bluuebunny/crossref_metadata_2025 huggingface dataset:
P696 Initiation of Vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A Prospective Study Including Rheumatological and Blinded Imaging Assessments
Authors: Rohekar S , Boyd T , Lambert R , Beaton M , Chande N , Gregor J , Lennox H , McIntosh K , Ponich T , Rahman A , Sharma T , Sey M , Tauqir M , Jairath V
Published: January 2024

Background

Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis.

Methods

We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader.

Results

Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab.

Conclusion

Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.
P701 Evaluation of the effectiveness of vedolizumab in patients with Crohn's disease: a multicenter real-life study from Argentina
Authors: Balderramo D C , Etchevers J , Fuxman C , Lubrano P , Bellicoso M , Correa G , Trakal J , Defago M R , Montero J , Toro M , Novillo A , Bonardo M , Arancibia N , Motañez S , Quines S , Huernos S , Gil A , Gonzalez R , Goncalves S
Published: January 2024

Background

Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up.

Methods

A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence.

Results

A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m.

Conclusion

This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.
P743 A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitis
Authors: Croft A , Okano S , Hartel G , Lord A , Walker G , Radford-Smith G
Published: January 2024

Background

An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient’s disease course. Foreknowledge of a patient's likely response to intravenous corticosteroid therapy has significant clinical utility. Using a large prospectively collected acute UC patient database and machine learning-based techniques we aimed to derive and validate a personalised algorithm for identifying patients at high risk of corticosteroid therapy failure from variables available at hospital presentation.

Methods

A prospectively collected database of 600 consecutive presentations of acute UC was collated at a single referral centre between 1996 and 2022. An AIC-based Elastic Net model was used to select variables on the 419 earliest presentations of acute UC (1996-2017). Two risk-scoring algorithms, with and without utilising additional endoscopic variables, were constructed using logistic regression models. These risk scores were then validated on a separate cohort of 181 acute UC presentations (2018-2022).

Results

The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment; bowel frequency ≥6/24 hours; albumin; CRP ≥12mg/ml and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent.

The ROC AUCs in the validation cohort were 0.76 (95% CI: 0.69-0.83) and 0.78 (95% CI: 0.71-0.85) for the partial and full ROR scores, respectively. When incomplete cases were excluded, the full ROR score validation cohort ROC AUC increased from 0.78 to 0.80.

Conclusion

These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid treatment failure before or after endoscopic assessment. These patients may be suitable for consideration of early treatment escalation or screening for participation in clinical trials.
P832 Postoperative fever and CRP levels as predictive markers of postoperative recurrence of Crohn’s disease after ileocolic resection
Authors: Van Tieghem C , Bislenghi G , Fieuws S , Wolthuis A , D'Hoore A
Published: January 2024

Background

Studies have shown that postoperative C-reactive protein (CRP) levels in patients with Crohn’s disease (CD) undergoing ileocolic resections (ICR) are higher than in control patients operated for cancer. This study aims to verify the association between postoperative fever and CRP levels with CD recurrence.

Methods

We performed a single-centre retrospective study of all CD patients undergoing an ICR between 2009 and 2019. CRP levels and fever (body temperature >38.5 °C) were measured preoperatively and during the first 7 postoperative days (POD). A colonoscopy was performed within 12 months after surgery. Endoscopic postoperative recurrence (POR) was defined as a modified Rutgeerts score ≥i2b. Surgical recurrence as the need for reoperation due to CD recurrence at the level of the ileocolic anastomosis. A multivariate regression model for longitudinal measures was used to obtain estimates of postoperative CRP levels. Association between fever and estimates of CRP levels with endoscopic and surgical POR was evaluated through a multivariate analysis including sex, age, Montreal classification, use of advanced therapies prior to surgery, associated surgical procedures, smoking habit, and continuation/initiation of medical therapy after surgery.

