bluuebunny/crossref_metadata_2025 huggingface dataset:
P534 Dual biologic or small molecules therapy in refractory paediatric inflammatory bowel disease (DOUBLE-PIBD): A multi-center study from the paediatric IBD Porto group of ESPGHAN
Authors: Cohen S , Olbjorn C , Kolho K L , Aloi M , Musto F , de-Carpi J M , Lozano-Ruf A , Yogev D , Matar M , Scarallo L , Bramuzzo M , de Ridder L , Kang B , Norden C , Wilson D C , Tzivinikos C , Turner D , Yerushalmy-Feler A
Published: January 2023

Background

Current data on dual biologic or small molecules therapy in children are limited. The aim of the study was to evaluate the effectiveness and safety of dual therapy in paediatric patients with IBD.

Methods

This was a retrospective multicenter study from 14 centers affiliated with the IBD interest and Porto groups of ESPGHAN. We included children with IBD who were treated with combination of biologic agents or biologic and small molecule, with at least 3 months of follow-up under this therapy. Demographic, clinical, laboratory, endoscopic and imaging data were collected. Adverse events were recorded. All analyses were done in the intention-to-treat population. Children that discontinued therapy were considered treatment failures and were imputed for non-response, while missing data was imputed according to the last observation carried forward method.

Results

Sixty-two children [35 Crohn’s disease (CD), 27 ulcerative colitis (UC)], with a median age of 15.5 (IQR 13.1-16.8) years and disease duration of 3.8 (IQR 2.5-6.1) years were included. All children failed previous biologics and 47 (76%) failed at least two biologic agents. The dual therapy included anti-TNF agent and vedolizumab in 30 children (48%), anti-TNF and ustekinumab in 21 children (34%), vedolizumab and ustekinumab in 8 children (13%), and tofacitinib and other biologics in 3 children (5%). Clinical remission was observed in 21 (35%), 30 (50%) and 38 (63%) children at 3, 6 and 12 months, respectively. Of 27 children who were treated with corticosteroids at baseline, 20 (74.1%) were weaned within 3 months after the initiation of dual therapy. At 12 months of follow up, normalization of C-reactive protein and decrease in fecal calprotectin to < 250 mcg/g were achieved in 75% and 64%, respectively. Endoscopic and transmural healing were observed in 2/23 (9%) and 5/16 (31%) children, respectively. Male sex and diagnosis of UC were associated with higher likelihood of clinical remission (p=0.017 and p=0.020, respectively). Adverse events were reported in 29 (47%) children. While most adverse event were mild, 8 were regarded as serious and 6 (10%) led to discontinuation of dual therapy. The serious adverse events included infusion reaction to infliximab, fatigue and headache following vedolizumab infusion, severe skin eruptions (3 patients), cellulitis and skin abscess, elevated liver enzymes and deep vein thrombosis.

Conclusion

Dual biologic or small molecules therapy may be effective in children with otherwise refractory IBD. The risk of serious adverse events should be considered before recommending dual therapy.
P537 Prevalence of post-COVID-19 vaccination IBD flare-ups: a single-center prospective study.
Authors: Roblin X , Williet N , Faure J , Bastide L , Barrau M , Paul S
Published: January 2023

Background

Case reports of IBD flares after COVID-19 vaccination have been reported. These cases appear to be rare. In a recent study analyzing adverse event rates and impact on clinical activity of IBD after COVID-19 vaccination, the authors reported a rate of IBD reactivation in 2% of cases defined as reactivation of symptoms associated with a change in therapy (Prevent COVID Study) (Weaver et al. IBD 2022).

Methods

Any patient with IBD, followed as an outpatient in our department and having accepted to be vaccinated against COVID-19, was proposed this study. All the patients included in the study had to contact the department if, within one month of receiving the COVID-19 vaccine, they presented a clinical picture suggestive of an IBD relapse. The patients were reviewed in emergency and an assessment of IBD activity was made: clinical activity score, CRP and/or calprotectin dosage, short endoscopy in case of UC, colonoscopy or MRI in case of CD. The link between vaccine and relapse was defined by the absence of clinical activity for at least 3 months before vaccination and relapse of the disease at the latest within 30 days after vaccination without therapeutic modification in between.

Results

231 patients (mean age: 44.6 years, sex ratio M/F=1.1, 43.3% MC) were eligible. 176 patients had at least three doses of vaccine, all with mRNA, and 55 with no more than two doses. 97 patients (42%) were infected at least once with COVID 19, confirmed by PCR after at least one dose of vaccine, all without resorting to hospitalization, resuscitation or death. 29 patients (12.5%) developed IBD after vaccination (43.6% MC, sex ratio=1, 80% of cases after 3 doses of vaccine) after a median time of 8.5 days (5-17 days). Patient characteristics, treatment received, number of vaccinations, or Covid infection were comparable between groups with and without reactivation after COVID-19 vaccine (P=NS). The risk of relapse after vaccination was 29 per 646 vaccine doses (4.4%). Table 1 reports pre-exacerbation treatments and proposed treatment changes as well as medium-term response. For IBD flares, no severe forms, hospitalization or surgery were observed. Fifteen patients were optimized on their treatment and 18 were switched to another treatment. All were put into clinical remission of their disease. In univariate analysis, no clinical parameter (type of IBD, age, sex, smoking), the number of previous vaccinations, a previous infection with covid 19 or the type of treatment was associated with a significant risk of relapse after vaccination.

