bluuebunny/crossref_metadata_2025 huggingface dataset:
P798 Study of the concordance between the enzymatic activity of Thiopurine S-methyltransferase and polymorphisms in the TPMT gene in patients with Inflammatory Bowel Disease
Authors: Céspedes Martínez E , Robles-Alonso V , Castellote L , Bravo-Nieto D , Serra X , Herrera-De Guise C , Mayorga L , Pérez Z , Oller E , Garriga-Edo S , Casellas F , Borruel N
Published: January 2024

Background

Thiopurine therapy is associated with an increased risk of serious adverse events in patients with Inflammatory Bowel Disease (IBD). Thiopurine S-methyltransferase (TPMT) is the enzyme responsible for metabolism, and its determination helps identify patients at risk of toxicity. This study aims to explore the level of correspondence between the TPMT genotype and enzymatic activity (phenotype) with the objective of preventing adverse events prior to the commencement of thiopurine therapy.

Methods

Consecutive patients with IBD, Crohn’s Disease (CD) or Ulcerative Colitis (UC), were included. Genotype was conducted for the most prevalent TPMT variants (TPMT*2, TPMT*3B, TPMT*3C), TPMT enzymatic activity assessment, and quantification of 6-thioguanine nucleotide (6-TGN) levels. Adverse effects were documented, along with the administration of biologics, mesalazine, ACE inhibitors or allopurinol. The primary objective was to evaluate the concordance between TPMT genotype and phenotype. Secondary objectives included determining the prevalence of genotype and phenotype within our patient cohort, 6-TGN serum levels, the prevalence of adverse events and identifying potential pharmacological inducers of the phenotype.

Results

A total of 218 patients were included (131 with CD and 81 with UC). Thirteen patients did not initiate thiopurines, and 34.63% (71/205) had discontinued treatment. The most observed adverse events were myelotoxicity (15.12%), gastrointestinal toxicity (12.20%), and hepatic toxicity (5.37%). TPMT activity exhibited a trimodal distribution, with 87.61% (191/218) having normal activity, 11.47% having intermediate activity, and 1% having low activity. Genotypically, 90.83% (198/218) had a wild-type genotype, 8.72% (18/218) had a heterozygous genotype, and 0.5% (1/218) had a homozygous genotype. The concordance index between phenotype and genotype was calculated at 0.57. Significantly, myelotoxicity was associated with the presence of genotypic variants (p=0.004). 6-TGN levels did not correlate with TPMT activity and concurrent medications did not affect TPMT activity .

Conclusion

The proactive assessment of TPMT (phenotype or genotype) before initiating thiopurine therapy effectively mitigates the occurrence of myelotoxicity in IBD patients. Importantly, the level of concordance between TPMT activity and genotype is moderate, with genotyping serving as the more reliable approach for preselecting patients susceptible to myelotoxic reactions.
P811 Age as a Predictor of Serum Tumor Necrosis Factor Antagonist Drug and Anti-drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Retrospective Study
Authors: Shehab M , Alrashed F , Alfadhli A
Published: January 2024

Background

Tumor necrosis factor antagonists (anti-TNFs) are effective for the induction and maintenance of remission in inflammatory bowel disease (IBD). Several factors have been shown to be associated with anti-TNF treatment failure. We aim to investigate the relationship between age and serum anti TNF drug and Anti-drug Antibody Concentrations

Methods

This was a multicenter retrospective cohort study. Chart review was conducted by evaluating patients' charts from July 2018 until September 2023. The impact pf age on anti-drug antibodies and serum drug concentration in patients with IBD across seven hospitals was investigated. Logistic regression was performed to explore the relationship between age and serum anti TNF drug and Anti-drug Antibody Concentrations (ADAbs)

Results

1093 patients were included, of which 911 (83.3%) were above the age of 16. Mean age was 30.1 years old and 574 (52.2%) were males. 461(42.2%) patients were on infliximab and 632 (57.8%) patients were on adalimumab. In patients receiving infliximab, there was a significant association between older age and increasing ADAbs levels (p =0.036). Whereas in patients on adalimumab, there was no significant relationship between older age and ADAbs levels (p=0.771). Additionally, there was a significant association between older age and decreasing infliximab serum concentration (p = 0.02). Finally, there was no significant relationship between age and adalimumab serum concentration (p = 0.54).

Conclusion

In patients receiving infliximab, anti-drug antibodies were higher in older patients. Consistent with this, serum drug concentrations were lower in older patients on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among patients receiving adalimumab.
P813 A questionnaire-based study on fatigue and associated factors in Inflammatory Bowel Disease
Authors: Jeong N , Lee H H
Published: January 2024

Background

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue, and associated factors, in patients with IBD.

Methods

A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Demographic, clinical, and laboratory data were collected. Disease activity was assessed by the Mayo score or Crohn’s Disease Activity Index, as appropriate. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale

Results

Among 97 ulcerative colitis and 50 Crohn’s disease patients, the mean total MFI-K score was 59.0 ± 5.5. Age, sex, body mass index, disease duration, anemia, hypoalbuminemia, and use of steroids did not affect the total MFI-K score. The anxiety and depression scores did not correlate with the fatigue score. Moderate and high disease activity significantly increased the MFI-K general and physical fatigue subscale scores compared to remission and mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, P = 0.009), while the use of biologics significantly decreased the total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, P = 0.031). Multiple linear regression showed that fatigue was significantly increased by a history of surgery for IBD and decreased by the use of biologics.

