
P0883 Proactive pharmacogenomics in azathioprine-treated pediatric inflammatory bowel disease at a Chinese tertiary hospital
Authors: Long C , Huang Y
Published: January 2025

Background

Despite the emergence of numerous innovative targeted therapies for the management of pediatric inflammatory bowel disease (IBD), azathioprine continues to be a pivotal first-line therapeutic agent. Nonetheless, the considerable frequency of myelotoxicity associated with its use warrants careful consideration and further investigation.

Methods

A retrospective analysis was performed on the clinical data of pediatric IBD who had undergone azathioprine pharmacogenomic testing at the Department of Gastroenterology, Children's Hospital of Fudan University, between July 2019 and May 2024. The study aimed to summarize the prevalence of metabolic gene abnormalities associated with azathioprine and to assess the incidence of myelosuppression among these patients during the subsequent follow-up period.

Results

Among the 227 patients underwent pharmacogenetic testing, abnormal genetypes occurred in 66 patients, among which 7 patients exhibited aberrant TPMT and 59 had aberrant NUDT15. Of the 58 patients who were treated with azathioprine, 23 cases experienced myelosuppression. All three children with heterozygous mutations in NUDT15 developed leukopenia following azathioprine treatment. Among patients with normal pharmacogenetic results, 20 cases (36.4%) developed myelosuppression, while 35 cases (63.6%) did not. The dose of azathioprine was below the recommended level in guidelines. The mean dose of azathioprine (mg/kg/day) in the myelosuppression group was 1.22±0.32, compared to 1.42±0.42 in the non-myelosuppression group, which represented a statistically significant difference (p<0.05). However, age, gender, and the use of concomitant biologics, mesalazine, or glucocorticoids did not show significant differences between the groups (p>0.05).

Conclusion

NUDT15 C415T was prevalent in China and optimal dose of azathioprine should be reconsidered in Chinese pediatric IBD.
P0886 The association of psychological factors and future exacerbation of Inflammatory activity in Crohn’s Disease: A prospective Cohort Study
Authors: Barda L , Talan Asher A , Yablecovitch D , Haj O , Haberman ziv Y , Ungar B , Eliakim R , Kopylov U , Ben-Horin S
Published: January 2025

Background

Recent research has highlighted the complex relationship between Inflammatory bowel disease (IBD), inflammatory activity, and psychological factors such as depression, stress, and anxiety. However, there are scant data from prospective study exploring a putative contributing role of psychological factors in promoting the inflammatory process in the gut. We aimed to explore the temporal relations between depression, stress and anxiety states with the future trajectory of inflammatory intestinal activity as assessed by video capsule endoscopy (VCE) to try to disentangle the correlation between these emotional states and inflammation.

Methods

The CORE prospective observational cohort study included patients with Crohn’s disease (CD) in clinical remission. All patients underwent six-monthly assessments by C-reactive protein (CRP), fecal calprotectin levels, VCE examination, microbiome analysis, the Crohn's disease activity score (CDAI) score and the validated Depression, Anxiety and Stress Scale - 21 Items score (DASS21) for assessment of emotional state. We compared the psychological scores' results with VCE-gauged intestinal activity from two time points: baseline and six months later.

Results

50 patients were included (median age 35.22, sex – 72% men) on a stable treatment. We observed a mild but significant increase in small bowel inflammation between baseline and the six-month follow-up, as reflected by the VCE Lewis score (median 225 vs. 360, p = 0.0002) and an increase at the depression score (p=0.029). There was no significant correlation between the baseline levels of anxiety, depression, or stress and the subsequent exacerbation of mucosal inflammation except for a weak inverse correlation observed for anxiety (p = 0.018, r = -0.33), Similarly, there was no correlation between baseline anxiety, depression or stress levels to subsequent calprotectin trajectory.

Conclusion

Understanding the relationship between IBD, inflammatory markers, and psychological factors is crucial for clinical practice. In our cohort of patients with CD in clinical remission, who were prospectively and rigorously followed with VCE, we found no evidence that anxiety, stress, or depression are associated with an increased risk of future worsening of mucosal activity. Further research is needed to explore the complex interplay and the potential mediators of relationship of stress and mucosal inflammation.
P0889 Efficacy and safety of obefazimod for the fourth and sixth year of open-label maintenance treatment in patients with moderately to severely active ulcerative colitis (UC): 2-year interim analysis after dose de-escalation to 25 mg
Authors: Danese S , Sands B E , Dulai P S , Peyrin-Biroulet L , Dubinsky M , Tilg H , Siegmund B , Hisamatsu T , Shan K , Ploncard P , Jacobstein D , Cataldi F , Rabbat C , Vermeire S
Published: January 2025

Background

Obefazimod is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124. Obefazimod demonstrated efficacy and safety in patients with moderate to severe active UC at week-8 in two double-blind, placebo-controlled induction trials and in subsequent open-label maintenance (OLM) studies [1-3], and a randomized controlled phase 3 study, ABTECT, is ongoing.

