bluuebunny/crossref_metadata_2025 huggingface dataset:
P566 Colitis due to immunotherapy with anti-PD-1: a case series
Authors: De Ruvo M , Barberio B , Zingone F , Bonanno L , Dal Maso A , Stefano F , Chiarion Sileni V , Savarino E V
Published: January 2023

Background

Anti-programmed death-1 (PD-1) drugs have been associated with immune-mediated gastrointestinal adverse events in 0.5-9% of the cases. The aim of this study was to investigate the characteristics of colitis occurring in oncological patients treated with anti-PD-1 drugs.

Methods

This is a prospective cohort study including patients referred for new onset colitis at Azienda Ospedaliera of Padua between 2020 and 2022.

All patients were treated with anti-PD-1 drugs at Istituto Oncologico Veneto due to oncological disease [n=2 melanoma, n=1 colorectal cancer, n=1 pleural mesothelioma, n=14 non-small-cell lung cancer (NSCLC)].

Median duration of follow up was 10 months.

Results

Eighteen patients who developed diarrhea (≥G2, CTCAE) following treatment with anti-PD-1 were included (n=12 males, median age 70 years).

The diarrhea began after a mean of seven months of therapy and after two to six months its discontinuation in 3/18 patients.

The mean fecal calprotectin values at diarrhea onset was 1063 ug/g.

Most of the patients (14/18) had their immunotherapy suspended, among them four required hospitalization. All patients were initially treated with systemic steroids (1 mg/kg). Seven patients had ulcerative colitis (UC)-like colitis (n=5 pancolitis, n=2 left colitis) while the others (60%) had microscopic colitis (MC, n=9 collagenous, n=1 lymphocytic) with unspecific inflammatory mucosal abnormalities in half of the cases.

Among patients with UC-like colitis, two were hospitalized and treated with anti-TNFα because of steroid refractoriness; all remaining patients with UC-like colitis are maintaining remission with oral mesalamine or with budesonide non-MMX or low-dose systemic steroid (0.1 mg/kg). Two patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, with mesalamine as maintenance therapy.

Among patients who developed a MC, one required Vedolizumab as maintenance therapy, while 8/10 achieved partial or complete remission with oral budesonide non-MMX or low-dose systemic steroid. Three patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, taking budesonide non-MMX as maintenance therapy.

In our cohort of study all patients with MC were previously treated with anti-PD-1 drugs for NSCLC, while those with UC-like colitis were treated for NSCLC (n=4), melanoma (n=2) and colorectal cancer (n=1).

Conclusion

We observed a significant proportion of microscopic colitis in patients with NSCLC, while UC-like colitis was equally distributed in the other forms of neoplasia.

Men are at higher risk to develop anti-PD-1 induced MC in NSCLC, rather than women.

Anti-PD-1 induced microscopic colitis presents more frequently endoscopic signs of inflammation.
P569 Can thiopurines prevent crohn’s disease endoscopic postoperative recurrence in at risk patients?
Authors: Chehaider A , Serghini M , Labidy A , Ben Mustapha N , Fekih M , Boubaker J
Published: January 2023

Background

Postoperative relapse (POR) of Crohn’s disease (CD) is frequent in the absence of prophylactic treatment. Screening for known risk factors allows to stratify patients and consider appropriate therapy. In Tunisia, the cost-effectiveness of thiopurines makes it prescribed even when moderate or high risk of POR. The aim was to describe the efficacy of thiopurines in preventing endoscopic POR in patients at risk.

Methods

We conducted a retrospective study enrolling CD patients who underwent curative ileo-caecal resection and received thiopurines to prevent POR. They all had at least one risk factor for POR knowing: smoking, fistulizing phenotype, extensive ileal resection (≥ 50 cm), previous bowel resection. The risk was moderate in the presence of one risk factor and high if at least two factors. Patients with a follow-up less than 6 months were excluded. All patients had undergone ileocoloscopy to screen for endoscopic POR wich was stratified according to the Rutgeerts score. Endoscopic POR was defined by a score ≥ i2 and was severe if score ≥i3.