Conclusion

The degree of fatigue in patients with IBD is high, and disease activity is the most important contributing factor.
P858 Real World Outcomes of Dual Advanced Therapy in Inflammatory Bowel Disease in Children and Young Adults
Authors: Kellar A , Dolinger M , Spencer E , Dubinsky M
Published: January 2024

Background

There is mounting interest in dual advanced therapy (DAT), combining 2 biologics or biologics with small molecules, in patients with refractory disease or partial responders. We evaluated the real-world efficacy and safety of DAT in pediatric and young adults with IBD.

Methods

Single-center, cross-sectional cohort study, conducted between 2018-2023. Primary outcome was DAT remission (clinical (Harvey Bradshaw Index ≤ 4 or partial Mayo Score ≤ 2) and biomarker (C-reactive protein ≤ 5 mg/L and/or fecal calprotectin ≤ 250 ug/g) at first efficacy assessment (T1). Secondary outcomes included remission at T2 if intensification or de-intensification occurred at T1 and T3 remission if re-intensification performed at T2. Failures defined those not achieving remission. Adverse events, surgical and therapy outcomes as of last follow up were evaluated. Descriptive statistics summarized the data.

Results

30 patients were included [43% female, 57% CD, median age of 18.3 [15.1-19.8] years, 46% <18 years, and median IBD duration of 5.2 [4.0-6.9] years at DAT start] (Table 1). Of 11 (37%) treated with TOFA + UST, 100% achieved T1 remission. Of the 10 de-intensified at T1, 6 failed at T2, and all 4/6 that re-intensified achieved T3 DAT remission. Of 9 (30%) TOFA + VDZ patients, 6 (67%) achieved T1 remission and of the 3 T1 failures, 1 had colectomy, and 1 of 2 attempting VDZ intensification achieved T2 remission. All 6 with T1 remission de-intensified, but 5 (83%) failed and only 1/5 attempted re-intensification and failed. Of 4 (13%) VDZ + UST patients, 3 (75%) achieved T1 remission and the 1 T1 failure achieved T2 remission after VDZ intensification. The 2/4 de-intensified failed at T2 and none were re-intensified. Of 5 (17%) UPA + UST patients, 4 (80%) achieved T1 DAT remission and the 1 failure achieved T2 remission after UPA intensification. The 1 who de-intensified failed at T2 but in T3 remission post re-intensification. One (3%) VDZ + OZA patient achieved T1 remission and successfully de-intensified to monotherapy OZA at T2. One TOFA + UST patient developed mild leukopenia and responded to TOFA de-intensification, and 1 developed septic arthritis on TOFA +VDZ on prednisone and resumed TOFA once resolved. At last follow-up, 14/30 (47%) patients were on DAT, 11 (37%) changed therapy, 1 of which underwent colectomy and 5 (17%) were on monotherapy (Figure 1).

Conclusion

The majority of IBD patients treated with DAT achieved clinical and biomarker remission with minimal safety events; however, de-intensification to monotherapy has limited success and supports continuing DAT in more refractory patients. Future studies are needed to guide management.
P860 Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis - a six-year follow-up study
Authors: Gros B , Ross H , Nwabueze M , Constantine-Cooke N , Derikx L A , Lyons M , O'Hare C , Noble C , Arnott I D , Jones G R , Lees C W , Plevris N
Published: January 2024

Background

Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years.

Methods

We performed a retrospective, observational, cohort study. All adult IBD patients who had received VDZ induction for UC/IBDU were included. Baseline phenotype and follow-up data were collected via review of electronic medical records.

Results

We included 290 patients (UC n=271 [93.4%], IBDU n=19 [6.6%]) with a median time on VDZ of 27.6 months (IQR 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. Median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ≥1 advanced therapy, steroid use at baseline; and disease extension were independent predictors for VDZ persistence (Table 1). Clinical remission (partial Mayo <2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at year 1,3 and 5 respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up.

Conclusion

VDZ persistence is influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline. VDZ effectiveness is enduring with favourable long-term safety profile.
P875 Filgotinib in ulcerative colitis: early real-world multicentre UK experience
Authors: Young D , Rahmany S , Taylor D , Davis E , Campbell R , Hazel K , Sethi-Arora K , Ritchie S , Dhar A , Limdi J , Cooney R , Seenan J P , Walsh A , Cummings F
Published: January 2024

Background

Phase 3 RCTs recruit a carefully selected population to demonstrate efficacy which may not reflect the population treated in clinical practice. We aimed to describe the use and effectiveness of filgotinib in a large UK real-world cohort of ulcerative colitis (UC) patients.

Methods

A retrospective observational cohort evaluation was conducted across six UK IBD centres. Baseline demographic and clinical data (including risk factors for serious adverse events and prior advanced therapy exposure), clinical (Simple Clinical Colitis Activity Index or Partial Mayo score) and endoscopic activity indices, and laboratory parameters (CRP and faecal calprotectin) were collected at baseline, 8 to 12 weeks after initiation (post induction), and during maintenance (the most recent review).

Results

A total of 216 patients are included in this analysis from May 2022 to November 2023 (mean follow-up period 202 days). The median [IQR] age at filgotinib initiation was 38 [27, 50] years (eight ≥65 years), 139 (64%) were male and median disease duration was 5.3 [1.9, 11.1] years. Disease extent (n=204) was: E1: 23 (11%), E2: 78 (38%) and E3: 103 (50%). 77 (36%) patients were naïve to advanced therapy; 66 (31%), 40 (18%), 25 (11%) and 8 (4%) patients had prior exposure to 1, 2, 3 or 4 advanced therapy modes of action(s) respectively, including 17 (8%) patients with prior exposure to tofacitinib. 48 (22%) patients had at least one risk factor included in the EMA warning. Of 137 patients who had endoscopic assessment at baseline, 56 (41%) and 20 (16%) had moderate or severe disease respectively. The median baseline faecal calprotectin and CRP were 800 [464, 1800] µg/g and 4 [1, 11] mg/L respectively. 82 (49%) were on concomitant corticosteroids at baseline (n=166).