Results

We identified 372 patients, of which 299 (80.4%) had complicated CD (Montreal B2+B3) and 166 (44.7%) already received advanced therapies before surgery. 92 (24.7%) were active smokers at the time of surgery. In 26 patients (7.0%), one or more strictureplasties were performed simultaneously to the ICR. Prophylactic medical treatment was restarted/initiated immediately after surgery in only 9.7% of the patients. Estimates of CRP level at POD -1, +1, +3, and +5 were 9.23 mg/L (CI 7.85;10.86), 63.05 mg/L (CI 58.63;67.80), 82.55 mg/L (CI 75.09;90.76), and 56.79 mg/L (CI 49.76;64.81), respectively. Overall, 154/367 patients (42.0%) with available body temperature measures, experienced fever postoperatively. Endoscopic POR occurred in 144/332 patients (43.37%) with an available colonoscopy within 12 months postoperatively (Table 1). Surgical POR was 7.0% (CI 4.9%-11.1%) and 11.8% (CI 5.7%-8.8%) at 3 and 5 years follow-up, respectively (Figure 1). No association between postoperative fever and CRP levels estimates with either endoscopic (p=0.49; p=0.06) or surgical POR (p=0.52; p=0.07] was observed.

Conclusion

Despite previous evidence suggesting that CD patients develop an enhanced postoperative inflammatory response, CRP levels and fever after ICR do not seem predictive of early endoscopic (<12 months) or long-term surgical POR. Therefore, they should not be considered to stratify patients for postoperative medical prophylactic therapy.
P886 Ustekinumab concentrations in induction are associated with mid-term endoscopic outcomes in patients with inflammatory bowel disease
Authors: Serra-Ruiz X , Céspedes Martínez E , Mayorga Ayala L , Herrera de-Guise C , Robles Alonso V , Pérez Martínez Z , Oller E , Borruel Sainz N
Published: January 2024

Background

It is unclear whether ustekinumab (UST) concentrations can predict the clinical course of inflammatory bowel disease (IBD) and guide treatment algorithms during the induction phase. The aim of our study was to assess the association between serum UST concentrations during the induction phase and clinical outcomes at week 24 and to determine the validity of a UST threshold for guiding intensification strategies.

Methods

We conducted a retrospective study including Crohn's disease (CD) and ulcerative colitis (UC) patients who started UST treatment between June 2022 and February 2023. Intensification strategies were determined according to standard clinical practice. UST concentrations were collected at weeks 8, 16, and 24. Quartile analysis and logistic regression were performed to evaluate the association between UST concentrations and treatment targets. Definitions are clinical steroid-free remission as a Harvey-Bradshaw index <5 and a partial Mayo score <2; endoscopic remission as a simple endoscopic score (SES-CD) ≤2 and Mayo endoscopic score (EMS) ≤1; and endoscopic response as a ≥50% reduction in SES-CD and ≥1 point in EMS.

Results

We included 42 patients (CD: 24). At week 24, clinical remission rates of 67% and endoscopic response and remission rates of 57% and 28%, respectively, were achieved. At week 24, the majority of patients continued intensified treatment: 90 mg subcutaneously every 4 weeks in 55% and 130 mg intravenously every 4 weeks in 36%. Patients who achieved an endoscopic response at week 24 had higher UST levels at week 8 (4.1 vs. 2.9 µg/ml, p=0.029). No significant differences between endoscopic remission rates and UST levels at any week were observed. The differences observed in the quartile analysis between the UST concentrations at week 8 and the endoscopic response were not statistically significant (p=0.451). The area under the ROC curve value for UST levels at week 8 to predict endoscopic response was 0.734 (p=0.012). Logistic regression analysis identified prior exposure to vedolizumab and absence of perianal disease as predictors of endoscopic response and remission at week 24 in univariate analysis, but not in multivariate analysis. No association was observed between UST levels and drug persistence rates.

Conclusion

In this real-world cohort, higher UST concentrations at week 8 were associated with higher rates of endoscopic response at week 24. A reliable concentration threshold for predicting endoscopic response and treatment intensification could not be determined, probably due to the insufficient number of patients included in the study and the relatively poor performance of the ROC curve. Prospective, randomized studies are needed to validate these results.
P905 Symptomatic remission and IUS improvements in a multi-national real-world cohort of UC patients treated with Upadacitinib - First results from the IBD-DACH study EUROPE
Authors: Zeissig S , Schmelz R , Helwig U , Moschen A R , Greuter T , Fischer I , Hammer L , Rath S , Kucharzik T , Maaser C
Published: January 2024

Background

Upadacitinib (UPA) is an oral, reversible and selective Januskinase-inhibitor (JAKi) that was approved for the treatment of several immune-mediated inflammatory diseases, including moderate to severe ulcerative colitis (UC) (1). While the efficacy of UPA has been demonstrated in clinical trials in UC, real-word (RW) evidence on the effectiveness and safety of UPA in UC remains scarce (2). Here, we shed light on the clinical and sonographic results after 2 and 8 weeks of UPA induction in a large, multinational RW cohort of UC patients.

