bluuebunny/crossref_metadata_2025 huggingface dataset:
P542 Short term efficacy, safety and thromboembolic risk of tofacitinib in moderate to severe Ulcerative Colitis
Authors: Cingolani L , Barberio B , Zelante A , Ribaldone D , Testa G , Bertani L , Buda A , Zingone F , Savarino E V
Published: January 2023

Background

Tofacitinib is a small oral molecule approved to treat moderate to severe ulcerative colitis (UC), which effectiveness and safety is still poorly known in UC patients. Recent concerns have been raised regarding its administration at high dosage in UC patients because of a likely higher incidence of drug-related thromboembolic events.

Methods

The aim of this study was to evaluate short-term effectiveness and safety of tofacitinib. As secondary aim, we analyzed the state of blood coagulation at baseline in order to evaluate whether it could predict thromboembolic events in relation to demographic, clinical and biochemical characteristics.

A multicenter, retrospective, observational study was conducted, including patients from March 2021 to October 2022; a prospective single-centre sub-study concerning the thromboembolic risk was performed. At baseline, demographic, clinical, biochemical and endoscopic data, and previous therapies were recorded; quality of life was evaluated through IBD-Disability Index (IBD-DI) and Pittsburgh Sleep Quality Index (PSQI). In a subgroup of patients, a thrombophilic screening and a Rotational Thromboelastometry (ROTEM) were performed at baseline. Patients were reassessed after 8 weeks, 6 months and 1 year, evaluating for each timepoint clinical and biochemical characteristics, IBD-DI and PSQI, and reporting adverse events (AEs) and discontinuation of therapy. The following clinical outcomes were considered: benefit, steroid-free remission and response.

Results

44 adult patients were enrolled. The overall clinical benefit was 54.2%, summing up 45.8% of subjects in steroid-free clinical remission and 8.3% with clinical response; significant short-term improvement of IBD-DI and PSQI scores (p=0.000 in both cases after 6 months of therapy) was observed. Patients previously treated with less than two different biological therapies had major rates of clinical benefit at 6 months (p=0.045). Ten AEs, including one venous thrombosis, were reported; global therapy failure rate was 31.4%. In the subgroup with additional data on coagulation (17 patients), we did not observe significant alterations of coagulating factors or inhibitors, nor of ROTEM parameters, although some coagulation features were significantly increased in obese patients (FII, p=0.030; FIX, p=0.000; FX, p=0.000; fibrinogen blood levels, p=0.030) and subjects older than 40 years old (FVIII, p=0.020). We did not find significant correlation with gender, smoking habit, concomitant steroid therapy, CRP, fecal calprotectin.

Conclusion

Our data confirm literature ones on effectiveness and safety of tofacitinib in UC patients, while the risk of thrombosis needs to be better evaluated in larger longitudinal studies.
P546 Comparative efficacy and safety of upadacitinib versus ustekinumab as induction therapy in patients with moderately to severely active ulcerative colitis: A matching-adjusted indirect comparison
Authors: Reinisch W , Panaccione R , Duijvestein M , Ceballos Santos D , Melmed G Y , Xuan S , Wegrzyn L , Levy G , Ilo D , Sanchez Gonzalez Y
Published: January 2023

Background

Upadacitinib (UPA), an oral Janus kinase inhibitor, and ustekinumab (UST), a parenteral IL-12/23 inhibitor, are approved therapies for patients (pts) with moderately to severely active Ulcerative Colitis (UC). In the absence of head-to-head data, we conducted a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) to compare efficacy and safety of UPA vs UST during induction.

Methods

Pts received UPA 45 mg oral, once daily for 8 weeks or PBO in the phase 3 studies U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026), and UST 6 mg/kg IV at week 0 with 8-week follow up or PBO in the phase 3 study UNIFI (NCT02407236). Efficacy outcomes were stratified by previous biologic exposure (ie, no prior exposure [bio-naïve] or inadequate response, loss of response, or intolerance to biologics [bio-failed]). Baseline characteristics for age, gender, extent and duration of disease, total Inflammatory Bowel Disease Questionnaire score, total Mayo score, high-sensitivity CRP, faecal calprotectin levels, weight, and UC medication use from the UPA trials were weighted to match the UNIFI trial. Efficacy outcomes at Week 8 were clinical remission per full Mayo score (FMS; FMS ≤2 with no subscore >1), clinical response (decrease in FMS ≥3 points and ≥30%, plus a decrease in rectal bleeding score [RBS] of ≥1 or an absolute RBS of 0 or 1), endoscopic improvement (endoscopic subscore 0 or 1), and histologic-endoscopic mucosal improvement (HEMI). Safety outcomes evaluated in the overall population were adverse events (AEs) and serious AEs (SAEs), comprising the only safety assessments consistently collected across trials. Numbers needed to treat/harm (NNT/NNH) were calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes between UPA and UST.

Results

The MAIC included 824 UPA and 625 UST pts with efficacy data and 839 UPA and 639 UST pts with safety data. A greater proportion of pts receiving UPA vs UST in bio-naïve and bio-failed groups achieved clinical remission, endoscopic improvement, and HEMI after weighting (p≤0.01, Table 1) with NNTs <10. In bio-naïve pts, differences in the proportion of pts with clinical remission, clinical response, endoscopic improvement, and HEMI for UPA vs UST were 0.172, 0.146, 0.312, and 0.255, respectively, and 0.105, 0.235, 0.135, and 0.118 for bio-failed pts. AEs and SAEs were not statistically different between UPA and UST.

