bluuebunny/crossref_metadata_2025 huggingface dataset:
P751 Off-label dose escalation of Ustekinumab in Inflammatory Bowel Disease patients. Safety profil of different patterns
Authors: García-Morales N , Agra-Blanco I , Gayoso-Rey M , Carmona A , Ayude M , De Castro Parga M L , Rodriguez-Prada I
Published: January 2024

Background

Approved maintenance regimens for UST in patients with inflammatory bowel disease (IBD) are 90 mg subcutaneously every 8 (Q8) or 12 weeks (Q12). In the real world, off-label dose escalation is frequently performed after inadequate response or loss of response, and has been shown to be effective. However, different dosing regimens are used and the best strategy is still unknown. Our aim is to evaluate the safety profile of UST dose escalation in IBD patients.

Methods

We performed an observational cohort study in 2 hospitals in Vigo-Spain. All patients who started UST between 1 June 2017 and 31 December 2022 to control their active IBD were enrolled. The primary endpoints were the rate of serious adverse events (AE) and the need to discontinue UST treatment in off-label dose escalation patients.

Results

173 IBD patients received UST: females 53,8% (93), mean age 49.7(15.5) years, Crohn´s disease 82% (142), previous anti-TNF 93,6% (162) and vedolizumab 22,5% (39) (Table 1). At 16 weeks, subcutaneous UST was maintained Q8 in 110 (63.6%) and Q12 in 60 (34.7%). Dose escalation was performed in 56 patients (32,4%) with different patterns: 30 Q4 (54,5%), 12 intravenous reinduction plus Q4 (21,8%), 7 Q6 (12.7%) and 6 only intravenous reinduction (10,9). In 11 patients (6,4%) a second dose escalation was performed.

196 adverse events were reported in 95 patients (54,9%), mostly infections 63 (32,1%) and musculoskeletal disorders 46 (23,5%) (Figure 1). More than one AE was reported in 67 patients (38.7%), showing 2 AE in 41 (23.7%), 3 AE in 12 (6.9%) and 4 AE in 14 (8.1%). Twelve adverse events were considered serious (12,5%) as they lead to hospitalization and in 4 cases to discontinuation of treatment (0.02%). Infections were the most frequent cause of serious AE (50%). With a fmedian ollow-up time of 13,5 (11) months, IBD patients scheduled to off-label UST dose escalation regimens showed no higher incidence of AE or severe AE than standard regimens.

Conclusion

In IBD patients, off-label UST dose escalation showed a good safety profile. Most of the reported adverse events were mild infections that did not change the UST treatment regimen. The schemes of dose-escalation were very heterogeneous between the participants.
P756 Efficacy and safety of medical therapies for maintenance of surgically induced remission in Crohn’s disease: A systematic review and network meta-analysis
Authors: Sinopoulou V , Gordon M , Vuyyuru S , Darie A M , Limdi J , Moran G
Published: January 2024

Background

Approximately half of patients with Crohn’s disease (CD) undergo surgical resection in first decade after diagnosis. Majority experience disease recurrence following surgery requiring further intervention. There is limited evidence on efficacy of medical therapies in this setting. We performed a network meta-analysis to evaluate comparative efficacies of medical therapies for the prevention of clinical and endoscopic relapse after surgical resection.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). Outcomes assessed were clinical relapse, endoscopic relapse, and safety outcomes including adverse events (AE), withdrawal due to AE, and serious AE. We performed random-effects network meta- analysis using a frequentist approach, and estimated relative risk (RRs), 95% CI values and used GRADE to ascertain certainty of evidence.

Results

A total of 37 RCTs comprising 4411 patients were included. On network meta-analysis of clinical relapse outcome, there was moderate certainty of evidence favouring adalimumab (RR 0.14, 95% CI [0.03-0.7]) over placebo with number needed to treat (NNT) of 3. There was low certainty of evidence supporting 5-amainosalycilates (RR 0.81, 95% CI [0.71-0.92]; NNT of 13) and purine analogues (RR 0.82, 95% CI [0.72-0.93]; NNT of 14) but the effect size was trivial (Figure 1). Whereas for endoscopic relapse outcome, vedolizumab (RR 0.23, 95% CI [0.07-0.8]) and adalimumab (RR 0.32, 95% CI [0.17-0.62], low certainty) and infliximab (RR 0.63, 95% CI [0.48-0.82], low certainty) were the only agents superior to placebo but not purine analogues (RR 0.87, 95% CI [0.7-1.08], very low certainty), 5-ASA (RR 1.04, 95% CI [0.85-1.26], very low certainty), antibiotics (RR 1.13, 95% CI [0.83-1.53], very low certainty), probiotics (RR 1.15, 95% CI [0.94-1.39], very low certainty), vitamin-D (RR 0.9, 95% CI [0.62-1.31], very low certainty) and curcumin (RR 1.17, 95% CI [0.73-1.87], low certainty). On analysis of total adverse events outcomes, all therapies were safe.