Methods

Patients with UC on obefazimod 50mg QD with endoscopic improvement (Mayo Endoscopic subscore = 0 or 1), could enrol in an open label study in which they were administered obefazimod 25mg QD for up to an additional 54 months. This interim analysis (cut-off date: September 11, 2024) reports the findings of patients who completed Weeks 48 (W48) and 96 (W96) visit (as observed analysis).

Results

Patients with UC were treated with obefazimod 50mg QD for approximately four years in the Phase 2a OLM study and for approximately two years in the Phase 2b OLM study. Out of 174 patients who completed these studies (10 in Phase 2a OLM, 164 in Phase 2b OLM), 138 were eligible. As of the cut-off date, 130 patients rolled over in the 25 mg OLM and were dosed. Among this cohort, 16 patients (12%) discontinued prior to W48 and 6 (5%) discontinued between W48 and W96. Overall, 113 patients (87%) completed the W48 visit, 74 (57%) completed the W96 visit. After dose de-escalation, rates of clinical remission at W48 and W96 were 84% (95/113) and 87% (64/74), respectively. At W48 and W96, 91% (103/113) and 91% (68/75) of patients were in symptomatic remission, respectively. Similar trends were observed with other efficacy analyses (Table 1).

At W48, the levels of fecal calprotectin (FCP) were <250 and <150 µg/g for 90% (85/94) and 81% (76/94) of patients with available FCP values, respectively. At W96, 75% (49/65) of patients had FCP levels <250 µg/g, and 69% (45/65) had levels <150 µg/g. No new safety findings were identified over these 96 weeks.

Conclusion

Following 2-4 years of open-label treatment with obefazimod at a dose of 50 mg QD, large percentages of patients maintained efficacy measures on a lower maintenance dose of 25 mg od for two additional years. No new safety signals were observed over up to six years of obefazimod treatment, supporting a favorable long-term risk-benefit profile.

References

1.Vermeire S, et al. J Crohns Colitis 2023

2.Vermeire S, et al. Gastroenterology 2021

3.Vermeire S, et al. The Lancet Gastroenterol & Hepatol 2022.
P0891 Efficacy and safety of subcutaneous guselkumab rescue therapy in patients with moderately to severely active Crohn’s disease and inadequate response to ustekinumab: Phase 2 GALAXI 1 study long-term extension results
Authors: Afzali A , Wolf D , Leong R , Salese L , Gao L L , Busse C , Panés J
Published: January 2025

Background

Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that is being evaluated in Crohn’s disease (CD). The GALAXI 1 study (NCT03466411) is a phase 2b study that evaluated GUS in participants (pts) with moderately to severely active CD. Pts treated with ustekinumab (UST) who met inadequate response criteria during long term extension (LTE) could cross over to GUS 200 mg q4w SC. Here, we present efficacy and safety results in pts who received GUS after experiencing an inadequate response to UST in the LTE.

Methods

Individuals with prior inadequate response or intolerance to UST were excluded from GALAXI 1; however, during the LTE, pts treated with UST ~6 mg/kg IV→UST 90 mg SC q8w who met inadequate treatment response criteria (not in clinical response [≥100-point reduction in CDAI score from baseline or CDAI<150] and CDAI ≥220) between Weeks 52-80 of the LTE were eligible for a treatment switch to GUS 200 mg q4w SC, without IV induction. Clinical response and clinical remission were both assessed 16 weeks after treatment switch. Endoscopic response and endoscopic remission were assessed at Weeks 96 and 144 (definitions in Figure). Safety was assessed through Week 144.

Results

In total, 17 pts treated with UST underwent treatment switch to continuing GUS 200 mg q4w SC therapy due to meeting inadequate treatment response criteria between Weeks 52-80 of the LTE. Pts who crossed over to GUS exhibited similar baseline demographics and disease characteristics to all GUS LTE pts (Table).

The proportions of pts achieving clinical response and clinical remission 16 weeks after treatment switch from UST to GUS 200 mg SC q4w were 58.8% and 52.9%, respectively. The proportions of pts achieving endoscopic response and endoscopic remission were 52.9% and 35.3% at study Week 96, respectively, and were maintained through Week 144 (Figure).

Key safety event rates through Week 144 were consistent with the known safety profile of GUS in approved indications.