Conclusion

The risk of IBD relapse in patients in durable clinical remission is possible after COVID-19 mRNA vaccination but remains low (4%). No risk factors were isolated in this work.
P538 Suboptimal disease control is common in patients with Crohn’s perianal fistulas with capacity to optimise medical and surgical treatment in real-world experience: A cross-sectional analysis of baseline disease characteristics in the FINESS study
Authors: De Gregorio M , D’Souza B , Connell W , Kamm M A , Woods R , Connor S J , Thompson A J , Ding N S
Published: January 2023

Background

Crohn’s perianal fistula treatment is often challenging, requiring combined medical and surgical treatment with heterogeneity in real-world practice. We herein evaluate disease activity and management history of patients with Crohn’s perianal fistulas, identifying those with active disease amenable for treatment optimisation.

Methods

We present the results of a cross-sectional study of disease characteristics among patients with Crohn’s perianal fistulas at a single specialist Inflammatory Bowel Disease service. Patients with Crohn’s perianal fistulas seen in clinic from February 2021 to June 2022 (new and review appointments) were sequentially enrolled. Patients were excluded based on rectovaginal or rectovesical fistulas, proctectomy, pregnancy or breastfeeding. Baseline disease activity was defined as active (stage A/B: sepsis, actively draining), optimised with a chronic seton in situ (stage C), or remission (stage D: no discharge from fistula tract external opening). Radiologic disease activity was assessed with magnetic resonance imaging using the Van Assche Index (VAI), VAI-inflammatory sub-score (VAIinfl; derived from T2-hyperintesnity, collections >3mm diameter, and rectal wall involvement), and Magnetic Resonance Novel Index for Fistula Imaging in Crohn’s Disease (MAGNIFI-CD) score.

Results

Sixty patients were included with a median age of 39 years (IQR 17.7), 52% male, median clinic attendance of 6 years (IQR 7.9), median Crohn’s and perianal disease duration of 13 (IQR 16.8) and 8 (IQR 13.5) years, respectively. Majority were on anti-tumour necrosis factor-α therapy (28% infliximab, 40% adalimumab) and an immunomodulator (55% thiopurine, 5% methotrexate). Forty-two percent had undergone perianal surgical intervention within the preceding 12 months, see Table 1. Forty-eight percent (n=29), 7% (n=4), and 45% (n=27) had stage A/B, C, and D disease activity, respectively. Radiologic disease activity scoring indices were lower between stage D and A/B (VAI 4 vs 12; VAIinfl 0 vs 8; MAGNIFI-CD 2 vs 6, respectively), see Table 2. Of those with stage A/B disease activity, 31% were not on a biologic (63% new diagnosis, 25% prior remission, 13% comorbidities precluding), 52% were infliximab naïve (71% new diagnosis, 14% prior remission, 14% contraindications), 85% who were on a biologic had potential for initial or further dose escalation, and 31% did not undergo perianal surgical intervention in the preceding 12 months.

Conclusion

In a single specialist centre, almost half the patients with Crohn’s perianal fistulas have clinically active disease, with capacity to optimise medical and/or surgical treatment in the majority. Prospective assessment of a model of care directed towards optimising treatment in these patients is needed.
P544 Low TNF production and low TREM1 expression as negative predictors for remission under adalimumab therapy in Crohn′s Disease patients
Authors: Jessen B , Tóth M , Freise I , Staudacher J , Haag L M , Kredel L , Schumann M , Weidinger C , Sonnenberg E , Siegmund B
Published: January 2023

Background

Approximately one third of IBD patients show a primary non-response to anti-TNF therapy. An individualized treatment approach requires clinical predictors. Our previous study showed that LPS-stimulated TNF production can be used to predict response to infliximab in Crohn′s Disease patients. The expression of the myeloid receptor TREM1 is also known as a potential predictive marker for anti-TNF therapy response. The aim of this study is to compare these two predictors for response to adalimumab.

Methods

In this prospective observational study 24 adults with Crohn′s Disease starting adalimumab treatment were included. Disease activity was assessed clinically (Harvey-Bradshaw-Index (HBI)), through lab results (leukocytes, C-reactive protein, calprotectin) and per ultrasound (Limberg-Score) at the time point of adalimumab induction, after 6 and 12 weeks. TNF-production of LPS-stimulated peripheral blood mononuclear cells was measured via ELISA at the baseline. The expression of TREM1 and its soluble isoform TREM1sv was quantified from whole blood RNA via qPCR. Primary endpoints were clinical response after week 6 and 12. Response was defined as a decrease in HBI ≥2, remission as HBI <5. Cut-off values for low- and high-producers were defined via receiver operating characteristic (ROC). Results were tested for significance with chi²-Test.

Results

Of 24 recruited patients 18 have currently reached week 12. 5 patients have not reached remission within 6 weeks, 4 have not reached remission within 12 weeks. TNF production and TREM1 expression differed among patients at baseline. After definition of a cut-off value 6 low-TNF-producers, 8 low-TREM1-producers and 7 low-TREM1sv-producers could be identified. Three out of 6 low-TNF-producers were in non-remission after 6 weeks compared to 2 out of 12 high-TNF-producers (p=0.1366). Five out of 8 low-TREM1-producers were in non-remission after 6 weeks compared to 0 out of 9 high-TREM1-producers (p=0.0048, 1 missing value). Four out of 7 low-TREM1sv-producers were in non-remission after 6 weeks compared to 1 out of 10 high-TREM1sv-producers (p=0.0488, 1 missing value).