Conclusion

On network meta-analysis, adalimumab had a large magnitude of effect size for preventing clinical and endoscopic relapse (low certainty), vedolizumab a large magnitude for preventing endoscopic relapse (low certainty) and 5-ASA a small magnitude result for preventing clinical relapse (low certainty). Overall certainty of evidence is very low to low suggesting need for further research in this field.
P761 Clinical efficacy and durability of subcutaneous infliximab in patients with moderate-to-severe inflammatory bowel disease : a real-world data from a Korean multicentre prospective cohort study
Authors: Kim K , Hong S N H , Kang S B K , Lee K M , Koo J S K , Jung Y , Lee B J L , Yoon H Y , Kim H W , Lim Y J , Lee H S , Lee Y J , Lee J , Lee C K , Moon J M , Shin S Y , Seo J , Choi C H
Published: January 2024

Background

Subcutaneous infliximab (IFX-SC) has shown comparable efficacy and safety with IV infliximab in ulcerative colitis (UC) or Crohn's disease (CD) since its launching in 2021. We aimed to investigate the one-year real-life efficacy and durability of IFX-SC in Korea.

Methods

From September 2021 to November 2023, patients with moderate-to-severe UC or CD, who are naive to any types of biologic agents or IFX were prospectively enrolled from 41 tertiary referral centers in Korea. After IV infliximab induction from Week (W) 0 to W2, patients received IFX-SC every 2 weeks from W6. Patients who administered IFX-SC less than W14 were excluded. Clinical remission (CREM), clinical response (CRES) at W26, W50, and one-year drug survival were assessed. In patients with CD, CREM was defined as Crohn’s disease activity index (CDAI) <150 points, and CRES was defined as a reduction in CDAI ≥70 points from baseline. In patients with UC, CREM was defined as partial Mayo score(pMS) of ≤1 points with no individual subscore of >1 point, and CRES was defined as a reduction from baseline in pMS of ≥2 points and ≥30% along with either a reduction in rectal bleeding subscore (RBS) of ≥1 point or an absolute RBS of ≤1 point19. Drug survival was evaluated based on the time of drug persistence from W0 to the last date of IFX-SC administration among drug-off cases.

Results

A total of 192 patients (UC with 53, and CD with 139) were enrolled, consisting of about 80% of biologic naïve cohort. Enrolled patients included young adults with a male predominance (Table 1). At W26, patients with UC showed 54.5% CREM and 88.6% CRES (Figure 1A). Among patients with CD, rates of CREM and CRES were 92.1% and 97.0%, respectively. Similarly, W50 CREM and CRES were also favorable with a rate of 57.1% and 89.3% among UC patients. In addition, among CD patients, favorable outcome was more obvious, showing 84.6% and 93.8% of CREM and CRES. Meanwhile, one-year drug survival was also investigated. As shown on the Figure 1B, one-year drug survival probability seemed favorable with a survival rate over 97% in both UC and CD patients (UC; 98.1% at W26 with 95% confidence interval [CI], 0.874–0.852, 96.1% at W50, 95% CI, 0.852–0.990, and CD; 97.8% at W26 with 95% CI, 0.933–0.993, 97.8% at W50 with 95% CI, 0.933–0.993). During the study, 3.1% (six patients) of serious adverse events were reported.

Conclusion

IFX-SC seems to be efficacious therapeutic option for patients with moderate-to-severe UC or CD patients in real-world settings. With a favorable drug survival and tolerable safety profile, it may facilitate individualized treatment with a good compliance.
P773 Clinical decision support tool for vedolizumab is useful in predicting endoscopic remission in Crohn's disease – a retrospective real-life single-centre cohort study
Authors: Maček P , Molinari N , Ocepek A
Published: January 2024

Background

Early control of inflammation could modify the disease course and improve outcomes in patients with Crohn's disease (CD). Positioning of advanced therapies is becoming more important as treatment options expand. Dulai et al. derived and externally validated a clinical decision support tool (CDST) for predicting response to vedolizumab (VDZ). They noticed that the high probability group, according to CDST, has the highest probability of achieving clinical remission (CR), corticosteroid-free remission (CSFR) and mucosal healing. In contrast, low and intermediate-probability groups are more likely to need surgery.