Conclusion

Among pts who experienced inadequate response to UST in the LTE, more than half achieved clinical remission 16 weeks after treatment switch to GUS 200 mg SC q4w and >50% were in endoscopic response at Week 96. These data suggest pts with an inadequate treatment response to UST may benefit from GUS treatment. Results are limited by small sample size and direct treatment switch to GUS SC maintenance dosing without IV induction.
P0895 The Prognostic Significance of Visceral Adiposity indices in conjunction with Plasma Trace Elements in Newly Diagnosed Crohn's Disease
Authors: Luo J , Li G , Hu W , Shen K , Huang X , Xu D , Wang X , Ma Y , lv M , Li S , Chen Y , Yu Q
Published: January 2025

Background

While imbalances in trace elements are recognized for causing dysfunction in adipose tissue and disease onset and progression of CD, the relationship between the initial status of trace elements and the risk of VAT accumulation in patients with CD remains uncertain. This study aims to investigate the prevalence of trace element deficiencies among newly diagnosed CD patients, explore how these deficiencies relate to VAT accumulation, and examine their implications for disease progression. In particular, we focus on magnesium due to its potential therapeutic effects, evaluating its role in experimental colitis models to assess its impact on inflammation and immune responses.

Methods

The analysis was based on an inception cohort of 300 patients newly diagnosed with CD between July 2019 and June 2022. Plasma trace element levels were measured at baseline. VAT was evaluated using computed tomography (CT) scans obtained at first diagnosis. Patients were followed for a period of two years to monitor outcomes. Logistic regression analyses were performed for statistical assessment. To elucidate magnesium's therapeutic mechanisms, we employed DSS-induced colitis mouse models and conducted in vitro CD4+ T cell activation experiments. Gut microbiota composition was analyzed using 16S rRNA sequencing.

Results

Deficiency in iron was most prevalent affecting 25.67% of the patients, with zinc deficiency at a rate of 3.67%. An inverse correlation was observed between magnesium levels and VAT index (β=-0.24, p<0.001). Reduced levels of zinc and magnesium were predictive of adverse clinical outcomes (OR=0.51, p=0.002; OR=0.52, p=0.001) and drug outcomes (OR=0.39, p<0.001; OR=0.57, p=0.004). Further stratified analysis revealed that the protecive effect of magnesium was significant exclusively in patients with a VAT-to-subcutaneous adipose tissue ratio (VAT/SAT) ≥1. Magnesium supplementation attenuated colonic inflammation in DSS-induced colitis mouse model, reduced infiltration of CD4⁺T cells, and enhanced gut microbiota diversity. Notably, there was a significant increase in beneficial bacteria, including butyrate-producing genera such as Intestinimonas, Clostridia_UCG-014, and Paludicola. In vitro studies further demonstrated magnesium's capacity to suppress inflammatory cytokine production by CD4⁺ T cells from patients with CD.

Conclusion

Disruptions in baseline trace elements correlate with poor outcomes in CD patients. The interaction between trace elements and VAT may impact disease progression. Magnesium's therapeutic effects, mediated through immunomodulation and microbiota regulation, highlight its potential as a therapeutic target for personalized treatment approaches in inflammatory bowel disease.
P0897 Association of HLA Genotypes with Anti-Drug Antibody Development in Taiwanese Inflammatory Bowel Disease Patients Undergoing Biologic Therapies
Authors: Weng M T , Yao C Y , Lin W C , Lai S K , Chen P L , Tung C C , Wong J M , Wei S C
Published: January 2025

Background

Anti-drug antibodies (ADAs) are a primary factor in the loss of response to infliximab and other adverse drug reactions. The genetic variant HLA-DQA1*05 has been associated with infliximab antibody development in Crohn’s disease (CD) among European populations. This study aims to assess the relationship between HLA genotypes and ADA formation in non-European inflammatory bowel disease (IBD) patients receiving anti-tumor necrosis factor (TNF), anti-integrin, or anti-IL-12/23 therapies.

Methods

This prospective cohort study enrolled patients with IBD receiving anti-TNF, anti-integrin, or anti-IL-12/23 therapy between January 2022 and March 2024. NGS-based HLA genotyping was performed for all participants. The occurrence of ADAs was assessed, and the frequencies of specific HLA alleles were compared between patients who developed ADAs and those who did not. Additionally, HLA allele frequencies in ADA-positive patients were analyzed against the general population in Taiwan.

