bluuebunny/crossref_metadata_2025_split huggingface dataset:
P576 Endoscopic healing with vedolizumab in Crohn's disease occurs predominantly in the first 6 months and is independent of serum concentrations: Data from LOVE-CD
Authors: D'Haens G , Bossuyt P , Baert F , Molnár T , Clasquin E , Lowenberg M , Montazeri N , Peeters H , Lambrecht G , Vermeire S 
Published: January 2023

Abstract

Background
Endoscopic healing is an important treatment goal in Crohn’s disease (CD). Vedolizumab (VDZ) was shown to induce endoscopic healing after 6 months in a significantly greater proportion of pts with early CD than in those with late CD (&gt;2 years)(UEGW 2022). We investigated whether further endoscopic healing could be attained with 6 more months of VDZ treatment in those pts with no SES-CD worsening at month 6 compared to baseline.

Methods
Pts in the LOVE-CD study received standard doses of VDZ and had ileocolonoscopies at baseline, w26 and 52. We studied the kinetics of endoscopic improvement during continued VDZ treatment. Endoscopies were scored by independent readers.
So far, 157 pts completed the LOVE-CD trial with available central reading results. We here report the results of 76 pts (48%) who had stable endoscopic diseases or any degree of endoscopic improvement at w26 with 3 centrally read endoscopy scores (baseline, w26 and 52) available at present. VDZ serum conc were also measured and correlated to endoscopic improvement.

Results
We studied 76 pts (mean age 36.7, 51 (67%) female, median baseline SES-CD 10 (range 3-30) who reached w52 and had no SES-CD worsening at w26. We identified 3 endoscopic improvement patterns: 1) 24 pts (32%, 12 early, 12 late CD) with median baseline SES-CD 7.5 (range 3-21) had a SES-CD score of 0 at w26. Three of these pts had again mild lesions at w52 (SES-CD 1-4), the rest maintained SES-CD=0 at w52 (endoscopic healing); 2) 20 pts (26%, 6 early, 14 late CD) with median baseline SES-CD 8 (range 3-27) had a SES-CD of 1-3 at w26 (endoscopic remission defined as SES-CD&lt;4). At w52, 10/20 had a score of 0, 7/20 the same score as at w26 and only 3/20 a higher score; 3) 32 pts (42%, 5 early, 27 late CD) with median baseline SES-CD 14 (range 5-30) had no endoscopic remission at w26 (SES-CD &gt;4) with a drop to median SES-CD 7 (range 5-20) at w26 and further to median SES-CD 5 (range 0-15) at w52. Figure 1 shows the evolution of the SES-CD.
The mean VDZ serum conc was (1) 19.36 mg/l at w26 and 22.23 mg/l at w52 in the group with endoscopic healing, (2) 19.52 mg/l at w26 and 21.69 mg/l at w52 in the group with endoscopic remission, and (3) 17.38 mg/l at w26 and 20.09 mg/l at w52 in the group without endoscopic healing or remission.

Conclusion
In this subset of LOVE-CD pts with endoscopic improvement or unchanged SES-CD at w26, the majority of pts (44/76) reached endoscopic remission (SES-CD&lt;4). Overall, endoscopic improvement in this subgroup of responders by SES-CD score was a median of 7 (range -1 to 25) SES-CD points between w0 and w26 and a median of 0 (range -10 to +15) SES-CD points between w26 and w52. The degree of endoscopic improvement beyond month 6 was unrelated to VDZ serum conc.
P580 Upadacitinib is effective and safe for Ulcerative Colitis: prospective real-world experience
Authors: Friedberg S , Choi D , Hunold T , Choi N K , Garcia N M , Picker E A , Cohen N A , Cohen R D , Dalal S R , Pekow J , Sakuraba A , Krugliak Cleveland N , Rubin D T 
Published: January 2023

Abstract

Background
Upadacitinib (upa) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) and has received regulatory approval for UC. We report a large prospective real-world experience with upa in patients with UC.

Methods
We performed a prospective analysis of clinical outcomes during upa therapy in patients with UC using pre-determined follow-up intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol. We used the Simplified Clinical Colitis Activity Index (SCCAI), C-reactive protein (CRP) and fecal calprotectin (FCP). Clinically active disease was defined as SCCAI ≥ 3. Clinical response was defined as a decrease of ≥ 3 points from baseline SCCAI. Clinical remission was defined as SCAAI &lt; 3. Corticosteroid free clinical remission (CSFR) was defined as those in clinical remission, not taking systemic corticosteroid at the specific time point. CRP normalization was defined as baseline elevated and then within the normal range for the lab used (Quest Diagnostics (Secaucus, New Jersey) ≤8 mg/L or UChicago Medicine ≤5 mg/L). FCP response and remission was assessed at three different cutoffs: less than 250 μg/g, 150 μg/g, and 50μg/g. Adverse events were recorded as treatment-related adverse events (AE) and serious adverse events (SAE).

