bluuebunny/crossref_metadata_2025 huggingface dataset:
P986 Effectiveness of the adjuvanted recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) among patients ≥50 years of age with Inflammatory Bowel Disease in the United States: A retrospective real-world database analysis from 2018 to 2021
Authors: Constenla D , Lonnet G , Aris E , Wang H , Rk R , Mwakingwe-Omari A , Yun H
Published: January 2024

Background

Patients with inflammatory bowel disease (IBD) are at higher risk of developing HZ compared to general population.1 The US Food and Drug Administration (FDA) approved RZV for adults ≥50 years of age (YOA) in Oct 2017 and for adults ≥18 YOA who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression, as patients with IBD, in Jul 2021. This study addresses an information gap for RZV vaccine effectiveness (VE) in preventing HZ among IBD patients ≥50 YOA.

Methods

We conducted a retrospective matched cohort study using the Optum Clinformatics Data Mart healthcare administrative claims database from Jan 2018 to Dec 2021. Patients ≥50 YOA with IBD who received 2 RZV doses with dose interval ≥28 days (RZV [2-dose] cohort) were 1:3 matched to their unvaccinated counterparts (non-RZV cohort) by age, medication category, and other confounders (propensity score). The index date for RZV cohort was the date of the second dose and for non-RZV cohort was the same index date as their vaccinated match. Follow-up started from index date +30 days until earliest date of HZ occurrence, end of enrolment, death, receipt of HZ vaccine, or study end. The first HZ episode during follow-up was identified using an algorithm that included ICD-10 diagnosis code, inpatient or outpatient claims and/or HZ antiviral medication used within 7 days pre/post-HZ diagnosis. Incidence rates (IRs) of HZ were calculated overall, stratified by condition (ulcerative colitis [UC], Crohn’s disease [CD]) and age. Cox hazards models were used to estimate overall and stratified hazard ratios (HRs). VE (%) was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose.

Results

We identified 6501 RZV vaccinated and 19962 matched unvaccinated IBD patients who were included in the 2-dose analysis (Table). The IR of HZ was 2.92/1000 person-years (PY) in the RZV cohort and 10.96/1000 PY in the non-RZV cohort, resulting in a VE of 73.4% (95% confidence intervals [CIs]: 60.8-82.0) for IBD patients (Figure). VE against HZ was 63.5% (95%CIs: 43.0-76.6) and 85.7% (95%CIs: 69.5-93.3) in UC and CD 2-dose cohorts. IRs and VE stratified by condition and age are presented in Figure. Adjusted VE for IBD patients who received 1 RZV dose was 63.4% (95%CIs: 24.9-82.2).

Conclusion

Our analysis provides real-world evidence that RZV vaccination is effective in preventing HZ in IBD patients ≥50 YOA and reduce the burden in this population with increased risk of HZ. These findings are consistent with the available literature on RZV effectiveness in patients with IBD, suggesting that this population could greatly benefit from RZV vaccination.

1. Yun H et al, Arthritis Rheumatol 2016;68:2328-37

Funding

GSK
P1004 Proportion of agents for refractory ulcerative colitis and the efficacy of immunomodulator in 5-aminosalicylic acid intolerance
Authors: Madarame A , Fukuzawa M , Naito S , Yamauchi Y , Yamaguchi H , Koyama Y , Kagawa Y , Ichimiya T , Shinohara H , Nemoto D , Itoi T
Published: January 2024

Background

5-Aminosalicylic acid (5-ASA) is effective for ulcerative colitis (UC), yet several patients exhibit intolerance to this medication. Although biologics and immunomodulators are often employed in cases of 5-ASA intolerance in UC, reports on their induction rates and effectiveness are sparse. This study aims to ascertain the proportion of therapeutic agents for refractory UC and evaluate the efficacy of immunomodulators in patients intolerant to 5-ASA.

Methods

We conducted a retrospective chart review of 182 consecutive UC patients treated for refractory UC at our tertiary referral hospital from 2014 to 2023. The 5-ASA intolerance group comprised patients who initiated oral 5-ASA therapy, discontinued one or more oral 5-ASA treatments within 6 months due to adverse effects, and were unable to continue oral 5-ASA therapy for over 6 months. Those who had been on oral 5-ASA for more than 6 months were categorised as the 5-ASA tolerance group. We compared the types of agents for refractory UC (immunomodulators, calcineurin inhibitors, anti-TNF-α agents, vedolizumab, ustekinumab, JAK inhibitors), disease duration, and clinical background (age at diagnosis, history of acute severe UC [ASUC], disease extent) between the groups. Additionally, we examined the discontinuation rates due to adverse effects and the continuation rate of immunomodulators.