Methods

EUROPE is an ongoing, prospective, non-interventional, multi-country study in patients with active UC who initiate therapy with UPA. The study assesses the early clinical effectiveness and the predictive value of early disease improvements including sonographic parameters for the long-term outcome after 52 and 104 weeks. For this interim analysis, we report clinical and sonographic results at baseline (BL), week 2 (2W) and week 8 (8W) of 124 UC patients with a visit after 8W until August 2023. For 75 patients, sonographic BL data for the most affected bowel segment was available.

Results

Of the 124 UC patients, most were male (60.5%, n = 75) with a median age and disease duration of 37.5 years (27.5 – 50.9) and 6.58 years (2.40–12.13). Almost half of all patients had a pancolitis (48.4%, n = 60) The vast majority of patients was bio-experienced (85.5%, n = 106), a third had been exposed to ≥ 3 biologicals (28.2%, n = 35). At BL, patients had a median bowel wall thickness (BWT) of 5.0 mm (3.8-7.0) in the sigmoid colon. It was the most affected segment in 44.4% of patients (n = 55). Disease activity per paMayo score was 3.0 (2.0-5.0) points, with 72.6% (n = 90) and 38.8% (n = 48) of patients reporting ≥ 3 more stools than usual/day and blood in most stools or bleeding without stool, respectively.

At 2W after UPA induction, stool frequency and rectal bleeding substantially improved as reflected by the rate of patients in symptomatic remission significantly increasing from 16.9% (n = 21) at BL to 43.5% (n = 54) at 2W and to 64.5% (n = 80) at W8 (both p < 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p < 0.001) and was ≤ 3mm in more than half of all patients. Considering the overall population, 156 patients were included in the safety analysis. Of these, 23.7% (n = 37) experienced an adverse event of which most were non-serious.

Conclusion

In this first interim analysis of the EUROPE study, UPA treatment in UC was associated with early clinical and sonographic improvement, with most patients achieving symptomatic remission and/or normalization of BWT by week 8 of treatment.

1-SmPC Upadacitinib

2-Danese, Vermeire et al. Lancet. 2022 Jun 4;399(10341):2113-2128
P915 Multi-Omics Biomarkers for the Prediction of Response to Biologics in Patients with Inflammatory Bowel Disease
Authors: Chen L , Zhang C , Niu R , Mao R , Qiu Y , Feng R
Published: January 2024

Background

The treatment concept for inflammatory bowel disease (IBD) has been transformed with biologics now recommended as the first-line therapy for moderate-to-severe patients. However, the significant heterogeneity among IBD patients has limited the efficacy of selected biologics based on traditional clinical factors. Therefore, it is imperative to molecularly stratify patients to match them with the most appropriate biologics. In this study, we systematically reviewed baseline omics biomarkers that have the potential to predict response to biological therapies, aiming to facilitate precision medicine in IBD.

Methods

We conducted a comprehensive literature search using PubMed by which we included studies that explore the role of omics biomarkers in predicting the efficacy of various biologics including anti-TNFα, anti-integrin, anti-IL-12/23P40 and anti-IL-23 P19 in patients with IBD.

Results

Our review included 110 studies. Of these, 86 studies focused on anti-TNFα, 17 focused on anti-integrin and 7 focused on anti-IL-12/23P40 and/or anti-IL-23P19. These studies investigated multi-levels baseline biomarkers, including genomics, transcriptomics (bulk RNA and sc-RNA sequence), proteomics, microbiome, and metabolomics (derived from serum, urine, or stool). Furthermore, recent studies already focused on integrating multiple omics analysis and showed that the predictive model based on multi-omics data could significantly enhance their performance. Among the available biomarkers, mucosal transcription of OSM (AUROC = 0.83), IL-13RA2 (AUROC = 0.90), and TREM-1 transcription in mucosal biopsy (AUROC = 0.77) as well as in PBMC ( AUROC varies between 0.78 and 0.94) could accurately predict the response to anti-TNFα. The mucosal IL-23A transcription could discriminate responders from non-responders to anti-IL-12/23P40 with an AUROC of 0.90. OSM, biomarkers of intestinal collagen turnover like C4M, IL-17, IL-22, and TNFα in serum also showed significant potential in predicting the response to anti-TNFα, anti-integrin and anti-IL-12/23P40. In addition, single-cell molecular signatures with sc-RNA sequencing provided more profound insights into predicting the response to biologics. The lack of reproducibility in results across different groups may be due to the disparity in patient selection, methodology, and study designs among different investigations.