Results
55 patients with UC received ≥4 weeks of upa (Table 1). 100% had previously received anti-TNF therapy and 81.8% had received ≥2 advanced therapies (biologic, small molecule, calcineurin-inhibitor). At 4 and 8 weeks of treatment, 18/22 (81.8%) and 19/21 (90.5%) achieved clinical response and 17/22 (77.3%) and 17/21 (81.0%) achieved clinical remission, respectively (Table 2). Of those who were on steroids at baseline, 100% (7 of 7) achieved CSFR. Results were seen as early as week 2 with clinical remission rates of 36.0%. Mean SCCAI decreased from 5.3 (SD 3.6) at week 0 to 1.71 (SD 3.96) at week 8 (p = &lt;0.0001, Figure 1). Mean FCP decreased from 1028.5 (SD 1291) μg/g at week 0 to 530.2 (SD 715.1) μg/g (p = 0.0881). Of those with FCP &gt;150 μg/g at baseline, 33.3% (2/6) achieved FCP &lt;150 μg/g by week 8 (Table 2). Mean CRP (mg/L) decreased from 5.1 (SD 5.0) mg/L at week 0 to 2.5 (SD 3.3) mg/L at week 8. Of those with CRP &gt;5 at week 0, 60% (3/5) achieved CRP &lt;5 by week 8 (Table 2). 30.9% of patients had an AE after starting upa (Table 3). The most common of these was acne (23.6%). Two AEs led to discontinuation. There were no SAEs.

Conclusion
In this large prospective real-world experience in medically-resistant patients with UC, we describe that upadacitinib is rapidly effective and safe, with remission rates that exceed those seen in the pivotal trial.
P585 Duration of response to ozanimod after treatment withdrawal: results from the phase 3 True North study
Authors: Vermeire S , Abraham B , Bressler B , Reinisch W , Jain A , Memaj A , Akukwe L , Liu W J , Osterman M , Canavan J B , Sands B E 
Published: January 2023

Abstract

Background
The phase 3 True North randomised trial demonstrated the efficacy and safety of ozanimod (OZA) in patients with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to loss of OZA response in patients who discontinued OZA and switched to placebo (PBO) in the True North maintenance period (MP).

Methods
In True North, patients were randomised to once-daily oral OZA 0.92 mg or PBO or to open-label OZA during a 10-week induction period (IP). Patients with clinical response to OZA at Week 10 were rerandomised to OZA (OZA/OZA) or PBO (OZA/PBO) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points vs Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in OZA/OZA and OZA/PBO patients who entered the MP after achieving clinical remission (CRM) or clinical response (CRS only, excluding patients in CRM) at Week 10.

Results
In the True North MP, 230 patients continued OZA (CRM, n=82; CRS only, n=148) and 227 patients switched to PBO (CRM, n=79; CRS only, n=148). Baseline characteristics were generally similar between groups. Patients in CRS only at Week 10 had a numerically higher proportion with severe disease and prior immunosuppressive medication use vs CRM patients (Table). Differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of OZA/OZA patients were without relapse vs OZA/PBO patients (Figure). MP Week 42 Kaplan-Meier estimates of no relapse were 86.1% and 62.6% for OZA/OZA and OZA/PBO patients, respectively. Additionally, patients in CRM at Week 10 had higher rates of nonrelapse during the MP vs those in CRS only at MP entry. Kaplan-Meier estimates of nonrelapse at MP Week 42 were 67.9% and 59.7% in OZA/PBO patients with CRM and CRS, respectively, and 90.9% and 83.4% in OZA/OZA patients with CRM and CRS, respectively.

Conclusion
This analysis shows that OZA is effective at preventing disease relapse over 42 weeks of maintenance treatment in patients who achieve clinical response at Week 10. These data show that OZA maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.
P591 Negative impact of high body mass index on the efficacy of anti-TNFα agents in patients with Inflammatory Bowel Disease
Authors: Hamoir F , De Leuze F , Denis M , De Vroey B , De Suray N , Burnet G , Piessevaux H , Dewit O 
Published: January 2023

Abstract

Background
Anti-tumor necrosis factor (TNF)-α agents are a therapy of choice in the induction and maintenance treatment of inflammatory bowel disease (IBD). Unfortunately, their efficacy varies. Some IBD patients are primary non-responders and many will experience a secondary loss of response. However, we do not yet have good predictors of their efficacy. Obesity, which prevalence increases worldwide, is also increasingly found in IBD population. Some studies suggest an association between obesity and poorer response to anti-TNFα therapy in IBD patients, although with conflicting results.
The aim of this study is to assess the impact of patients’ body mass index (BMI) on the efficacy of anti-TNFα agents in IBD and if there is difference according to the route of administration (intravenous (IV) vs subcutaneous (SC)) or the type of disease (Crohn’s disease (CD) vs ulcerative colitis (UC)).