Figure 1) Remission after 6 weeks of adalimumab treatment - low vs. high TNF

Figure 2) Remission after 6 weeks of adalimumab treatment - low vs. high TREM1

Figure 3) Remission after 6 weeks of adalimumab treatment - low vs. high TREM1sv

Conclusion

Low TREM1 and TREM1sv expression seem to be stronger predictors for non-remission after 6 weeks of adalimumab treatment compared to TNF-production. These results are to be validated with increased patient numbers.
P547 Rate of Colectomy Increases within Twelve Months of Sequential Therapy for Ulcerative Colitis
Authors: Barnes E , Zhang X , Long M , Herfarth H , Kappelman M
Published: January 2023

Background

Even the best medical treatments for ulcerative colitis (UC) are often ineffective, with up to 15% of patients requiring a colectomy within the first 10 years of diagnosis. In the current era, patients have access to an increasing number of medical therapies that may prevent and/or delay surgery. To evaluate the relative effectiveness of sequential therapies for UC, we evaluated the 12-month colectomy rate among patients switching to a second, third, or fourth-line biologic or small molecule therapy for UC.

Methods

We conducted a retrospective cohort study, using a new-user design, evaluating patients with commercial insurance in the MarketScan database between 2000 and 2019. The index date for the study was defined as the date of the first claim for a second, third, or fourth biologic or small molecule therapy. The primary outcome was defined as colectomy-free survival at 12 months after the index date. Significance of 12-month colectomy rates over time was evaluated using the Cochran-Armitage test of trend and a Generalized Estimating Equation (GEE) model adjusting for age (18-35, 36-55, >55), sex and index year (year 2007-2014 and 2015-2019).

Results

We identified 3,325 patients with UC that made at least 1 switch in biologic or small molecule therapy during the study period. Among these, 50% were female and the median age was 41 years (interquartile range 31-52 years, Table 1). The most frequent initial biologic switches were from an anti-tumor necrosis factor alpha (TNF) to an anti-TNF (1895 patients [57%]) and anti-TNF to vedolizumab (980 patients [30%]) were the most common sequences of therapies (Table 2). Overall, 392 (12%) patients underwent colectomy within 12 months of the first switch while 116 of 695 (17%) patients underwent colectomy within 12 months of the second switch. Among 161 patients that underwent 3 switches, 30 (19%) underwent colectomy within 12 months of the third switch (p<0.001, Table 3). The rate of UC-related hospitalizations in the 12 months after switch also increased significantly with each subsequent switch (11% vs. 15% vs. 19% for first, second and third switches respectively, p<0.001). The colectomy rate per switch in therapy appeared stable when stratifying by index date and age at index date (Figure 1).

Conclusion

Despite increases in the number of available mechanisms for the treatment of UC, a substantial proportion of patients will still require colectomy for UC. The absolute risk of colectomy within 12 months and other negative outcomes increase with each subsequent treatment. These data can help inform complex decisions regarding the timing of surgery relative to initiation of subsequent therapy in patients with medically-refractory disease.
P552 Anti-TNF Treatment and Risk of Atrial Fibrillation in Inflammatory Bowel Disease Patients
Authors: Cohen Y , Fischman M , Waterman M , Dolnikov K , Azzam Z S , Ghersin I
Published: January 2023

Background

Inflammation is thought to play a role in the development of atrial fibrillation (AF). Previous studies suggested that inflammatory bowel disease (IBD) is associated with increased risk of AF. These studies also found IBD patients receiving biologic agents were at higher risk of AF than patients not receiving them.

We sought to determine the association between anti-TNF treatment and the risk of AF in IBD patients

Methods

In this observational cohort, we included all adult IBD patients who were registered in Rambam Medical Center, diagnosed with IBD from November 1983 to October 2021. We excluded patients who were diagnosed with AF and/or stroke prior to IBD diagnosis. Disease severity was based upon IBD treatment. Mild disease was defined as no treatment, 5-ASA, or topical steroids, while moderate-to-severe disease was defined as any immunomodulator, biologic or systemic steroid therapy.

Primary outcome was AF diagnosis.

We used Cox proportional hazard model to compare AF in patients receiving anti-TNF treatment to those with mild disease. We further adjusted the hazard ratio of AF development based on known AF risk factors, including age, male gender, cardiovascular disease, chronic kidney disease, pervious venous thromboembolism, hyperlipidemia, diabetes, and thyroid disease.

Results

Our initial cohort included 5,326 patients. After exclusion, 4,886 patients were included.

Median follow-up time was 8.49 years

2,720 patients were considered as having mild IBD, while 787 patients received anti-TNF medications.

During follow-up period, cumulative incidence of AF was 1.50% (n=41) and 0.89% (n=7), respectively (p=0.21).

Unadjusted hazard ratio of AF occurrence in anti-TNF patients was 0.6 (95% CI; 0.27-1.3, p=0.211). After adjustment, hazard ratio of AF occurence was 1.33 (95% CI; 0.53-3.3, p=0.545).

Conclusion

Anti-TNF treatment was not associated with increased risk of AF among IBD patients. This provides reassurance regarding the cardiovascular safety of anti-TNFs in a real-world IBD cohort.
P553 Active tuberculosis and opportunistic infections: Pooled safety analysis of ustekinumab through up to 5 years across all approved indications
Authors: Ghosh S , Long M , Ott E , Gasink C , Baker T , Godwin B , Miao Y , Loftus E
Published: January 2023

Background

Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment.