Conclusion

During induction, greater efficacy with similar safety was observed with UPA vs UST for pts with moderately to severely active UC based on MAIC. Potential bias due to unobserved confounders may exist with MAIC methodology. Further analyses to assess longer-term outcomes are warranted.
P567 How can we predict the development of antibodies to infliximab in Crohn’s disease?
Authors: Ferreira A I , Lima Capela T , Macedo Silva V , Xavier S , Arieira C , Cúrdia Gonçalves T , Dias de Castro F , Moreira M J , Cotter J
Published: January 2023

Background

Anti-tumour necrosis factor-α (anti-TNF-α) therapy is an effective treatment for Crohn’s disease (CD). However, treatment failure is common. Our aim was to identify predictors of anti-TNF-α therapy failure.

Methods

Retrospective single-center study including anti-TNF-α naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate(ESR), c-reactive protein(CRP), faecal calprotectin, infliximab serum concentrations and antibodies to infliximab(ATI). Anti-TNF-α therapy failure was defined as ATI development at 6 or 12 months, absence of clinical response at 6 months, absence of clinical remission or objective response at 12 months. Clinical response was defined as reduction in Harvey-Bradshaw index(HBI) of≥3points comparing with initial value or HBI<5points if initial HBI≥7points and clinical remission as HBI≤4points. Objective response was assessed by endoscopic studies (improvement of mucosal inflammation and absence of deep ulcerations) or imaging (improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement).

Results

Totally 53 CD patients were included, 49.1%treated with combination of anti-TNF-α and immunomodulatory therapy. Anti-TNF-α therapy failure occurred in 21 patients(39.6%). At 6 months, ATI development occurred in 6 patients(11.3%) and absence of clinical response in 9(17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0%.

At 6 months, ATI development was significantly higher in patients with lower infliximab serum concentrations at week 14 (with ATI 5.9±3.2 vs without 14.3±7.7, p<0.001). Additionally, ATI development was significantly higher in patients with a higher initial value of ESR (with ATI median 35 vs without median 13, p=0.045). The infliximab serum concentrations at week 14 (AUC 0.828;p=0.009; sensitivity 0.833, specificity 0.404 for values≤11.6) and the initial value of ESR (AUC 0.754;p=0.045; sensitivity 0.833, specificity 0.468 for values≥15) had very good and good discriminative capacity, respectively, in predicting ATI development. No statistically significant differences were found in initial values of CRP and faecal calprotectin. The other definers of anti-TNF-α therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of biochemical parameters.

Conclusion

Infliximab serum concentration after induction is the most important factor in ATI development, influencing treatment response, regardless of the combination with immunomodulatory therapy. Higher initial value of ESR can also predict the development of ATI.
P571 Frequency and risk factors of advanced neoplasia in Korean IBD patients with Low Grade Dysplasia in previous surveillance
Authors: Park Y E , Kim D H , Park S K , Lee Y J , Lee C K , Kim E S , Kim K O
Published: January 2023

Background

There are insufficient studies on clinical outcome after surveillance of low grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD). We aimed to evaluate the clinical feature, frequency and risk factors of advanced neoplasia in IBD patients after diagnosis of LGD

Methods

From 2003 to 2020, medical records of 166 IBD patients from 6 university hospitals in Korea were reviewed retrospectively. All of the patients were diagnosed as LGD in surveillance. Patents’ baseline characteristics, disease status, polyp characteristics and treatment were evaluated. The frequency and risk factors of advanced neoplasia were also analyzed.

Results

Disease duration was 11.47 years (7.85-14.50), and follow-up duration was 3.74 years (1.95-7.58). Colitis associated LGD was noted in 56 cases (33.7%), Advanced neoplasia developed in 12 cases (6 large LGD, 3 tubulovillous adenoma, 3 high grade dysplasia) and all the cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo score and colitis-related dysplasia were more common than sporadic lesions (83.3% vs. 29.9%; P<0.001). In multivariate analysis, colitis-associated LGD significantly increased the risk of developing advanced neoplasia (Odds ratio [OR], 10.516; 95% confidence interval [CI], 2.064-53.577; P=0.005). Among patients with colitis-associated lesions, a significant risk factor for advanced neoplasia was a history of LGD (OR, 9.429; 95% CI, 1.330-66.863; P=0.025).

Conclusion

Advanced neoplasia developed in 7.2% of IBD patients with LGD. Because most of advanced neoplasia developed from colitis-associated lesions, more careful examination is suggested in patients with colitis -associated LGD, especially with previous history, in surveillance colonoscopy.
P595 Time of Therapeutic Drug Monitoring of infliximab during induction and its relationship with clinical remission in Inflammatory Bowel Disease
Authors: Muñoz-Villafranca C , Arreba P , Gomez M , Ispizua Madariaga N , Buendia L , Lopez M L , Ugarte A , de la Fuente I , Prado N , Irusta L , Jimenez M A , Santa Cruz M , Gonzalez M , Bilbao A , Ortiz de Zárate J
Published: January 2023

Background

The usefulness of therapeutic drug monitoring(TDM) of infliximab during induction and its relationship with clinical outcome in patients with inflammatory bowel disease(IBD) is well established. However, the optimal time of monitoring in terms of clinical outcomes remains unclear.

The aim is to evaluate the TDM at various times during induction and its association with clinical remission.