Results

A total of 95 patients with IBD were included in the study, along with HLA genotype data from 1,097 control individuals obtained from the Taiwan Biobank. Among the IBD patients, 58 received anti-TNF therapy, 27 underwent anti-integrin therapy, and 10 were treated with anti-IL-12/23 therapy. According to the reimbursement criteria in Taiwan, all patients have to be treated with conventional therapy and when with inadequate response or with adverse effects, then biologics would be reimbursed. Therefore, all the 95 patients were under the biologics and immunosuppressive agents (either thiopurine or methotrexate) combination therapy. No ADA development was observed in patients treated with anti-integrin or anti-IL-12/23 therapies. However, among the 58 patients treated with anti-TNF therapy (38 with infliximab and 20 with adalimumab), 21 developed ADAs (18 infliximab-related and 3 adalimumab-related). A comparison of patients with and without ADAs revealed a significant association between the HLA-C*03:04:01 allele and ADA development (33.3% vs. 10.8%, p=0.035), whereas the HLA-DQA1*05 allele showed no association (52.3% vs. 51.4%, p=0.940). The frequency of the HLA-C*03:04:01 allele was comparable between IBD patients and the broader Taiwanese population (16.8% vs. 11.2%, p=0.0915).

Conclusion

This study demonstrated that the different HLA locus associated with ADA development among different ethnics. While HLA-DQA1*05 was found in European cohort, our data showed that HLA-C*03:04:01 was significantly associated with an increased risk of anti-TNF antibodies formation in Taiwanese IBD patients.

References

1.Sazonovs A, Kennedy NA, Moutsianas L, et al. HLA-DQA1*05 Carriage Associated WithDevelopment of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients WithCrohn's Disease. Gastroenterology 2020;158:189-199.
P0899 Previous extended colectomy is associated with particularly high risk of postoperative small bowel fistula in Crohn’s disease patients
Authors: Iesalnieks I , Bercher M , Schmitz A
Published: January 2025

Background

Postoperative small bowel fistula is one of the most detrimental complications in abdominal surgery. Patients with Crohn’s disease seem to be at higher risk. Performing small bowel surgery in patients with previous extended colectomy, surgeons face diffuse small bowel adhesions. Moreover, patients with small bowel disease after previous (total) colectomy pose one of the most vulnerable populations. Present analysis was conducted in order to analyze the incidence of small bowel fistula following abdominal surgery in Crohn’s disease patients.

Methods

Consecutive patients with Crohn’s disease undergoing intestinal resection between 1992 and 2024 were included in current analysis using a prospectively maintained database. “Small bowel fistula” was defined as any small bowel perforation away from any anastomoses, strictureplasties or any other kind of small bowel sutures. “Previous extended colectomies” were total abdominal colectomies or proctocolectomies in patients’ history prior to the current surgery.

Results

973 patients undergoing 1096 bowel resections were included. There were 804 ileocolic resections, 254 colonic resections and 38 other resections (small bowel resection, ileostomy resections, pouch excisions and abdominoperineal resections). Postoperative intraabdominal septic complications occurred in 162 patients (15%), 8 patients died (0.7%). Postoperative small bowel fistula occurred in 9 patients (0.8%). 52 patients attended current surgery with a history of previous (procto-)colectomy. Current surgery consisted of 13 resections of ileosigmoid or ileorectal anastomoses, 12 ileostomy resections, 10 abdominoperineal resections, 9 small bowel resections, 5 J-Pouch excisions, 1 Kock pouch excisions, 1 Redo-Pouch and 1 IPAA in the study population. 10 of 52 patients (19%) with a history of previous extended colectomy underwent laparoscopic surgery with one patient converted to open. The history of previous extended colectomy was the only factor associated with an increased risk of postoperative small bowel fistula by a multivariate analysis (7.7% vs. 0.5%, Hazard ratio 7.1, p<0.001) but not for all intraabdominal septic complications (15% in both groups). The risk of postoperative small bowel fistula was not increased in patients with a history of any other previous intestinal resection than extended colectomy.

Conclusion

Crohn’s disease patients with a history of previous total colectomy or proctocolectomy are at a particularly high risk of postoperative small bowel fistula when they undergo further surgeries. Surgeons must be aware of this complication in cases of unexpected postoperative symptoms.
P0900 Hyperbaric oxygen therapy downstages refractory perianal fistulizing Crohn’s disease and allows for surgical closure
Authors: Mulders L , Beek K , Becker M , Koelink P , Zwart M , van der Bilt J , Vlug M , Tielbeek J , Rietdijk S , Jansen J , Ridderikhof M , de Jonge W , Bemelman W , Stoker J , D'Haens G , van Hulst R , Wildenberg M , Buskens C , Gecse K ,   AMFIBIO study group
Published: January 2025

Background

Hyperbaric Oxygen Therapy (HBOT) has previously shown benefit in treatment-refractory perianal fistulizing Crohn’s disease (PFCD). However, the biological mechanisms underlying therapy response remain poorly understood. In this prospective study, we aimed to assess the feasibility, efficacy, and safety of HBOT followed by surgical closure, while also investigating translational changes associated with HBOT.