Methods

Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or >16 weeks after the last UST dose for UST pts who switched to PBO.

Results

Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table 1); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a Hungarian CD pt 10 months after receiving last UST dose) and UST (n=1) pts (Table 1). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1).

Conclusion

Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 yrs with 13807 PYs of follow-up and not higher in UST pts vs PBO pts, suggesting no increased risk of OI with long-term UST treatment.
P554 Extended induction response in patients treated with mirikizumab with moderately to severely active ulcerative colitis in the LUCENT trials
Authors: D'Haens G , Higgins P D R , Peyrin-Biroulet L , Sands B E , Lee S , Moses R E , Redondo I , Escobar R , Morris N , Kobayashi T
Published: January 2023

Background

The efficacy and safety of mirikizumab (miri) for moderately to severely active ulcerative colitis (UC) was demonstrated in the Phase 3 LUCENT trials (LUCENT-1 and -2; NCT03518086, NCT03524092).1,2 Some patients may improve more slowly and require a prolonged course of induction before achieving clinical response. Therefore, we evaluated clinical response in patients who had not responded by the end of the 12-week(W) induction period and who received extended induction treatment for an additional 12W.

Methods

Patients not responding to intravenous (IV) administration of 300 mg miri every 4 weeks (Q4W) (n=272) at W12 (LUCENT-1), received extended 12-W induction treatment of open label 300 mg miri IV Q4W for 3 additional doses (LUCENT-2). Patients responding at W24 (n=144) of continuous IV treatment, entered open label maintenance and received 200 mg miri Q4W subcutaneously (SC) until W52. Key outcomes through 52W are reported (Definitions in Table).

Results

Among the 272 patients who failed to achieve a clinical response after 12W of induction treatment, 72.4% had a Mayo endoscopic subscore of 3, indicating severe disease. Of these patients, 146 (53.7%) achieved a clinical response and 31 (11.4%) achieved clinical remission at W24.

Of the 144 responders at 24W entering the open label maintenance study, 52 (36.1%) patients achieved clinical remission, 104 (72.2%) achieved clinical response, 62 (43.1%) achieved endoscopic remission and 60 (41.7%) patients achieved histologic improvement at W52. Furthermore, for these patients, there was a 3.8 (±2.7) point reduction from baseline in bowel urgency (BU) severity and 58.8% achieved clinically meaningful improvement in BU (Table). Among these patients, 38.3% demonstrated treatment-emergent adverse events (TEAEs). Most TEAEs were mild (21.4%), while only 5.4% were serious. Overall, there was a 3.2% of discontinuation due to TEAEs. No new safety signals or deaths were reported.

Conclusion

Among patients who did not initially respond to induction treatment with miri at 12W, 3 additional miri induction doses induced clinical response and remission in patients, highlighting the potential benefit of extended induction treatment with miri in those patients with more severe inflammation at baseline.

1.D’Haens et al., OP26: Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study, Crohn's and Colitis, Vol. 16, Iss. Supplement_1, Jan. 2022, i028–i029

2.Dubinsky et al., 867e: Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 Lucent-2 study, Gastroenterology, Vol. 162, Iss. 7, S-1393-94
P559 SARS-CoV-2 vaccination does not increase the risk for flares in Inflammatory Bowel Disease patients
Authors: Rossier L , Seibold F
Published: January 2023

Background

Vaccination hesitancy is an important barrier to vaccination among inflammatory bowel disease (IBD) patients. The development of adverse events is the main concern reported. With this study we wanted to assess the SARS-CoV-2 vaccination safety by evaluating the post-vaccination flare risk and incidence of overall adverse events.

Methods

Surveys were distributed three consecutive months to each IBD patient coming in for a consultation in the Intesto Crohn & Colitis centre (Bern, Switzerland). Information about their vaccination-status and the occurrence of subsequent side effects was recorded. Their electronic medical record was then reviewed. Their baseline- and IBD- characteristics were transcribed as well as the dates of any flare occurring in 2021. These characteristics and the flare incidence were compared between the vaccinated and unvaccinated patients. Among the vaccinated population, the flare-risk was analysed at three different points in time: pre-vaccination, 1 month after any vaccination and over 1 month after any vaccination. Effect measurements according to Poisson models were applied. The characteristics of patients developing side effects were compared to those who did not.

Results

396 IBD patients were enrolled, of which 91% were vaccinated, predominantly with mRNA vaccines. Throughout 2021, 85 flares were recorded with no difference between the vaccinated and unvaccinated groups. Among the vaccinated group, there was no statistically significant difference between the flare-incidence in the pre-vaccination, 1 month after any vaccination and over 1 month after any vaccination subgroups as well as the Moderna- and Pfizer-subgroups. Overall, 37% patients reported side effects following any vaccination, mostly mild flu-like symptoms. More side effects were reported in the patients who were vaccinated with the mRNA-1273/ Spikevax (NIH-Moderna) vaccine in comparison with BNT162b2/Cominarty (Pfizer-BioNTech).