Results

Among the patients treated with agents for refractory UC, 19 belonged to the 5-ASA intolerance group and 163 to the 5-ASA tolerance group. The time to initiation of treatment for refractory UC was significantly shorter in the 5-ASA intolerance group compared to the 5-ASA tolerance group (median 69 days vs 1431 days, p < 0.001). The induction of immunomodulators occurred in 78.9% of the 5-ASA intolerance group, versus 38.0% in the 5-ASA tolerance group (p = 0.001). Anti-TNF-α agents was not used in the 5-ASA intolerance group, while 33.7% of the 5-ASA tolerance group received it (p = 0.001). 15 patients in the 5-ASA intolerance group and 53 in the 5-ASA tolerance group were introduced to immunomodulators to maintain remission. Discontinuations due to adverse effects were noted in 33.3% of the 5-ASA intolerance group and 18.9% in the 5-ASA tolerance group, but the differences were not significant. The one-year cumulative continuation rate of immunomodulators, excluding patients who discontinued due to adverse effects, was 93.3% in the 5-ASA intolerance group and 77.4% in the 5-ASA tolerance group, with no significant difference observed.

Conclusion

Immunomodulators are frequently introduced in cases of 5-ASA intolerance. No significant difference was found in the discontinuation rate of immunomodulators, with a high cumulative continuation rate observed in the 5-ASA intolerance group.
P1008 Efficacy and safety of retreatment with upadacitinib after treatment interruption in ulcerative colitis: Data from the phase 3 open-label extension study U-ACTIVATE
Authors: Panaccione R , Colombel J F , Dubinsky M , Hisamatsu T , Remple V , Garrison A , Klaff J , Kujawski M , Vermeire S
Published: January 2024

Background

Upadacitinib (UPA) is an oral reversible Janus kinase (JAK) inhibitor designed to preferentially inhibit JAK1 approved for the treatment of moderately to severely active ulcerative colitis (UC). UPA may be temporarily discontinued for many reasons including adverse events (AEs) and lack of efficacy.1 As clinical consequences of discontinuing and restarting UPA are yet to be characterised, here, we assess the efficacy and safety of UPA retreatment in patients (pts) who lost response following UPA treatment withdrawal.

Methods

Pts with a clinical response to 8 weeks’ (wks) UPA 45 mg once daily (QD; UPA45) induction therapy in the Phase 3 U-ACHIEVE or U-ACCOMPLISH studies were re-randomised to placebo (PBO), UPA 15 mg QD (UPA15) or UPA 30 mg QD (UPA30) for the 52-wk maintenance phase of U-ACHIEVE. Pts randomised to PBO who lost response could enter the long-term extension (LTE), U-ACTIVATE, and be retreated with UPA15. Efficacy was analysed (i) at wk 4 of the LTE and (ii) at wk 48 of the LTE among pts with an inadequate response to UPA15 who dose escalated to UPA30 between wks 2 and 36. Exposure-adjusted event rates (EAERs) of treatment-emergent AE (TEAE) were assessed throughout.

Results

Of 223 pts with a clinical response to UPA45 induction randomised to PBO during maintenance, 112 (50.2%) lost response (mean [standard deviation (SD)] days to loss of response: 135.4 [84.6]) and 110 subsequently entered the LTE. Pts with loss of response vs those without were more likely to have a history of inadequate response, loss of response, or intolerance to ≥1 biologic (57.1% vs 46.8%, respectively) or corticosteroid use at baseline (42.0% vs 33.3%). After 4 wks of retreatment with UPA15, 75/108 (69.4%) and 39/108 (36.1%) pts achieved clinical response and remission, respectively (Figure A). In total, 38 (34.5%) pts dose escalated to UPA30 (mean [SD] days to escalation: 80.3 [57.8]); 30/31 (96.8%) and 22/31 (71.0%) achieved clinical response and remission at wk 48 of retreatment, respectively (Figure B). For safety during maintenance, 225 pts with 128.7 patient-years (PYs) of exposure (loss of response [n=112], 42.6 PYs; no loss of response [n=113], 86.1 PYs) were analysed. Generally, the EAERs of serious TEAEs were numerically lower in patients with vs without loss of response. However, patient years of exposure were low, restricting interpretation. During the LTE, EAERs were generally similar in pts who underwent dose escalation vs all pts.

Conclusion

In pts who experience loss of response following UPA withdrawal, efficacy can be recaptured following retreatment with UPA15 and UPA30. No new safety signals were identified.

Reference

1. Sandborn WJ, et al. Gastroenterology. 2020;158(8):2139−2149.e14.
P1019 "Totality-of-the-evidence" of proposed ustekinumab biosimilar SB17"
Authors: Armuzzi A , Girolomoni G , Feldman S , Goncalves J , Park Y , Ye B D
Published: January 2024

Background

SB17 is a proposed biosimilar to Stelara [ustekinumab reference product (UST-RP)], which is a fully human IgG1/kappa monoclonal antibody to interleukin (IL)-12/23. In accordance with regulatory guidelines, "totality-of-the-evidence" proofs similarity between a proposed biosimilar and its reference product and includes analytical, non-clinical and clinical data.1, 2 SB17 is under review by regulatory agencies to be approved as ustekinumab biosimilar. The proposed justification for extrapolation of indications for SB17 was justified based on "totality-of-the-evidence" (i) MoA of ustekinumab binding to p40 subunit of IL-12/23, which has been associated with immune-mediated diseases, including approved indications of UST-RP (ii) overall data from the comparability comparison to UST-RP using analytical methods showing similar molecular structure and in vitro function (iii) PK studies showing similar exposure, and PD studies in healthy subject and (iv) efficacy and safety (including immunogenicity) based on studies in patients with moderate-to-severe psoriasis (PsO). The phase III study was conducted in ustekinumab-naïve patients with PsO as the most sensitive design to assess potential differences in efficacy and the risk of immunogenicity. The objective of this report is to describe the biosimilarity of SB17 to UST-RP with regard to potential extrapolation from PsO to other indications.