Conclusion

Numerous omics markers have shown great potential in predicting the efficacy of biologics. However, it is crucial to explore and validate these novel biomarkers in larger cohorts using harmonized protocols to facilitate their evaluation into actual clinical practice, especially for newer biologics like anti-IL-12/23P40 and anti-IL-23P19.
P959 Dose escalated vedolizumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Mcnamara J , Alshiwanna B , Wilson W , Pipicella J L , Ghaly S , Gearry R , Begun J , Ng W , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Andrews J A , Connor S J
Published: January 2024

Background

Vedolizumab is a gut specific integrin antagonist with established efficacy in inflammatory bowel disease (IBD). Many people with IBD fail to achieve adequate or sustained response to standard dosing, thus requiring dose escalation (DE). We aimed to explore the need for escalated dosing and subsequent outcomes in a large real-world cohort.

Methods

We utilised data from the CCC registry entered during routine clinical care at 14 centres across Australia and New Zealand. Data were extracted in October 2023 and included patients on intravenous (IV) and subcutaneous (SC) therapy. DE was defined as maintenance dosing > 108mg SC fortnightly, > 300mg IV Q8weekly and/or additional induction doses. We examined data prior to and at 12 months post DE.

Results

919 people with IBD received Vedolizumab, with 28% (n=261) receiving DE therapy. Median age for the DE cohort was 40 years (IQR 29-56) with median age at diagnosis 26 (IQR 19-39). Median age, age at diagnosis, disease duration and BMI did not vary significantly between the DE and standard dosing cohorts. Most of the DE cohort had Crohn’s (60%) followed by ulcerative colitis (38%) and IBD-unclassified (2%). Half the DE cohort was female (49.8%) with median time to dose escalation being 6 months. 57% (n=111) continued on DE Vedolizumab after 12 months.

Median drug level (where measured) increased from 10.3mg/L pre-DE to 19.8mg/L post. Rates of faecal calprotectin (FCP) remission, (FCP <250ug/g) increased at 12 months post DE as did rates of PRO2 and endoscopic remission (p=0.007, 0.034 & 0.016 respectively). Improved remission rates coincided with decreased systemic steroid requirements, which fell by >50% at 12 months post DE (p=0.001). Hospital admissions and radiological investigations were unchanged over the study period, however the need for endoscopic assessment decreased 12 months post DE. Patients receiving DE therapy had increased encounters healthcare providers, with more clinical assessment and Healthline calls at 12 months post DE (p=0.001 & 0.001 respectively).

Conclusion

In an Australasian cohort of people with IBD, over a quarter of individuals receiving Vedolizumab therapy required DE. DE Vedolizumab correlated with improved endoscopic, PRO2 and FCP remission rates at 12 months with reduced steroid use. As biosimilars reduce the cost of DE therapy, further research beyond 12 months examining remission rates, healthcare utilisation and cost analysis in more detail is needed.
P974 Incidence of Perianal Complications in Clinical Trials for Therapies for Moderate to Severe Inflammatory Bowel Disease
Authors: McDonald B , Choi N , St-Pierre J , Klein J , Rubin D
Published: January 2024

Background

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) with distinct clinical consequences. Distinct from patients with UC is that nearly 25% of patients with CD patients have or will develop perianal disease. Predictors for the development of new perianal disease or complications from existing perianal disease are not well described but such occurrences are included as adverse events (AEs) in clinical trials for IBD. We performed a systematic review and meta-analysis of perianal AEs in pivotal trials of therapies for IBD.

Methods

We conducted a search of PubMed, EMBASE, MEDLINE, Medline Plus, and CDSR library databases for registry and pivotal Phase II-III clinical trials of therapies for IBD. Safety data from clinicaltrials.gov was reviewed to identify incidence of perianal AEs using the terms "abscess" and "fistula." Reported perianal AEs included the following: anal abscess, fissure, fistula; perianal abscess, fistula; perineal abscess; perirectal and rectal abscess; subcutaneous (gluteal) abscess.