Methods

We performed a retrospective single-centre cohort study based on the UR-CARE registry. Data for 57 CD patients treated with VDZ from July 2016 until April 2023 were analysed. We stratified patients according to CDST for CD into three response probability groups: group 0 with low (≤13 points), group 1 with intermediate (14-19 points) and group 2 with high (>19 points) probability of response to VDZ. CDST was calculated using five variables: no prior bowel surgery, no prior tumour necrosis factor (TNF) alpha antagonist exposure, no prior fistulising disease, baseline albumin and baseline C-reactive protein (CRP). For analysis of the association between CDST, CR (defined as PRO2 ≤1 with rectal bleeding score 0), CSFR and endoscopic activity (defined as no change in endoscopic activity, endoscopic improvement (EI), or endoscopic remission (ER)) chi2 test was used.

Results

In our cohort, 38.6% of CD patients were male, the median age was 34 years at the time of diagnosis, and the median duration of disease until VDZ treatment was 4.1 years. Fistulising disease was present in 33.3%, 24.6% had upper gastrointestinal involvement, 56.1% had prior surgery, and 57.9% had prior anti-TNF exposure. The average follow-up duration was 27.0 (standard deviation = 19.2 months). We found a significant association between the CDST group and endoscopic activity at follow-up endoscopy but no statistically significant association between the CDST group and CR nor CSFR at weeks 14 and 52. The majority (69.2%) of patients stratified into CDST group 0 had endoscopically active disease, while in contrast, 68.8% of patients in CDST group 2 achieved ER. In group 1, EI was found in 45.8% and ER in 41.7% of patients.

Conclusion

In our retrospective study, CDST for VDZ predicted ER and EI in our cohort of patients with CD. We could not confirm the association between CDST and CR or CSFR, probably due to the definition used in a retrospective design, namely PRO2, which does not correlate well with endoscopic activity in CD.
P777 Is the long-term Budesonide use have any influence on Bone Mineral Density in Inflammatory Bowel Diseases?
Authors: Eskazan T , Durcan E , Bakkaloglu O K , Kurt E A , Onal U , Hatemi İ , Erzin Y Z , Celik A F
Published: January 2024

Background

Systemic steroid use, and IBD itself, both have negative effect on bone mineral density. Budesonide is a synthetic steroid with high topical glucocorticoid activity and low systemic bioavailability. When compared to systemic steroids, the frequency of side effects of budesonide appears to be quite low, however, there is no documented report about the long term budesonide use on BMD in IBD patients. We also do not know other potential side effects of long term budesonide use. In this study, we aimed to evaluate the long term budesonide use on BMD and its’ other potential side effects, in IBD patients.

Methods

We retrospectively reviewed the files of the patients who had been using budesonide for ≥24 months and had DEXA measurements during the follow-up period (Budesonide group). Patients in the budesonide group were matched 1:1 with patients without a history of budesonide use, in relation to pre or post registry number of each index case under budesonide. Matching between groups has been done, in terms of gender, age, type of IBD, history of resection, concomitant medications, and comorbidities. For the exact matching, move on for the next or further next available patient, pre or post of each index case, was taken as a choice. (Control group). At the initiation and completion of budesonide treatment, DEXA scans were taken, and biochemical parameters and bone fractures were recorded. We also recorded other causes of secondary osteoporosis in patients (such as comorbidities, medications, alcohol, and cigarette use), as well as cumulative steroid doses and durations in those using conventional corticosteroids.

Results

A total of 104 patients were included in the study, with 52 in the budesonide group and 52 in the control group. The mean duration of budesonide use was 46.13 ± 15.4 months (range: 25-94 months), and the mean cumulative budesonide usage dose was found to be 34.9 ± 11.8 g (range: 14-64.8 g) in the budesonide group. Table 1a presents the comparison of the two groups. None of the patients in the budesonide group showed deterioration in BMD during the follow-up (Table 1b and 1c). No other prominent long term side effects, valued for the file recording, was found.

