bluuebunny/crossref_metadata_2025_split huggingface dataset:
P759 Perianal Crohn’s disease – therapeutic response and anal cancer risk - a single centre retrospective cohort
Authors: Conceição D , Rajão Saraiva M , Lemos Garcia J , Rosa I , Moleiro J , Simões C , Claro I 
Published: January 2023

Abstract

Background
Perianal manifestations of Crohn’s disease (CD) occur in up to 43% of CD patients, and are strongly associated with colonic and rectal involvement. They have negative effects on patients’ quality of life and the risk of anal cancer (AC) is two to three times higher than the general population. The management of perianal disease (pCD) often includes a local approach but also a systemic therapeutic escalation.

Methods
Aim: to evaluate the response to therapy and the incidence of AC in patients with pCD. Retrospective single-centre study, recruiting all adult patients with pCD. We analysed the population demography, extraintestinal manifestations, the presence of perianal disease at diagnosis, the subtype of pCD, PDAI score, baseline treatment and the need for readjustment. We evaluated the clinical and MRI response atsix months, further therapeutic changes required, the incidence of anal and rectal cancer and the status at last follow-up.

Results
174 patients with CD, 50 with pCD (29%) – from these: 59% Male; Age 22-77 (median 51); Extraintestinal manifestations 16 (31%); pCD at the diagnosis of CD 29 (57%). pCD characterization: fistula 46 (92%) (simple 6; complex 40); abscess 27 (54%); fissure 12 (24%). PDAI score: 1-17 (median 7,5). Approach: fistulotomy 25 (49%); seton placement 13 (25%); protective stoma 5 (9,8%). Antibiotics in 43 (86%). Therapeutic change 40 (84%) -started: corticosteroid course 9 (18%) (all with rectal disease activity), anti-TNF 28 (55%), thiopurine 23 (45%) 13 of them in monotherapy. At 6 months: global clinical improvement 41 (81%); healed PD 18 (35%). Follow up 2-49 years (mean 20); Subsequent treatment change during follow up: 28 (55%). At last follow-up: luminal CD in clinical remission 44 (86%); pCD improvement 43 (84%) and deep remission in 32 (64%). By univariate analysis there was no significant association between starting anti-TNF therapy or monotherapy with thiopurine and clinical response at 6 months, or at last follow up, with MRI improvement. During follow up, 3 patients (6%) develop AC (2 perianal fistula-related cancer; 1 adenocarcinoma). There was no significant association with the use of anti-TNF (p 0,356) or thiopurine (p 0,312) but there was an association with absence of clinical response at 6 months (p 0,050) and lack of MRI improvement (p 0,057). There were no rectal cancer cases.

Conclusion
Most patients with pCD required therapeutic changes, the majority of them initiating anti-TNF – this resulted in luminal disease remission and at least pCD improvement in more than 80% of patients. The small sample size limited our results, but AC seemed to be more common in patients with chronically active pCD.
P764 Effectiveness and safety of COVID-19 Vaccine among Patients with Inflammatory Bowel Disease: A medical center hospital-based study in central Taiwan
Authors: Wu Y H , Chou J W , Huang P J , Wang C P , Cheng K S 
Published: January 2023

Abstract

Background
In 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). COVID-19 infection resulted in many complications for IBD patients. However, the association of IBD patients with COVID-19 who had been vaccinated receiving biologics, immunomodulators, or steroids therapies is lacking in Taiwan. Thus, we hypothesized that the first wave of the COVID-19 pandemic would have some effects on IBD patients who were vaccinated and performed this retrospective study. The aim of this study was to investigate the effectiveness and safety of COVID-19 vaccines in patients with IBD receiving biologics, immunomodulators, or steroids therapies in a medical center hospital in middle Taiwan.