Methods

Analytical comparability of SB17 to UST-RP was assessed in ELISA binding assays. PK equivalence, efficacy, safety, tolerability, and immunogenicity similarity were assessed in clinical trials of healthy subjects and PsO patients.

Results

In the analytical assessment, SB17 was highly similar to the EU- and US-UST-RP in overall critical and non-critical quality attributes. Evaluation of IL-12 and IL-23 neutralization and binding activities, MoA-related biological activities, showed similarity between SB17, EU-, and US-UST-RP. 3

In a phase I study, SB17 and EU- and US-UST-RP had similar PK and comparable safety, tolerability, and immunogenicity (Table 1).4

In a phase III study of 503 patients with moderate to severe PsO, SB17 had equivalent efficacy and comparable safety and immunogenicity to UST-RP up to Week 28 (Table 1).5

Conclusion

With similar target binding and PK and confirmed similarity in efficacy and safety for PsO patients, SB17 is proposed to be highly similar to UST-RP in physicochemical, non-clinical, and clinical similarity studies. "Totality-of-the-evidence" data for SB17 supports its extrapolation to UST-RP indications.
P1020 Developing and Validating a Clinical Prediction Model Using Biomarkers to Assess Clinical Response and Severity of Crohn's Disease 12 Weeks After Initiation of Biological Therapy
Authors: Al-Ali A , Alamer A , Alomar M , Sharrofna A , Abualrahi D , Al Lehaibi L , Alothman A , Aldosari S , Alameel T
Published: January 2024

Background

Despite the evolution of therapeutic strategies for Crohn’s disease (CD), many patients exhibit resistance to numerous biological agents, necessitating a transition to other advanced therapies. Therefore, the early and accurate prediction of the response to biological agents in treating CD is crucial. We sought to evaluate potentially useful biomarkers in predicting clinical response to biological agents in the management of CD.

Methods

This retrospective cohort study included data from adult CD patients who were naïve to biological treatments and maintained regular follow-up at a tertiary referral hospital between January, 2017 to June, 2022. Two prediction models were built to predict the Crohn's Disease Activity Index (CDAI) response at 12 weeks in its ordinal scale. The two clinical models included age, gender, and previous CD surgery. In model-1, we included 8-weeks neutrophile-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in their log scale as biomarkers of interest. Model-2 had 8-weeks neutrophile, platelet, monocyte, and lymphocyte counts in their natural scale. We built the prediction models using proportional odds model. Performance metrics were C-statistic for discrimination, brier score, visual calibration curve with bootstrap internal validation were used.

Results

A total of 104 patients were included, with a male predominance of 57.7% of the sample. The median age of the participants was 26 years (IQR: 21.00 – 36.00), and the median CDAI score was 237 (IQR: 125.25 – 256.0). Additionally, 43.3% of our population had undergone previous IBD surgery . The majority of the cohort initiated their treatment infliximab (59.6%), followed by adalimumab (35.6%). Model-1 has C-statistic of 0.678 compared to 0.682 for model-2. Brier scores for models 1 and 2 were 0.187 and 0.180, respectively. However, visual calibration curves showed better calibration of model-1 after bootstrapping internal validation corrected for over optimism. Odds ratio (OR) estimates of having higher odds of severe CDAI score at 12 weeks for model 1 were being female (OR: 2.20, 95% CI 1.04 –4.66; p = 0.04), higher NLR at week 8 (OR: 1.94, 95% CI 1.03– 3.65; p = 0.04), higher PLR at week 8 (OR 1.38, 95% CI 1.05– 1.8; p = 0.02), and higher CDAI score prior to the initiation of biological therapy (OR: 2.15, 95% CI 1.12– 4.13; p = 0.02).

Conclusion

The clinical prediction model that includes potentially useful biomarkers such as NLR and PLR at 8-weeks were well calibrated to predict a CDAI score at week 12 for the treatment response. Clinicians may find useful to implement prediction models in their clinical practice to evaluate the response of their patients.
P1034 The Egyptian ICRID-IBDQ: A novel IBD knowledge questionnaire from development and validation to comparison of different patient education modalities
Authors: Badary H A , Megally C , Anwar I , Hashem M B , Shehab H
Published: January 2024

Background

Inflammatory bowel diseases are chronic debilitating diseases whose proper management depends on patients’ good knowledge. It is the role of the physician to ensure good knowledge by tailoring appropriate methods of patient education.