Results

Perianal AE incidence across all trials reviewed was 0.47% (91/19,327 patients). Perianal AEs were more likely to occur in patients with CD (0.77%, 70/9,046) than UC (0.20%, 21/10,281). Perianal AEs occurred more frequently in populations of drug-exposed patients than in patients exposed to placebo. In drug-exposed patients with UC, 0.22% (16/7,415) of patients experienced a perianal AE vs 0.17% (5/2,935) of patients exposed to placebo. In drug-exposed patients with CD, 0.76% (55/7,271) of patients experienced a perianal AE vs 0.61% (15/2,465) of patients exposed to placebo. The results are summarized in Table 1.

Conclusion

We found that perianal AEs occur in pivotal UC and CD clinical trials. Expectedly, the frequency of perianal AEs was higher in trials of CD than those for UC. However, the development of perianal AEs in trials of UC suggests that these patients may have been misclassified and have CD. Available data do not allow distinction between development of a perianal AE in a patient with known perianal disease or progression of undiagnosed clinical or subclinical perianal disease, nor does it allow for distinction in a patient not responding to the experimental agent. The finding that perianal AEs occurred more frequently with drug exposure than placebo may be due to fistula healing with consequential abscess formation or unique mechanistic effects that worsen perianal disease. These results highlight a probable rate of misclassification of patients with UC in pivotal trials, and suggest the possibility of subclinical perianal disease in some patients. Further clarification and study of these AEs and their implications are warranted.
P1037 Treatment sequences and time on specific treatments in patients with inflammatory bowel disease under advanced treatment – a German claims data analysis
Authors: Dignass A , Teich N , Kudernatsch R , Sünwoldt J , Grellmann C , Sende F , Kaiser S
Published: January 2024

Background

The number of advanced therapies (ADT) approved for the treatment (Tx) of inflammatory bowel disease (IBD) in is increasing, however, yet no guidance on optimal sequencing of treatments is available in Germany (and elsewhere). This study aims to investigate applied Tx sequences of ADT in claims data based on real-world setting across Germany in patients (pts) with IBD.

Methods

A retrospective healthcare claims data analysis was conducted using claims data from approx. 4.5 Mio pts within German statutory health insurance, including pts diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) from 2014 to 2021. Pts were followed up for at least 6 months after the first prescription of ADT (index date) if not deceased. A pre-index period of at least 12 months was applied to only include pts naïve to ADT. The study assessed Tx sequences and time to next treatment (TTNT) among other parameters. Data was not adjusted to disease severity and only descriptively reflects real world Tx patterns within the database.

Results

The database included 15.041/18.361 pts with CD/UC. Pts with CD/UC starting ADT between 2014 to 2021 received either Adalimumab (ADA: 923/337), Infliximab (IFX: 616/419), Ustekinumab (UST: 113/25) or Vedolizumab (VDZ: 139/248). In an analysis of ADT sequences and TTNT defined as start of first line (1L) Tx to start of second line (2L) Tx we found that during the observation period the majority of pts (71.4%) have not switched to 2L Tx yet. In 1L, ADA was observed as the preferred Tx in CD pts (51.5%) followed by IFX (34.4%), VDZ (7.8%) and UST (6.3%), in UC pts IFX (40.7%) was mostly prescribed as 1L followed by ADA (32.8%), VDZ (24.1%) and UST (2.4%). The proportion (%) of pts not switched to 2L Tx within one year for CD/UC were: ADA (83.6/70.3), IFX (79.0/73.1), UST (93.5/96.0) and VDZ (85.4/86.6). Within three years proportions of pts not switched to 2L Tx changed for CD/UC: ADA (68.1/54.5), IFX (57.8/56.8), UST (82.5/72.0) and VDZ (72.7/73.0) (table1). For pts who had a switch to a different ADT, the switch occurred within one year in over 50% of all pts. Most Tx switches (45.8%) were observed in pts who received IFX as 1L Tx, both in the UC and CD population. The majority of CD pts that received 2L Tx were switched to UST (35.7%), while in UC, a high proportion of pts were switched to VDZ (44.3%). Further Tx pathways and proportions of switches are summarized in Figure 1.