Methods
We retrospectively collected data from 188 patients with IBD, aged ≥ 18 years, treated with a first anti-TNFα agent started in our center between January 2002 and December 2020 to avoid missing data. A lack or loss of response to anti-TNFα therapy was defined by the need to optimize or change the treatment or by the initiation of any intercurrent treatment (steroid therapy, hospitalization, or surgery). Frequency of the event and time to its occurrence were analyzed and compared according to BMI using uni- and multivariate logistic regression models and survival curves (Kaplan-Meier), represented by BMI categories (&lt;18.5; 18.5-25; 25-30 and ≥ 30 kg/m²).

Results
In this cohort of 188 patients (143 CD, 43 UC, 2 Indeterminate Colitis), 8% were obese. We observed that the higher the patient’s BMI, the earlier the risk of optimization or change of treatment (HR=1.043, p=0.045). Association was even stronger for obese patients (HR=2.13, p=0.018). After adjustment for IBD type and administration route, association with obesity persisted.

Two other characteristics - female gender (HR=1.56, p=0.012) and higher CRP (HR=1.14, p=0.021) – were associated with earlier optimization or treatment change. Similarly, analysis of survival curves showed a significant difference in time to optimization or change of treatment between BMI categories in patients with CD (p=0.02) but not in those with UC (p=0.87).

No association was found between BMI and need for intercurrent treatment.

Conclusion
This study confirms an association between higher BMI – specifically obesity - and an earlier loss of efficacy of a first anti-TNFα treatment, regardless of IBD type or route of drug administration. Prospective studies with analysis of trough levels are required for a better understanding of the mechanisms involved in the response to anti-TNFα therapy in IBD obese patient.
P596 Ustekinumab and anti-TNF agents are equally safe and effective in elderly Crohn's disease patients: A propensity adjusted multi-centre cohort study
Authors: Gebeyehu G G , Broglio G , Liu E , Limdi J K , Selinger C , Fiske J , Razsanskaite V , Smith P J , Flanagan P K , Subramanian S 
Published: January 2023

Abstract

Background
Anti-tumour necrosis factor (anti-TNF) agents are associated with increased infection risk among elderly inflammatory bowel disease (IBD) patients and thus alternative biologics may be preferable. Previous cohort studies have demonstrated a superior safety profile for vedolizumab compared to anti-TNF agents in the elderly. However, there is limited comparative data on the safety and effectiveness of ustekinumab in elderly IBD patients. We aimed to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn’s disease (CD) patients.

Methods
Patients ≥60 years old who commenced ustekinumab or an anti-TNF agent for CD were included in this multi-centre retrospective cohort study. The primary outcome was time to development of any infection. Secondary outcomes included incidence of serious infections, defined as requiring hospitalisation and effectiveness assessed by treatment persistence and clinical response rates. We appropriately adjusted for confounders using propensity score matched analysis weighted by the inverse predicted probability of treatment weighting and performed a logistic regression analysis to assess factors associated with infections and treatment persistence.

Results
83 patients treated with ustekinumab and 124 patients (30 infliximab and 94 adalimumab) treated with anti-TNF therapy were included. A greater proportion of patients treated with ustekinumab were on concomitant steroids at baseline (37% vs 7.3%, p&lt;0.001). After propensity adjustment, the infection free survival at 12 months was comparable between ustekinumab and anti-TNF agents (HR 0.79, 95% CI 0.58-1.07, p=0.128). Serious infection rate for ustekinumab was 7.55/100 patient years and 5.30/100 for anti-TNFs (p=0.3). None of the variables including Charlson co-morbidity index were associated with infection risk in a multi-variable model.
Unadjusted treatment persistence rates at 12 months were lower for ustekinumab compared to anti-TNF agents (68.1% vs 82.8% respectively, p=0.020). After propensity adjustment, there was no difference in treatment persistence at 6 months (OR 1.23, 95% CI 0.37-4.10, p=0.741) and 12 months (OR 1.07, 95% CI 0.45-2.55, p=0.9). There was a significant reduction in HBI at 6 and 12 months compared to baseline in both groups (p&lt;0.001). In a multivariable model, only concomitant thiopurine use was associated with treatment persistence at 12 months (OR 4.6, 95% CI 1.2-30.3, p=0.049).