Conclusion

Budesonide treatment seems to be safe in consideration for maintaining long term remission in IBD. Relatively low number of patients, not considering the first two year’s follow up and dropping of the cases with earlier side effects, missed for the long-term judgement under budesonide, may explain the lacking of the other potential side effects (indicated in the literature).
P784 Efficacy of ustekinumab in biologically naïve patients with Inflammatory Bowel Disease
Authors: Šubic Ž , Novak G
Published: January 2024

Background

In recent years, there are several new treatment options for inflammatory bowel disease (IBD). Tumour necrosis factor α inhibitors have been joined by novel advanced therapies (vedolizumab, ustekinumab (UST) and Janus kinase inhibitors). These drugs are mostly used as second-line treatments after tumor necrosis factor α inhibitors, with subsequent poorer efficacy. There are few data available on the efficacy of first-line treatment with UST. The aim of our study was to assess efficacy of UST in biologically naïve patients with IBD.

Methods

All patients older than 18 years who had a confirmed diagnosis of IBD, treated in a tertiary IBD centre (University Medical Centre Ljubljana, Slovenia), who started first-line treatment with UST, were included in this retrospective cross-sectional cohort study. Demographics, clinical characteristics of patients, treatment persistence of UST, clinical disease activity scores, C-reactive protein (CRP), faecal calprotectin (FC), UST concentrations, and endoscopic scores were collected retrospectively in medical files. We determined a Kaplan-Meier curve of treatment persistence.

Results

We included 71 patients, 11 of which had ulcerative colitis and 60 had Crohn’s disease. Persistence of treatment with UST in biologically naïve patients is 88% at one year (Figure 1). Clinical remission was achieved in 57.7% of patients. Biochemical remission was achieved in 77.6% (CRP<5mg/ml) and 71.1% (FC<100mg/kg) of patients. Endoscopic remission (Mayo endoscopic score <2 in ulcerative colitis or absence of ulcers in Crohn’s disease) was achieved in 50.0% of patients. There was no significant difference (P>0.05) between the median serum concentrations of UST in the group of patients who achieved remission (clinical (5.86μg/ml), biochemical (5.93μg/ml based on CRP, 5.63μg/ml based on FC) and endoscopic (7.14μg/ml)) and who did not achieve remission (5.31μg/ml, 3.25μg/ml, 4.47μg/ml and 4.64μg/ml, respectively).

Conclusion

Treatment of UST in biologically naïve IBD patients shows high treatment persistence with high biochemical and endoscopic remission rates. It appears that UST is more efficacious if used as first-line therapy compared to the use after other advanced therapies. Further prospective data are needed to confirm our findings.
P791 Trends in gender representation in inflammatory bowel disease randomized trials from 1955-2023
Authors: Gros B , Bassi M , Sleiman J , Charabaty A
Published: January 2024

Background

Historically women have been underrepresented in the field of gastroenterology and continue to be under-represented in academic scholarship and leadership despite the rising number of female medical graduates in recent years.This study aims to characterize the representation of women in authorship of published clinical trials in inflammatory bowel diseases (IBD) and the trend in gender representation since 1955.

Methods

IBD randomized trials published between 1955 to 2023 were included. Author gender, trial specifics (phase, intervention, population) source of funding were examined.

Results

We included 241 trials with a total of 3,264 authors: 2,418 were men (74.1%), 834 women (25.6%) and 12 (0.4%) had unknown gender. Women authorship representation increased from 0% in 1971 up to 30% in 2023 (0.41% annual increase) Figure 1A. Women were first, second, corresponding and last authors in 36/241 (14.2%), 41/241 (15.3%), 27/241 (10.5%) and 30/241 (11.7%) of published trials, respectively, Figure 1. Statistical differences in authorship by gender were found in all study categories, with women being less represented than men in unicenter vs multicenter trials, adult vs pediatric population trials, different trial phases, type of intervention [standard, advance or other] and source of funding (p<0.0001 for all comparisons) Table 1.

From 2000 to 2023, industry-sponsored studies (n=119) included 1,680 authors, with 1,295 (77.1%) men and 379 (22.9%) women. Among these authors, 576 had industry affiliation, and 318 (55.2%) were men and 258 (44.8%) women. Women were first, second, corresponding and last authors in 15/119 (12.6%), 12/119 (10.1%), 11/119 (11.2), 10/119 (8.4%) of these studies.

Linear regression analysis revealed an upward trend since 1995 in the total number of authors listed per published trial, but with men consistently outnumbering women authors, the ratio of women to men authors per publication remains low over the years (p<0.0001) Figure 1B.