Results

Thirty nine patients were included with a sex ratio M/F =1.8 and a mean age of 31 years. CD was ileal and ileocolic in 92.3% and 7.7% respectively, with perineal involvement in 7.2%. The mean extent of ileal resection was 39.7±4 cm. The ileal and colonic histological margins were pathologic in 17.9% and 7.7% respectively. Risk factors for POR were distributed as follow: Active smoking (28.2%), previous bowel resection (17.9%), fistulizing phenotype (84.6%) extensive resection (35.9%).

The risk was high in 51.3% and moderate in 48.7% of cases. The delay of introduction of thiopurines was on average 31.8±53 days from the restoration of digestive continuity at a mean dose of 2.3 mg/kg and ileocoloscopy was performed at a mean delay of 19.3 months. Rutgeerts' score was as follows: i0, i1, i2, i3 and i4 in 34.7%, 8.2%, 16.3%, 6.1% and 10.2% respectively. Endoscopic POR was noted in 43.6% and was severe in 21.6% of cases.

The cumulative POR rate was 16% at 6 months, 52% at 12 months and 67.5% at 24 months. In univariate analysis, factors associated with endoscopic POR on thiopurines were male gender (p=0.012), laparotomy (p=0.02), the extent of ileal resection and extensive ileal resection (p=0.003). In multivariate analysis, the factors retained were male gender with an OR=11 (p= 0.024) and the extent of ileal resection with an OR=1.05 (p=0.02). Time to introduction of thiopurines, fistulising phenotype and smoking did not significantly influence the risk of POR.

Conclusion

Thiopurines would be able to prevent endoscopic POR in more than half of the patients at risk. However, anti-TNF therapy should be indicated immediately in males and in cases of extended ileal resection.
P572 Coexisting Inflammatory bowel disease and Ankylosing spondylitis: Management and clinical outcomes
Authors: Savin E , Levartovsky A , Gendelman O , Lidar M , Ben-Horin S , Kopylov U
Published: January 2023

Background

Ankylosing spondylitis (AS), which occurs in about 10% of inflammatory bowel disease (IBD) patients, is more common in Crohn's disease and does not correlate with bowel activity. The occurrence of IBD in patients with AS is 5-10%. We aimed to investigate the patterns of treatment modifications following newly diagnosed AS in patients with IBD or a new IBD diagnosis in patients with AS.

Methods

This is a retrospective observational study that included patients with coexisting IBD and AS that were followed simultaneously by the gastroenterology and the rheumatology departments of the Sheba Medical Center. Patients with a follow-up duration of at least 3 months since the second diagnosis were included.

Results

The cohort consisted of 68 patients, 41 with a first diagnosis of IBD (fIBD-group) and 27 with a first diagnosis of AS (fAS-group). Patients in the fAS-group were younger (median age of 36 years, inter quartile range (IQR) 25-48 vs. 43 years IQR 35-56, p=0.043), had more Crohn's disease (92.6% vs. 68.3%, p=0.016), had a shorter interval up to the second diagnosis (median of 3 years, IQR 1-6 vs. 6 years, IQR 2-11.5, p=0.03), and had an increased rate of past/current biologic treatment (81% vs. 51%, p=0.019) compared with the fIBD-group. Therapy modifications rates were 78% in the fIBD-group and 96% in the fAS-group as presented in Figure 1. The most common modification for the fIBD-group was initiation of biologic therapy in 18/32 patients (Adalimumab 44%, Infliximab 33%, Golimumab 5.75%, Etanercept 5.75%, Certolizumab pegol 5.75%, Ustekinumab 5.75%). In the fAS-group, switching biologic agent to Adalimumab or Infliximab (42%) and ceasing NSAIDs (27%) were the most common.

