bluuebunny/crossref_metadata_2025 huggingface dataset:
P742 Real-world evidence comparison on the effectiveness of ustekinumab vs anti-TNF or vedolizumab in ulcerative colitis: induction phase results from the prospective, observational RUN-UC study
Authors: Bokemeyer B , Plachta-Danielzek S , Howaldt S , Mohl W , Efken P , Ehehalt R , Kahl M , Krause T , Trentmann L , Lügering A , Schnoy E , Jochum C , Fajardo Salmon S , Hartmann P , Gilman E , Schreiber S
Published: January 2023

Background

Observational real-world evidence (RWE) studies on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are required in addition to RCTs, which are usually confined to selected patients and thus may not represent distinct treatment patterns and everyday clinical practice. For this reason, the prospective, controlled, propensity score (PS)-adjusted RUN-UC study was conducted in UC patients starting a newly initiated biologics therapy with a follow-up period of 3 years. The aim of the present analysis was to investigate the induction phase effectiveness of UST vs anti-TNF vs vedolizumab (VEDO) in UC in terms of clinical and steroid-free remission.

Methods

Between 2020-2022, 507 UC patients starting a new therapy with UST or other biologics were enrolled in 34 IBD-experienced centres across Germany. After exclusion of small molecules and missing outcomes, the final sample consisted of 317 patients. Response modified (reduction of partial Mayo score (pMayo) by ≥ 3 points from baseline to week-16 and a reduction of at least 30% or reaching remission at week-16), clinical remission (pMayo ≤ 1 plus a bleeding subscore=0), and steroid-free remission (pMayo ≤ 1, bleeding subscore=0 and no systemic use of steroids or oral budesonide during the last 8 weeks) were considered as outcomes. To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Health-related quality of life was assessed by using the self-reported visual analogue scale (EQ-VAS) of the EQ-5D. Changes in EQ-VAS from baseline to week-16 were assessed with a linear model.

Results

101 UST (bio-naïve: 6), 106 anti-TNF (ADA: 24.5%, IFX: 65.1%, GOL: 10.4%) (bio-naïve: 70) and 110 VEDO (bio-naïve: 73) UC-patients were included. PS adjustment removed systematic differences between the three groups (UST/anti-TNF/VEDO: 44.9/43.8/48.1% males, 6.7/9.9/5.5% smokers, 7.9/12.5/9.3% EIM). The effectiveness of UST in terms of response, clinical and steroid-free remission was comparable to that of anti-TNF and VEDO at week 16 (Tab. 1). We observed a significant increase in EQ-VAS within all three groups (Tab. 2). The increase in the UST group was significantly higher than in the VEDO group and numerically higher than in the anti-TNF group.

Conclusion

In this prospective RUN-UC study, with propensity score weighted groups, UST showed similar induction phase effectiveness in comparison with anti-TNF and VEDO. Quality of life was significantly improved in the UST group vs VEDO and was numerically higher than anti-TNF after the induction phase.
P746 Identification of Altered Microbial Genera at Baseline in Adalimumab Clinical Remitters and an Absence of Change in Total Microbial Composition Post Induction Treatment in the SERENE UC Study
Authors: Morsy Y , Pivorunas V , Leitner C , Birchler T , Guay H , Scharl M
Published: January 2023

Background

The gut microbiome plays an integral role in the pathogenesis of Inflammatory Bowel Disease (IBD). However, there have been a limited number of studies investigating the composition of the gut microbiome in anti-TNF-treated Ulcerative Colitis (UC) patients. The aims of this study were to 1) identify novel microbial baseline predictors of clinical response and remission to Adalimumab treatment, and 2) assess the impact of Adalimumab induction treatment on the gut microbiome of UC patients.

Methods

The SERENE UC study (NCT02065622) compared the efficacy of higher adalimumab dosing regimens to the standard regimen in patients with moderately to severely active UC. 16S rRNA gene sequencing was performed on 204 stool samples from 107 UC patients at baseline and Week 8. An ANOVA test followed by Tukey HSD was used to compare microbial content within (baseline) or across (baseline vs Week 8) visits between clinical remitters (n=16), clinical responders (n=38), and patients who failed to respond to Adalimumab treatment (n=53). Clinical response was defined as a full Mayo score decrease of ≥3 points and ≥30% from baseline, plus ≥1-point decrease in rectal bleeding score or absolute bleeding score ≤1 at Week 8. Clinical remission was defined as a full Mayo score ≤2 with no sub-score >1 at Week 8.