Conclusion

Our findings underscore persistent gender disparities in published IBD trials authorship. Despite an increase in representation over time, women still make up less than 35% of authors and less than 15% of lead authors with little if any improvement over recent years (Figure 1C, 1D). Recognizing that lead authorship in trials has an impact on research funding and academic promotion, this gender disparity in authorship contributes to the many barriers women face in advancing their career in the field of IBD.
P795 Efficacy and safety of etrasimod as a first-line advanced treatment following 5-aminosalicylic acid and/or thiopurines: Data from the ELEVATE UC 52 and ELEVATE UC 12 phase 3 clinical trials
Authors: Sonnenberg E , Lees C W , Baert F , Piperni C , Wu J , Bhattacharjee A , Wosik K , Marshall J K
Published: January 2024

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We present data from the ELEVATE UC 52 and ELEVATE UC 12 phase 3 clinical trials1 assessing etrasimod efficacy and safety in patients (pts) who were biologic/Janus kinase inhibitor (JAKi)-naïve and previously took 5-aminosalicylic acid (5-ASA) and/or thiopurines.

Methods

In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), eligible pts were randomised 2:1 to etrasimod 2 mg once daily or placebo (PBO). Pts in this post hoc analysis were naïve to prior biologic and/or JAKi treatments, and included regardless of prior/concomitant corticosteroids (CS). Pts in Cohort A were previously exposed to or currently taking 5-ASA, but naïve to prior thiopurines; pts in Cohort B were previously exposed to a thiopurine with/without prior/concomitant 5-ASA. Efficacy endpoints included clinical remission and endoscopic improvement (Weeks [Wks] 12 and 52), CS-free remission and sustained clinical remission (Wk 52) and symptomatic response (Wks 2, 4, 8 and 12). Data up to Wk 12 were pooled from both trials; Wk 52 data were from ELEVATE UC 52. Safety was assessed up to 52 wks.

Results

In Cohort A, 135 and 62 pts were randomised to etrasimod and PBO, respectively; more pts in the etrasimod vs PBO arm achieved clinical remission (Wks 12 and 52), endoscopic improvement (Wks 12 and 52), CS-free remission (Wk 52) and sustained clinical remission (Wk 52; all p<0.05; Figure 1A). In Cohort B, 69 and 35 pts were randomised to etrasimod and PBO, respectively; significantly more pts in the etrasimod vs PBO arm achieved clinical remission and endoscopic improvement (Wk 12) and sustained remission (Wk 52; all p<0.05; Figure 1B). In both cohorts, numerical differences in the etrasimod vs PBO arm in pts achieving symptomatic response were seen starting at Week 2. In both cohorts, safety findings were consistent with the overall population, with no increases in incidence rates of serious AEs or serious infections in the etrasimod vs PBO arm.

Conclusion

This post hoc analysis further characterises the efficacy and safety of etrasimod as a first-line advanced treatment after conventional 5-ASA and/or thiopurine therapy, and is consistent with previous results in the cohort of pts naïve to biologic/JAKi which showed greater treatment effects than in pts experienced with advanced treatments.2 Limitations included post hoc analysis and small cohort sample sizes.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.

2. Feagan B et al. United European Gastroenterol J 2022; 10: 388–389.
P802 Impact of early use of immunomodulator on the outcomes of Crohn's disease: A Systematic Review and Meta-Analysis
Authors: Yoo J H , Yoon J , Jun Y K , Lee H S , Park J J
Published: January 2024

Background

Although immunomodulators play a crucial role in the treatment of Crohn's disease, robust evidence regarding the impact of early use of immunomodulators on its outcomes is still limited.

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify articles analyzing clinical outcomes according to the timing of immunomodulator administration in Crohn's disease. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs]. Types of immunomodulators include thiopurines or methotrexate.

Results

A total of 7 studies were identified as eligible for the meta-analysis. Early immunomodulator administration within 1 to 3 years after diagnosis was associated with a lower risk of bowel resection surgery (HRs 0.57, 95% confidence interval [CI] 0.45-0.71), but it was not associated with a lower risk of perianal surgery (HRs 0.62, 95% CI 0.27 - 1.39). In subgroup analyses, early immunomodulators were effective in lowering the risk of intestinal resection in both adults and the young population.