Methods

Patients with active PFCD refractory to 6 months of optimized medical therapy were included. After receiving a seton, patients started HBOT (40 sessions, 110 minutes each with 5-minute air breaks, 100% oxygen at 2.4 atmosphere). Half-way, at week 4, the seton was removed and surgical closure of the internal fistula opening was attempted. All patients continued stable dose of medical treatment during the study. Response was assessed clinically, by pelvic MRI and by patient-reported QoL. RNAseq data of surgical biopsies of the internal fistula opening were explored between patients after completion of HBOT and matched non-HBOT patients.

Results

Sixteen patients completed HBOT and all of them could undergo a technically successful surgical procedure at week 4 (See Table 1). Clinical remission (no draining fistula openings) was achieved in 43% (W9), 42% (W26) and 70% (W52), and PDAI remission (≤4) was achieved by 31% (W9), 58% (W26) and 70% (W52) (Figure 1). MRI remission (MAGNIFI-CD ≤6) was achieved by 42% (W26) and 57% (W52), and MRI healing (MAGNIFI-CD = 0) was achieved by 8% (W26) and 40% (W52). Quality of Life (CAFQOL) improved significantly with a mean improvement of 10.7 (SE 3.9) by W26 and 22.7 (SE 6.0) by W52. (S)AEs included one patient with a potential oxygen toxicity seizure without long term effects, and one patient reported claustrophobia, no new AEs were reported.

Surgical biopsies obtained after HBOT displayed increased expression of cornification markers including CRNN, KRT4, KRT13 and SPRR2B. Pathway analysis confirmed biological activity of ‘keratinization’ and ‘dermal development’ in post-HBOT samples. This is similar to those observed previously in cryptoglandular fistulas. In contrast, patients without HBOT on stable medical treatment mainly showed general immune activation.

Conclusion

HBOT resulted in downstaging of active PFCD, which became amenable to surgical closure. The combined treatment approach resulted in sustained clinical and MRI remission in patients with refractory disease. HBOT resulted in enhanced activity of pathways associated with keratinization and dermal development. These data support a model where HBOT shifts an active Crohn’s disease fistula towards a more manageable cryptoglandular-like phenotype.
P0902 Development and validation of a novel model based on clinical characteristic variables to predict disease behavior progression in patients with stricturing Crohn's disease
Authors: Wang Y , Chen X , Liu Z , Gu Y , Mao R
Published: January 2025

Background

The risk factors for disease behavior progression in CD patients with strictures remain unclear. This study aims to construct a predictive model based on commonly used clinical indicators to identify high-risk CD patients with early progression.

Methods

We conducted a retrospective analysis of clinical data from stricturing Crohn’s disease patients at The First Affiliated Hospital of Sun Yat-sen University from October 2016 to October 2023. The disease behavioural progression was defined as progression to B3 classification or under surgery due to intestinal strictures. The data were split into a test set and an internal validation set in a 7:3 ratio. Classification models, including logistic regression (LR), random forest (RF) and extreme-gradient Boosting (XGB) Models, were constructed. Finally, all models were validated in an independent external validation cohort from Ruijin Hospital, Shanghai Jiaotong University School of Medicine.[Figure 1]

Results

The study included 341 patients, with 190 in the internal training set, 81 in the test set, and 70 in the external validation set. Obstructive symptoms, globulin (GLB), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are independent predictors of disease behavior progression. The areas under the receiver-operating characteristic curves (AUROCs) of the LR, RF, and XGB models were 0.861, 0.477 and 0.559, respectively. The logistic regression model achieved the highest AUROC value of 0.752 in the external validation. The further transformed nomogram has a similar prediction accuracy to the logistic regression.

Conclusion

In patients with stricturing CD, obstructive symptoms score, CRP, ESR and GLB were independent and validated predictors of disease behavior progression in stricturing Crohn's disease. We found no evidence of better performance of machine learning-based models in predicting disease behavior progression in stricturing CD. A nomogram based on the logistic regression model might aid in the management of stricturing CD patients.
P0904 Factors influencing postoperative bowel movement frequency following primary Ileo-Cecal resection in Crohn’s Disease patients
Authors: Naveh H , white I , wasserberg N , gurevich N , rozenstein Y
Published: January 2025

Background

Ileo-cecal resection is an effective treatment in Crohn’s patients, while diarrhea is a common postoperative negative outcome, with significant effect on patient’s quality of life. The aim of this study is to assess the effect of pre, peri and post-operative variables on the number of post-surgical bowel movements.