Conclusion

In this mono-centric study SARS-CoV-2 vaccination with mRNA vaccines seems safe with the occurrence of mostly mild side effects. The flare risk is not increased in the month following any vaccination.
P568 Patients with ulcerative colitis after pouch surgery are at risk for low spinal bone mineral density: a cross sectional study
Authors: Pfeffer-Gik T , Godny L , Ollech J , Wasserberg N , White I , Barkan R , Cohen S , Avni-Biron I , Banai H , Snir Y , Yanai H , Yackobovich Gavan M , Shimon I , Tsvetov G , Broitman Y , Dotan I
Published: January 2023

Background

Low bone mineral density (BMD) is prevalent in patients with inflammatory bowel diseases (IBD), specifically Crohn’s disease (CD) due to multiple factors including active inflammation, use of corticosteroids, surgeries and nutritional deficiencies. Patients with ulcerative colitis (UC) who undergo total proctocolectomy and pouch surgery may develop small bowel inflammation (pouchitis) resembling CD. Data regarding their BMD are scarce. We assessed low BMD rates and risk factors in these patientsץ

Methods

Patients with UC-pouch ages 18-50 without BMD assessment in the past 5 years were recruited. BMD was assessed by dual-energy x-ray absorptiometry (DEXA). Clinical data, biochemical and inflammatory markers were detected and dietary patterns were assessed using validated questionnaires.

Results

Patients recruited-30: male/female 14/16; Median age 45 (IQR 31-51.7) years; median BMI 23.2 (IQR 21-26.5); median IBD duration 23 (IQR 15-30) years; median pouch age 17 (IQR 10-25) years. Low BMD detected in 16/30 (53.3%): 6/30 (20%) osteoporosis,10/30 (33.3%) osteopenia. Low L1-L4 T-scores correlated with younger age, lower BMI and shorter disease duration (p= 0.001; p= 0.001; p= 0.023, respectively). In univariate analysis patients with low and normal BMD were comparable in age, gender, BMI, smoking, past and current medical treatment. In multivariate analysis younger age and lower BMI remained significant (age SE= 0.22, β 0.422 p=0.043, BMI SE=0.06, β=0.531 p=0.006)

independently of sex, years since IBD diagnosis, and smoking. Dietary patterns were comparable (p=0.715).

Conclusion

Abnormally low BMD was prevalent in over half of patients with UC-Pouch. Interestingly younger age and lower BMI were risk factors for low spinal BMD. Dietary patterns did not account for the findings. BMD should be routinely assessed in patients with UC-pouch and intervention to correct abnormally low BMD should be planned.
P592 Clinical evaluation of leukocytapheresis compared to vedolizumab in patients with Ulcerative Colitis with contraindications to anti-TNF-alpha: a single-centre experience
Authors: Ferronato A , Rigno M , Rodriguez-Castro K I , Brozzi L , Errigo G , Castelli M , Baldassarre G
Published: January 2023

Background

Various therapeutic advances have led to a paradigm shift in the clinical management of patients with Inflammatory Bowel Diseases (IBD). Recently vedolizumab and other biologic agents have been introduced as a second choice to anti-TNF-alpha and in whom an anti-TNF-alpha cannot be used. Moreover, leukocytapheresis (LA) is a recognized potential option for the treatment for these IBD patients. The aim of this study is to assess if leukocytapheresis can still have a use in selected Ulcerative Colitis (UC) patients comparing it with vedolizumab.

Methods

From February 2019 to November 2021, 15 patients with UC were evaluated: 8 patients treated with leukocytapheresis (5 weekly apheresis session) (group 1) and 7 with vedolizumab (group 2). All patients had contraindications to anti-TNF-alpha use. The choice of treatment was driven by disease severity, presence of recognized optimal indications for leukocytapheresis and patient’s choice. We evaluated patients by clinical disease activity indexes and blood parameters levels at the beginning of therapy, then after 3 and 12 months.

Results

In group 1 after 12 months of follow up (FU) 5 patients achieved clinical remission with 3 patients receiving monthly maintenance therapy. During the FU 3 patients lost response and started biological therapy (vedolizumab). In group 2 after 12 months 3 patients achieved clinical remission with no treatment failure. In table 1 is shown the clinical disease activity for each patient according to Mayo partial score (MPS). The development of the blood parameters is similar in the two groups, with a general reduction of inflammatory parameters after 12 months. In group 1: leukocyte from 6,1 to 5,8 103/mm3; erythrocyte sedimentation rate (ESR) from 21,1 to 15,6 mm/h; platelets (PLT) from 286,6 to 269,5 103/mm3, faecal calprotectin (FC) from 579,1 to 208,5 mg/kg. In group 2: leukocyte from 8,7 to 7,7; ESR from 42,2 to 45,5; PLT from 320,8 to 266,3; FC from 586,2 to 257,2.

Conclusion

There is an indication overlap between leukocytapheresis and vedolizumab, with a trend in research favouring new biologics. From this clinical experience apheresis appears to be effective as second-choice biological drugs. This type of therapy should not be abandoned but should be investigated further with other comparative study to select patients for the best therapy in terms of efficacy, security and compliance. Moreover, a synergistic approach between these therapies could also be evaluated in the future.
P594 Bowel ultrasound is useful in predicting relapse in patients with Ulcerative Colitis in remission
Authors: Maeda M , Sagami S , Tashima M , Yamana Y , Karashima R , Miyatani Y , Hojo A , Nakano M , Hibi T , Kobayashi T
Published: January 2023

Background

Endoscopic remission is associated with better long-term outcomes of ulcerative colitis (UC), and therefore, it is considered a treatment target. However, endoscopy is invasive and frequent monitoring is not feasible. We have reported that bowel ultrasound (BUS) is useful in predicting endoscopic and histologic severity and in determining response to treatment (Sagami S et al, APT 2020 & 2022). However, it is unclear whether BUS can predict the relapse of UC in remission.