Cumulative probabilities of filgotinib persistence were 86%, 76% and 58% at 3, 6 and 12 months respectively (figure 1A). Prior exposure to multiple advanced therapies or tofacitinib did not appear to impact persistence (p=0.3 and 0.08 respectively). Reasons for filgotinib discontinuation are shown in figure 1B. There was a significant improvement in the disease activity scores in patients continuing filgotinib (figure 1C). In the cohort with prior tofacitinib exposure (11 failed to respond or lost response to tofacitinib), 7 remain on filgotinib with a median duration of 281 days.

Eight patients discontinued filgotinib due to adverse events including one episode of venous thromboembolism.

Conclusion

In a large real-world cohort of UC patients, filgotinib appears to be effective and well-tolerated.
P883 Impaired long-term quantitative cellular response to SARS-COV-2 vaccine in thiopurine-treated IBD patients
Authors: Mayorga Ayala L F , Herrera-deGuise C , Esperalba J , Martinez-Gomez X , Céspedes Martinez E , Serra Ruiz X , Robles V , Lastiri E , Perez Z , Oller E , Fernandez-Naval C , Martinez-Gallo M , Casellas F , Borruel N
Published: January 2024

Background

SARS-CoV-2 mRNA vaccine induces a robust immune response in most patients with inflammatory bowel disease (IBD). However, humoral short-term response appears to be reduced in patients receiving anti-TNF agents or tofacitinib, even after booster doses. Data on long-term immune response is limited. We aimed to assess short and long-term humoral and T-cell response to SARS-CoV-2 mRNA vaccine in IBD patients receiving anti-TNF and/or thiopurines.

Methods

A prospective, longitudinal study was carried out in IBD patients receiving thiopurines, anti-TNF mono, or combo therapy. Patients had received between 2 and 4 doses of mRNA SARS-CoV-2 vaccine. Cellular and humoral response to the vaccine was assessed by serum interferon-gamma release assay (IGRA) and antibody SARS-CoV-2, respectively. We defined short-term response as humoral and T-cell response six weeks after the second vaccine and long-term response 6 to 12 months after that. Primary outcome was to determine if T-cell immune response differs in IBD patients receiving anti-TNF versus thiopurines.

Results

We recruited 148 IBD patients, 57 treated with anti-TNF monotherapy, 53 with anti-TNF combo, and 38 with thiopurines. Short-term T-cell and humoral responses were similar between the three groups. However, long-term T-cell concentration was reduced in thiopurine-treated (median 0.7 UI/mL [0.26-2.35]; p<0.05) and anti-TNF-combo-treated patients (median 0.4 UI/mL [0.22-1.13]; p<0.01) when compared to anti-TNF monotherapy (median 2.2 UI/mL [1-4.15]). Multivariate analysis showed that anti-TNF monotherapy (-0.93, p<0.05) and decreased time between vaccination and T-cell response measurement (0.04 [.00005-.078] p=0.05) were associated with increased T-cell concentration long-term when compared to the other groups of patients.

Conclusion

We found a diminished long-term quantitative cellular response in our cohort of IBD patients vaccinated for SARS-CoV-2 treated with thiopurines or combo therapy compared with anti-TNF monotherapy. These findings highlight the recommendation to receive booster doses in IBD patients, specially those receiving thiopurines.
P965 Ulcerative proctitis treated with biologics: is it too hard to treat?
Authors: Bertani L , Tricò D , Barberio B , Bretto E , Ceccarelli L , Calabrese F , Pasta A , Bertin L , Fabiana Z , Maniero D , Frara S , De Bernardi A , Bodini G , Ribaldone D G , Costa F , Savarino E V
Published: January 2024

Background

Patients with ulcerative proctitis are widely considered a challenging population because the reported reduced response rate to conventional medical treatment. On the other hand, data on the role of biological therapies in this specific cohort are currently scarce

Methods

We retrospectively evaluated all patients with proctitis (defined as the mucosal inflammation of only the rectum with ulcerative colitis confirmed by histology) treated with biologics (infliximab, adalimumab, vedolizumab -VDZ-, ustekinumab -UST) and tofacitinib (TOFA) at four referral centers in the last 5 years. All patients were treated with concomitant topical mesalamine. We included in this study only patients who underwent colonoscopy at baseline and after 52 weeks of treatment, in order to evaluate therapeutic response in terms of mucosal healing (defined as a Mayo Endoscopic Score -MES- <2), besides that clinical remission (defined as a Partial Mayo Score -PMS- <2 without oral or topical corticosteroid therapy). We collect clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and after the induction of therapy

Results

Among 64 patients enrolled (age 50.8±16.5 years, 29 [45.3%] women), 33 (51.6%) were treated with anti-TNF), 15 with VDZ, 13 with UST, and 3 with TOFA. Globally, 51 (79.7%) patients achieved clinical remission and 37 (57.8%) patients achieved endoscopic remission at 52 weeks. There were no group differences in age, sex, BMI, disease duration, PMS, MES, drug, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [IQ range] 297 [158, 475] versus 442 [230, 1545] µg/mL, p=0.036), but not in those who achieved clinical remission. After the induction phase, lower calprotectin levels were observed in patients achieving clinical (46 [15, 166] versus 553 [72, 1649] µg/mL, p=0.001) and endoscopic remission (38 [15, 112] versus 328 [52, 2171] µg/mL, p=0.0002), compared with non-responders. The effects of post-induction calprotectin levels on clinical remission (β= -0.001, p=0.020) and endoscopic remission (β= -0.007, p=0.006) remained significant in multivariable models adjusted for age, sex, BMI, disease duration, and biological treatment. A cut point of 200 µg/mL post-induction was identified to predict endoscopic remission (sensitivity 92%, specificity 64%, ROC AUC 0.781)