Methods

A retrospective cohort study of 168 Crohn’s patients undergoing primary ileo-cecal resection (2015–2023) at a high-volume center (Rabin Medical Center). Bowel movements were analyzed at three intervals (first check-up, 6–12 months, ≥2 years). We assessed the impact of multiple factors on post-operative number of bowel movements for both absolute and percentage change in bowel movements. Recurrent or concomitant resections were excluded

Results

168 patients who underwent primary ileo-cecal resection were included. The mean number of bowel movements raised from 2.77 pre-operative to 3.59 post-surgery (p=0.001). Longer resected bowel portions showed correlation at every follow up interval when examined as a percentage change (p=0.001 at first check up, p<0.001, after 6-12M and after 2 years<) or as an absolute number (p<0.001 at each corresponding check up). Short resection (up to 50 cm) vs. long resection (51 cm>) resulted in 62% more bowel movements in the short resection group at the two years follow up compared to pre-surgery, with the long resection group increasing by 164% (p<0.001). Active smokers preoperatively has a statistically significant increase in the number of bowel movements vs. non-smokers at all follow up intervals, peaking at 2 years post-op with mean absolute number of bowel movements 5.28 vs. 2.81 (p=0.003) and percentage rise of 127% vs. 71% respectively (p=0.041). Patients receiving pre-surgical TPN nutrition suffered more compared to enteral nutrition (55% vs. 121% after 6-12 months P=0.009 and 64% vs. 148% after> 2 years p=0.02). Patients with combined B2B3 disease behavior had an elevated number of bowel movements 2 years after the surgery compered to patients with B1/B2/B3 alone (P=0.02 for B2B3 vs. B1, P=0.03 for B2B3 vs. B2/B3). Patients treated with anti-diarrhea medications post-surgery had longer time from diagnosis to surgery compared with those without (P=0.049).

Conclusion

Primary ileo-cecal resection increases bowel movements for all Crohn’s Disease patients, but especially in patients with extended resections, pre-op TPN, smokers, or B2B3 disease behavior. Although a statistically significant correlation between time from diagnosis to surgery and post-surgical bowel symptoms was not observed, we found that patients who waited longer for surgery were more likely to use anti-diarrheal medications, suggesting an advantage to earlier surgical intervention after diagnosis.
P0907 Health literacy and digital health literacy in Inflammatory Bowel Disease as conditions for individualized adapted digital health information
Authors: Maurud S , Lunde L , Moen A , Opheim R
Published: January 2025

Background

Digital health information appears inadequate of providing medical expertise and clinical guidelines in IBD, including optimized accessibility, relevance and understandability for effective self-management. This study examines IBD patients’ health literacy (HL) and digital health literacy (DHL) and their covariance with various patient characteristics as implications for a digital health information platform.

Methods

IBD patients at a Norwegian university hospital underwent a cross-sectional survey. Clinical data were extracted from EHR. Other data were reported via questionnaire with the following instruments: HL – Health Literacy Questionnaire; DHL – eHealth Literacy Questionnaire; Quality of Life (QoL) – EQ-5D-5L; Self-efficacy (GSE) - General Self-Efficacy Scale; Illness perception (IP) – Brief Illness Perception Questionnaire; Medication adherence (MA) – The OsloMet Adherence to medication Survey tool. Data underwent a canonical correlation analysis (CCA) followed by hierarchical clustering. Variables omitted from CCA underwent bivariate analyses and logistic regression to assess cluster affiliation.

Results

Of 380 patients, 173 had UC and 53 % were male. Mean age was 43.6 years. No diagnose-specific PROM differences were found. CCA demonstrated positive associations for GSE, IP and health status against having sufficient capability to understand, assess and act upon health information and digital health services (p < .001). CCA also proved a negative association for age and actively engaging with digital health services (p < .001). Two clusters were identified (p <. 05). Cluster 1 embodied the oldest patients, lowest levels of HL, DHL, GSE, health status, IP and longest disease duration. Compared to Cluster 2, Cluster 1 significantly demonstrated lower MA (p <.05), higher shares of unemployment (p <.05), active disease (p <.001), and more severe QoL problems in terms of mobility (p < .05), usual activities (p < .001), pain/discomfort (p < .001) and anxiety/depression (p < .001). Disease activity (p <. 01) and biological treatment (p < .001) proved to be the strongest factors for cluster affiliation in a logistic model.