Conclusion
We observed comparable safety and effectiveness in a propensity score adjusted comparison of ustekinumab and anti-TNF treated elderly CD patients. The rates of serious infections were comparable between the two groups.
P603 Real-world Scottish experience of anti-TNF therapy in paediatric Crohn’s disease 2016-2020 against the ECCO-ESPGHAN recommendations
Authors: Wands D , Scott G , Wilson D C , Hansen R , Chalmers I 
Published: January 2023

Abstract

Background
ECCO-ESPGHAN updated the guideline on the management of paediatric Crohn’s disease (CD) in 2021. This promoted a move to early risk stratification and a ‘top-down’ (anti-TNF within 4 weeks of diagnosis) approach for patients who were deemed high-risk. High-risk was defined by extensive panenteric or severe disease, perianal, stricturing and/or penetrating behaviour. We sought to compare the use of anti-TNF therapy against the new guidance by conducting a Scottish nationwide retrospective multi-centre study (all three regional PGHAN units).

Methods
We analysed a prospectively identified nationwide cohort of all new paediatric CD patients (&lt;18 years) diagnosed in Scotland between 01/01/16 and 31/12/20. We retrospectively collected data from electronic medical records on the use of anti-TNF therapy (infliximab or adalimumab) within 18 months of diagnosis. Paris location and behaviour at diagnosis were determined, allowing us to split the patient group into high-risk or low/medium-risk as per latest ECCO-ESPGHAN guidance. Data regarding surgical intervention was collected and defined as: Perianal (Seton suture or drainage of abscess) and/or bowel resection +/- stoma formation.

Results
419 patients were included (259/419 male; median age at diagnosis 13.2 yrs). Disease phenotype and behaviour are shown in tables 1 and 2. 225/419 (54%) were classified as high-risk and 194/419 (46%) as low/medium-risk. 171/225 (76%) high-risk and 78/194 (40%) low/medium-risk patients received anti-TNF within 18 months of diagnosis, with median start at 5 months (IQR: 1- 8 m) and 6.5 months (IQR: 3 – 13 m) respectively. Figure 1 demonstrates cumulative anti-TNF new starts by month. Of these patients, 49/171 (40%) high-risk and 12/78 (15.3%) low-risk received anti-TNF within 4 weeks of diagnosis. High-risk patients were more likely to receive anti-TNF (76.0% vs 40.2%, p&lt;0.0001). 37 (8.8%) patients underwent surgical intervention; 31/225 (13.7%) high-risk and 6/194 (3.1%) low/medium-risk (13.7% vs 3.1%, p= 0.0002).

Conclusion
The ECCO-ESPGHAN guidance seeks to shift practice towards “top-down” anti-TNF therapy in high-risk patients. Our real-world data supports this view by showing that high-risk patients are more likely to require biologics within 18 months and more likely to require surgery than low/medium-risk patients. The ECCO-ESPGHAN approach would however have led to unnecessary anti-TNF in 24% of our high-risk cohort within 18 months of diagnosis. The financial cost and risk:benefit profile of this group should be considered carefully both in clinical practice and future guidance.
P607 HLA-DQA1*05 Allele Carriage and Anti-TNF Therapy Persistence in Inflammatory Bowel Disease
Authors: Doherty J , Ryan A , Quinn E , Dolan J , Corcoran R , O' Hara F , Bailey Y , McNamara D , Doherty G , Kevans D 
Published: January 2023

Abstract

Background
Carriage of HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADA) in patients with Crohn’s Disease (CD) receiving anti-TNF therapy. The presence of ADA is not uniformly associated with anti-TNF therapy failure as patients with adequate trough drug concentrations, even where ADA are present, can maintain therapy response. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of anti-TNF therapy evaluated by drug persistence in routine clinical practice.

Methods
A multi-centre retrospective study of IBD patients treated with anti-TNF therapy was performed. HLA-DQA1*05 genotypes were generated for each included patient by imputation from whole genome sequence using HIBAG. Only outcome of first anti-TNF therapy received by patients was evaluated in this study. Study primary endpoint was anti-TNF therapy persistence, expressed as time to discontinuation of anti-TNF therapy, segregated by HLA-DQA1*05 allele genotype. Patients discontinuing anti-TNF therapy due to primary or secondary loss of response or due to side-effects were considered therapy failures. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR).