Conclusion

High rates of clinical and endoscopic remission with biological therapies could be achieved in patients with ulcerative proctitis. Fecal calprotectin levels after the induction of biological therapies seem to predict the therapeutic response in patients with ulcerative proctitis
P970 Iatrogenic adrenal insufficiency on discontinuation of glucocorticoid treatment in children and adolescent patients with inflammatory bowel disease: to screen or not to screen?
Authors: Chadokufa S N , Huggett B , Lashley C , Buckingham R , Sawney T , Kiparissi F , Gaynor E , Huggett Bonita
Published: January 2024

Background

Glucocorticoids are a mainstay of inflammatory bowel disease (IBD) treatment, with oral tapering courses frequently used to induce remission or limit flares. Iatrogenic adrenal insufficiency (AI), due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an established side effect of exogenous glucocorticoids. The rate of AI in this population is unknown. There is no standard guidance to suggest routine screening in paediatric IBD (pIBD). This study aimed to better understand the rates of AI with a screening and management protocol developed for pIBD patients given glucocorticoid therapy (GT)

Methods

All patients with IBD under 18 years treated with GT (prednisolone) for 3 weeks or longer from March 2022 to August 2023 were identified. Patients on other GT were excluded. Patients were screened for AI by serum early morning cortisol (Vitros Ortho Clinical Diagnostics immunoassay) and ACTH, and if indicated underwent standard short synacthen(SST) testing. Adrenal axis function was divided into normal allowing cessation of GT, or impaired response requiring hydrocortisone maintenance therapy (see figure1). A serum morning cortisol >250nmol/l indicated a normal adrenal axis; whereas dynamic adrenal axis testing was recommended for cortisol of 175-249 nmol/l. Those with cortisol <175nmol were diagnosed with AI and started on maintenance hydrocortisone. Repeat testing with SST was performed 3 monthly to reassess the adrenal-axis. Patients with an abnormal SST at the 6-month mark were referred to endocrinology

Results

14 subjects were identified (8 male),7 with Ulcerative colitis, 4 with Crohn’s disease, 1 with IBD-U,2 with early-onset IBD. Median age at diagnosis was 10 years (range 8 months -14 years). Duration of GT was for an average 3 months (range 6 - 16 weeks). 42%(n=6) initiated GT with IV methylprednisolone before switching to 2mg/kg oral prednisolone (maximum 40mg) for 2 weeks, weaning 5mg every week. At the end of initial GT, morning cortisol was deficient in 42% (n=6), insufficient in 35% (n=5) requiring SST. Of those undergoing a SST at this stage, 60% (n=3) had a normal response, 40% (n=2) demonstrating AI. Overall, 57% (n=8) had significant AI at the end of initial treatment. Repeat adrenal axis testing was offered at 3 months (5 of 8) and at 6 months (4 of 4). AI was noted in 100% and 75% at 3 and 6-month respectively. No child suffered an adrenal crisis during the study period

Conclusion

AI following glucocorticoid therapy is common in this small cohort. Screening for AI should be considered in pIBD patients receiving conventional doses of glucocorticoids longer than 3 weeks, with appropriate advice given. The incidence and risks of iatrogenic adrenal insufficiency (AI) requires further investigation
P973 Real-world data on the effectiveness on IBD of anti-IL23 drugs prescribed for psoriasis indication
Authors: Ribaldone D G , Palumbo A , Cariti C , Susca S , Merli M , Saracco G M , Quaglino P , Dapavo P , Vernero M
Published: January 2024

Background

There is a significant association between psoriasis and IBD, which share the pathogenic role of IL-23. In the dermatological field, drugs targeting the p19 subunit of IL-23, such as risankizumab, guselkumab, and tildrakizumab, have been approved for the treatment of moderate to severe psoriasis. However, there are still no real-life data on the efficacy and safety profile of IL-23 inhibitors in patients with IBD.

Methods

A prospective, single center observational study was conducted on patients with IBD and psoriasis from April 2021 to March 2023 at the gastroenterological-dermatological outpatient clinic at “Città della Salute e della Scienza of Turin”, Italy. Patients received a dermatological indication to start drug therapy with IL-23 inhibitors according to the dermatological dosing schedule. They were treated either with guselkumab subcutaneously at a dose of 100 mg every 8 weeks, or with risankizumab subcutaneously at a dose of 150 mg every 12 weeks, or with tildrakizumab 100 mg every 12 weeks subcutaneously. Objectives of this study included evaluating the achievement of clinical remission at 3, 6, and 12 months, defined as disease activity with Harvey-Bradshaw Index (HBI) < of 5 in CD and pMAYO < of 2 in UC.

Results

At 3 months after the start of drug treatment, clinical remission was achieved by 73.3% of patients (p=0.006). This number also remained almost constant at 6 (62.4%, p=0.008) and 12 months (60.3%, p=0.04). In addition, there was a statistically superior steroid-free clinical remission compared to T0 at 3 (15.3% vs 73.3%, p=0.006) and 6 months (7.1% vs 54.1%, p=0.04). No major side effects were reported. Two cases of arthralgias (11.8%) and one case of fever with chills (5.9%) were reported. IL-23 inhibitors appear to be effective in maintaining the steroid-free clinical remission. In addition, there was a reduction in fecal calprotectin values to a median value at 6 months of 81.0 (95%IC= 28.2-249.8; p=0.03) from a median value at T0 of 343.1 (95%IC= 44.8-869.7). The maintenance rate of IL-23 inhibitors therapy at the end of follow-up was 75.8%.