Conclusion

Our results imply a relation between health status, age, self-efficacy, biological treatment, disease perception and disease activity for IBD patients with low HL and DHL. The findings are implicative for a targeted intervention addressing digital health information dissemination for IBD patients.
P0910 Evaluating Tryptophan as a Biomarker for Treatment Success in Ulcerative Colitis Patients Undergoing Mirikizumab Therapy
Authors: Hatem Y , Maaß C , Marquardt J , Solbach P
Published: January 2025

Background

The treatment of ulcerative colitis (UC) has advanced significantly with the introduction of targeted medications, such as IL-23-Inhibitors. However, treatment success in inflammatory bowel diseases (IBD) varies and requires reliable biomarkers to assess therapeutic efficacy. Tryptophan (Trp), an essential amino acid, plays a central role in gut metabolism and immune modulation. Recent studies have shown that Trp metabolism is associated with inflammatory processes and correlates with IBD activity.

Aim of the Study

We hypothesized that Trp can serve as a reliable marker for assessing treatment success in patients with UC undergoing Mirikizumab therapy. To test this, Trp levels were correlated with established laboratory parameters (leukocytes, C-reactive protein in serum (CRP), fecal Calprotectin (fCal), as well as clinical parameters (IBD Disc).

Methods

Laboratory and clinical parameters during induction and maintenance therapy of four patients with UC who were treated with Mirikizumab were analyzed. Using SPSS, the Spearman correlation coefficient was used to examine the correlations between Trp and established markers.

Results

A significant negative correlation between Trp and CRP (n = 18, rs = −0.75, p < 0.001) suggests that lower Trp levels are associated with increased inflammatory activity. Correlations with leukocyte count (n = 18, rs = 0.27, p = 0.39), fCal (n = 10, rs = −0.33, p = 0.35), and the IBD Disk Score (n = 14, rs = −0.25, p = 0.40) were weak and not significant.

Conclusion

The significant correlation between Trp and CRP suggests that Trp could serve as a potential monitoring tool for assessing the inflammatory status in UC patients undergoing Mirikizumab therapy. However, Trp appears to have limited value as a standalone marker, and no cut-off levels have been established. Further prospective studies with larger sample sizes are necessary to confirm the clinical relevance of Trp as a biomarker for treatment response to Mirikizumab.

References

Harris, D. M. M., Szymczak, S., Schuchardt, S., Labrenz, J., Tran, F., Welz, L., Graßhoff, H., Zirpel, H., Sümbül, M., Oumari, M., Engelbogen, N., Junker, R., Conrad, C., Thaçi, D., Frey, N., Franke, A., Weidinger, S., Hoyer, B., Rosenstiel, P., … Aden, K. (2024). Tryptophan degradation as a systems phenomenon in inflammation-an analysis across 13 chronic inflammatory diseases. www.thelancet.com

Nikolaus, S., Schulte, B., Al-Massad, N., Thieme, F., Schulte, D. M., Bethge, J., Rehman, A., Tran, F., Aden, K., Häsler, R., Moll, N., Schütze, G., Schwarz, M. J., Waetzig, G. H., Rosenstiel, P., Krawczak, M., Szymczak, S., & Schreiber, S. (2017). Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology, 153(6). https://doi.org/10.1053/j.gastro.2017.08.028
P0916 Lusvertikimab is efficacious in severe ulcerative colitis (UC) patients with high fecal calprotectin (FCP): results from the CoTikiS study
Authors: Reinisch W , Kierkus J , Corallo F , Bourreille A ,   CoTikiS
Published: January 2025

Background

Fecal calprotectin (FCP) is an objective marker of inflammation in ulcerative colitis (UC) patients and may predict sustained clinical and endoscopic response. In the CoTikiS study (NCT04882007), 2 doses (450 mg or 850 mg) of OSE-127 Lusvertikimab (L) were administered for 10 weeks in patients with moderately or severely active UC. Additional analyses compared the effects of these 2 doses versus placebo on FCP and their efficacy in patients with high FCP at baseline.

Methods

Stool samples were collected at weeks 0 (w0), 2, 6 and 10 in all patients, frozen at -20°C and shipped to a central laboratory where FCP was measured using a validated analytical method. FCP values were analysed by treatment groups and by visit and the changes versus baseline were compared between each treatment group and placebo. A FCP value > 250 µg/g is considered as a threshold of active inflammatory disease. The efficacy of L850 and L450 was compared to that of placebo in patients with FCP > 250 µg/g at baseline.

Results

At baseline, FCP was not different between treatment groups: 1192 µg/g, 1088 µg/g, 1148 µg/g and 1459 µg/g for L850, L450, L850/450 and placebo (p=NS) respectively. At w10, FCP was significantly reduced in patients treated with L850 (p=0.018) and L450 (p=0.009).