At 1-year follow-up there were no significant differences in clinical outcomes (treatment failure, surgery/hospitalization, clinical remission) between fIBD and fAS groups. However, patients in both groups with treatment modifications, had a trend for higher rate of IBD clinical remission than patients without (72% vs. 40%, p=0.066). No difference was found in AS clinical outcome.

Conclusion

Treatment modifications are common among newly coexisting IBD and AS patients, preferably biologic drug modifications. These modifications may contribute to IBD clinical remission.
P574 Characterization of plasma inflammatory protein abundance in patients with ulcerative colitis treated with etrasimod: an exploratory analysis of the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials
Authors: Siegmund B , Ryan R , Abreu M T , Vermeire S , Dotan I , Goetsch M , Crosby C , Woolcott J , Komori H K , Danese S
Published: January 2023

Background

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5) in development for the treatment of moderately to severely active ulcerative colitis (UC). To better understand how etrasimod reduces inflammation and induces clinical remission, the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials included a per protocol exploratory analysis of peripheral blood inflammatory proteomics, the results of which are presented here.

Methods

In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). Plasma was collected at baseline and week 12 for both trials and week 52 for ELEVATE UC 52. Characterization of plasma inflammatory protein abundance and changes in abundance over time were assessed by proximity extension assay using the Olink Target 96 Inflammation panel. Normalized protein expression and change from baseline by visit were summarized by descriptive statistics; fold changes in Olink measurements were expressed as log2.

Results

Plasma samples were collected and analysed from 238 patients in ELEVATE UC 52 (162 etrasimod, 76 PBO) and 163 patients in ELEVATE UC 12 (108 etrasimod, 55 PBO). While no meaningful changes in protein biomarkers were observed over time in PBO-treated patients, factors modulated by etrasimod included those associated with tissue remodelling (MMP-1, MMP-10), T-cell response (CD5, CD6, CD8A, TNFRSF9), chemotaxis (CCL11, CCL19, CCL28, CX3CL1), and pleiotropic cytokine response (IL-7, IL-17A, IL-10, OSM), with a high degree of overlap and consistency in trends between the two trials (Figure 1). Etrasimod induced statistically significant reductions in circulating inflammatory proteins including IL-17A and OSM at week 12, and these remained decreased at week 52. Decreases in IL-17A and OSM at weeks 12 and 52 correlated with efficacy outcome measures across various clinical subgroups in responders vs nonresponders (Table 1).

Conclusion

In this per protocol exploratory analysis of two independent phase 3 randomised controlled trials, etrasimod induced consistent, statistically significant changes in circulating inflammatory proteins involved in tissue remodelling, T-cell response, chemotaxis, and cytokine response, including IL-17A and OSM. The reduction in activated immune cells in the peripheral blood of responders suggests etrasimod induces a reduction in inflammation that could contribute to remission.
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

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 (>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<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 >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<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

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 < 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 = <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 >150 μg/g at baseline, 33.3% (2/6) achieved FCP <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 >5 at week 0, 60% (3/5) achieved CRP <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

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

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 (<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

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<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<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

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 (<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<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

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

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.
P610 Real-world effectiveness and safety of advanced therapies for the treatment of moderate-to-severe ulcerative colitis (UC): evidence from a systematic literature review (SLR)
Authors: Irving P M , Hur P , Gautam R , Guo X , Vermeire S
Published: January 2023

Background

Since advanced therapies (ATs) for moderate to severe UC are increasing, their effectiveness and safety in real-world (RW) settings should be assessed.

Methods

A SLR was done as per method described by Cochrane Collaboration and PRISMA guidelines, using Embase, MEDLINE and MEDLINE-In Process databases to find RW studies of biologics (adalimumab/ADA, golimumab/GOL, infliximab/IFX, vedolizumab/VEDO and ustekinumab/UST) or small molecules (filgotinib/FIL, ozanimod/OZA and tofacitinib/TOFA) in patients (pts) with UC. Only products approved at the time of search were included. Studies published in English as full papers (Jan-2005–Feb-2022) or congress abstracts (Jan-2019–Feb-2022) were included. Studies with <30 pts or with only bio-naïve pts were excluded.