Methods

This study included 105 patients with established diagnosis of IBD presenting to the Integrated Clinical and Research Center for Intestinal Disorders (ICRID) unit, Department of Endemic hepato-gastroenterology and infectious diseases, Faculty of medicine-Kasr Al Ainy Hospital, Cairo university. It included 2 phases: The first was cross-sectional analytical where the Egyptian “ICRID-IBDQ” questionnaire assessing the IBD patients’ knowledge was developed, validated, and used within the study population. This questionnaire comprised questions about the nature of the disease, lifestyle, diet, treatment modalities along with its effect on pregnancy and fertility; and the knowledge level was estimated by the number of correct answers considering scores above 75% as “Good”, 50-75% as “Fair”, and below 50% “Poor”. The second phase was comparative interventional where the patients were randomly allocated to 3 different educational methods: Direct education by physician, by infographic videos, and both combined, with the utility of the three in patient education compared using the ICRID-IBQ.

Results

The estimated patient knowledge of IBD is 26.3%, corresponding to “Poor”. The factors significantly associated with better knowledge on multivariate analysis are higher level of education (college or more) (p value <0.001, OR 8.7), female gender (p value 0.002, OR 4.9) and positive family history (p value 0.042, OR 7.7). All fields had “poor” knowledge, and the field with the most defective knowledge was surgery. All patients receiving education improved, total percentage of improvement measured from 26.3% to 78.9% (p value <0.001). There was no statistical difference between the 3 educational groups: Direct education by physician, infographic video or both combined (p value 0.09).

Conclusion

The importance of patient education has to be seriously addressed and tailored educational programs using combined methods have to be implemented by healthcare facilities to improve IBD patients’ quality of treatment and of life. Infographic videos are valuable tools which may aid in improving knowledge by patient education.
P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in Finland
Authors: Metsärinne K , Säävuori N , Ahmed W , Pollock-Wilkins R , Salminen K
Published: January 2024

Background

Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland.

Methods

A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects.

Results

Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention.

Conclusion

Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.
P1052 High doses of methylprednisolone in inducing remission in acute severe ulcerative colitis
Authors: Marszk D , Treder A , Szlagatys-Sidorkiewicz A , Brzeziński M
Published: January 2024

Background

Ulcerative colitis (UC), characterized by mucosal inflammation progressing proximally through the colon, is increasing in incidence, including among pediatric populations. UC clinically manifests through symptoms such as abdominal pain, diarrhea, and hematochezia. Treatment aims primarily to induce and maintain remission. For those inadequately responding to 5-aminosalicylic acid, remission may be induced via oral steroids or, in severe instances, intravenous methylprednisolone (1.5mg/kg per day). This retrospective analysis aims to evaluate the efficacy of high-dose intravenous methylprednisolone pulses (30 mg/kg, max 1g per day for 3-5 days) in inducing remission in moderate and severe pediatric UC cases used in patients not responding to standard doses of steroids. In the fields of nephrology, rheumatology, oncology and neurology, the efficacy of high-dose glucocorticoids has been proven.

Methods

From a cohort of 121 pediatric patients (<18 years) hospitalized 2018-2021 due to acute flare of UC, 15 were treated with high doses of methylprednisolone to induce remission. The Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to determine the response to treatment- considering a 20-point reduction or a score below 10 as significant improvement and indicative of remission induction.

Results

The activity of the disease was moderate in 2 children and severe in 13 out of the analyzed group. We observed a clinically significant response in 9/15 patients (60%) with a mean PUCAI decrease of 30±23,4 points. The average duration to clinical remission was 4.06 days. For the 6/15 non-responders to methylprednisolone pulses, treatment was escalated (4 received infliximab, 1 adalimumab, and 1 initiated with cyclosporine followed by infliximab); notably, 3 required colectomy. Adverse effects were not observed during the treatment period.

Conclusion

In conclusion, high-dose methylprednisolone appears to be a viable alternative for inducing remission in pediatric UC. However, due to limitations such as the small patient group and the retrospective nature of this analysis, further prospective studies are essential to validate these findings.
P1054 Clinical outcomes for ulcerative colitis patients stopping 5-aminosalicylates starting biologics and/or immunomodulator therapy: A Systematic review and meta-analysis
Authors: Moon J R , Na J E , Ji J H , Lee H S , Park J J
Published: January 2024

Background

Although 5-aminosalicylic acid (5-ASA), a crucial agent in the treatment of ulcerative colitis (UC), its role in the context of more advanced therapies, including immunomodulators and/or biologics, is not well defined. We sought to perform a systematic review and meta-analysis to assess the pooled consequences of discontinuing 5-ASA in patients with UC undergoing treatment with immunomodulators or biologics.

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify articles analyzing clinical outcomes associated with either discontinuing or maintaining 5-ASA in UC patients receiving immunomodulators or biologic treatments. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies.

Results

A total of 6 studies were identified as eligible for the meta-analysis. In UC patients receiving immunomodulators and/or biologics, stopping 5-ASA was not associated with steroid use (HR 0.86, 95% confidence interval [CI] 0.65-1.14 and OR 0.84, 95% CI 0.47-1.51), UC-related hospitalization (HR 0.92, 95% CI 0.69-1.22), UC-related surgery (HR 0.88, 95% CI 0.65-1.18), one-year clinical (OR 0.93, 95% CI 0.63-1.39) and endoscopic (OR 1.24, 95% CI 0.30-5.08) remission.