Results

There were no differences in alpha diversity in terms of richness and evenness when comparing samples from patients across response categories, or alpha and beta diversity when comparing paired samples from patients pre- and post-treatment. In addition, principal coordinate analysis of the microbiome did not highlight any clustering of the samples between response groups or visits. When stratifying patients by clinical response status at Week 8, we identified 4 genera that were significantly altered at baseline in the clinical remitters compared to the clinical responders and/or non-responders, including Dorea, Ruminococcus torques group, Subdoligranulum, and Collinsella. Unexpectedly, when comparing paired pre- and post-treatment samples within a response group, we failed to detect any significant changes on the total microbiome composition regardless of response status at Week 8.

Conclusion

These findings suggest that baseline microbial composition is significantly altered in UC patients who achieve clinical remission, but that Adalimumab treatment does not significantly alter the composition of the gut microbiome after 8 weeks of treatment. Future work is focused on achieving a deeper understanding of the gut landscape in UC patients treated with Adalimumab through 1) investigation of bacterial, viral, and fungal composition by metagenomics, and 2) integration of serum metabolomics data.
P752 Predictors of time to relapse upon ozanimod withdrawal in patients with moderately to severely active ulcerative colitis
Authors: Vermeire S , Abraham B , Bressler B , Reinisch W , Axelrad J E , Jain A , Memaj A , Akukwe L , Liu W J , Osterman M T , Canavan J B , Sands B E
Published: January 2023

Background

Ozanimod (OZA) is approved in the EU, US, and other countries for the treatment of moderately to severely active ulcerative colitis (UC) in adults based on the phase 3 True North (TN) trial. Data on time to disease relapse in patients (pts) who withdrew OZA treatment in TN were previously reported (Sands BE et al. Am J Gastroenterol. 2022;17(suppl):S506-7). The objective of this post hoc analysis was to identify predictive and prognostic variables of time to disease relapse in the TN maintenance period (MP).

Methods

Pts in TN were randomised to once-daily oral OZA 0.92 mg or placebo (PBO) in a double-blind manner or to open-label OZA for a 10-week induction period. Those with clinical response to OZA at Week 10 were then rerandomised to continue OZA (OZA/OZA) or switch to PBO (OZA/PBO) in the MP. Disease relapse was defined as an increase in partial Mayo score of ≥2 points from Week 10, absolute partial Mayo score ≥4, Mayo endoscopy subscore (MES) ≥2, and exclusion of other causes of increased disease activity unrelated to UC. Time to disease relapse was estimated using the Kaplan-Meier method in both MP groups. The saturated Cox proportional-hazards model for assessing predictors of time to disease relapse included demographics, disease characteristics, prior medications, and laboratory and efficacy variables at the end of the induction period. Insignificant terms at α=0.05 were removed via backward elimination.

Results

The OZA/OZA arm (n=230) had a slightly higher proportion of pts with baseline severe endoscopic disease than the OZA/PBO arm (n=227). Otherwise, baseline and Week 10 characteristics were balanced across MP arms (Tables 1 and 2). In multivariable analyses, corticosteroid use at Week 10 was prognostic for time to relapse (P<0.0001; no interaction with individual treatment arms). MES >1 and clinical response but not remission at Week 10 were also assessed as prognostic variables, but these did not achieve statistical significance at α=0.05 (P=0.071 and P=0.171, respectively). Relapse rates were low and similar regardless of prior biologic exposure in the OZA/OZA arm. Prior biologic exposure was an independent predictor of time to relapse after withdrawal of OZA in the OZA/PBO arm (P=0.027) (Figure 1). For OZA/PBO pts, Week 16 Kaplan-Meier estimates and 95% CI of no relapse were 83.8% (76.7–88.8%), 72.1% (54.4–83.9%), and 48.5% (30.8–64.1%) for the biologic-naive, 1 failed biologic, and ≥2 failed biologics groups, respectively.

Conclusion

Increasing numbers of prior biologics were predictive of increased rates of disease relapse in pts who discontinued OZA. Pts with UC, especially those with prior biologic failures, should minimise OZA discontinuation to mitigate the risk of disease relapse.
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

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

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

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 <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<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

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 <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

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 < 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 < 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

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

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

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<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.
P801 Maintenance phase effectiveness and persistence after two years in biologic-naïve ulcerative colitis patients treated with vedolizumab or anti-TNF (VEDO-IBD-study)
Authors: Plachta-Danielzik S , Bokemeyer B , Efken P , Mohl W , Krause T , Hoffstadt M , Ehehalt R , Trentmann L , Schweitzer A , Jessen P , Franzenburg S , Hartmann P , di Giuseppe R , Schreiber S
Published: January 2023

Background

In this two-arm prospective real-world-evidence (RWE) study with propensity score adjustment, we aimed to analyse the persistence of biologic therapy in biologic-naïve ulcerative colitis (UC) patients and to compare the 2-year effectiveness of vedolizumab (VEDO) and anti-TNF.