Methods

An observational, retrospective and single-centre study of patients with active disease ,Crohn’s disease (CD) or ulcerative colitis(UC), was performed. Induction treatment with infliximab 0, 2, 6 weeks was conducted and if there was response, maintenance therapy was provided.

Antibody levels were measured in serum samples at week 2 and week 14 by using an enzyme-linked immunosorbent assay, within the therapeutic range(3-8 µg/ml). Patients were followed at least for one year or until loss of response. The clinical response was assessed in week 14 and week 52 by Harvey-Bradshaw Index in CD and Mayo Partial Index in UC.

Results

Out of 93 patients that were evaluated, 23 with UC(24.73%) and 70 with CD(75.27%,), 65 (69.89%) and 58 patients(62.37%) achieved remission at week 14 and week 52 respectively. Infliximab levels at week 14 but not at week 2 were significantly higher in patients who achieved clinical remission in both week 14 (5.8 vs 2.1 µg/ml; p=0.0002) as in week 52 (6.4 vs 1.9 µg/ml; p=0.0001).

The levels at week 14, but not at week 2 had predictive value of remission, in both week 14 [OR 1,4 (CI 1.14-1.76) p=0.001] and week 52 [OR 1.4 (CI 1.15-1.87); p=0.001]. The patients with immunosuppressants at week 14 presented the highest rate of remission in week 52 (77.78 vs 52.63; p=0.014). The intensification of treatment was a negative factor to achieve remission both in week 14 and at week 52.

Conclusion

The levels of infliximab in week 14 are higher and have predictive value of clinical remission both in early (week 14) and long-term (week 52). Levels of infliximab in week 2 did not provide significant predictive value of clinical response. The use of immunosuppressants could be a favourable factor of clinical outcome.
P598 The utility of the “Low Anterior Resection Syndrome SCORE” in assessing the postoperative outcomes of patients undergoing restorative proctocolectomy with ileal pouch anal-anastomosis for Ulcerative Colitis
Authors: Perotti S , Mineccia M , Daperno M , Massucco P , Gonella F , Ferrero A
Published: January 2023

Background

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) in a J-pouch configuration is the treatment of choice for patients with ulcerative colitis. Some patients who have undergone this surgery present symptoms including fecal or gas incontinence, urgency, clustering, and frequency, that occurs after anal sphincter-sparing surgery for the treatment of rectal cancer. There is a lack in standardization and evaluation of functional outcomes. Our aim is to evaluate the effectiveness of the LARS (low anterior resection syndrome) score in this cohort of patients.

Methods

We conducted a retrospective analysis of a prospectively maintained single center database. We assessed the quality of life by using the Inflammatory Bowel Disease Questionnaire (IBDQ-32). The functional bowel complaints were assessed using the LARS score.

Results

Between 2015 and 2020, 70 patients with ulcerative colitis underwent total colectomy and subsequent IPAA with J-Pouch configuration. Among these, 49 patients who closed the ileostomy and were followed for at least 6 months, were selected for the present study. Nineteen patients did not have the LARS; among 30 who complained the LARS, 17 had a major LARS (tab.1). The latter had a worse quality of life on the IBDQ-32 questionnaire, especially in relation to urgency and frequency (Fig.1). We compared the two scores using Spearman's test correlation coefficient, detecting a significant correlation (rho -0.7664185; p-value <0.005); a significant correlation between the urgency sub-category with LARS score (rho -0.6515759; p-value <0.005) and frequency (rho -0.6744705; p-value <0.005) was evaluated.

Tab 1: Patients characteristics:

Fig.1:IBDQ-32 value in different LARS categories

Conclusion

In our experience LARS score appears to be a useful, effective and simple tool to predict functional outcomes and QoL not only in oncological rectal sphincter-sparing surgery but also in functional surgery for ulcerative colitis.
P615 The safety and efficacy of ustekinumab combined with sphincter-preserving surgery for perianal fistulizing Crohn’s disease:a single-center retrospective study
Authors: Li Y , Gu Y
Published: January 2023

Background

To assess the clinical efficacy and safety of ustekinumab(UST) combined with sphincter-preserving surgery in the treatment of perianal fistulizing Crohn’s disease(pfCD).

Methods

A single-center retrospective study. The baseline data of pfCD patients who met the inclusion and exclusion criteria and visited the Anorectal Department of the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2020 to March 2022 were collected. Patients were assessed for fistula response and remission by rectal magnetic resonance image(MRI) and perianal disease activity index(PDAI). Patients' fistula response and remission were assessed by rectal MRI and PDAI. Patients were assessed for clinical response and remission by using Crohn's disease activity Index( CDAI). Patients' anal function was assessed by using the Wexner score. The differences in CDAI,PDAI and inflammatory parameters, including C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR), at 0 week, 8 weeks and 16 weeks were statistically analyzed.

Results

A total of 64 pfCD patients were included. Fistula response was 23.4% (8 weeks), 40.6% (16 weeks), and 51.6% (follow-up endpoint); fistula remission was 21.9% (follow-up endpoint); fistula MRI remission was 9.3% (follow-up endpoint); clinical response was 68.8% (8 weeks) and 79.7% (16 weeks); and clinical remission was 46.9% (8 weeks) and 59.4% (16 weeks). CDAI, PDAI and inflammatory parameters at the 8th and 16th week of treatment were significantly lower than those before treatment (p<0.05). There was no significant difference in postoperative anal function (p<0.05). The incidence of adverse events was 1.6%.