Methods

We conducted a retrospective cohort study enrolling UC patients who underwent BUS from Jul 2018 to Jul 2021 during clinical remission (Patient Reported Outcome-2 ≦ 1 and no rectal bleeding) for at least 3 months and followed for 1 year. Spearman rank correlation coefficient was used to analyse the correlation between BUS and Mayo endoscopic subscore (MES) (evaluation of the most severe part of the colon). The association between BUS findings (bowel wall thickness (BWT), bowel wall flow (BWF), bowel wall stratification (BWS), enlarged lymph nodes), Milan Ultrasound Criteria (MUC = 1.4 × colonic BWT + 2 × colonic BWF (0 = absence, 1 = presence of colour Doppler signal)) (Allocca M et al, UEGJ 2021), MES, CRP and faecal calprotectin (FC) and subsequent clinical relapse was evaluated. Relapse was defined as rectal bleeding score ≧ 1, stool frequency score ≧ 2, or treatment intensification for symptoms.

Results

A total of 58 patients were included in the study. The median age was 46 years, 37 (63.8%) were male, 39 (67.2%) were pancolitis, and the median disease duration was 116 months. BWT and BWF were moderately correlated with MES but MUC showed a numerically highest coefficiency (0.61) when evaluated for the colon. Overall, 18 patients (31.0%) relapsed within 1 year. Neither BWT, BWF, BWS, enlarged lymph nodes, nor CRP was predictive for relapse. The log-rank test showed MUC > 6.2 (p = 0.019), MES ≥ 1 (p = 0.013), and FC ≥ 250 μg/g (p = 0.040) were associated with a shorter time to relapse. Cox proportional hazards model showed MUC > 6.2 (HR 3.22: 95%CI 1.14-9.08, p = 0.027), MES ≥1 (HR 8.70: 95%CI 1.11-68.1, p = 0.040) had a higher risk of relapse in 1 year. Sensitivity, specificity, PPV, and NPV of MUC > 6.2 for relapses of different time points (3, 6, and 12 months) showed high specificity of 0.90-0.91 and NPV of 0.74-0.90. Interestingly, 4 out of 9 patients with MUC > 6.2 relapsed within 3 months, suggesting MUC > 6.2 is a risk of short-term relapse.

Conclusion

BUS in UC patients in remission can predict relapse using MUC. In particular, the MUC score ≤ 6.2 is associated with a lower risk of relapse and could be a treatment-target alternative to endoscopic healing.
P597 Usefulness of histological monitoring in predicting relapse after de-escalation of thiopurines in Ulcerative Colitis
Authors: Yamana Y , Sagami S , Maeda M , Karashima R , Miyatani Y , Hojo A , Nakano M , Maeda I , Hibi T , Kobayashi T
Published: January 2023

Background

Thiopurines are useful to maintain remission for ulcerative colitis (UC) and to inhibit immunogenicity in combination with biologics while their long-term use may increase risks of infections and malignancies. Therefore, the risk-benefit balance should be evaluated, and de-escalation needs to be discussed. However, optimal de-escalation strategy such as dosing and monitoring has not been well studied.

Methods

UC patients in clinical remission (partial Mayo score ≤ 2 and rectal bleeding subscore of 0) who de-escalated thiopurines (dose-reduction or discontinuation) were enrolled. The risk of relapse and changes in Mayo endoscopic subscore (MES) and histological findings after thiopurine de-escalation were retrospectively investigated. The correlation with relapse (treatment escalation (including topical therapy) with the exacerbation of symptoms or rectal bleeding score ≥ 1) was analyzed by logistic regression analysis.

Results

A total of 69 de-escalation steps (51 dose-reductions and 18 discontinuations) were conducted in 39 patients. The mean duration and dose of thiopurine use were 3.5 years and 66.6mg (converted to azathioprine). Thiopurines were used in combination with biologics in 16 (41.0%). Relapse occurred in 17/69 (24.6%) de-escalation steps (10/17 discontinuations). In 36 de-escalations remaining in remission with available data before and after de-escalations, worsening of MES occurred in 13%, whereas exacerbations of any histopathological finding occurred in 44% (crypt architectural irregularities 25%, chronic inflammatory cell infiltrate 19％, acute inflammatory cell infiltrate 16％, basal plasmacytosis 13%, mucin depletion 13%, crypt abscess 8%). Chronic inflammatory cellular infiltrate (p=0.002), basal plasmacytosis (p=0.008), and acute inflammatory cell infiltrate (p=0.039) at de-escalation were significantly associated with relapse after de-escalation. Nancy Index was also associated with relapse (p=0.011), while MES was not.

Conclusion

Histological worsening may precede clinical relapse thus may be useful to predict relapse after thiopurine withdrawal.
P601 Pneumococcal vaccination in patients with immunomediated inflammatory diseases (IMIDs) using a real-world multidisciplinary project
Authors: Martins A , Silva F , Canelas G , Ribeiro L , Pinto S , Sarmento A , Magro F , Ferreira de Abreu C M
Published: January 2023

Background

Vaccination is a crucial element in managing patients with IMIDs, however rates of vaccination remains suboptimal. This study assessed the adherence to pneumococcal vaccination.

Methods

A prospective cohort study was conducted between January 2020 and December 2021. Vaccine prescription and adherence were assessed during an Infectious Diseases (ID) consultation. Were considered pneumococcal conjugate (PCV13) and polysaccharide (PPS23) vaccines.