Conclusion

In this study risankizumab, guselkumab, and tildrakizumab appear to be effective in inducing clinical remission and steroid-free clinical remission in patients with IBD. In addition, they appear to be effective in maintaining steroid-free clinical remission. IL-23 inhibitors demonstrated a good safety profile in patients with IBD. Despite the limitations of the study with the need to publish further real-world data on a larger scale and with higher dosing of IL-23 inhibitors, the results obtained are promising as they, for the first time, provide real-life support for the clinical potential of these drugs as treatment for IBD in addition to psoriasis.
P977 Combined F18-FDG-PET-MRI-imaging can predict clinical remission in small bowel Crohn’s disease
Authors: Mattila J , Kallio J , Nuutila P , Koffert J
Published: January 2024

Background

Diagnostics and follow-up of small bowel Crohn’s disease (CD) can be difficult. Combined PET-MRI enterography (MRE) can be used to evaluate intestinal inflammation. Lack of standardized methods and diagnostic thresholds has limited its clinical use in diagnostics and monitoring of small bowel CD. There is no previous data on the use of PET-MRI in follow-up of small bowel CD.

Methods

34 patients with suspected CD in small bowel were recruited from Turku University Hospital’s outpatient clinic. A static PET-MRE was obtained with [18F]-FDG (fluorodeoxyglucose) tracer. CD diagnosis was confirmed with small bowel capsule endoscopy. Patients diagnosed with CD were started with appropriate treatment chosen by clinicians. Endoscopic findings including histopathology, laboratory results (Hb, CRP, serum albumin (Alb) and fecal calprotectin (FC)) and medication data were collected. Patients diagnosed with CD (N=16) went through control PET-MRE median 105 days after initial imaging. Highest SUVmax (standardized uptake value) in small intestine was measured and MRE-images with diffusion weighted imaging (DWI) were analyzed by an experienced abdominal radiologist and severity of inflammation was graded from 1-4. Hb, CRP, Alb and FC were measured from the patients at the time of imaging.

Results

Median SUVmax was significantly lower after three months of medical treatment (3.2 vs. 2.1) (p=0.016). FC was significantly lower at the time of control imaging (p=0.030) (median 725 ug/g vs. 141 ug/g). 10 patients had FC <250 ug/g at the time of control imaging. Using this as a cut- off for clinical response, ROC-curve showed AUC 0.73 for SUVmax and AUC 0.65 for MRE-grading. Sensitivity and specificity were highest at SUVmax 2.4 (83% and 80%).

Conclusion

Decreased SUVmax measured after starting CD medication seems to predict clinical remission and a cut-off level 2.4 could be used in diagnostics. Diagnostic yield was higher for SUVmax compared to MRE-grading. Here we have shown for the first time that PET-MRE can be used for disease activity monitoring in small bowel CD.
P1001 Predictive factors of colectomy in patients admitted with Acute Severe Ulcerative Colitis
Authors: Karpavičiūtė V , Kiudelis G , Kupčinskas J , Kupčinskas L
Published: January 2024

Background

Acute severe ulcerative colitis (ASUC) is a life-threatening condition which requires quick decision making and urgent treatment. To facilitate this process, it is essential to identify patients at a high risk of emergency colectomy. The aim of this study is to identify predictors for emergency colectomy in patients with ASUC.

Methods

A retrospective study of 121 patients admitted with ASUC to a single gastroenterology centre between 2010 and 2020 was performed. Clinical and demographic data, laboratory and endoscopic examinations results were analysed as potential predictors of colectomy. Albumin and C-reactive protein (CRP) levels were recorded at baseline and at the 3rd day after intravenous steroids (IVS) initiation.

Results

119 patients initially received IVS, while 2 patients with suspected intestinal perforation underwent emergency colectomy on the first day. 64 (53%) were women, with a median age of all patients of 33 (IQR 27-49) yrs. 15 (12.4%) patients admitted with ASUC underwent colectomy, while mortality rate during hospitalization was 1.7%. During the entire follow-up period, with a median duration of 46.5 months (23-88.25), colectomy was performed in 19 (15.7%) patients. Overall, in the study group, colectomy rate at 1 month, 3 months and 2 years were 12.4%, 12.4%, and 14.0%, respectively. Assessing further outcomes after colectomy, during the follow-up period, 13 (68.4%) achieved clinical remission, 1 died during the operation, and 5 (26.3%) patients still have an active course of the disease requiring immunosuppressive treatment.

When comparing patients in the colectomy group (n=13) with patients who avoided colectomy during this hospitalization (n=105), no significant differences were found in age, sex, duration of illness, body mass index, endoscopic activity, the use of prednisolone or azathioprine prior to admission or previous treatment with biologics. The presence of cytomegalovirus and Clostridium difficile infection was also not associated with a higher risk of colectomy. Significant differences between the groups were found comparing the laboratory findings: the strongest predictor of colectomy was the CRP/albumin ratio at day 3 after IVS initiation (median value was 1.26 (0,81-3,26) in colectomy group vs. 0,64 (0,25-1,36) in non-colectomy group, p<0.001). The difference was also observed when comparing albumin (median 26 (24-28) vs. 29 (27-32), p=0.012) and CRP (median 33 (25-83) vs. 16 (8-37), p=0.003) levels separately on the 3rd day, while at baseline there was no significant differences in laboratory findings.