Conclusion

UST combined with sphincter-preserving surgery is safe and effective in the treatment of pfCD.This therapy can effectively improve the fistula condition and systemic manifestations.
P616 Fatigue in pediatric inflammatory bowel diseases – systematic review and rates in a prospective cohort
Authors: Focht G , Turner S , Carmon N , Lev-Tzion R , Orlanski-Meyer E , Ledder O , Yogev D , Assa A , Turner D
Published: January 2023

Background

Studies in adults suggest that fatigue is amongst the most commonly reported symptoms, reaching ~50% of patients, often even while the patients enter clinical remission. However, fatigue has been rarely discussed in children and no study hitherto determined the rate of fatigue in pediatric IBD (PIBD). We aimed to perform a systematic review of the literature in children with either CD or UC and to explore the rate of fatigue in a prospective inception cohort of PIBD.

Methods

A systematic review of the literature was conducted for pediatric studies of any design reporting fatigue as an outcome. Manuscripts were reviewed by 2 authors, inclusion was based on consensus. Next, children with new onset IBD were asked to complete the IMPACT-III, a health-related quality of life (QOL) questionnaire at 4 months after diagnosis, to capture response to treatment. Children <9 years who are unable to reliably report fatigue by themselves were excluded. Four fatigue-related questions were analyzed (Table 1). Each question has 5 response options each assigning 25 points according to the users’ guide (i.e. 0, 25, 50, 75, 100 points when the latter implies higher QOL and lack of fatigue). Remission was defined as wPCDAI<12.5 for CD and PUCAI<10 for UC. Explicit clinical and demographic data were prospectively recorded.

Results

In the systematic review only 12 studies reported on fatigue in pediatric IBD were identified,8 of which reported fatigue as primary outcome and 1 was an intervention trial. None provided rate of fatigue,also since unlike in adults,no PIBD-specific fatigue measuring scale was available. A total of 86 children were included in the inception cohort (median age 14.5[IQR 12.8-15.9] years,39[45%] females;59[69%] CD,27[31%] UC;47(55%) in clinical remission). At 4 months, only 4 patients (4.6%) selected the highest score (100) for all 4 questions, i.e. no fatigue). Forty four children (53%) had min 2 questions with a score <100,of whom 27 (61%) were in clinical remission. Twenty-eight children (33%) did not score 100 in neither of the 4 questions and 12(14%) had scored all 4 questions≤50. Of the 47 children who were in clinical remission,33(70%) had at least 2 of the 4 questions scored<100.

Conclusion

The reporting and assessment of fatigue among pediatric IBD literature is extremely limited. This study is the first to report fatigue rate in children. We show that after induction treatment fatigue rate of any severity may be as high as 53%, moderate fatigue as 33% and severe fatigue as 14%. Fatigue was common also in those in clinical remission. Our results call for a more standardized tool of measuring fatigue in PIBD since its quantification can facilitate a more methodical management of this disabling and underreported symptom.
P629 Real-life treatment persistence and treatment outcomes of Finnish patients with Inflammatory Bowel Disease receiving vedolizumab as first-line biological treatment
Authors: Ylisaukko-oja T , Af Björkesten C G , Erbel A , Nuutinen H , Jussila A , Molander P , Koskela R , Blomster T , Pajala M , Ilus T , Haiko P , Kovac B , Silvola S , Smith S , Jokelainen J , Sipponen T
Published: January 2023

Background

Vedolizumab is a gut selective anti-lymphocyte trafficking monoclonal antibody directed towards the integrin α 4β 7. The efficacy and safety of vedolizumab in the treatment of adults with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC) are well-established in randomized clinical trials and real-world evidence studies. However, real-world data are limited on vedolizumab therapy used on biological naïve CD and UC patients. Here, we analyse treatment persistence, treatment outcomes, and reasons for treatment discontinuation of vedolizumab as a first-line biological treatment in CD and UC patients in a Finnish real-world setting.

Methods

This was an observational, retrospective, multi-centre registry study. The cohort included all adult (≥ 18 years of age) patients with a diagnosis of CD or UC who initiated vedolizumab as a first-line biological treatment between May 2014, and June 2020, in the five Finnish university hospital districts. Clinical data were collected from electronic health records. The Prescription Register by the Finnish Social Insurance Institution was the data source for prescribed IBD treatments. Treatment persistence was defined as the time from initiation to discontinuation of therapy. P-values were calculated by using paired t-test.

Results

The cohort consisted of 54 CD and 69 UC patients treated with vedolizumab as a first-line biological treatment. The mean ages were 61.9 and 56.8 years for CD and UC at the time of vedolizumab start, respectively. Disease duration was 10.9 years in CD and 10.5 years in UC. Altogether, 35.8% of patients had a history of cancer. At month 12, treatment persistence was 84.9% (n=44) in CD and 64.7% (n=41) in UC cohorts (Figure 1). Most vedolizumab discontinuations (CD, n=11; UC, n=26) were due to lack of efficacy, and treatment discontinuations due to adverse events were rare (n<5). Vedolizumab was associated with favourable treatment outcomes, as indicated by efficacy improvements at 12 months compared with baseline in Harvey-Bradshaw Index (CD, 3.2 vs 4.9, p=0.025), Partial Mayo Score (UC, 3.8 vs 5.1, p=0.021), Physician’s Global Assessment (CD, 0.9 vs 1.8, p<0.001; and UC, 0.4 vs 2.1, p<0.001) scores, and positive endoscopic Mayo Score (UC, 0.7 vs 2.2, p<0.001) and biochemical outcomes.