Results
921 IBD patients were identified with 877 included in the study population. Baseline demographics for the entire cohort and segregated by HLA-DQA1*05 allele status are summarised in Figure 1. In the study population, 543 (62%) had no copy, 281 (32%) one copy and 53 (6%) two copies of HLA-DQA1*05 allele. Median time to anti-TNF therapy discontinuation in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared to patients with 1 or no copy at 700-days follow-up: 418 versus 513 versus 541 days respectively, p=0.007 (Figure 2) with similar results observed at 2000-days follow-up (p=0.04). In a multivariate regression, factors independently associated with time to anti-TNF therapy discontinuation included: carriage of HLA-DQA1*05 allele OR 1.2, p=0.02; male gender OR 1.6, p=4.2 x 10-5; CD phenotype OR 0.7, p=0.009; and anti-TNF therapy type (infliximab) OR 1.5, p=0.002. Concomitant immunomodulator use was not associated with time to anti-TNF therapy discontinuation in this model, OR 0.97, p=0.84.

Conclusion
Carriage of two HLA-DQA1*05 alleles is associated with a less favorable outcome of anti-TNF therapy with shorter time to therapy discontinuation. Carriage of one HLA-DQA1*05 allele is not associated with outcome of anti-TNF therapy. Assessing HLA-DQA1*05 genotype has value in routine clinical practice as HLA-DQA1*05 homozygotes are at increased risk of anti-TNF failure which should be a consideration in IBD therapy selection.
P609 Impact of prior biologic exposure on durability of recaptured response to ozanimod during the True North open-label extension study
Authors: Colombel J F , Rubin D T , Vermeire S , Jain A , Canavan J B , Wu H , Lawlor G , Osterman M T , Dignass A , Regueiro R 
Published: January 2023

Abstract

Background
In the phase 3 True North (TN) study, ozanimod (OZA) 0.92 mg once daily showed efficacy and safety for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis, and is approved for adults in the EU, US, and other countries for this indication. This analysis (data cutoff: 10 January 2022) evaluated the impact of prior biologic exposure on the long-term durability of response in pts who experienced disease relapse while on placebo (PBO) during the TN maintenance period (MP) and then recaptured response to OZA during the TN open-label extension (OLE).

Methods
Responders to OZA 10-week induction therapy who were biologic-naive or exposed to prior biologics at baseline were rerandomised 1:1 to OZA (n=230) or PBO (n=227) during the TN MP. Pts who relapsed while on PBO subsequently entered the OLE and reinitiated open-label OZA in this interim OLE analysis. Symptomatic, clinical, endoscopic, and histologic endpoints were evaluated by observed case (OC) and nonresponder imputation (NRI) analyses.

Results
This analysis included 38 biologic-naive and 38 biologic-exposed pts who entered the OLE after disease relapse on PBO (median time to relapse, 13.1 and 11.2 weeks, respectively). Symptomatic clinical response based on NRI was achieved by 26/38 (68.4%) of biologic-naive and 20/38 (52.6%) of biologic-exposed pts 5 weeks after restarting OZA in the OLE. Symptomatic clinical response by OC analysis at OLE Week 5 was achieved in 72.2% (26/36) and 55.6% (20/36) of biologic-naive and -exposed pts, respectively. Although a greater proportion of biologic-naive vs -exposed pts completed OLE Week 94 (65.8% vs 39.5%), OC rates of symptomatic clinical response at OLE Week 94 were similar (biologic-naive: 95.0% [19/20] vs biologic-exposed: 100.0% [13/13]). Key clinical, endoscopic, and histologic endpoints are shown in Fig 1. Durability of response between OLE Weeks 46 and 94 was similar in biologic-naive (40%–56%) vs -exposed pts (50%–67%) but varied depending on endpoints (NRI analysis). Reductions in mean [SD] total Mayo score were similar and sustained through OLE Week 94 in biologic-naive and -exposed pts (OLE Week 0: 8.9 [1.8] and 9.3 [1.6], respectively; OLE Week 46: 2.3 [1.7] and 4.2 [2.6], respectively; OLE Week 94: 2.6 [2.0] and 2.6 [1.4], respectively) (Fig 2).

Conclusion
In pts who lost clinical response after OZA treatment withdrawal, symptomatic clinical response was recaptured within 5 weeks of OZA reinitiation in the majority of pts, and clinical benefit was maintained for up to 94 weeks (extent of current analysis) in biologic-naive and -exposed pts. This suggests that in clinical practice, pts who experience a disease relapse after temporarily holding OZA may benefit from resumption of OZA.