Methods
From January 1980 to October 2022, a total of 286 consecutive patients with IBD (UC: 184 patients; CD: 102 patients) was enrolled into our current study. There were 155 patients had received vaccine for at least one dose. Finally, 51 patients who were vaccinated still suffered from COVID-19 with an infection rate of 32.9%. We analyzed the clinical manifestations of COVID-19-positive in IBD patients. Clinical characteristic, and treatment outcomes of all patients with COVID-19 who had been vaccinated were analyzed.

Results
The mean diagnostic age of these enrolled patients was 45.1years. Male accounted for the majority of our all patients in the study (76.5%). There were 54.1% patients had received COVID-19 vaccine for at least one dose. The mean dose of COVID-19 vaccine was 2.16. Patients with UC presented significantly higher infection rate of COVID-19 than patients with CD. (Table 1). The most common clinical manifestations were sore throat, followed by fever, cough, runny nose and fatigue. The most common type of biologics used in these patients with IBD was Vedolizumab, followed by Adalimumab and Infliximab. There were no differences in the COVID-19 infection rate in different treatment groups among patients with UC or CD patients(Table 2, 3).

Conclusion
Our current study showed the risk of COVID-19 in IBD patients is not specifically higher than the general population. Our 51 patients with COVID-19 infection had a good outcome and none one needed hospitalization. Patients with UC presented significantly higher infection rate of COVID-19 than patients with CD. The use of biologics or immunomodulators was not associated with an increased risk of COVID-19 in patients with IBD. The use of steroids was also not associated with an increased risk of COVID-19 in patients with IBD if steroids were held two weeks or decreased dosage before vaccinations. Furthermore, we found that IBD patients under adequate therapy can reduce the severity of COVID-19.
P772 Association of histological remission with long-term clinical outcomes in patients with ulcerative colitis: a multi-national retrospective study with centralized histological assessment
Authors: Jairath V , Armuzzi A , Pai R K , Sun D , Li Y , Bassel M , Brett N R , Bojic D 
Published: January 2023

Abstract

Background
Histological remission (HR) is an achievable therapeutic target in ulcerative colitis (UC), however there is limited data on the association of HR with long-term clinical outcomes. We evaluated the association between HR and a composite outcome of colectomy, UC-related hospitalization, or intravenous (IV) corticosteroid use in patients with UC.

Methods
This was a multi-national retrospective study of adult patients with UC treated with a biologic or small molecule drug between 09/01/2005 and 06/30/2019 in Canada, Italy, Netherlands and United States. The study included biologic-naïve (bio-naïve) and biologic-experienced (bio-exp) patients. Biopsies taken during routine practice were procured and re-assessed for histological activity by blinded gastrointestinal pathologists in a central laboratory. HR was defined as the absence of neutrophilic inflammation (Nancy Histological Index ≤1 or Robarts Histological Index ≤3 plus Geboes subgrades 2B.0/3.0) at the most recent endoscopic evaluation within 3 to 9 months after treatment initiation. Cumulative risk of time-to-event outcome over 12 months from treatment initiation was evaluated using Kaplan-Meier (KM) methods and Cox proportional hazard analysis. Statistical significance was set as p-value &lt;0.05.

Results
We included 227 patients with UC (bio-naïve and bio-exp) (Table 1); of whom, 132 (58%) were bio-naïve (Table 2). Of the bio-naïve patients, 62 (47%) achieved HR and 70 (53%) had histologic activity; 9 (6.8%) underwent colectomy, 16 (12.1%) had UC-related hospitalizations, and 8 (6.1%) received IV corticosteroid. Unadjusted time-to-event for the composite outcome was significantly greater in bio-naïve patients who achieved HR compared to those who did not (p=0.0023; Figure 1A). In multivariable analysis, the association of HR on the composite outcome in bio-naïve patients was not statistically significant (adjusted hazard ratio [aHR], 0.26; 95% CI, 0.02-4.42). In the overall patients (bio-naïve and bio-exp), unadjusted (p&lt;0.001; Figure 1B) and multivariable (aHR, 0.32; 95% CI, 0.06-1.75) associations of HR and the composite outcome were similar to the bio-naïve patients.