Conclusion

The study found that most IBD pts started ADT with ADA or IFX, but unadjusted time on 1L data may suggest a trend towards superior TTNT of VDZ and UST in UC and CD. Data should be interpreted carefully, as pts for >1L are limited and UST and VDZ were approved during the study period.
P1057 Upadacitinib as Salvage Therapy for Acute Severe Ulcerative Colitis: A Single-Center Experience
Authors: St-Pierre J , Choi D , Krugliak Cleveland N , Miyatani Y , Friedberg S , Choi N K , Picker E A , Fear E , Fine Z , Han J , Labas J , Rubin D T
Published: January 2024

Background

Ulcerative colitis (UC) often leads to hospitalization and may be resistant to standard treatments, necessitating colectomy. Upadacitinib (UPA), an oral selective Janus kinase 1 inhibitor, offers a novel mechanism and the benefit of rapid and predictable pharmacokinetics which suggest it may be efficacious in acute severe UC (ASUC). However, there are a limited number of cases using different dosing regimens describing the potential of this treatment for ASUC. We describe the efficacy and safety of UPA in hospitalized patients with ASUC at our center.

Methods

We conducted an observational cohort study of patients hospitalized for ASUC treated with UPA 45 mg/d as a rescue therapy after failure or incomplete response to other therapies, including corticosteroids. Patient demographics, disease characteristics, and clinical data were collected. The Simple Clinical Colitis Activity Index (SCCAI) was used to monitor clinical response. Clinical outcomes, including loss of response and colectomy, were collected.

Results

Ten patients (ages 21-78, 40% female) hospitalized for ASUC were treated with UPA (population characteristics and clinical summarized in Table 1). The majority of patients (8/10) had prior exposure to two or more advanced therapies. The median SCCAI score at the time of UPA initiation was 8.5, with improvement in five patients on upadacitinib at week 2 (Figure 1). Six of 10 patients discontinued UPA, 3 of whom underwent colectomy during the same hospitalization due to inadequate response. Two patients underwent surgical intervention after discharge from the hospital. Patients who underwent colectomy had a significantly lower albumin level at the time of UPA initiation compared to patients who didn’t undergo colectomy (3.0 and 4.2 g/dL, respectively; p = 0.005), but not CRP (28.5 and 29.8 mg/L, respectively; p = 0.48). One patient had discontinuation of upadacitinib during the induction phase due to elevated liver enzymes. The median time to discontinuation was 7.5 days. Of the 4 patients on ongoing therapy with UPA after initiation in hospital, 2 have been on the maintenance dose for over 6 months with ongoing remission.

Conclusion

Our experience with UPA 45 mg/d for salvage therapy in ASUC patients demonstrated a higher colectomy rate than reported in earlier studies, which . Although some patients benefited from UPA with an improvement in SCCAI scores by week 2, the colectomy rate highlights the need for further research to identify which patients are most likely to benefit from UPA therapy. Our findings underscore the importance of personalized approaches to ASUC treatment and warrant further investigation in larger, controlled studies.
P1069 One-year clinical outcomes of switching to subcutaneous infliximab in patients with inflammatory bowel disease on maintenance of intravenous infliximab therapy with or without remission: A multicentre cohort study
Authors: Bae J H , Park J B , Baek J E , Lee Y J , Kim K O , Kim E S , Jo H H , Hong S W , Park S H , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Kim E Y , Hwang S W
Published: January 2024

Background

An elective switching to the subcutaneous (SC) formulation of infliximab (IFX) has shown effectiveness and safety in patients with inflammatory bowel disease (IBD) on intravenous (IV) IFX maintenance therapy. However, data on long-term outcomes in patients not in clinical remission during maintenance therapy is limited. This study aims to evaluate the long-term outcomes of SC switching in patients who were in clinical remission and not in remission during IV IFX maintenance therapy.

Methods

This retrospective multicentre study was conducted from January 2021 to October 2023. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) <150 for Crohn’s disease (CD) and partial Mayo score <2 for ulcerative colitis. Biological remission was defined as faecal calprotectin (FC) <250 µg/g and C-reactive protein (CRP) <0.5 mg/dL. The primary outcome measure was 1-year treatment persistence of SC IFX.