Conclusion

Vedolizumab showed high treatment persistence and positive treatment outcomes such as improvements in efficacy, endoscopic activity, and biochemical parameters when used as the first-line biological treatment.
P630 Upadacitinib Improves Clinical Outcomes in Patients with Moderate to Severely Active Crohn’s Disease Irrespective of Previous Failure to Respond to Biologics or Conventional Therapies
Authors: Schreiber S W , Lim A , Lacerda A P , Allegretti J R , Watanabe K , Lukin D , Dubenco E , Ford S , Oomen J , Zhou Q , Liu J , Louis E
Published: January 2023

Background

Upadacitinib (UPA), an oral, selective Janus kinase inhibitor, demonstrated significantly greater efficacy compared with placebo (PBO) in patients (pts) with moderately to severely active Crohn’s disease (CD) in phase 3 multicentre, double-blind, PBO-controlled induction U-EXCEL and U-EXCEED, and maintenance U-ENDURE trials.1-3 This analysis compared clinical outcomes in pts treated with UPA vs PBO once daily (QD) among pts without or with a history of biologic failure.

Methods

Eligible pts with an average daily very soft/liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2, plus a Simple Endoscopic Score for CD (excluding the narrowing component) ≥6 (≥4 for pts with isolated ileal disease) were randomized (2:1) to UPA 45 mg (UPA45) or PBO in U-EXCEL and U-EXCEED. Induction responders (≥30% decrease in average daily very soft/liquid SF and/or APS, neither worse than baseline) to 12-week (wk) UPA45 were re-randomized 1:1:1 for maintenance to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO QD in U-ENDURE. Clinical remission, response (CR-100), and maintenance of clinical remission, along with adverse events (AEs) were assessed through maintenance wk 52.

Results

Baseline demographics/characteristics were similar for all treatment groups; pts with prior biologic failure were 71.5% PBO and 72.0% UPA45 in induction and 76.4% PBO, 73.4% UPA15 and 75.6% UPA30 in maintenance. Among pts without/with biologic failure history, those treated with UPA45 exhibited higher rates for clinical remission at wk 12 (CDAI: UPA45 54.1%/40.5% vs PBO 39.4%/19.4%; SF/APS: UPA45 54.0%/42.2% vs PBO 28.3%/14.1%, Fig. 1A). Similar results were observed at wk 52 with UPA15 and UPA30 vs PBO (Fig. 1B). Irrespective of biologic failure status, a higher proportion of patients on either UPA dose maintained clinical remission from maintenance wk 0 to wk 52 (Fig. 1C). Higher proportions of pts with prior biologic failure achieved CR-100 with UPA45 vs PBO at wk 12 (53.2% vs 26. 9%); at wk 52 differences from PBO were found for either UPA dose in pts without or with prior biologic failure (Fig. 1D). Serious AEs and serious infections were similar across treatment groups (Tables 1-2). No tuberculosis or adjudicated cardiovascular events were reported. Malignancy, opportunistic infections, thrombotic events, and gastrointestinal perforations were infrequent (<1.0% or 10 E/100PY).

Conclusion

All upadacitinib doses achieved greater clinical efficacy than placebo during induction and maintenance periods, irrespective of patient prior exposure to biologic therapy, with an acceptable safety profile.
P637 Targeting mucosal healing: dose optimization of Vedolizumab in IBD patients with inadequate endoscopic response to standard dosing
Authors: Dal Buono A , Gabbiadini R , Migliorisi G , Solitano V , Canziani L , Repici A , Armuzzi A
Published: January 2023

Background

The GEMINI trial assessed improved clinical outcomes after an increase to 4-weekly dosing of Vedolizumab in nearly 40% of patients with insufficient response to standard 8-weekly dosing. However, later real-world data have partially questioned the efficacy of dose optimization due to the early randomization in the study design. The investigation on dose escalation efficacy of Vedolizumab in inflammatory bowel diseases (IBD) remains scarce. We aimed to explore the clinical benefit of Vedolizumab dose escalation every 4 weeks in a cohort of IBD patients with insufficient endoscopic response to the standard dosing regimen.

Methods

This is a retrospective single-center study. IBD patients, who showed persistent endoscopic activity (Mayo score ≥ 2 or SES-CD ≥7) with 8-weekly dosing Vedolizumab were included. Clinical data were retrieved from patients’ charts. Response after therapy optimization was compared to standard 8-weekley dosing through Wilcoxon signed-rank test for quantitative variables with non-normal distribution; univariate analysis of different factors impacting on therapy response was performed.

Results

A total of 52 IBD patients, 30 (57.7%) and 22 (42.3%) with ulcerative colitis and Crohn’s disease, respectively, were included. Overall, the median disease’s duration at Vedolizumab start was 12.5 month (range 3 36); 31 patients (59.6%) had been previously treated with anti-TNFs. Before Vedolizumab dose escalation 32/52 patients (61.5%) and 20/52 patients (38.5%) showed moderate (Mayo score =2; SES-CD= 7-15) and severe endoscopic activity (Mayo score =3; SES-CD ≥ 15), respectively. We observed a significant reduction of fecal calprotectin from baseline [median 133 μg/g (range 21-3800)] after Vedolizumab optimization [median 77 μg/g (range 6.0-521)] (p<0.001). After Vedolizumab optimization 28/52 patients (53.8%) obtained further endoscopic response (78.6%) or remission (21.4%) (p<0.001). At univariate analysis non exposure to anti-TNF and a lower disease duration at Vedolizumab start significantly correlated with endoscopic response after optimization (HR 0.28, 95%CI 0.32 – 0.76, and HR 0.32, 95%CI 0.25 – 0.66, respectively, p<0.001). No adverse events were observed after dose optimization in our cohort.