Conclusion

The cessation of 5-ASA in UC patients treated with immunomodulators and/or biological agents is not related to worsening of clinical outcomes. This finding suggests a limited role for 5-ASA in the setting of more advanced therapies
P1067 Pan-enteric mucosal inflammation in CD patients treated with vedolizumab assessed by capsule endoscopy– interim results of a prospective observational study
Authors: Ukashi O , Lahat A , Ungar B , Levy H , Eidler P , Ben-Horin S , Eliakim R , Kopylov U
Published: January 2024

Background

Mucosal healing (MH) is a paramount treatment goal in Crohn’s disease (CD). The vast majority of data pertains to MH in the colon and terminal ileum; nonetheless, proximal small-bowel involvement can be detected in up to 50% of CD patients assessed by capsule endoscopy (CE). Data regarding pan-enteric MH among patients with active CD who were treated with vedolizumab (VDZ) are lacking. We aimed to evaluate the efficacy of VDZ for achieving pan-enteric MH using pan-enteric CE.

Methods

This was a prospective open-label observational study. Patients with CD who have started on VDZ, were included. Patients underwent small-bowel patency-assessment using patency capsule (PC) and were followed by CE (PillCam Crohn’s, Medtronic, USA) before /within 40 days of treatment onset and after 14 and 52 weeks. In patients with exclusive small-bowel involvement, colonic preparation was not performed and colon was not assessed in subsequent CE. Accordingly, Lewis score (LS) and Pan-enteric Pillcam score (PS) were calculated, when available. The primary outcome was pan-enteric MH defined as LS<135 and LS<135 & PS<4 for CE confined to the SB/SB &colon, respectively. The main secondary outcomes were small-bowel MH (LS<135) and colonic-MH (colonic PS<4).

Results

57 patients were recruited, 41 patients were enrolled (median age: 28 [23-45] years, male-44%) and 16 patients were excluded (6- retained PC, 1- technical reason, 2 -did not start VDZ, 7-withdrew consent). Of them, six patients (1- retained PC, 1- multiple strictures, 1- lost to follow-up, 3- clinical flare) and eight patients (4- discontinued VDZ, 2- capsule adverse events, 1- lost to follow-up, 1- clinical flare) were dropped-out before week 14 and week 52, respectively. Pan-enteric MH was observed in 7/39 (18%) patients at week 14, and in 7/30 (23%) patients at week 52 (two patients and 11 patients have not yet reached 14/52-week, respectively). We observed higher rates of both small-bowel MH and colonic-MH during follow-up compared to baseline (Figure 1), and it was consistent with significant improvement at week 14 in both LS (900 [225-900] vs. 450 [0-900], p<0.001) and PS (12 [2-18] vs. 6 [0-14], p=0.001) compared to baseline. Improvement was even more prominent at week 52 (LS- 0 [0-300] PS- 2 [2-6]). No cases of retained capsule were observed during follow-up.

Conclusion

VDZ induces MH in both the small-bowel and the colon among patients with CD, and this effect may persist up to 52 weeks of treatment.
P1086 Re-administration of infliximab in patients with extremely refractory perianal Crohn’s disease
Authors: Mousourakis K , Veretanos C , Arvanitis K , Georgiadi T , Nousias G , Kozompoli D , Mylonas I , Paparizou A , Karaouzas L , Kalogiros G , Patsi M , Provi D , Christidou A , Mela M , Archavlis E , Papastergiou V , Varytimiadis K , Katopodi K , Chatzievangelinou C , Viazis N
Published: January 2024

Background

This study aims to evaluate the efficacy of infliximab re-administration to a cohort of patients with extremely refractory perianal Crohn's Disease (CD).

Methods

Retrospective analysis of prospectively collected data in CD patients with perianal disease, who despite being treated with infliximab, had to change treatment either because of primary non-response, secondary loss of response, or due to the occurrence of an allergic reaction. They then became resistant to the other therapies tested, resulting in Infliximab being given again. We then evaluated the clinical response to fistula management (Perianal Disease Activity Index PDAI ≤ 4), as well as the occurrence of adverse reactions in these patients.

Results

We included 14 patients (8 women), with a mean age (SD) of 38.2 (9.5) years. According to the Montreal classification our patients had L1 (n=2), L2 (n=2) and L3 (n=10) disease. After the initial Infliximab failure (even after dose escalation), patients received vedolizumab, ustekinumab and adalimumab without response or with secondary loss of response. Therefore, it was decided to re-administer infliximab with concomitant administration of azathioprine. After 1 year of follow up clinical response (PDAI ≤ 4) was seen in 4 patients (28.5%). Re-administration of infliximab was discontinued in 2 patients due to severe allergic reaction; however, the remaining patients did not experience side effects.

Conclusion

Re-administration of Infliximab may be able to help a small percentage of treatment resistant patients with perianal CD.
P1091 Cross-domain dynamics of the fungal-bacterial microbiome in patients with ulcerative colitis
Authors: Jangi S , Hsia K , Zhao N , Michaud D
Published: January 2024

Background

Background: Candida in the gut has been recently linked to inflammatory activity in UC. However, the relationship between Candida abundance and the bacterial microbiome remains poorly understood, and how these relationships evolve over disease course in UC is unknown.