Methods

Between 2017 and 2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with UC and CD (Crohn’s disease) were prospectively included in the VEDOIBD study from 45 IBD-experienced centres across Germany. After the exclusion of biologic-experienced patients, CD, and missing outcomes, the final sample consisted of 314 biologic-naïve UC patients with 2-year follow-up data. In this mITT analysis switching was considered as outcome failure, and clinical remission and (steroid-free) remission rates (pMayo ≤1 plus a bleeding subscore=0 - and no systemic use of steroids or oral budesonide at two years) at two years were predefined as outcomes. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI).

Results

The two-year maintenance phase effectiveness of 182 VEDO and 132 anti-TNF (ADA: 25.8%; IFX: 58.3%; GOL 15.9%) biologic-naïve UC patients were analysed in this prospective RWE-comparison of VEDO vs anti-TNF. Significantly more patients switched to another biologic in the anti-TNF group when compared to the VEDO group up to 2 years (54% vs 29%; p<0.0001) (Fig. 1). In the mITT analysis after 2 years a statistically significant higher clinical remission rate of 43.2% was found for VEDO vs 25.8% for anti-TNF (OR 95% 2.18 (1.19-3.99), p=0.011) (Fig. 2). Considering the two-year effectiveness of ADA and IFX the response rates of VEDO were numerically higher than those of ADA (45.2% vs 37.9%) but not statistically significant. In contrast, for VEDO versus IFX, there was a clear difference in favour of VEDO that resulted in a clinical remission rate of 43.1% versus 16.5% for IFX (p=0.0003).

Conclusion

As shown previously, in the induction phase, there is comparable effectiveness for VEDO and anti-TNF, although the remission rates are relatively low and similar to the range reported in RCTs. Over one year, the effectiveness tends to improve in favour of VEDO, potentially due to better treatment persistence. After two years, the clinical remission rate in the VEDO group is statistically significantly higher than in the anti-TNF group. The higher treatment persistence of VEDO vs anti-TNF and the higher effectiveness may suggest VEDO as a first-line biologics therapy option in UC patients.
P802 Relationships between validated clinical, endoscopic and histological indices in ulcerative colitis
Authors: Walsh A , Kormilitzin A , Friedrich M , Pakpoor J , Hosack T , Matini L , Kantschuster R , Sharda A , Dunbar G , Cheung V T F , Ambrose T , Brain A O , Palmer R , Satsangi J , Travis S P L
Published: January 2023

Background

The simple clinical colitis activity index (SCCAI) is increasingly used in practice for monitoring symptoms, because it documents urgency and nocturnal stool frequency, which are excluded from other indices. The question is how the SCCAI relates to validated endoscopic and histological indices, so that SCCAI thresholds for remission and active disease can be defined.

Methods

The SCCAI (range 0-19) was collected in real time from patients with ulcerative colitis (UC) using web-based TrueColours-IBD monitoring and collated with endoscopic activity (UCEIS, 0-8) and Nancy histological index (NHI, 0-4) for patients who had recorded SCCAI data up to 14d before endoscopy.

Results

482 SCCAI/endoscopy/biopsy trios were analysed from 323 unique patients (162 male) aged 18 to 86 years (male: mean = 43.8, SD = 15.9; female: mean = 44, SD = 14.9). Disease extent for male: Normal=48, E1=23, E2=116, E3=43, female: Normal=45, E1=42, E2=110, E3=27. Spearman's rank correlation coefficient between UCEIS and NHI scores was r=0.77 (95% confidence interval [CI] 0.72 - 0.82, p <0.001). When the UCEIS was ≤ 1, or NHI ≤ 1, which is consistent with remission, the median (IQR) SCCAI was 2 (1 to 4) (Fig 1A, 1B). When the SCCAI was ≥5, the median (IQR) UCEIS was 4 (3 to 5) and the median (IQR) NHI was 3 (2 to 4). For patients with both histologic and endoscopic mucosal remission (HEMR), defined as NHI ≤ 1 and UCEIS ≤ 1, the median (IQR) SCCAI was 2 (0.25 to 4) (Fig 1C). Patients with SCCAI scores outside the IQR (n=8 for UCEIS, n=5 for NHI) had symptoms primarily driven by bowel urgency or poor general wellbeing. Four groups of patients could be identified using linear regression analysis modelling of relationships between bowel urgency and UCEIS score: ‘no urgency without active disease’; ‘urgency without active disease’; ‘urgency with active disease’; and ‘no urgency with active disease’ (Fig 2).