Conclusion
We used central reading to evaluate the association of HR and clinical outcomes in patients with UC. While unadjusted KM curves showed that HR was associated with decreased risk of the composite outcome, the association was no longer significant after adjustment for covariates. The target sample size for this study was not achieved and the number of events was small, resulting in reduced statistical power. Future studies are warranted to explore the association further.
P779 COMPARATIVE EFFECTIVENESS AND SAFETY OF VEDOLIZUMAB VS ANTI-TNFs IN ULCERATIVE COLITIS BIO-NAÏVE PATIENTS AND PATIENTS WITH FAILURE OF ONE PREVIOUS ANTI-TNFα (EVOLVE-IBERIA STUDY)
Authors: Casellas Jorda F , Rodríguez C , Gisbert J P , Bernardo S , Aparicio J , Tagarro I , Muñoz F 
Published: January 2023

Abstract

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
This was a retrospective cohort study based on review of patients charts from sites in 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 UC patients, either as the first biologic or after failure to a single anti-TNFα. Inverse probability treatment weights (IPTW) were used to balance both cohorts on the baseline demographic and clinical characteristics.

Results
199 UC patients were included with a median follow-up of 24 months. One hundred and two (51%) patients started treatment with VDZ, and 44% of them were bio-naïve. In the anti-TNFα cohort, 77% of patients were bio-naïve. Clinical response rates were similar in both groups at week 14, 81% in VDZ cohort vs. 80% in anti-TNFα cohort (p=0.91) and at week 52, 76% in VDZ treated patients vs. 73% anti-TNFα treated patients (p=0.72). Clinical remission rates at week 14 were 52% for VDZ group vs. 55% in anti-TNFα group (p=0.76). At week 52, clinical remission rates were 57% for VDZ vs. 62% for anti-TNFα (p=0.49). Treatment intensification was needed in 44% of VDZ treated patients vs. 40% in the anti-TNFα group (p=0.58), and median time (months) to first treatment intensification was 6.4 in the VDZ group vs 5.8 in the anti-TNFα group (p=0.96). Discontinuation rates during the follow up were 40% for VDZ treated patients vs. 50% for anti-TNFα treated patients (p=0.17) (Fig.1). Among patients with endoscopic assessments available at week 52, endoscopic remission rates were 36% in VDZ cohort (n=9/25) vs. 36% in anti-TNFα cohort (n=9/25) (p=0.95). And among those patients with biochemical assessment available, biochemical remission (fecal calprotectin &lt;250 μg/mg) occurred in 59% of patients in VDZ group (n=41/69) vs. 54% in anti-TNFα group (n=29/54) (p=0.54) at week 52. VDZ treated patients showed a significant lower rate of treatment related adverse events vs. anti-TNFα cohort: 0.23 vs. 1.10 per 100 patients-year, respectively (p=0.037). Adverse events of special interest (infections, serious infections, and malignancies) were also less frequent in the VDZ than in the anti-TNFα cohort: 0.75 vs. 2.42 per 100 patients-year (p=0.008) (Fig.2).

Conclusion
Overall, these findings show similar effectiveness with VDZ and anti-TNFα when used as the first or second biologic for UC patients after 1 year, but a safety advantage in favor of VDZ, supporting a favorable benefit-risk ratio in favor of VDZ.
P780 Prognosis and optimal treatment for 5-aminosalicylic acid-intolerant patients with Ulcerative Colitis
Authors: Yaguchi K , Kinoshita H , Kunisaki R , Madarame A , Tatsuno M , Nishikawa Y , Hama T , Onishi M , Kobayashi K , Shibui S , Toritani K , Nishida D , Matsubayashi M , Nakamori Y , Nishio M , Umezawa S , Ogashiwa T , Sasaki T , Fujii A , Kimura H , Kato J , Maeda S 
Published: January 2023

Abstract

Background
5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients.