Results

Among 127 patients included in the study, 80 (62.9%) had CD, and 47 (37.1%) had UC. At the time of switching, 90 patients (70.9 %) were in clinical remission; whereas, 37 (29.1 %) were in a non-remission state. The treatment persistence rate at 1 year was high at 92.9%. Treatment persistence rates between the clinical remission and non-remission groups did not differ significantly (94.4% vs. 89.2%, p=0.287). In both groups, IFX pharmacokinetics and biomarkers between baseline and 12 months (p<0.01) significantly improved. The median infliximab levels increased from a baseline of 3.3 µg/mL (interquartile range [IQR] 1.3–5.1) to 14.4 µg/mL (IQR 9.4–23.0, p<0.001) at 12 months. Disease activity index was stable in the remission group, and decreased in the non-remission group (partial Mayo score, p<0.001; CDAI, p=0.063). At the one-year follow-up, clinical remission and biological remission were achieved in 86.6% and 60.6%, respectively, an increase from baseline (70.9% and 48.0%, respectively). Biologics exposure before IFX was the only significant variable associated with treatment persistence (odds ratio 5.138, 95% confidence interval 1.150–22.951, p=0.032). The concomitant use of immunomodulators was not associated. The incidence of IFX-related adverse events was 14.2%, with only three patients discontinuing treatment.

Conclusion

Switching to SC IFX from IV IFX maintenance therapy demonstrated high treatment persistence and favourable safety profiles, irrespective of remission status at the time of switching. Patients in both remission or non-remission states showed significant improvement in pharmacokinetics and biomarkers, and/or stable disease activity indices.
P1089 Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era – A Swedish nationwide cohort study 2007-2021
Authors: Bröms G , Forss A , Eriksson J , Linder M , Eriksson C , Askling J , Halfvarson J , Ludvigsson J F , Olen O
Published: January 2024

Background

Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics.

Methods

Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression.

Results

The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1).

Conclusion

The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.
P1101 Patient-reported physical activity of IBD patients is of concern when weighed with the international physical activity questionnaire regardless of disease activity and IBD phenotype: barriers and facilitators emerged from the extended "BE-FIT-IBD" cross-sectional study
Authors: Gravina A G , Pellegrino R , Palladino G , Imperio G , D'Onofrio R , Arboretto G , Romeo M , Ciamarra P , Dallio M , Federico A
Published: January 2024

Background

As the World Health Organization recommends, regular physical activity (PA) determines quality of life. The qualitative/quantitative characteristics of ideal PA to be suggested for inflammatory bowel diseases (IBD) nor the relationship with disease activity are not yet well defined. This study aimed to weigh PA levels and barriers/facilitators to PA in a cross-sectional group of patients with IBD.

Methods

Consecutive Italian non-severe IBD patients (assessed with partial Mayo score for and Harvey-Bradshaw index) received an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire (IPAQ), disease activity as Patient-Reported Outcomes 2 (PRO-2), and finally habits, beliefs, and barriers in conducting regular PA. Clinical, anthropometric, and demographic data were also collected. PA was processed as continuous units of resting metabolic rate in minutes/week (Met min/wk). Three PA groups were identified: inactive (< 700 Met min/wk), sufficiently active (700-2500 Met min/wk) and Health Enhancing PA (i.e., HEPA active, > 2500 Met min/wk) patients.

Results

The 219 patients enrolled exhibited overall PA levels of 834.5 Met min/wk, with a large proportion (94, 42.9%) classified as inactive. Only a minority (9, 4.1%) resulted as health-enhancing PA. Patients with a non-dyslipidaemia metabolic profile (p < 0.0001) or on biologics therapy (p=0.022) showed better IPAQ scores in moderate activities. PRO-2 correlated negatively with IPAQ intense activities scores (τ= -0.156, p=0.038) in ulcerative colitis patients. PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity (AUC < 0.6). IPAQ showed no notable differences when related to disease activity categories according to PRO-2 (p > 0.05). Physically active patients were more willing to discuss their PA with their IBDologists. Several barriers (e.g., diagnosis of IBD and fear of flare-ups after PA) are firmly rooted in physically inactive patients. Evacuation urgency (rectal syndrome) is the IBD-related barrier most physically inactive patients reported. Some fears about PA were worse felt in the absence of a stable partner (i.e., fear of worsening or recurrence of IBD, p < 0.05).