Conclusion

A low serum albumin level, higher CRP and CRP/albumin ratio are predictive factors of emergency colectomy in ASUC patients.
P1010 Guselkumab improves abdominal pain and bowel urgency symptoms in patients with moderately to severely active ulcerative colitis: Results from the phase 3 QUASAR induction study
Authors: Rubin D , Panés J , Feagan B , Yarandi S , Huang K H , Germinaro M , Han C , Miao Y , Zhang H , Qiu Y , Klopocka M , Duvall G , Lichtenstein G , Hisamatsu T , Bressler B , Peyrin-Biroulet L
Published: January 2024

Background

Abdominal pain and bowel urgency are prevalent, burdensome symptoms experienced by patients (pts) with ulcerative colitis (UC) that impact daily life, including social activities. In this study, we use data from the Phase 3 QUASAR Induction Study to assess efficacy of guselkumab (GUS) on abdominal pain, bowel urgency, and the impact of bowel urgency on pts’ lives.

Methods

Pts were randomized 3:2 to receive IV GUS 200mg or placebo (PBO) at Weeks (Wks) 0, 4, and 8. Abdominal pain and bowel urgency were evaluated at baseline and Wk12 using items from the Inflammatory Bowel Disease Questionnaire, where pts rated trouble with abdominal pain, symptoms of bowel urgency, and the impact of bowel urgency over the past 2 wks using 7-point scales (1=all of the time to 7=none of the time). A ≥2 point increase from baseline was clinically meaningful improvement. All analyses were prespecified but not multiplicity controlled; all p-values are nominal.

Results

At baseline, percentages of pts with abdominal pain (GUS 77.7% and PBO 77.9%), symptoms of bowel urgency (GUS 86.0% and PBO 83.2%), and impact of bowel urgency (GUS 70.8% and PBO 70.4%) at least a little of the time (score ≤5) were similar between groups. GUS-treated pts showed greater improvements at Wk12 in these outcomes compared with PBO (Table 1). For abdominal pain, 52.0% of GUS-treated pts had clinically meaningful improvements from baseline at Wk12 vs 33.0% in the PBO group (p<0.001), and 21.1% vs 12.3%, respectively, of those with abdominal pain at baseline had resolution at Wk12 (p=0.004; Fig. 1A). For symptoms of bowel urgency, 58.6% vs 33.0%, respectively, had clinically meaningful improvements (p<0.001; Fig. 1B), and 24.0% vs 9.8%, respectively, of those with symptoms of bowel urgency at baseline had resolution at Wk12 (p<0.001). Similarly, 57.7% vs 33.0%, respectively, had clinically meaningful improvements in the impact of bowel urgency (p<0.001; Fig. 1B), and 32.4% vs 13.1%, respectively, of those impacted at baseline had resolution at Wk12 (p<0.001). Symptoms and impact of bowel urgency were combined into a bowel urgency score; of pts with symptoms or impact scores ≤6 at baseline, 19.7% versus 8.2%, respectively, had resolution of both at Wk12 (p<0.001; Fig. 1B).

Conclusion

Pts receiving GUS showed clinically meaningful improvements in health-related quality of life measures related to abdominal pain and bowel urgency, including both the symptoms of bowel urgency and impact on pts’ lives.
P1030 Inflammatory Bowel Disease helpline contact trends in a real-world Australasian cohort: Crohn’s Colitis Cure (CCC) data insight’s program
Authors: Pipicella J L , Wilson W , Ghaly S , Antoniades S , Kate L , Grafton R , Ng W , Sechi A , Somes K , Arnold K , Connor S J , Andrews J M
Published: January 2024

Background

For optimal outcomes, Inflammatory Bowel Disease (IBD) necessitates lifelong engagement in care. Specialized-IBD-nurse-led helplines improve access to care and reduce associated costs1,2. Despite this evidence, IBD nurses and helplines receive variable funding and little is known about their use across care sites. We therefore analysed IBD-helpline usage in a large, multi-site real-world Australasian cohort.

Methods

Crohn’s Colitis Care (CCCare), is a cloud-based IBD-specific electronic medical record used in Australia and New Zealand. It includes a "Helpline" tab to support helpline encounter documentation during the point of contact. All entered data feed into an associated, de-identified clinical quality registry (CQR). Helpline-associated data fields, including contact reason and type, were extracted from CCCare’s CQR in November 2023. Data from 6 large adult care sites across Australia and New Zealand were analysed.

Results

In 2022, a total of 6,717 helpline encounters were documented. There was a roughly equal split in contact type; phone accounting for 50.9% (n=3,416) and email for 49.1% (n=3301). The most common reasons for contact were related to medications (n=2,577; 38.4%), investigations (n=1,719; 25.6%) and clinical (n=1,060; 15.8%).

More encounters were seen in 2023 (to date of data extract), with 7,540 helpline entries to date (Figure 1). In 2023, the most common form of patient contact was email (70.3%), with phone contact accounting for only (29.8%). The most common reasons for contact were again related to medications (n=2,577; 31.1%), investigations (n=1,162; 22.0%) and clinical (n=1,439; 19.1%). In both years, helpline activity was lowest in January and February, perhaps corresponding to the Holiday season (southern hemisphere summer).

Conclusion

A number of helpline entries were recorded across these 2 years, with activity lowest each summer. The data show a shift in the predominant mode of contact from phone to email in 2023, reflecting evolving communication preferences and making scheduling of helpline support easier.

1 - Nicolaides S, Vasudevan A, Van Langenberg D. Inflammatory Bowel Disease Helpline Reduces Subsequent Inpatient Admission Rates. J Crohns Colitis. 2020 Feb 10;14(2):281. doi: 10.1093/ecco-jcc/jjz141. PMID: 31374121.