Conclusion

An increase in Vedolizumab dosing frequency is a viable treatment approach for a subset of patients with insufficient endoscopic response standard 8-weekly dosing. Higher response rates might be assessed in anti-TNF naïve patients and with a lower disease duration at therapy start. Prospective studies are needed to confirm these data.
P654 Controversies in the management of anti-TNF therapy in Crohn’s disease patients. A Delphi consensus
Authors: Gonzalez Lama Y , Ricart E , Carpio D , Bastida G , Ceballos D , Ginard D , Marín-Jimenéz I , Menchén L , Muñoz F
Published: January 2023

Background

Over the last years significant advances have arisen in CD. New therapies with different mechanisms of action have been approved for the management of Crohn’s disease (CD). However, there is limited evidence on optimal positioning of agents as first-or second-line therapies due to the lack of head-to-head robust comparative data. Our aim was to establish feasible and practical recommendations for the management of patients with moderate to severe CD with the use of anti-tumour necrosis factor (TNF) drugs, with special focus on controversial areas.

Methods

A group of 9 expert gastroenterologists identified current relevant clinical controversies in the management of CD with anti-TNF therapies. A comprehensive literature review was performed to analyze them and a survey was launched to examine current clinical practice. This was a structured survey organized in 2 main sections that included several questions: 1) Sociodemographic and practice related questions; 2) Opinion and attitude in daily practice related to: the use of anti-TNFs, vedolizumab or ustekinumab in naïve and refractory patients, the role of HLA-DQA105, or monitoring of drug levels. An invitation to participate was emailed to a representative number of 244 IBD treating physicians all over the country. The results of the literature review and survey were discussed in a nominal group meeting, and a set of statements were proposed for a Delphi process. The participants of the survey were also invited to the Delphi. Agreement was defined if at least 70% of the participants voted ≥7 (from 1, totally disagree to 10, totally agree). For each statement, the level of evidence and grade of recommendation was established based on the Oxford Evidence Based Medicine categorization.

Results

A total of 14 statements were generated (table 1 depicts the statements and the results of the Delphi). All but two achieved required level of agreement. The statements cover the following areas: 1) use of first-line non-anti-TNF biologic therapy; 2) role of HLA-DQA1*05 in daily practice; 3) attitudes in primary nonresponse and loss of response to anti-TNF therapy due to immunogenicity; 4) ustekinumab or vedolizumab if a change of mechanism of action is considered; 5) anti-TNF drug levels monitoring during induction; 6) combined therapy with an immunomodulator and anti-TNF monotherapy.

Conclusion

This document sought to pull together the experts’ attitudes when dealing with different clinical scenarios of patients with CD on anti-TNF.
P656 Superior treatment persistence with ustekinumab in biologic-experienced luminal Crohn’s disease: real-world registry data from the Persistence Australian National IBD Cohort (PANIC) study
Authors: Chetwood J , Ko Y , Pudipeddi A , Kariyawasam V , Paramsothy S , Leong R
Published: January 2023

Background

Ustekinumab has been shown equivalent to adalimumab in the treatment of biologic-naïve patients with Crohn’s disease (CD) at 1 year. However the real world persistence of these medications, and particularly when used sequentially in biologic-experienced patients is unknown. Prescription data provides real-world evidence about treatment efficacy, tolerability and prescriber and patient acceptability.

Methods

Persistent of medication was analysed from the Australian Pharmaceutical Benefits Scheme (PBS) registry data 2005-2019 for luminal Crohn’s disease, using a 10% representative sample.

Results

There were 2029 patients over the 15 year period with 5618 years of patient follow up. The median age was 43 years (interquartile range (IQR): 34-58), with 891/2029 (43.9%) male. Via therapy, 915/2029 (45.1%) were on adalimumab, 722/2029 (35.6%) were on infliximab 155/2029 (7.6%) were on vedolizumab, and 237/2029 (11.7%) were on ustekinumab. Used as a first-line biologic (bio-naïve), there was no difference between any agent for persistence (p>0.05). Used after first-line (bio-experienced), ustekinumab had significantly better persistence than TNFa inhibitors (TNFi) (p= 0.006) and vedolizumab (p<0.001), additionally vedolizumab had poorer persistence than TNFi (p=0.028). In bio-experienced patients, ustekinumab persistence was greater than non-ustekinumab biologic agents (p= 0.0018). TNFi persistence was significantly poorer in bio-experienced vs naïve patients (p=0.042), with a non-significant trend for poorer outcomes in vedolizumab (p= 0.059), but did not differ for ustekinumab (p=0.509). Used after a TNFi agent, ustekinumab had superior persistence to an alternative TNFi agent (p=0.033). Using a propensity score matched analysis for age, immunomodulator use and line of therapy, ustekinumab had superior to persistence to non-ustekinumab agents (p=0.0044) and to TNFi (p=0.01). Multivariate predictors of loss of persistence were biologic used (adjusted hazard ratios (aHR): 0.84, p=0.001), and line of therapy (aHR: 1.16, p=0.003).