Conclusion

Many Italian IBD patients show a worrying rate of physical inactivity, depriving themselves of the multidimensional benefits that regular PA can bring. There is a need for IBDologists to act by removing barriers to PA and engaging in a regular discussion on the importance of PA with IBD patients. IPAQ has shown good feasibility and patient acceptance in this setting.
P1123 Social isolation, loneliness, and incident inflammatory bowel disease: results from a large prospective cohorts and Mendelian randomization
Authors: Zhao J , Zhang M , Ye J , Li X
Published: January 2024

Background

Background Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD).

Methods

Methods 275,157 UK adults from the UK Biobank (UKB) was analyzed. The exposures of interest were social isolation and loneliness. Social isolation was measured by the frequency of meeting family/friends, leisure and social activity, and communal/solitary living. Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others. The primary endpoint was incident IBD, including UC and CD. The twosample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB and the a nonoverlapping European ancestry GWAS study.

Results

Results The UKB cohort study documented 1,565 IBD (1063 UC and 492 CD) cases during a mean follow-up of 13.49 years. Social isolation and loneliness showed significant associations with an elevated risk of IBD in UKB (social isolation [moderate vs least]: aHR 1.13, 95% CI 1.02-1.26; social isolation [most vs least]: aHR 1.31, 95% CI 1.01-1.70; loneliness [yes vs no]: aHR 1.29, 95% CI 1.04-1.60). These associations were evident among moderate genetic susceptibility to IBD. Social isolation and loneliness jointly increase the risk of IBD onset, with an aHR of 1.60 (95% CI 1.21-2.12). Two-sample MR analyses determined that engaging in fewer leisure/social activities (OR 3.42, 95% CI 1.55-7.58; 3.32, 95% CI 1.29-8.55; 3.09, 95% CI 1.35-7.07) were associated with increased IBD, UC and CD risk, whereas more activities-sports club or gym (OR 0.37, 95% CI 0.15-0.88) was associated with reduced IBD risk.

Conclusion

Conclusion Social isolation and loneliness are each associated with an elevated risk of IBD especially for individuals with a moderate genetic risk for IBD, with MR analyses suggesting potential causal links. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of IBD prevention strategies.
P1200 Study of correlation between polymorphisms of vitamin D metabolism genes and perianal disease in Crohn's disease
Authors: Ribaldone D G , Cafasso C , Antonucci M , Palermiti A , Caviglia G P , Vernero M , D'Avolio A , Cusato J
Published: January 2024

Background

Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1.

Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements.

As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients.

Methods

The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed.

Results

Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01.

Conclusion

In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.
Evaluation of bone-related mechanical properties in female patients with long-term remission of Cushing's syndrome using quantitative computed tomography–based finite element analysis
Authors: Giuliodori Agustina , Soudah Eduardo , Malouf Jorge , Martel-Duguech Luciana , Amodru Vincent , Gil Joan , Hernández Joaquín A , Domingo Manuel Puig , Webb Susan M , Valassi Elena
Published: January 2024

Background

Hypercortisolism in Cushing's syndrome (CS) is associated with bone loss, skeletal fragility, and altered bone quality. No studies evaluated bone geometric and strain–stress values in CS patients after remission thus far.

Patients and methods

Thirty-two women with CS in remission (mean age [±SD] 51 ± 11; body mass index [BMI], 27 ± 4 kg/m2; mean time of remission, 120 ± 90 months) and 32 age-, BMI-, and gonadal status–matched female controls. Quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD) and buckling ratio, cross-sectional area, and average cortical thickness at the level of the proximal femur. Finite element (FE) models were generated from QCT to calculate strain and stress values (maximum principal strain [MPE], maximum strain energy density [SED], maximum Von Mises [VM], and maximum principal stress [MPS]). Areal BMD (aBMD) and trabecular bone score (TBS) were assessed by dual-energy X-ray absorptiometry (2D DXA).

Results

Trabecular vBMD at total hip and trochanter were lower in CS as compared with controls (P < .05). Average cortical thickness was lower, and buckling ratio was greater in CS vs controls (P < .01). All strain and stress values were higher in CS patients vs controls (P < .05). 2D DXA–derived measures were similar between patients and controls (P > .05). Prior hypercortisolism predicted both VM (β .30, P = .014) and MPS (β .30, P = .015), after adjusting for age, BMI, menopause, delay to diagnosis, and duration of remission.

Conclusions

Women with prior hypercortisolism have reduced trabecular vBMD and impaired bone geometrical and mechanical properties, which may contribute to an elevated fracture risk despite long-term remission.