Results

Of 3930 results, 139 studies were included (18 comparative and 121 single AT). 13% of studies had only bio-exposed pts, 63% had >50% bio-exposed pts and 28% had subanalysis for bio-exposed pts.

Comparative studies of VEDO vs TNF inhibitors (TNFIs; n=10); TOFA vs VEDO (4), TNFIs (3) or UST (1). In comparative effectiveness studies (16), rates of clinical remission (CR) with VEDO were numerically higher vs TNFIs (Fig1). For TOFA vs VEDO, the effectiveness of TOFA in multiple outcomes was numerically (occasionally significantly) greater (Fig2). The study of UST vs TOFA showed similar rates of steroid-free CR (Dalal 2021). In 2 studies, IFX was the most effective TNFI.

Comparative safety studies (14) mostly reported % pts with any/serious adverse events (AEs/SAEs) with limited reporting of incidence of MACE and malignancy. A study showed no significant differences in the risk of SAEs (HR0.899;95%CI0.502–1.612) or serious infections (HR1.235;95%CI0.608–2.511) for VEDO vs TNFIs (Lukin 2022). Two studies showed comparable AE rates for TOFA and VEDO. One study showed that VEDO pts had higher chance of experiencing AEs than TOFA pts (OR1.83;95%CI1.10–3.03) but similar number of SAEs (OR0.39;95%CI0.03–4.33; Straatmijer 2022). A study of TOFA vs UST showed similar overall AE rates (Dalal 2021). AE rates for TNFIs were comparable.

In single AT studies (VEDO n=50, TOFA 24, ADA 18, GOL 14, IFX 10, and UST 5), % of pts with CR and AEs/SAEs varied widely.

No studies were found for FIL and OZA.

Conclusion

In comparative studies of largely bio-exposed pts, CR rates with TOFA were generally numerically higher vs VEDO and comparable with UST; and numerically higher for VEDO vs TNFIs. IFX was most effective TNFI. SAE rates were similar across ATs. The results should be interpreted cautiously due to varied baseline characteristics though few studies were propensity scores matched. More comparative studies are needed as CR in single AT studies varied widely.
P619 Inflammatory bowel disease meets fertility: a physicians and patients survey
Authors: Vieujean S , De Vos M , D’Amico F , Paridaens K , Daftary G , Peyrin-Biroulet L , Danese S
Published: January 2023

Background

Inflammatory bowel diseases (IBD) affect patients during their childbearing years. Literature evidence is scarce regarding the level of knowledge among health care professionals (HCPs) and patients out the impact of IBD on fertility. The aim of this survey was to investigate HCPs' and patients' knowledge on fertility, pregnancy, and sexual function, to evaluate how HCPs approach this topic and to report patients’ reproductive outcomes.

Methods

Subjects were invited to anonymously complete an online questionnaire collecting data on demographics, patients' disease characteristics, Crohn's and colitis pregnancy-specific disease-related knowledge (CCPKnow), family planning, reason of childlessness, pregnancy outcomes, need for assisted reproductive technology, impact on sexual function, and availability of patients’ information regarding IBD and pregnancy.