Results

There were 262 patients included (215 with inflammatory bowel disease and 47 with rheumatological diseases), 136 (52%) were male, median age was 41±15 years and 167 (64%) were on immunossuppresive therapy. At baseline, 26 (10%) patients were fully vaccinated against pneumococcal disease and for 236 (90%) vaccination was prescribed as such: PCV13 followed by PPSV23 in 86 (36%) patients, PCV13 in 126 (54%) and PPSV23 in 24 (10%). Adherence to PCV13 occurred in 185 (87%) patients and to PPSV23 in 76 (69%). In patients with both vaccines prescribed (n=86), 57 (66%) had complete adherence and the remaining had at least one of them. In this group (n=86), patients with complete adherence were older than the remaining (45±17 vs. 38±12 years, p=0.03) but no difference was found concerning the baseline disease. After the ID consultation, 175 patients from 236 (74%) became fully vaccinated against pneumococcal disease.

Conclusion

A multidisciplinary approach and adequate local interventions shall be considered to improve vaccine adherence. ID physicians can play a role in the process of increasing vaccine prescription and adherence.
P606 Significant regional differences in referral patterns for bowel resection in Crohn’s disease patients
Authors: Iesalnieks I , Adamou A , Bercher M , Streetz K
Published: January 2023

Background

Preoperative factors - mainly patients’ condition and disease phenotype – are main determinants of postoperative outcome. However, those factors might be strongly dictated by regional traditions and treatment patterns of referring gastroenterologists. The present prospective observational study compared two German IBD-referral centers located in two different geographical regions regarding patients’ characteristics and postoperative outcome.

Methods

Consecutive patients referred to undergo intestinal resections at two different regional centers of IBD-surgery were included in present prospective observational study. Both surgical departments were headed by same surgeon, thus, decisions to perform surgery, preoperative routine and the postoperative management did not differ between hospitals. One hospital (Hospital 1) was located in Bavaria. Patients underwent intestinal surgery at this hospital between 2019 and 2021. The second hospital (Hospital 2) was located in North Rhine-Westphalia. All surgeries at Hospital 2 were performed 2022. The distance between both hospitals was about 600km.

Results

181 patients underwent bowel resections – 102 at Hospital 1 and 79 at Hospital 2. There were significant differences between both hospitals regarding preoperative variables: Azathioprine intake (8% vs. 23%, p=0.005), Steroid intake (13% vs. 29%, p=0.008) and presence of colonic disease (27% vs. 46%, p=0.013). Also, the frequency of some intraoperative procedures differed significantly: ostomy formation at surgery (16% vs. 29%, p=0.044), ileocolic resections (78% vs. 58%, p=0.001), colonic resections (15% vs. 34%, p=0.003). Postoperatively, there was difference in incidence of postoperative ileus (8% vs. 18%, p=0.041). Also, overall complication rate was lower in Hospital 1 (21% vs. 31%), however, the difference was not statistically significant (p=0.12).

Conclusion

Different referral patterns might exist between various hospitals and regions leading to different perioperative outcomes. This should be taken in consideration when results of studies are compared.
P611 COMPARATIVE EFFECTIVENESS AND SAFETY OF VEDOLIZUMAB VS. ANTI-TNFs IN CROHN’S DISEASE BIO-NAÏVE PATIENTS AND PATIENTS WITH FAILURE OF ONE PREVIOUS ANTI-TNFα (EVOLVE-IBERIA STUDY)
Authors: Muñoz Nuñez J F , Rodríguez C , Gisbert J P , Bernardo S , Aparicio J , Tagarro I , Casellas F
Published: January 2023

Background

Vedolizumab (VDZ) is a gut-selective, anti- lymphocyte trafficking drug inhibiting α4β7-integrin approved for treatment of moderately to severely Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Medical charts from CD patients were retrospectively reviewed in sites from Spain and Portugal. The primary objectives are to compare real-world clinical effectiveness and treatment patterns data on the use VDZ vs. anti-TNFα in CD patients, either as the first biologic or after failure to a single anti-TNFα. Inverse probability of treatment weights (IPTW) were used to balance both study cohorts for the baseline demographic and clinical patient characteristics.

Results

210 CD patients were included with a median follow-up of 26.0 months. Eighty-three (40%) patients started treatment with VDZ, being 57% of them bio-naïve. In the anti-TNFα cohort, 76% of patients were bio-naïve. Clinical response rates at week 14 were higher for anti-TNFα group (88%) vs. VDZ group (68%) (p=0.007). However, at week 52, clinical response rates were comparable with 75% in the VDZ group and 70% in the anti-TNFα group (p=0.48). Clinical remission rates at week 14 were higher for anti-TNFα group (79%) vs. VDZ group (56%) (p=0.005). However, at week 52, clinical remission rates were comparable among VDZ and anti-TNFα cohorts, 51% vs. 67%, respectively (p=0.07). The rate of treatment intensification was 31% in VDZ vs. 42% in the anti-TNFα group (p=0.13). Median time (months) to first treatment intensification was 8.8 in the VDZ group vs. 6.3 in the anti-TNFα group (p=0.83). The overall discontinuation rates were 39% with VDZ vs 49% with anti-TNFα (p=0.16) (Fig.1). Among patients with endoscopic assessments available, endoscopic remission occurred in 47% of patients in the VDZ group (n=7/15), and in 42% of patients in the anti-TNFα arm (n=10/24) (p=0.86) at week 52. And among those patients with biochemical assessment available, biochemical remission (CRP<5mg/L) was achieved by 70% of patients in VDZ cohort (n=49/70) vs. 75% patients in anti-TNFα cohort (n=88/118) (p=0.45) at week 14, and by 74% of patients in both arms (n=45/61 and 78/106, respectively) at week 52. VDZ treated patients showed a significant lower rate of treatment related adverse events vs. anti-TNFα cohort: 1.15 vs. 2.7 per 100 patients-year, respectively (p=0.024). Infections, serious infections, and malignancies were also less frequent in the VDZ than in the anti-TNFα cohort: 0.48 vs. 1.75 per 100 patients-year, respectively (p=0.015) (Fig.2).