2 - Karimi N, Sechi AJ, Harb M, Sawyer E, Williams AJ, Ng W, Connor SJ. The effect of a nurse-led advice line and virtual clinic on inflammatory bowel disease service delivery: an Australian study. Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e771-e776. doi: 10.1097/MEG.0000000000002249. PMID: 34402467.
P1038 Does combination immunomodulator therapy impact real-world biologic effectiveness in Inflammatory Bowel Diseases?A propensity score analysis in patients treated with anti-TNF and non-anti-TNF biologics in the UK IBD BioResource
Authors: Desoki R , Kapizioni C , Lam D , Balendran K , Al-Sulais E , Subramanian S , Pele L , Parkes M , Raine T
Published: January 2024

Background

Randomised controlled trials have demonstrated that the combination of infliximab and azathioprine is superior to either drug as monotherapy both in patients with Crohn’s Disease (CD) and ulcerative colitis (UC). Data on the combination of other biological agents -including other anti-TNFs, vedolizumab and ustekinumab- and immunomodulators (IMMs) is lacking or shows conflicting results. Given the risks of combination therapy, physicians are often hesitant on whether to combine IMMs with biologic therapies.

Methods

We measured the effectivenessof biologic therapies [infliximab (IFX), adalimumab (ADA), golimumab (GLM), vedolizumab (VDZ) and ustekinumab (UST)] in patients with UC and CD with and without IMM use enrolled in the UK Inflammatory Bowel Disease (IBD) BioResource over long durations of followup.Demographic, disease, treatment and outcome data were retrieved. Inverse probability of treatment weighting (IPTW) was used to balance groups of those receiving vs those not receiving IMM using a propensity score-weighting approach accounting for baseline patient or disease related clinical characteristics. Effectiveness of treatment was based on persistence free of treatment discontinuation or treatment failure. Failure was defined as occurring if any of the following occurred: (a) clinician-recorded treatment failure (b) start of treatment with a different advanced therapy (c) occurrence of resectional or defunctioning bowel surgery. We compared Kaplan Meier curves for treatment failure-free survival after IPTW and used a log rank test for differences between the groups.

Results

In UC, we included 2479 patients receiving IFX (1173 on IMM), 1117 ADA (401 on IMM), 188 GLM (77 on IMM) and 1256 VDZ (392 on IMM). In CD, we included 5956 patients receiving IFX (3062 on IMM), 4524 ADA (1898 on IMM), 1067 VDZ (340 on IMM) and 627 UST (198 on IMM).As expected, combination IMM therapy was associated with increased drug effectiveness for IFX in both UC and CD. Combination IMM therapy was also associated with increased effectiveness of ADA in CD. For all other drugs, there was no significant benefit for combination IMM. Hazard ratios(HRs) for the effect of IMM of each drug effectiveness in UC and CD are summarised (Figure 1).

Conclusion

We confirm prior results indicated that IFX effectiveness is improved by concomitant use of an IMM in both UC and CD.In contrast to RCT data but in accordance to other robust real-world studies, we find evidence that for ADA in CD concomitant IMM can increase drug effectiveness. We find no evidence of benefit for concomitant IMM for other biologics in UC or CD.
P1074 Impact of body mass index (BMI) on clinical outcomes and drug levels in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study
Authors: Yarur A , Hanauer S B , Schreiber S , Colombel J F , Deepak P , Jeong A L , Kim D H , Lee Y N , Danese S
Published: January 2024

Background

Obesity and high levels of visceral adipose tissue are associated with lower response rates to intravenous (IV) infliximab (IFX).1 Subcutaneous (SC) IFX is a novel formulation that demonstrated superiority to placebo as maintenance therapy in patients (pts) with moderate-to-severe active Crohn’s disease (CD) in the Phase 3 LIBERTY-CD study. Assessing efficacy of SC IFX by BMI is important as, unlike the IV formulation, pts receive a fixed dose. This post hoc analysis aimed to assess the association between BMI and the efficacy of SC IFX therapy.

Methods

Data from LIBERTY-CD (NCT03945019) were analysed; 231 pts from the SC IFX arm were divided into four subsets by their BMI: underweight (BMI <18.5 kg/m2, n=27); normal (18.5–24.9 kg/m2, n=133); overweight (25–29.9 kg/m2, n=53); obese (≥30 kg/m2, n=18). Co-primary endpoints at Week (W) 54 (clinical remission [CD Activity Index (CDAI) score <150]; endoscopic response [≥50% decrease in Simple Endoscopic Score for CD (SES-CD) from baseline (BL)]) and W54 change from BL in CDAI score were assessed by BMI subset. Correlations between BMI and CDAI score, SES-CD or median trough level of infliximab (TLI), and the impact of BMI on W54 TLI, were evaluated. Analyses were conducted in a descriptive manner.

Results

At W54, there were no statistically significant differences in co-primary endpoints or change from BL in CDAI score across BMI subsets, despite descending trends in rates of achieving co-primary endpoints, change in CDAI score and TLI with increasing BMI (Table). From the underweight to obese subsets, clinical remission rates were 63.0%, 66.2%, 58.5% and 44.4% (p=0.125), endoscopic response rates were 55.6%, 36.1%, 41.5% and 27.8% (p=0.207) and median changes from BL in CDAI score were −227.3, −212.9, −196.2 and −204.5 (p=0.358). No significant correlations were observed between BMI and CDAI score (Pearson r=0.0972/p=0.141; Spearman rank r=0.0619/p=0.349) or BMI and SES-CD (Pearson r=0.0446/p=0.507; Spearman rank r=0.0375/p=0.577), while there was a weak, but significant, negative correlation between BMI and TLI (Pearson r=−0.2808/p<0.001; Spearman rank r=−0.2829/p<0.001) (Figure). Additionally, there was a significant difference in median W54 TLI across BMI subsets from underweight to obese (17.0, 13.6, 9.3 and 6.6 µg/mL; p=0.007) (Table).