Results

A total of 257 HCPs from 40 countries and 793 patients (615 females, 176 males and 2 who preferred not to disclose their gender; 396 (50%) with ulcerative colitis, 381 (48%) with Crohn’s disease, 14 (1.8%) with undetermined IBD) from 4 countries completed the survey. The characteristics of participants are listed in Table 1. In total, 98.4% of HCPs had good or very good pregnancy-specific knowledge according to CCPKnow score, compared to only 29.3% of patients. Of the women surveyed, 56.3% had no children (14.1% due to a voluntary choice). A total of 427 pregnancies and 401 live births were reported in 266 women. Twenty-four pregnancies (5.6%) in 22 women required assisted reproductive technologies (ART). There were no more complications in pregnancies resulting from ART compared with spontaneous conception (5/24; 20.8% vs 211/401; 52.6%). Three quarters of IBD patients (75.6%) had breastfed. An impaired sexual function was found in one-fifth (21.9%) of men with IBD, while two-thirds (66.1%) of the women reported sexual function impairment. Surprisingly, 63% of patients reported not having received any information about IBD and pregnancy, and only 10% of patients had received information from their IBD specialist. In addition, 42.1% and 36% of HCPs had already referred a patients to a medically assisted reproduction centre to receive general information about their reproductive health and about options of fertility preservation (e.g., cryopreservation), respectively.

Conclusion

IBD patients have a poor knowledge about the impact of IBD on fertility and pregnancy and HCPs does not sufficiently inform their patients. More information on these topics is needed for IBD patients.
P620 Can ustekinumab trough and antidrug antibody levels post induction predict treatment failure?
Authors: Mccrossan M , O’Moráin N , Kumar L , Rowan C , Sheridan J , Cullen G , Doherty G , Mulcahy H
Published: January 2023

Background

Ustekinumab (UST), a monoclonal antibody that blocks interleukins IL-12 and IL-23, is increasingly used in the treatment of Crohn’s disease and Ulcerative Colitis. While therapeutic drug monitoring (TDM) is used with increasing frequency in other biologic agents, there is a paucity of data regarding the clinical utility of TDM for UST. This pilot study aimed to determine whether loss of response (LOR) and treatment failure (TF) can be predicted by post UST-induction serum trough concentrations and antibody levels.

Methods

A pilot retrospective observational study of patients who received subcutaneous (SC) induction of UST, following LOR to anti-TNF, for treatment of Crohn’s disease in 2016 was performed. We previously demonstrated comparable drug trough levels following SC rather than intravenous UST induction. Patients with available 74 month follow up data were included. Frozen serum samples used for this measurement were retrospectively tested for antibody levels using ELISA. Our IBD database and admissions data were analysed from 2016-2022. We recorded treatment duration, interval shortening, and treatment failure. Treatment failure was defined as switch to another biologic agent and/or surgery. Data were analysed using SPSS software [IBM], with Wilcoxon Rank Sum Test used for hypothesis testing.

Results

In this pilot study, a total of 10 patients (female=1, mean age 38.5 y) met the inclusion criteria. During the 74 month follow-up period, 3 patients failed treatment (mean age 30 y) while 7 remained on UST (mean age 42 y). All patients required interval shortening (4 weekly dosing). There was no difference in Crohn’s phenotype or smoking status between groups. All TF patients were switched to alternative biologic agents, with 1 patient requiring surgery. The patients who failed treatment were noted to have higher antibody levels (median 6.57 Au/ml vs 5.87 AU/ml, p=0.03) [Fig 1]. Two of these patients were noted to have lower trough levels than those who continued on UST, with one having a higher trough level (median 2.9mcg/ml vs 5.8mcg/ml, p=0.52) [Fig 2].

Conclusion

Shortening of dose interval with UST therapy in Crohn’s disease is frequently required. This pilot study suggests an association between treatment failure and higher antidrug antibody levels 8 weeks post induction of UST. There was no significant difference in drug trough levels between groups. The patient with the highest trough level in the cohort failed treatment – This raises the possibility of multiple mechanisms of failure; however, it is impossible to draw conclusions given the sample size. Further studies are required to assess whether measurement of post induction antibody and drug trough levels has clinical utility in guiding treatment decisions.
P622 Change in Dietary Inflammatory Index Score in patients with Crohn’s disease and healthy volunteers following the Groningen Anti Inflammatory Diet (GrAID)
Authors: Barth I , Stevens C L , Dijkstra G , Campmans-Kuijpers M J E
Published: January 2023

Background

Dietary patterns play an important role in Inflammatory Bowel Disease (IBD). The Dietary Inflammatory Index (DII) is a diet quality score that estimates the inflammatory potential of a dietary pattern on inflammatory markers. Recently, the Groningen Anti-Inflammatory Diet (GrAID) was developed to improve disease course in patients with IBD. The aim of this study is to investigate whether following the GrAID improves diet quality based on the DII compared to baseline intake in patients with Crohn’s disease (CD) and healthy volunteers (HV).