FCP was analysed in patients with baseline values > 250 µg/g, which represented 69.5% of the total population. There were no differences in demographics or disease characteristics between those subgroups. The corresponding baseline FCP values were 1713.1, 1673.9, and 1817.9 µg/g for L850, L450 and placebo, respectively). L450 and L850 significantly decreased FCP as compared to placebo.

FCP values were reduced below 250 µg/g at w10 in 45.2% and 38.1% of patients treated with L850 and L450 vs only 18.2% in the placebo group. In this subgroup of patients, the MMS was significantly improved versus placebo at w10: L850mg=-0.94, L450mg=-1.47 and L850/450=-1.16. UC Endoscopic Index of Severity (UCEIS) also markedly improved: L850mg=-0.74, L450 mg=-1.69, L850/450=-1.12 vs placebo.

Conclusion

Lusvertikimab, a pure IL-7 receptor antagonist, significantly decreased FCP after 10 weeks of treatment and achieved improvements in clinical and endoscopic outcomes in UC patients with active inflammation per FCP > 250 µg/g at baseline. These data strengthen the overall results of the primary and key secondary endpoints from the CoTikiS study.
P0917 Corticosteroid sparing effects of treatment with guselkumab in patients with moderate to severely active Crohn’s disease: Phase 3 GALAXI 2/3 results through week 48
Authors: Panés J , Hisamatsu T , Armuzzi A , Terry N A , Salese L , Van Rampelbergh R , Yee J , Wan K Y , Yang Z , Pin S , Sands B E , Rubin D T
Published: January 2025

Background

GALAXI 2 & GALAXI 3 (G2 & G3) are identical 48-week (Wk), randomized, double-blind, head-to-head, placebo- and active-comparator (ustekinumab; UST) treat-through trials assessing the efficacy and safety of guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with Crohn’s disease (CD). Here we report the corticosteroid (CS)-sparing effects of treatment with GUS vs UST from the pooled G2 & G3 studies through Wk48.

Methods

Pts with moderately to severely active CD (based on CDAI and SES-CD scoring) and inadequate response or intolerance to conventional or biologic (BIO-IR) therapy were eligible. Pts were randomized 2:2:2:1 to GUS 200mg IV q4w(x3)→200mg SC q4w, GUS 200mg IV q4w(x3)→100mg SC q8w, UST ~6mg/kg IV(x1)→90mg SC q8w, or placebo. Pts receiving oral CS upon entry (up to 40mg/day of prednisone-equivalent dose) were required to begin tapering their daily CS dose at Wk12, unless not medically feasible. CS use and 90-day CS-free clinical outcomes at Wk48 were assessed vs UST.

Results

The primary analysis (all pts) included 508 (G2) and 513 (G3) pts. Baseline (BL) characteristics were similar across trials: mean [SD] CDAI (G2: 295.0 [52.0], G3: 294.7 [53.8]), mean [SD] SES-CD (13.1 [7.3], 12.8 [7.3]), BIO-IR history (52.8%, 51.9%), BIO-naïve (41.9%, 41.5%), and oral CS use (37.4%, 36.1%). In analyses of pooled data (G2+G3), the proportion of pts receiving oral CS at BL was similar across treatment groups (GUS 100mg q8w: 38.1%; GUS 200mg q4w: 35.8%; UST: 37.5%). Greater proportions of pts receiving both GUS doses achieved 90-day CS-free Wk-48 outcomes of endoscopic response vs UST (100 mg q8w vs UST: ∆11.2%; 200 mg q4w vs UST: ∆14.5%), endoscopic remission (∆9.5%, ∆11.9%), the composite endpoint of clinical remission + endoscopic response (∆8.1%, ∆12.4%), the composite endpoint of clinical remission + endoscopic remission (∆8.0%, ∆10.9%), and clinical remission (∆4.1%, ∆5.3%) (Table 1). The 90-day CS-free outcomes vs UST in BIO-IR and BIO-naïve pts in the primary analysis were also assessed at Wk48 (Table 1).

Among all pts receiving oral CS at BL, greater proportions of GUS-treated pts (100mg q8w: 71.6%; 200mg q4w: 75.5%) were not receiving CS at Wk 48 vs UST (67.0%). Also, among all pts receiving oral CS at BL, greater proportions of GUS-treated pts achieved 90-day CS-free outcomes at Wk48 vs UST, including endoscopic response (41.3%, 42.5% vs 31.2%) and endoscopic remission (30.3%, 28.3% vs 20.2%), and similar proportions for clinical remission (52.3%, 54.7% vs 53.2%).

Conclusion

In CD, greater proportions of GUS-treated pts achieved CS-free endoscopic-based efficacy outcomes through Wk48 vs UST, regardless of prior biologic exposure status.