bluuebunny/crossref_metadata_2025_split huggingface dataset:
P677 The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD): Analysis of 40,000 Patient Years of Anti-TNF Use
Authors: Al-Hillawi L , Liao H , Powell Doherty R , Bedke N , Azzu H , Cripps S , Prabhu A , White L , Ambrose T , Cheung V , Palmer R , Walsh A , Travis S , Ternette N , Brain O , Satsangi J ,   The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD)
Published: January 2024

Abstract

Background
Anti-TNF therapy is established as a mainstay in IBD management. Recent data raise controversies regarding efficacy of these agents, sustainability of response, and identification of factors that may influence outcomes, including dose escalation and need for long-term concurrent immunosuppression (Lancet Gastro.Hep.2019;4:341).

Methods
We report a retrospective cohort study of 699 IBD patients on anti-TNF at our centre between 2005-2022. Clinical data were obtained from patient records and pharmacy database (TABLE 1). Primary outcomes were overall loss of response (LOR) at any timepoint; and secondary LOR (after an initial clinical response to therapy). Cox regression analysis was performed to identify variables independently affecting outcome. Kaplan-Meyer survival curves were constructed to demonstrate overall response rates (persistence on drug) and secondary LOR (Figure 1a-d). Dose adjustments were made proactively in a Virtual Clinic.

Results
204 patients had a diagnosis of ulcerative colitis (UC), 481 Crohn’s Disease (CD) and 14 IBD-unclassified. 126 patients received both infliximab (IFX) and adalimumab (ADA). Median duration on IFX was 42 months (range 0-204); median duration on ADA was 48.5 months (range 0-180). 48% of patients on IFX underwent dose escalation, as did 40% on ADA. Overall, 58 patients (7.6%) remained on treatment at 120 months.
Overall survival rates for IFX at 12 months were 83% (82%CD vs. 82%UC); and at 36 months were 71% (69%CD vs. 74%UC). Overall survival rates for ADA at 12 months were 84% (89%CD vs. 59%UC); and at 36 months were 72% (78% CD vs. 42% UC) (Figure 1a-b).
Secondary LOR rates for IFX at 12 months were 6% (5%CD vs. 9%UC); and at 36 months were 16% (15%CD vs.19%UC). Secondary LOR rates for ADA at 12 months were 7% (5%CD vs. 19%UC); and at 36 months were 16% (12% CD vs. 42% UC) (Figure 1c-d). There was no difference in survival analysis for IFX between CD and UC.
On Cox regression analysis, for IFX, immunomodulation was associated with reduction in overall LOR (HR=0.48, p=1.07e-05) but not secondary LOR (HR=0.78, p=0.31) (Figure 1e-f). For ADA, outcomes were better for CD vs. UC for both overall LOR (HR=0.35, p=3.29e-07) and secondary LOR (HR=0.35, p=9.99e-05).

Conclusion
We demonstrate encouraging response rates in the first three years of therapy, with a small proportion remaining on therapy beyond 120 months. Survival rates on IFX were similar for UC and CD, but for ADA were significantly lower in UC. Secondary LOR was not affected by immunomodulation. Further analysis of relation to drug levels, dose escalation and genotyping is underway. This work was supported by The Leona M & Harry B Helmsley Charitable Trust.
P690 Monitoring ustekinumab levels in Inflammatory Bowel Disease in clinical practice: a window of opportunity
Authors: González Antuña J , Valdés Delgado T , Maldonado Pérez B , Castro Laria L , Merino Bohórquez V , Calleja Hernández M Á , Argüelles Arias F 
Published: January 2024

Abstract

Background
Ustekinumab (UST) is an effective drug in inflammatory bowel disease (IBD). Monitoring Ustekinumab trough levels in μg/mL (USTTL) can assist in the clinical management of these patients. Our objective was to analyze USTTL in patients with IBD, establish cutoff points associated with clinical response and remission, and analyze factors related to higher levels.

Methods
Observational, retrospective, and single-center study that included patients with IBD receiving UST treatment with at least one level determination.
Before the initiation of UST (baseline) and prior to level extraction (periods 1 and 2), clinical and analytical data were collected as follow: Harvey-Bradshaw Index (HBI) in Crohn's disease (CD), partial Mayo Index (pMayo) in ulcerative colitis (UC), fecal calprotectin (FC) and C-reactive protein (CRP).
Median and interquartile range (IQR) were used for quantitative variables, and percentage (%) for qualitative variables. Univariate and bivariate analyses were performed for response and clinical remission rates using ROC curves.

Results
A total of 125 patients with at least one USTTL determination were included. Figure 1 illustrates their baseline characteristics.
In period 1, 62.4% of patients were on subcutaneous maintenance, and the median USTTL was 3.1 (1.6-5.3). 64% of patients responded to treatment, with higher USTTL than non-responders [4.1 (2.0-6.2) vs. 2.1 (1.0-4.5); p=0.006]. 42.5% achieved clinical remission with higher USTTL than those who did not achieve it [4.0 (2.3-5.7) vs. 2.5 (1.2-5.2) p=0.039].
Furthermore, patients on subcutaneous maintenance* had lower USTTL than those on subcutaneous and intravenous intensification [2.2 (1.3-3.5)* vs. 7.4 (5.1-10.8) and vs. 5.3 (3.3-12); p&lt;0.001 and p=0.03, respectively).
In the 46 patients with two determinations, statistically significant differences were found between period 1 and period 2 in USTTL [3.4 (1.9-6.4) vs. 7.2 (4.7-11.7) p&lt;0.001], HBI [8 (4-9) vs. 4 (4-4.3); p&lt;0.001], pMayo [4.5 (3-5) vs. 1 (1-3.3); p=0,042], FC [700 (180-2000) vs. 400 (108-1571); p=0.032), and corticosteroid use (41.3% vs. 26.1%; p=0.024).
ROC curves were calculated for response and clinical remission in period 2. The USTTL cutoff points were 4.25 and 6.025μg/mL for response and clinical remission, respectively (figure 2).

Conclusion
Similar to previously published studies with anti-TNF, high levels of USTTL are associated with increased clinical remission and response. Patients undergoing UST treatment may benefit from a change in dosage to increase levels and achieve clinical remission. The cutoff point obtained for clinical remission was 6 μg/mL.
Therefore, the determination of USTTL in daily clinical practice is a useful tool for the treatment of patients with IBD.
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt;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 (&lt;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

Abstract

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 &lt;5 and a partial Mayo score &lt;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

Abstract

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 &lt; 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p &lt; 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