Methods

Methods: We utilized data from the Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD) from IBD Plexus to examine the taxonomic composition of the fungal mycobiome and bacterial microbiome cross-sectionally and longitudinally in time. Differential abundance was assessed using a log-transformed linear model on microbial relative abundances, with a false discovery rate of <0.25. Spearman’s correlations and co-abundance networks were utilized to examine relationships between fungi, bacteria, and disease activity. Changes in fungi and bacteria within-subjects was assessed over 2 timepoints, with respect to clinical inflammatory status, and abundances were compared using Wilcoxon signed rank tests.

Results

Results: Among 212 patients with UC, 166 patients were in clinical remission (78.3%) while 46 demonstrated clinical activity (21.7%). During clinical activity, there were increases in Candida (q-val<0.05), bacterial family Desulfovibrionaceae (q-val<0.05), and genus Bilophilia (q-val<0.05) [Fig 1A]. During remission, there were reductions in Candida, with increases in family Lachnospiraceae (q-val<0.05), including genus Anaerostipes (q-val=0.09), Blautia (q-val=0.09) and Roseburia (q-val=0.21) [Fig 1B]. Active disease positively correlated with Candida and Desulfovibrionaceae, and negatively correlated with family Lachnospiraceae. During remission, a positive network was present between family Lachnospiraceae, Bifidobacteriaceae, and Eggerthellaceae, which was disrupted during activity, while an antagonistic relationship was evident between Candida and Saccharomyces during remission.

Among 25 patients with persistent remission over time (median time interval ~ 4 months), there were no changes in fungal abundances over timepoints. Among patients evolving from activity to remission (n=7), Saccharomyces significantly increased (p-val<0.05), with no significant change in Candida, although there was a trend towards reduction (mean relative abundance at t1=0.28 vs t2=0.11). Concurrently among bacteria, both Bifidobacterium and Anaerostipes significantly increased (p-val<0.05).

Conclusions

Candida and bacteria from families Lachnospiraceae may have opposing associations with inflammatory status in ulcerative colitis, suggesting they may demonstrate competitive ecological niches. Whether reduction of Candida species may expand protective bacteria should be tested adjunctive to immunosuppressive or microbial modulation therapies.
P1094 Rectal cancer in patients with inflammatory bowel disease - a nationwide cohort study
Authors: Lundqvist E , Westerberg K , Dietrich C , Martling A , Myrelid P , Nordenvall C
Published: January 2024

Background

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. The aim of this study was to investigate surgical outcome and survival in patients with rectal cancer (RC) with and without IBD.

Methods

The study was performed as a national population-based cohort study based on the Colorectal Cancer Data Base (CRCBaSe). All patients ≥18 years of age with a diagnosis of stage I-III RC treated with curative intent during the period 1997-2021 were included, with preliminary data for 1997-2016 available. Overall and disease-free survival after surgery was compared between patients with and without a previous diagnosis of IBD. Adjusted flexible parametric survival models were used to estimate proportional and time-dependent hazard ratios (HRs) with 95% confidence intervals (CIs). Updated data until 2021 with addition of cause-specific survival and perioperative data will be made clear by the time of the ECCO congress.

Results

In all, 16,263 patients with RC were included in the study, 1997-2016, among whom 235 had IBD. Patients with IBD were significantly younger, had a higher CCI, and lower tumours at diagnosis of RC, compared with patients without IBD. Among IBD patients, 45 (19.2%) were previously operated with colectomy, and 14 of these were reconstructed with ileorectal anastomosis. Among IBD patients, pT4 tumours were more prevalent (8.9%) than in patients without IBD (5.1%). Clear resection margins were less common in patients with IBD (90.6%) versus patients without IBD (95.1%). From preliminary adjusted analyses allowing the relative mortality rate to vary over follow-up time, RC patients with IBD experienced worse progression-free survival during the second year after surgery, after which their progression-free survival was superior in comparison with IBD-free patients.

Conclusion

The prognosis in RC patients with and without IBD varied over time. RC patients with IBD had an inferior progression-free survival initially, followed by an improved prognosis for the majority of the follow-up time. Despite a higher rate of pT4 tumours, R1-resections and lower tumors among IBD patients, unadjusted overall survival did not differ significantly compared to non-IBD CRC patients.
P1095 Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide cohort study 2003-2021
Authors: Eriksson C , Sun J , Bryder M , Bröms G , Everhov Å H , Forss A , Jernberg T , Ludvigsson J F , Olén O
Published: January 2024

Background

There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD) and only a few previous reports include patients diagnosed in the last decade. The aim of this study was to assess the risk of ACS in a modern population of IBD patients vs general population comparators.

Methods

In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year of diagnosis, and area of residence with up to ten general population comparators. The primary outcome was incident ACS (i.e. ST-segment elevation myocardial infarction [MI], non–ST-segment elevation MI, unspecific MI and unstable angina). Cox proportional hazard models were used to estimate hazard ratios (HRs).