Conclusion

While there was a significant difference in TLI across BMI subsets, there was no statistically significant impact of BMI on W54 clinical or endoscopic outcomes. These results could be explained by the relatively high TLI achieved with the SC formulation. Further larger and longer-term studies including pts with morbid obesity and utilising body composition assessment are warranted.

1Yarur A et al. Gastroenterology 2023;165:963–75.
P1104 Shifting Surgical Landscape in Crohn's Colitis: Laparoscopic Supremacy and Robotic Upsurge
Authors: Violante T , Ferrari D , Novelli M , Larson D
Published: January 2024

Background

Crohn's disease (CD) is a chronic inflammatory bowel disorder that can cause transmural inflammation throughout the digestive tract. When CD affects the colon, it is known as Crohn's colitis (CC), a serious condition often requiring surgical resection. Surgical trends in CC have changed significantly over the past decade, shifting towards minimally invasive surgery, with laparoscopic and robotic procedures becoming increasingly common. This study examines how surgical trends in CC have changed in recent years and predicts how they may change.

Methods

We conducted a retrospective analysis using the ACS-NSQIP database, focusing on patients who underwent colonic resections for CC between 2012 and 2021, including 20,109 patients. Our main goal was to examine trends in open, laparoscopic, hand-assisted, and robotic surgery. We utilized time series analysis, specifically quarter and year of admission data, and employed Vector Autoregressive (VAR) models to explore the dynamic relationships among these surgical techniques. To analyze the time trends, we reported the quarter (Q) and year of admission. These models enabled us to forecast future trends, accompanied by 95% confidence intervals, extending our predictions up until Q2 of 2025.

Results

As shown in Figure 1, open surgery has been the most common approach to CC since Q1 2012, accounting for 52.3% of all procedures. Laparoscopic surgery was the next most common approach, at 33.3%, followed by hand-assisted laparoscopy at 14.4%. Laparoscopy rapidly expressed market supremacy, by steadily becoming the most widespread approach by Q2 of 2017, representing 42.2% of CC surgery and peaking in Q2 2020 at 43.5%. This growth in laparoscopy came at the expense of open surgery, which experienced a significant decline, reaching its lowest point of 28.5% in Q2 2021. Hand-assisted procedures gradually increased in popularity over the years but remained less popular than open and laparoscopic methods, peaking at 24.0% in Q4 2019. Robotic procedures experienced slow but steady growth, from 1.9% in Q1 2013 to 10% in Q2 2021.

Future trends suggest that laparoscopy will continue to grow steadily, reaching 45% (95% CI 28.2-61.7%) by the end of our prediction period. Robotic surgery is poised to significantly shift CC surgery trends, with resections expected to reach 12.6% (95% CI 9.3-15.8%) by Q2 2025, while a subsequent decline in open procedures to 20.8% (95% CI 0-43%).

Conclusion

Laparoscopic surgery has emerged as the favored surgical approach in CC and is expected to maintain its supremacy into the near future. Open colonic resections are anticipated to decline, making way for the increasing prevalence of robotic surgery.
P1110 Collagenous colitis, clinical features, risk factors and treatment outcome: A large case series from the largest teaching Hospital in London, UK
Authors: Kottwitz J , mudege T , Giaslakiotis K , Hoque PhD S S
Published: January 2024

Background

Microscopic colitis is a cause of chronic watery, non-bloody diarrhoea diagnosed mainly on histology after taking biopsy from macroscopically normal colonoscopy. Thereby mainly two subtypes can be identified: Lymphocytic and collagenous colitis. So far, no biomarkers for the diagnosis of microscopic colitis have been identified. Here, we looked at, risk factors and treatment outcome of collagenous colitis in large series of cases.

Methods

In this study, we analysed all cases of collagenous colitis diagnosed from 2018-2022 in the Northeast London from 5 different teaching hospitals. 104 cases were identified and their electronic health record from hospital and from the primary care physicians (GP) were manually reviewed.

Results

In this cohort, 24% male, 76% female with ratio of (1:3), with mean age of 65 years. Forty percent were active or ex-smoker. PPI uses were associated with in 81% cases. While NSAIDS and statin were associated in 56% and 49% cases respectively. We also found that SSRI use were noted about 31% cases.

Painless watery diarrhoea was the main cause for referral in 90% of cases, while complaint of abdominal pain noted in only 39% cases. Thirty-five (35%) cases noted to have history of weight loss. Forty-eight (48%) patients received treatment with Budesonide, 46% treated with loperamide, 5% with Immunomodulator or Biologics and 1% Bismuth Subsalicylates respectively. Other autoimmune disease were associated in 6% cases and 2% cases were associated with Coeliac disease. in Nineteen (19%) of cases symptoms improved immediately after stopping above associated drugs without any specific therapy.

Twenty-five (25%) percent relapses 6 months after stopping of therapy. Patients present with abdominal pain, and arthralgia were significantly (p<0.001) higher risk of relapsing compared to patients with other symptoms.

Conclusion

In this large series of collagenous colitis, we found that in addition to associated drug use is not only risk, patient presents with abdominal pain and arthralgia have higher risk of relapse, after stopping of therapy of collagenous colitis . Further studies are needed to identify biomarker of this frustrating disease which has significant impact on patients of quality of life.