Methods
This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents.

Results
Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P &lt; 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P &lt; 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81).

Conclusion
Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.
P791 Up to one third of rapid thiopurine-S-methyltransferase metabolizers manifest clinical and/or laboratory azathioprine side effects: A single centre experience
Authors: Lababidi N E , Pavel F 
Published: January 2023

Abstract

Background
According to ECCO-ESPGHAN consensus guidelines, azathioprine (AZA) can be used for maintenance of remission in paediatric Inflammatory Bowel Disease (IBD). AZA side effects are well documented. Haematological toxicity affects 2-14% of patients and pancreatitis affects up to 7% of them, requiring modification of AZA dosage or its cessation. Thiopurine-S-methyltransferase (TPMT) activity should be tested prior to AZA commencement. Slow metabolizers should not be started on AZA and intermediate ones should get a dose reduction. This study evaluates the incidence of AZA side effects in TPMT rapid metabolizers.

Methods
Retrospective evaluation of prospectively collected data in children tested for TPMT and who received AZA between 3/13 and 10/22. Focusing on the incidence of both clinical and laboratory side effects in rapid metabolizers.

Results
Ninety children had TPMT tested. Only 1 intermediate a 1 slow metabolizer were identified. All rapid metabolizers were diagnosed with IBD, 62 (70,5%) with Crohn’s (CD), 16 (18,2%) with Ulcerative Colitis (UC), 7 with Very Early Onset IBD (VEO-IBD) and 1 with IBD undifferentiated. Forty-seven were male (53,4%) and 41 female. The median age at diagnosis was 13.5±3,9 years. Of the 88 rapid metabolizers, 82 (93%) received AZA. The remaining 6 had different treatment strategies. Clinical and/or laboratory side effects were documented in 27 cases (32,9%). Haematological toxicity was most frequent affecting 19 participants (23.1%). In 13 cases (68,4%) leukopenia resolved spontaneously, in 4 cases (21%) dose reduction was required, and in 3 cases (15,8%) AZA had to be stopped. Pancreatitis was identified in 6 patients (7,3%). Half of the cases were discovered by laboratory findings and the remainder had a clinical correlate. In 2 cases, laboratory pancreatitis normalized on follow-up examination, in the remaining ones AZA had to be withdrawn. Clinical intolerance was found twice, once requiring split dosage, and once dose reduction. Haematological toxicity manifested on average within 10,9 months since treatment start (0.5-43 months), pancreatitis within 0,54 months with one case manifesting after 79 months of treatment. In this single case, autoimmune pancreatitis is debated. Clinical intolerance appeared within days from AZA commencement. Boys had AZA side effects slightly more frequently (15/27, 55%). CD patients had AZA side effects the most (16/27, 59%). However, CD was the most common diagnosis in the cohort.

Conclusion
Being a rapid TPMT metabolizer should reduce the risk of AZA side effects. However, these data demonstrate a 32,9% occurrence of them, emphasising the importance of clinical and laboratory follow-up in patients on AZA.
P792 Pharmacokinetics and clinical evaluation of vedolizumab based on real-life routine monitoring data in IBD patients
Authors: Markovic S , Kralj D , Odanovic O , Homšek A , Kalaba A , Svorcan P , Vučićević K 
Published: January 2023

Abstract

Background
Vedolizumab (VDZ) is recommended for induction of remissionin patients with inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) based on pharmacokinetic measurements of VDZ trough plasma concentrations adds-up on routine patients’ clinical follow-up. Great interpatient variability in VDZ serum concentrations is observed. Our aim was to investigate factors contributing to variations in VDZ levels by developing population pharmacokinetic model based on sparse TDM data, and understand its importance in reaching adequate response.