Results

Overall, 76,517 patients with IBD (Crohn's disease (CD), N=22,732; ulcerative colitis (UC), N=42,194 and IBD-unclassified, N=11,591) and 757,141 comparators were identified (Table 1). During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS as compared with 19,598 (28.0/10,000 person-years) in the general population comparators. This corresponded to an HR of 1.30 (95% confidence interval [CI]: 1.24-1.35) after adjustings for potential confounders, and approximately 1 extra case of ACS in 100 IBD patients followed for 10 years. HRs for ACS were higher during the first year of follow-up but remained increased even after 5 years of follow-up (Figure 1). The highest HRs for ACS were observed in patients with elderly onset IBD (≥60 years; HR: 1.35; 95% CI: 1.28-1.43) and in patients with CD and UC with extra-intestinal manifestations (HR in CD: 1.58; 95% CI: 1.20-2.09; HR in UC: 1.98; 95% CI: 1.63-2.40). When restricting analyes to patients with elderly onset IBD, the absolute risk increase corresponded to 1 additional case of ACS for every 30 IBD-patient followed for 10 years. In contrast, no increased HRs were observed in patients diagnosed with IBD before the age of 40. But of note, just a few of the patients diagnosed with IBD before 40 years of age were followed-up beyond 50 years of age. HRs for ACS were stable during the whole study period 2003-2021 with no signs of leveling off during recent years.

Conclusion

In this contemporary cohort of patients with IBD, exposed to modern IBD-care, an increased risk for ACS was observed as compared with individuals of the general population. The highest HRs were observed in patients with elderly onset IBD and in patients with CD and UC with extra-intestinal manifestations.
P1096 Increased incidence of IBD over 22 years in an Argentine cohort
Authors: Sanchez M B , Gonzalez Sueyro R , Sobrero M J , Etchevers M J , Martinez Elhelou S , Manduca P A , Mulinaris A B , Musso Enz V , Ligo M C , Brave C , de Paula J A , Marcolongo M M
Published: January 2024

Background

A considerable variation of IBD epidemiology around the world has been observed with certain regions showing a notable predisposition. The association between IBD and industrialized nations is well-known. However, a global increase of the incidence of such pathologies has been described, even in those regions with low incidence such as developing countries. Few data exist concerning the incidence of these pathologies in Argentina and Latin America during the last decades. Our objective is to determine the trend of incidence of IBD during a long term in an Argentine cohort.

Methods

A trend incidence study on a retrospective cohort was conducted. The study population comprised of affiliates of the Italian Hospital Medical Care Program (IHMCP), a prepaid health maintenance organization (HMO) with over 180,000 affiliates, of an urban area of Buenos Aires, Argentina. Patients with a diagnosis of IBD established between January 1st 2000 to December 31st 2022 were included. Data were extracted from the Institutional Registry of IBD (IRIBD) on a RedCap platform. Adjusted and raw cumulative incidence of IBD was calculated annually, using as denominator yearly affiliates to the IHMCP. Direct standardization was done considering the World Standard Population according to World Health Organization. Incidence was calculated over 100,000 persons with 95% confidence interval (95% CI). We evaluated the trend of incidence of IBD between 2000 and 2022, using a joinpoint regression analysis. The annual percentage change (APC) with 95% CI was calculated to detect increasing or decreasing trends according to an APC statistically different from zero (alpha 0,05), using Joinpoint Regression Program 4.5.0.1.

Results

Out of 530 affiliates of the IHMCP included in the IRIBD, 286 were diagnosed with IBD during the study period. One hundred and sixty two were women (56,6%). Mean age at diagnosis was 45,3 years (SD 22,2); 26 patients were diagnosed during pediatric ages (9%). Regarding the subtype of IBD, 78% were Ulcerative Colitis, 17% Crohn's disease and 5% IBD unclassified. Adjusted incidence rates of IBD over 100,000 persons per year are detailed in table 1, showing an incidence of IBD of 4,3 (95% CI 0.02 - 8.6) by 2000 and 11,8 (95% CI 5.9 - 17.7) by 2022. The adjusted trend of incidence of IBD showed an annual increase with a calculated APC of 6,4% (95% CI 0,9 – 12,2; p=0,023) (Figure 2).

Conclusion

Our study shows an increasing incidence of IBD with a sustained trend over the last 22 years in an argentine population. One of the strengths of this study is the long term analysis of a known cohort belonging to a centralized HMO. The detected increase in incidence reinforces reported evidence of a changing epidemiologic scenario of IBD in Latin America.
P1100 A multivariate time-dependent proportional hazard model to predict development of intestinal failure from Crohn’s Disease
Authors: Wu T H , Brandt C F , Scheike T , Burisch J , Jeppesen P B
Published: January 2024

Background

Intestinal Failure (IF) is a rare but severe complication of Crohn’s disease (CD). Advancement in therapy has not eliminated incident IF from CD (CDIF), and risk factors for developing IF from CD are not well characterised. The Copenhagen Intestinal Failure Database contains one of the largest, comprehensively described adult CDIF cohort1 from 1973 to 2018, which can be linked with a Danish nationwide CD cohort2 to explore healthcare utilisation patterns associated with developing IF from onset of CD.