Conclusion

The PANIC cohort with real-world data of non-hierarchical prescribing of biological agents does not support the superiority of any agent in biologic-naïve luminal CD. However for biologic experienced, the persistence is greater with ustekinumab than TNFa inhibitors, and vedolizumab persistence is significantly poorest. These findings will assist in the positioning of biological therapies in luminal CD.
P706 Monitoring asymptomatic patients with Crohn's disease: the role of intestinal ultrasound
Authors: Dussias N , Melotti L , Mazzotta E , Decorato A , Vanigli N , Rizzello F , Gionchetti P
Published: January 2023

Background

Intestinal Ultrasound (IUS) is a non-invasive, widely available technique that can rapidly evaluate bowel wall thickness and provide direct visualization of bowel vascularisation and motility. Studies have shown high concordance between ultrasound and MR enterography and endoscopy for disease location and activity, and fewer technical difficulties associated with IUS. While more is known about the role of IUS in evaluating response to pharmacologic treatment in CD patients, data regarding the monitoring of asymptomatic patients are scarce. Our objective was to study the impact of IUS in the management of patients with CD in stable clinical remission in a real-world setting.

Methods

We conducted a retrospective, monocentric observational study in patients with CD in clinical remission (Harvey Bradshaw Index ≤ 4), not in treatment with immunomodulators/immunosuppressants, in whom annual monitoring via IUS was performed. Biochemical data including C-reactive protein (CRP) and relevant ultrasound parameters (bowel wall thickness, extension and vascularization via Limberg score) were recorded. Changes in treatment or the need for second-level diagnostic tests based on ultrasound findings were registered along with outcomes at 1 year follow-up.

Results

A total of 201 patients with CD underwent IUS at our center between March and May 2021. Of these, 86 were in clinical remission with mesalazine treatment/no treatment. In 49/86 (57%) of cases, significant ultrasound findings were reported. In 27/49 cases, ultrasound findings led to a treatment modification or a second-level diagnostic test. Specifically, 12 patients were started on a course of oral budesonide or metronidazole; of these, 6 were in remission at 1 year follow-up, 3 patients required surgery within 1 year, and 2 experienced a disease flare treated with a second course of budesonide. Of the 15 patients in which a second-level diagnostic test was performed, in 12 cases disease activity was confirmed: 6 were started on a course of budesonide or metronidazole with persistent clinical remission at 1 year, 2 were started on biologics, and 4 developed complications during the follow-up period and were referred for surgery. In the remaining 3 cases, the second level diagnostic test excluded active disease and the patients maintained clinical remission at 1 year follow-up.

Conclusion

The results of this study demonstrate how IUS can be a useful tool that can modify treatment strategies and stratify patients requiring more invasive second-level diagnostic exams, with the objective of reducing clinical relapses. Prospective, randomized studies with large cohorts are needed to confirm these findings.
P710 Changes of gut microbiome after anti-TNF-α therapy and the prediction of clinical remission in patients with active ulcerative colitis
Authors: Shin Shin S , Oh H N , Moon J M , Joo H J , Sul W J , Choi C H
Published: January 2023

Background

The aims of this study are to explore the changes of gut microbiome after anti-TNF-α therapy (adalimumab; ADA) and to identify biomarkers to predict clinical remission to ADA in patients with active ulcerative colitis (UC).

Methods

Fecal samples were taken before (baseline) and after ADA administration at weeks 8 and 56 in patients with active UC. Fecal bacterial taxonomic composition and diversity were investigated by 16S sequencing and analyzed by divisive amplicon denoising algorithm version 2 (DADA2) at the level of amplicon sequence variant (ASV). The table was imported into R 4.0.2 to analyze for richness, diversity, heatmap and ordination plot . The linear discriminant analysis effect size (LEfSe) was used for statistical analysis. Clinical remission was assessed using the Mayo score.

Results

260 fecal samples from 146 patients with UC administering ADA and 40 fecal samples of healthy controls (HC) were analyzed. The mean age of the participants was 44 ±14.8 years, and 60.7% were male (patients 64.9%, healthy control 42.5%). Overall communities (β-diversity) of gut microbiota in HC clearly differed from those before, after 8 weeks, and after 56 weeks of ADA treatment in patients with UC regardless of remission. The compositions of microbiota were affected by the disease severity and extent. ADA treatment significantly reduced the dissimilarity among samples in remitters at both 8 and 56 weeks, which were not observed in non-remitters. In remitters, the abundance of genus Staphylococcus was significantly decreased and genera Bifidobacterium and Dorea were significantly increased during ADA treatment period. The baseline samples of remitter at week 8 showed a higher abundance of 40 ASVs, including Sporosarcina (ASV2803), Bacteroides sp. (ASV1298, ASV1490), and Enterobacter (ASV9330, ASV9332) compared to baseline of non-remitters. Given that the 48 ASVs increased or decreased in baseline samples of remitters at week 8, the best log ratio of average relative abundance of increased ASVs/decreased ASVs to predict remission for ADA treatment was 0.07459, with 72.4% sensitivity and 84.3% specificity on the receiver operating curve (area under the curve, 0.855).