Methods
Retrospective data from IBD patients undergoing treatment with VDZ were reviewed, and patients with measured VDZ serum concentration were included in analysis. In addition, demographic, therapy and clinical characteristics were collected; including various inflammatory biomarkers such as platelets, leucocytes, C-reactive protein, sedimentation rate, fecal calprotectin, etc., and calculated Mayo, SES scores, where appropriate. VDZ dose of 300 mg was administered as 30-minutes infusion at week: 0, 2 and 6 during induction, with a 4-, 6- or 8-week dosing interval during maintenance phase. Population modeling approach was applied to characterize pharmacokinetic profile of VDZ. In addition, logistic analysis was implemented to test correlation among VDZ concentration, disease biomarkers, and appropriate clinical scores.

Results
In total, 115 VDZ trough concentrations obtained from 107 patients were analysed. Patients’ characteristics are given in Table 1. VDZ concentrations were described by two-compartment model. Estimated typical value of VDZ clearance (CL) was 0.226 L/day, without any difference among ulcerative colitis (UC) and Crohn’s disease (CD) patients. We identified that previous treatment with anti-TNF biologics increases CL by on average 24.8%. In addition, our preliminary analyses indicate higher probability of thrombocytosis with lower VDZ levels. Median VDZ concentration in patients whose platelets were above and below 350 (109/L) were 15.33 and 20.29 microg/mL, respectively (Figure 1).

Conclusion
Our preliminary results suggest that platelets account as inflammation burden marker and previous antiTNF treatment may be predictive factors for proactive VDZ optimization.
P797 Self-reported efficacy and safety of infliximab and adalimumab biosimilars after non-medical switch in patients with Inflammatory Bowel Disease: Results of a multicenter survey
Authors: Bikar A , Farkas N , Resál T , Szepes Z , Klaudia F , Vincze Á , Miheller P , Molnár T , Sarlós P 
Published: January 2023

Abstract

Background
Several studies have proven similarity in terms of efficacy and safety between infliximab (IFX) or adalimumab (ADA) biosimilars and their corresponding originators. However, there is still a paucity of data on the impact of switching from an originator to a biosimilar on patients’ subjective disease control in clinical practice. In Hungary, a mandatory non-medical switch program regarding anti-TNFs was launched in 2021. We aimed to assess symptom control and perception of adverse events following non-medical switch in patients with inflammatory bowel disease (IBD).

Methods
In this cross-sectional, questionnaire-based study, Hungarian patients with IBD who switched from infliximab originator to biosimilar GP1111 or from adalimumab originator to biosimilar GP2017 after receiving at least one dose of biosimilar were interviewed. The subjective efficacy was measured using a 10-point interval rating scale, and adverse events were assessed. The difference in efficacy before and after the switch was calculated and compared within and between the two drugs. All statistical analysis was performed using R Statistical Software.

Results
A total of 179 patients were interviewed (median age 41 years, interquartile range 32 to 47; 135 and 44 patients with Crohn’s disease and ulcerative colitis, respectively). There were 73 ADA and 106 IFX switches in our cohort. The subjective efficacy of IFX biosimilar was rated lower compared to IFX reference product (8.72±1.68 vs. 7.77±2.34; p=0.001). The ADA biosimilar was rated higher than their reference product (9.02±1.61 vs. 8.42±1.93; p=0.017). Comparing the satisfaction of non-medical switch between biosimilar groups, patients receiving ADA were more satisfied with the new treatment as patients in the IFX group (p=0.032). The incidence of new perceived adverse events was 85 % in the ADA and 55 % in the IFX group (p&lt;0.001). 66 % of patients on ADA treatment reported pain at the subcutaneous injection site.

Conclusion
Our study confirmed the efficacy of the switch to a biosimilar in the case of ADA, while reduced efficacy was experienced with IFX biosimilar. Based on the different adverse event profiles of biosimilars, the importance of switching the product for medical reasons should be emphasized.