Conclusion

There is a ‘grey zone’ at low scores of symptom-based indices that cannot discriminate endoscopic or histologic remission from mildly active disease. The SCCAI threshold for active UC is >5, but with wide confidence intervals. Mechanisms behind symptoms in the absence of active inflammation need investigating.
P811 Combination biological or small molecule therapy in patients with refractory inflammatory bowel disease: a multicenter Brazilian experience
Authors: Feitosa F , Parra R , Queiroz N , Flores C , Schiavetti B , Azevedo M , Porto Alegre Rosa C , Chebli L , Chebli J
Published: January 2023

Background

This preliminary study describes the Brazilian experience on dual biologic therapy or small molecule combined with a biologic therapy in patients with inflammatory bowel disease (IBD) refractory to multiple biologics.

Methods

We identified patients from 6 IBD centers in Brazil between April 2020 and November 2022 who received treatment with a combination of two biologics or a biologic and a small molecule drug due to refractory disease or concomitant immunomediated condition. The primary endpoint was clinical remission at week 16, defined as a total Mayo score of ≤2 for UC and Harvey-Bradshaw Index (HBI) <4 for CD. Secondary endpoints were improvement in disease activity scores and biomarkers. Adverse events were monitored and summarized descriptively.

Results

Twenty-nine patients were identified (69% CD, n=20), 51.8% female, mean age 38.8 years old [SD= ± 14.8 years]). Seventy per cent (n=14) had penetrating behavior among CD patients. Twenty-seven had failed to, at least, one anti-TNF; 79.9% had failed to ustekinumab (UST), and 34.5% to vedolizumab (VEDO). Twenty-six patients were treated with combination advanced therapy due to loss of response to biologics and three patients had concomitant ankylosing spondylitis. The most common combination used was UST+ADA (n=12, 41.4%), followed by UST+VEDO (n=6, 21.7%). Mean treatment time was 53.8 weeks (SD= 40.4 weeks, CI 95% [37.5 – 70]). At week 16, clinical remission rates were 80% and 66% for CD and UC, respectively. All patients under VEDO + UST combination achieved clinical remission at 16w, in both diseases. Baseline HBI mean was 10.8 (SD= ± 3.6 points; CI 95% [9.1- 12.5]), decreasing to a mean of 5.5 at week 16 (SD= ± 3.5 points; CI 95% [3.8 - 7.2]) and plateauing at 7 by week 24 (SD= ±5.4 CI 95% [3.4- 10.6]). There was a notable decrease in HBI at week 16 (p< 0.001) and a significant decrease at week 24 (p= 0.02) compared to baseline. Mean CRP at week 16 was significantly lower than baseline in CD (17.4mg/dL vs 5.5 mg/dL, p=0.001) and numerically lower in UC (from 14.3mg/dL to 9.9mg/dL, p= 0.5). Fecal calprotectin decreased from 2509mcg/g to 1472mcg/g in both groups (p=0,2). In addition, all patients with ankylosing spondylitis showed symptomatic remission. No new safety signals were identified during follow-up

Conclusion

Despite combination of advanced therapies in IBD is not yet recommended by treatment guidelines, this strategy seems to be a promising option for patients with refractory IBD or concomitant autoimmune disease. Our data indicate that further investigation in this direction is worthwhile.
P819 Histologic activity and clinical outcomes in Ulcerative Colitis
Authors: Liang R , Lin H , Lim W C
Published: January 2023

Background

Microscopic inflammation persisting in ulcerative colitis (UC) patients with endoscopic remission (ER) may be associated with a higher risk of clinical relapse (CRL). Growing evidence suggests histologic remission (HR) improves clinical outcomes. Data from Asian UC patients is lacking. We hypothesize that achieving HR is associated with better clinical outcomes in Asian UC patients.

Methods

We performed a single-centre retrospective cohort study of UC patients in clinical remission (CR) who had a follow-up (‘index’) colonoscopy and minimum one-year follow-up post-colonoscopy. CR was defined as Simple Clinical Colitis Activity Index (SCCAI) ≤2. ER was defined as Mayo Endoscopic Sub-Score (MES) ≤1 at index colonoscopy. HR was defined as Nancy Index ≤1 at index colonoscopy.