Conclusion

This real-world study supports the long-term use of VDZ as the first or second biologic for CD patients, showing similar effectiveness than anti-TNFα after 1 year, but better safety outcomes.
P628 Tofacitinib in pediatric ulcerative colitis: a retrospective multi-center experience from the Paediatric IBD Porto group of ESPGHAN
Authors: Ledder O , Dubinsky M , Dolinger M , Fatima A , Suskind D , Scarlett J , Röeser D , Shouval D , Meyer G , Molle Rios Z , Pujol G , Lozano A , Kolho K L , Rohani P , Hussey S , de Mejj T , Ayers T , Navas López V M , Turner D , Tzivinikos C , Stein R , Savla , S
Published: January 2023

Background

Tofacitinib, a Janus kinase (JAK) inhibitor, has recently been approved for treatment of moderate to severe active ulcerative colitis (UC) in adults. Data on efficacy and safety in pediatrics are limited. In this multicenter study from the Paediatric IBD Porto group of ESPGHAN, we describe the short-term effectiveness and safety of tofacitinib in an international pediatric IBD cohort.

Methods

Retrospective review of children (2-18 years) diagnosed with UC treated with tofacitinib from 15 pediatric centers internationally. Primary outcome was corticosteroid-free clinical remission (PUCAI<10) at week 8, with secondary outcomes including clinical response (≥20 point decrease in PUCAI), colectomy rate and safety. Primary outcome was calculated utilizing non-response imputation (NRI), whereby drug cessation for any reason was considered treatment failure.

Results

78 patients (43 (55%) female, mean age at diagnosis 12.5 (±2.7) years, median disease duration 20 months (IQR 10.3-38.8)), all with previous biologic failure, including 20/78 (26%) with previous failure of three biologic classes.

15/78 (19%) patients achieved corticosteroid-free clinical remission at week 8 with a further 18/78 (23%) demonstrating clinical response. 9/78 (12%) underwent colectomy by week 8, and 21/78 (27%) by week 24. Twelve adverse events were reported including five infective (three of which deemed possibly related to treatment – zoster, HSV-2 cheilitis and septic arthritis), one case of pancreatitis, and abnormal blood test results in 5 children (anemia, lymphopenia, elevated hepatic transaminases and hypercholesterolemia).

Conclusion

In this largest real-life cohort of tofacitinib in pediatric UC to date, tofacitinib seemed effective in at least 19% of highly refractory patients by week 8. Adverse reactions and safety were largely consistent with adult data.
P635 Risankizumab - real world Israeli data in severe refractory IBD patients
Authors: Bar-Gil Shitrit A , Gil Y , Israeli E , Koslowsky B , Mazuz B , Israel I , Goldenberg R , Ben-Bassat O , Weisbrud A , Ledder O , Zinger A , Ben Horin S , Goldin E , Lahat A
Published: January 2023

Background

The landscape of inflammatory bowel disease (IBD) treatment is rapidly expanding with the development of new therapeutic options. Risankizumab (Skyrizi®), a humanised IgG monoclonal antibody that targets the p19 subunit of IL-23, was developed for the treatment of immunological and inflammatory disorders, and recently began to be investigated also in the field of IBD. Most patients who receive Risankizumab do so as part of clinical trials, but there are a number of patients with severe refractory disease who have received it as a compassion treatment and they present preliminary Real-World data for this drug.

Aim

to present the real-world data of patients with severe refractory IBD who received Risankizumab as a compassion treatment.

Methods

Retrospective Israeli multicenter study from 6 tertiary IBD centers (Shaare Zedek medical center, Wolfson, Ichilov, Hadassah , Sheba and Barzilai ) on 21 patients with severe refractory IBD (18 CD, 3 UC) who received Risankizumab (IV 600 mg at 0, 4, 8 weeks; then SC 180 or 360 mg SC every 8 weeks) as compassionate treatment with a median follow up of 30 weeks (4-52 weeks).

Results

Although some of the clinical and laboratory parameters are still being collected, we can present some trends. 21 patients were included in the analysis. 17 /21 were after ustekinumab failure. At week 12, there was a significant reduction in Harvey-Bradshaw index (HBI) for Crohn's disease, in CRP values and Calprotectin as compared with the baseline data (10.13 to 4.82, p=0.03; 4.16 to 1.62, p=0.004; 3758 to 961, p=0.02, Respectively). In addition, there was a reduction in the percentage of steroids dependent patients (0.44 to 0.14, p=0.07). In the margins of the study, it is worth noting that particularly patients with difficult and resistant disease, who were TPN dependent or on the verge of surgery, as a result of treatment were weaned from TPN or were able to avoid surgery.

Conclusion

According to real-world data, Risankizumab holds a great therapeutic promise even for patients with particularly serious and resistant diseases.