Conclusion

Early administration of immunomodulators in Crohn's patients is associated with a lower risk of bowel resection surgery. This finding suggests that when immunomodulators are administered within an optimal therapeutic window, they possess the potential to alter the disease course in Crohn's patients.
P808 Use of intestinal ultrasound influences the proportion of suboptimally controlled patients: IBD Podcast Study results
Authors: Dignass A , D'Amico F , Gomollón F , Bamias G , Heatta-Speicher T , Michelena N , Leitner C , Hammer L , Magro F
Published: January 2024

Background

The IBD-PODCAST study estimates the proportion of patients with Crohn’s disease (CD) and ulcerative colitis (UC) with suboptimal disease control (DC) in a real-world setting. Intestinal ultrasound (IUS) is recommended in international guidelines as a non-invasive tool to assess disease activity and to guide therapeutic decisions in IBD. It is easy to use, inexpensive, can be repeatedly used without limitations and provides an opportunity for immediate patient interaction. The aim of this descriptive analysis was to assess the impact of IUS on the proportion of suboptimal DC in this cohort.

Methods

IBD PODCAST was a non-interventional, cross-sectional, multi-center study conducted across 103 sites in 10 countries. Criteria for suboptimal DC were based on STRIDE-II. Retrospective data on the frequency of imaging (i.e. endoscopies, MRI/MRE/CT and IUS) in the 12 months prior to assessment were collected. We compared clinical decision making, subjective evaluation of DC by patients and physicians and objective criteria of suboptimal DC at the time of assessment (i.e. index) in patients with (i.e. CD+IUS12, UC+IUS12) and without IUS (CD-IUS, UC-IUS) in the past 12 months.

Results

2185 patients (CD: n=1108, UC n=1077) with a mean age (SD) of 44.0 (14.8) years and mean disease duration (SD) of 12.4 (9.2) years were included (52.2% male). Imaging was performed in 43.1% (n=477) of CD and 44.6% (n=480) of UC patients within 12 months prior to index. Endoscopy accounted for 77.6% and 88.8%, MRI/MRE/CT for 21.0% and 6.7%, and IUS for 19% (n=89/477) and 16% (n=77/480) of patients with CD and UC, respectively.

The proportion of patients with signs of active inflammation at index was higher in patients where IUS was used (CD+IUS12: 34% vs CD-IUS: 9.5%; UC+IUS12: 22.6% vs UC-IUS: 15.3%; Table 1).

For UC only, numerically more patients with parameters indicating clinically active disease at index were further monitored or had their treatment adjusted, when IUS was used within the past 12 months. (UC+IUS12: 58.6% vs UC-IUS: 50.7%).

Despite the high number of patients with suboptimal DC based on objective criteria, the use of IUS minorly improved the alignment of subjective evaluation of suboptimal DC between the patient and physician, and only in UC (UC+IUS12: 37.5% vs UC-IUS: 32.7%; Fig 1).

Conclusion

Only a minority of patients underwent IUS in this cohort. Yet, this non-invasive tool may be useful if used more frequently. Consistent with others, IUS could aid in holistic disease monitoring for the detection of suboptimal treatment response, clinical decision making and the opportunity for alignment with patients on treatment targets.
P820 Targeting MM-SES-CD < 22.5 for endoscopic improvement is feasible in a clinical trial of Crohn’s disease: A post-hoc analysis of SEAVUE
Authors: Narula N , Wong E C , Dulai P S , Marshall J K , Jairath V , Ungaro R C , Colombel J F , Reinisch W
Published: January 2024

Background

It has been demonstrated that a Modified Multiplier of the SES-CD (MM-SES-CD) < 22.5 is the optimal endoscopic threshold that is associated with a low risk of disease progression using data from the CALM long-term extension study. To determine whether or not this threshold would be a pragmatic target within the setting of a clinical trial, we performed a feasibility analysis using data from the phase 3 SEAVUE clinical trial.

Methods

We considered data from 373 patients from the SEAVUE clinical trial who had available endoscopic data at baseline and were treated with ustekinumab (n=187) or adalimumab (n=186). As participants were only required to have a single ulcer at the time of enrollment in SEAVUE, we further restricted the population to those with MM-SES-CD > 22.5. The primary outcome was MM-SES-CD < 22.5 at week 52. Secondary outcomes were common targets for endoscopic healing in clinical trials, including SES-CD reduction of ≥ 50%, SES-CD < 4, and SES-CD < 3. Clinical remission, defined as CDAI < 150, was also assessed at week 52. Sensitivity analyses were planned to restrict the population to those with moderate to severely active disease activity, defined as MM-SES-CD ≥ 31.