CRL was defined as either SCCAI>2 (sub-score >1 for stool frequency or rectal bleeding), medication escalation for active disease, hospitalisation for UC relapse or colectomy for refractory UC.

Kaplan-Meier survival analysis was performed to evaluate clinical relapse-free survival post-colonoscopy. Univariate and multivariate regression analyses were performed to assess predictors of CRL.

Results

169 consecutive UC patients who had undergone colonoscopy from 1 Jan 2000 to 30 Jul 2019 were assessed for eligibility. 100 patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients (80%) were in ER, with 20 patients having persistent endoscopic activity (Table 1). On follow-up, 41 patients (41%) experienced CRL, with 59 remaining in CR.

Of 80 patients in ER, 34 (42.5%) had persistent histologic activity (Nancy Index ≥2) and 29 (36.3%) relapsed during the follow-up period (Table 2). Amongst patients in CR and ER, those with HR had lower CRL rate (26.1% vs 50%, p=.028) and longer clinical relapse-free survival (mean 46.1 vs 31.5 months, p=.015) than those with persistent histologic activity (Figure 1).

On univariate and multivariate analysis of 100 patients in CR, HR was significantly associated with lower risk of CRL (Table 3).

Conclusion

Above and beyond CR and ER, achieving HR improves clinical outcomes in Asian UC patients. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.
P831 Clinical factors associated with severity in patients with Inflammatory Bowel Disease in Brazil (On Behalf of GEDIIB)
Authors: Froes R , Andrade A R , Faria M A G , Parra R S , Zaltman C , Souza H S P , Santos C H M D S , Bafutto M , Quaresma A B , Santana G O , Rafael Luís Luporini R L , Lima Junior S F D , Miszputen S J , Souza M M D , Herrerias G S P , Kaiser Junior R L , Nascimento C R D , Féres O , Barros J R D , Guimarães C D S , Sassaki L Y , Saad-Hossne R
Published: January 2023

Background

Brazil has shown an increase in Inflammatory Bowel Disease (IBD) cases. GEDIIB (Brazilian Organization of Crohn’s Disease and Colitis) established a data platform to create a national registry of IBD patients. The study aimed to characterize the profile of IBD patients and identify clinical factors associated with IBD severity.

Methods

A cohort study was conducted between Jul/20 and Aug/22. Data obtained from medical records and/or directly from patients were registered via REDCap. Local institutional review boards approved the study protocol. We designed a population-based risk model aimed at stratifying severe disease based on one or more outcome variables: previous hospitalization, surgery, and biologics. Univariate and bivariate analyses and Poisson modeling were used.

Results

A total of 1,179 patients were included: 600 (51%) with ulcerative colitis (UC), 568 (48%) with Crohn’s Disease (CD), and 11 (0.9%) with indeterminate colitis. The mean age was 34.4±14.7y, 59% female, 73% Caucasian, and 85.3% non-smoker. Regarding the initial symptoms, 42% presented diarrhea, 38% abdominal pain, and 20% weight loss. The age of IBD symptom onset ranged from 1-87 years (32.3±14.4). According to the Montreal classification of CD, A1: 5%, A2: 63%, A3: 32%; L1: 29.7%, L2: 14.3%, L3: 41.2%, B1: 32%, B2: 26.7%, B3: 11.3%; perianal 15.5%. In UC, 46.3% presented pancolitis and 30% left-sided colitis. Only 3.9% were malnourished, 30.9% were overweight, and 18% were obese. The main extraintestinal manifestations were rheumatologic (21%). Regarding medical treatment, 68.1% of the patients received biologics (45% Infliximab, 29% Adalimumab, 9.7% Vedolizumab, and 8.8% Ustekinumab), 67% salicylates, 47.6% immunosuppressors, and 0.8% Tofacitinib. Of those submitted to surgery (34.1%, n=439), 54% were elective versus 46% urgent; most procedures (80%) were open/laparotomy, while 20% were laparoscopic. Of those, 8.5% were colectomy. The presence of CD, pancolitis, the absence of (isolated) proctitis, younger age (<20 years), rheumatologic manifestations, and no history of smoking were found to be independent risk factors.

Conclusion

This is the first epidemiological study using the national patient registry organized by GEDIIB. The profile of patients with severe disease is consistent with the data in the literature, characterized by younger age, greater extent of disease, and extraintestinal manifestations. Further epidemiological studies should be encouraged to guide national policies aimed at the early diagnosis and treatment of IBD.