Methods

Between October 2021 and October 2022, patients with CD and HV completed a 12-week GrAID intervention as part of an ongoing trial: VITA-GrAID (NCT04913467). In this sub analysis, nutrient intake from a 3-day food diary was calculated at baseline (T0; habitual diet) and after 12 weeks (T3; following the GrAID), using Evry software (version 2.3.7.0). From both intakes the DII score according to the Shivappa method was calculated, based on 28 food parameters. Next, both scores were compared to the DII score of the GrAID, calculated assuming complete adherence to the GrAID. A lower DII score is regarded to having a higher anti-inflammatory potential. Paired nonparametric tests (Wilcoxon signed-rank) were performed to calculate differences between T0 and T3. Data were analysed using R (2021.09.0) and IBM SPSS Statistics 28.

Results

Eighteen individuals completed the 12-week GrAID intervention (12 patients with CD; and 6 HV) (table 1). Between T0 and T3, significant increases were found in fibre (16.5g), total protein (21g), total plant protein (14g), vitamin B2 (0.29ug) and beta carotene (1837ug) intake. Significant decreases were found in mono- and disaccharides (-18g), alcohol (- 5.3g), and sodium (-875mg) intake (Table 2). The median DII score at T0 was -0.112, IQR: [-1.269; 1.362] and was significantly lower at T3 (median: -2.040; IQR [-2.588; -1.417], p<0.05) (figure 1). Median DII score in patients with CD differed significant between T0 and T3 (0.323, IQR [-1.3897; 1.523] and -2.040, IQR [-2.665; -1.549] respectively, p<0.05), but not in HV (-0.692, IQR [-1.127; 0.566] and -1.998, IQR [-2.441; -1.336] respectively, p=0.09) (Figure 2).

Conclusion

These preliminary results show that diet quality improved in patients with CD after following the GrAID for 12 weeks. For HV, probably more participants are needed. Further research is necessary to determine whether a lower DII score will actually improve the disease course of patients with CD and the diversity of the microbiome in HV.
P626 Safety of recombinant zoster vaccine in patients with Inflammatory Bowel Disease: a single centre experience
Authors: Todeschini A , Geccherle A , Signoretto P , Variola A
Published: January 2023

Background

Patients with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. However, vaccination rates for HZ are low among IBD patients. Although the safety of recombinant zoster vaccine (RZV) are high among immunocompetent individuals, there are only few data in IBD patients treated with immunomodulating drugs. This study aims to evaluate safety of recombinant zoster vaccine in IBD patients.

Methods

This is a retrospective study among IBD patients after RZV vaccination. RZV was administrated to 31 IBD patients. Afterwards completed vaccination, telephone or in-person interviews were conducted to report adverse events (AEs) related to vaccination. Data on medical history and treatment was collected from electronic health records.

Results

32 patients, 12 CD and 20 UC, were enrolled. 77% received a complete RZV vaccination cycle. The vast majority of patients (97%) were in biological or immunomodulatory therapy and 80% had previous HZ infection. About 30% of patients had at least one side effect. Local pain at site of injection (27%) and fever (47%) were the most common AEs. Flares of the underlying IBD were not reported. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported.

Conclusion

The short-term vaccine reactions experienced in this cohort of IBD patients were self-limited, including local pain at the injection site and fever. We found a good safety profile of RZV vaccination in our cohort.