Conclusion

The composition of gut microbiota varies depending on the status of the disease and the effectiveness of the ADA treatment. Relative abundance of s fecal bacteria before treatment can be a biomarker for predicting efficacy of ADA in patients with UC.
P743 Relative association of bowel urgency improvement versus remission of stool frequency and rectal bleeding with Patient Global Rating of Severity or Change scores in moderately-to-severely active Ulcerative Colitis: An analysis from the LUCENT-1 and LUCENT-2 Phase 3 trials
Authors: Travis S , Wu J , Keohane A , Gibble T H , Hibi T
Published: January 2023

Background

Bowel urgency is a common and disruptive symptom of ulcerative colitis (UC), distinct from stool frequency (SF) and rectal bleeding (RB).1 Information is limited on the relationships between bowel urgency clinically meaningful improvement (CMI), bowel urgency remission, SF remission or RB remission and improvement in Patient Global Rating of Severity or Change (PGRS/PGRC) scores in patients with moderately-to-severely active UC. We estimated the associations of bowel urgency CMI or bowel urgency remission with PGRS/PGRC scores while adjusting for potential confounding effects of SF remission and RB remission, using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Methods

Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (NRS; 0=no urgency to 10=worst possible urgency).2 The 6-point PGRS scale (1=none to 6=very severe) was recorded using an electronic daily diary, and the weekly scores were averaged. The 7-point PGRC scale (1=very much better to 7=very much worse) was recorded at week (W) 12 and W52.3 Other outcomes included: bowel urgency remission (Urgency NRS score=0 or 1), bowel urgency CMI (≥3-point decrease in Urgency NRS score from baseline), SF remission (Modified Mayo subscore=0 or 1 with ≥1 point decrease from baseline) and RB remission (Modified Mayo subscore=0).2 Mediation analyses were performed to separately examine the relative association of the direct effects of bowel urgency CMI or bowel urgency remission (predictors) with PGRS/PGRC scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatmentagnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at W12 and 40 (W52 of the study).

Results

At W12, improvements in PGRS and PGRC scores were primarily due to bowel urgency remission (63.5%, 56.3%), relative to SF remission (21.0%, 21.6%) and RB remission (15.5%, 22.1%; Fig.1A). Similar results were observed for bowel urgency CMI at W12 (Fig.1B). At W52, bowel urgency remission accounted for 54.7% and 79.1% of the improvements in PGRS and PGRC scores (Fig.2A). The effects of bowel urgency CMI, SF remission, and RB remission on improvement in PGRS/PGRC scores are shown in Fig. 2B.

Conclusion

Improvements in PGRS or PGRC scores were primarily due to bowel urgency remission or bowel urgency CMI relative to SF remission or RB remission. These results support that bowel urgency may influence patients’ perceptions of disease severity and change in disease activity in UC.

References:

1Dubinsky MC, et al. J Crohns Colitis. 2020;14(1):S200.

2Dubinsky MC, et al. J Patient Rep Outcomes. 2022;6(1):114.

3Rubin DT, et al. Gastroenterology. 2022;162(3):S14-5.
P753 Comparing long-term outcomes in inflammatory bowel disease patients between switch and non-switch cohorts: no differences in infliximab persistence or safety outcomes after 54 months
Authors: Suo P , Thin L , Srinivasan A , Winston J , Jeffrey A , Menon S , Ghaly S , Haifer C
Published: January 2023

Background

Switching patients with inflammatory bowel disease (IBD) from originator to biosimilar infliximab has been demonstrated to be non-inferior to continuing originator infliximab by several studies. However, data comparing treatment outcomes beyond 12-months across switch and non-switch cohorts specific to IBD patients remains comparatively underreported. Here we report long-term (>48 weeks) treatment outcomes of the SAME study, a large-scale parallel cohort study of Australian IBD patients who underwent non-medical switching from originator to biosimilar (CT-P13) (n=204) or continued originator infliximab (n=141).

Methods

The SAME study was a multi-centre, prospective parallel cohort non-inferiority study across seven Australian hospitals over 48 weeks undertaken between May 2017 to October 2019. The data that we present here is the long-term extension study, obtained retrospectively, which sought to compare long-term infliximab persistence beyond 48 weeks across switch and non-switch cohorts. This study included five of the original seven sites, three of which switched from originator to biosimilar infliximab. The primary outcome was infliximab persistence, defined as the proportion of originator or biosimilar infliximab treated patients from the original cohort at last follow up. Secondary outcomes included disease worsening requiring infliximab dose escalation or discontinuation, rates of adverse events, and development of antibodies to infliximab (>10ng/mL).

Results

Data from 263 (90 Ulcerative colitis and 173 Crohn’s disease) of 345 (76%) patients enrolled in the original SAME study were included with median follow up of 54.2 months (IQR 46.1-59.3). At last follow-up, 103 (65.5%) and 68 (64.2%) patients across the switch and non-switch cohorts (p = 0.8) remained on infliximab. There were no differences in the proportions that discontinued infliximab due to clinical or biochemical worsening of disease (21.7 v 23.6%, p = 0.72); required infliximab dose escalation (35.2 v 32.4%, p=0.8); developed antibodies to infliximab (5.3 vs 11.3%, p = 0.09) or experienced drug related adverse events (7.8 vs 8.3%, p = 0.8) between switch and non-switch cohorts, at last follow-up.

Conclusion

Long-term infliximab persistence was similar between switch and non-switch cohorts after a median of 54 months. This study represent one of the longest ‘real-world’ comparisons between switch and non-switch cohorts specific to IBD, and should provide reassurance to clinicians and patients alike.