Methods

CDIF patients from Copenhagen Intestinal Failure Database and a nationwide CD cohort without IF were followed from CD diagnosis until IF, death, or censoring on 31/12/2018. Hospital contacts, surgeries, medication use and employment status were extracted from multiple Danish population-based registries. Unplanned hospitalisation or emergency department attendance (inpatient-contact), CD-related abdominal surgery, and stopping work for 6 months or more (in working-age CD patients, excluding full-time study and parental leave) were considered time-dependent covariates and tested for significance (p<0.05) in univariate proportional hazard models. Significant covariates were then modelled together with additional non-time-dependent clinical and demographic variables in multivariate proportional hazard models. Backward variable selection was performed to derive a final predictive model.

Results

175 CDIF and 22845 CD patients from whom data was available were followed for 2283.1 and 293536.5 patient-years, respectively. Univariate time-dependent proportional hazard models showed that every instance of unplanned IBD inpatient contact, CD-related abdominal surgery, and stopping work was significantly associated with increased hazard of developing IF, with a hazard ratio of 4.91 (95% CI 3.54-6.80, p<0.001), 29.79 (95% CI 9.70-91.48, p<0.001) and 1.61 (95% CI 1.15-2.26, p=0.005). In multivariate analysis, earlier decade of IBD onset, unplanned IBD inpatient contacts, length of stay of the inpatient contact, CD-related abdominal surgery, complicated surgery, number of previous admissions and surgeries and previous median-long term unemployment increased the rate of developing IF (Table), whereas age and comorbidity level at CD onset, non-IBD inpatient contacts, type of surgery, biologics use, and current employment status were not found to be significantly associated with IF development.

Conclusion

This is the first study to demonstrate significantly increased risks of developing IF from CD from increased healthcare utilisation patterns.

References:

1. Brandt et al.JPEN 41(4),566-574. https://doi.org/10.1177/0148607115612040

2. Lo et al. Scand.J.Gastroenterol.55(10),1171-1175. https://doi.org/10.1080/00365521.2020.1807598
P1118 High Crohn’s Disease burden but disproportionally low use of biologics in Crohn’s Disease patients with Intestinal Failure: a longitudinal comparative study from 1973-2018
Authors: Wu T H , Brandt C F , Scheike T , Burisch J , Jeppesen P
Published: January 2024

Background

Patients with Crohn’s Disease (CD) complicated by Intestinal Failure (CDIF) are considered to be among those with the most severe form of CD. Their clinical course before IF onset has not been well characterised. We aimed to describe and compare CD-specific natural history, disease burden and treatment between CDIF patients and CD patients without IF over a 40-year period.

Methods

CDIF patients from Copenhagen Intestinal Failure Database (1973-2018) and a Danish nationwide CD cohort without IF (1977-2018) were followed from onset of CD until IF, death, or 31/12/2018. Hospital contacts, surgeries, prescription dispensation, employment and mortality data were extracted from multiple population-based registries. Groups were compared using logistic regression for proportions and Poisson regression for rates. Standard mortality ratio (SMR) was calculated against age, gender and year-matched Danish population references, and an adjusted mortality rate ratio between CDIF and CD patients was obtained from Cox models.

Results

182 CDIF and 22845 CD patients were followed for 3035.7 and 293536.5 patient-years, respectively. At CD diagnosis, CDIF patients were younger (median age 24 years vs 35 years, p<0.0001), from earlier decades (71.5% vs 16.5% before 1991, p<0.0001), and had fewer comorbidities (6.9% vs 20.4%, p<0.0001). The 10-year cumulative incidence of IF declined from 2.7% in patients diagnosed with CD prior to 1980 to 0.2% in patients diagnosed after 2000, but the number of new CDIF patients has not declined over the decades (Table). A greater proportion CDIF patients received at least 1 course of steroids (70.8% versus 59.8%, p=0.02) and immunomodulators (59.3% vs 48.7%, p=0.03), had IBD-related hospital contacts (98.2% vs 55.2%, p<0.0001) and abdominal surgeries (94.9% vs 47.6%, p<0.0001), and stopped working for >6 months (65.8% vs 57.8% of working-age patients, p=0.05). However, in the biologics era (after 2000), CDIF patients were not treated with biologics more often (20.4% vs 21% had any biologics, p=ns). In those who were treated, CDIF patients had less cumulative time on biologics (3.9 years vs 11.2 years per 100 patient-years, p=0.001). CDIF and CD patients had a SMR of 3.7 (97.5% CI 2.79,4.72) and 1.7 (97.5% CI 1.61, 1.72), respectively. After adjusting for age, sex and co-morbidity, CDIF patients were at 3.42 times risk of dying compared to CD patients.

Conclusion

The incidence of CDIF has reduced in newly diagnosed CD patients, however the number of new CDIF patients has not yet declined due to increasing CD prevalence. Despite CDIF patients experiencing a significantly higher burden of CD before the onset of IF, they were not more likely to receive biologics. They also appear more refractory to biologics.