Results

Of the 373 participants, 55.2% (206/373) participants achieved a MM-SES-CD < 22.5. A total of 206 participants had a MM-SES-CD > 22.5 at baseline, of which 91 (44.2%) attained a MM-SES-CD < 22.5 at week 52. A greater proportion of participants achieved this outcome compared to SES-CD reduction of ≥ 50% (85/206, 41.3%), SES-CD < 4 (52/206, 25.2%), and SES-CD < 3 (36/206, 17.5%) at week 52 (Table 1). A total of 144 participants had moderate to severely active endoscopic disease at baseline (MM-SES-CD ≥ 31), of which 55 (38.2%) achieved a MM-SES-CD < 22.5 at week 52. This was similar to the number of patients who achieved SES-CD reduction of ≥ 50% (61/144, 42.4%), and greater than the number of patients who achieved SES-CD < 4 (34/144, 23.6%) or SES-CD < 3 (21/144, 14.6%) at week 52. Of the 144 participants with a MM-SES-CD ≥ 31 at baseline, a total of 71 received adalimumab and 73 received ustekinumab. Compared to adalimumab, a numerically greater proportion of those treated with ustekinumab achieved MM-SES-CD < 22.5 [33/71 (45.2%) vs. 22/71 (31%), p=0.079] and clinical remission [48/73 (65.8%) vs. 36/71 (50.7%), p=0.067] at week 52.

Conclusion

Based on this feasibility analysis, a MM-SES-CD < 22.5 is a feasible target to attain in clinical trials of Crohn’s disease. Further, use of the MM-SES-CD for measurement of endoscopic burden could lead to different conclusions being obtained from clinical trials of CD that are clinically and prognostically more relevant.
P855 Have biological agents changed the need for abdominal surgery in inflammatory bowel disease over time?
Authors: Suria C , Bosca-Watts M M , García-Trueba A , Tosca J , Antón C , Sanahuja A , Merino V , Abril C , Ballester M P , Romero E , Marti D , Galvez C , Ponce M , Pascual I ,   IBD Unit
Published: January 2024

Background

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory intestinal disorder with two main categories: Crohn’s disease (CD) and ulcerative colitis (UC). CD patients can develop strictures and penetrating complications over time, that can lead to an increased number of bowel resections which, if extensive, can end up as short bowel syndromes. Aggresive UC is related to an increased colectomy rate. Controlling flares in CD and achieving mucosal healing in UC may decrease the need for abdominal surgery. Irruption of biological agents at the begining of the twenty-first century could be related to the fulfillment of both objectives decreasing number of surgeries. Our aim was to analyze the impact of biological treatment in abdominal surgery among patients with CD and UC.

Methods

We conducted a retrospective two cohort study of patients with IBD and abdominal surgery, using our prospectively collected ENEIDA data base. Patients were included in two periods of time, before and after biological irruption. The first cohort included all the patients operated between 1993 and 1998 (before biologics) and the second one between 2013 and 2018. We analyzed differences in the number of surgeries per patient and time between IBD diagnosis and first surgery, among other variables.

Results

We included 55 patients (89.1% CD and 10.9% UC) in the first cohort and 69 patients (82.6% CD and 17.4% UC) in the second one. 44 patients in the second cohort (63.8%) received biological agents before first surgery. There were no significant differences in the number of surgeries (two or more) per patient in both periods of time (10.9% vs 7.3%, p 0.69). The main indication of surgery was strictures (44.6% vs 46.6%) followed by penetrating complications (25.0% vs 30.1%) and medical refractoriness (21.4% vs 15.1%). No differences were observed in the reason to indicate surgery (p 0.78). The main surgical procedure was ileocecal resection (60.0% vs 54.1%), followed by small bowel resection (11.7% vs 17.6%) and proctocolectomy (10.0% vs 5.4%), without significant differences over time (p 0.67). There were 7 immediate post-surgical complications in both cohorts (11.3% vs 9.5%) without significant differences between them (p 0.94). The median time between IBD diagnosis and first surgery was greater among patients in the second cohort who had received any biological agent (19.0 vs 71.2 months, p<0.05), [image 1].

Conclusion

Biological treatment considerably increases the time between IBD diagnosis and the first surgery. Future research will allow us to determine if this is associated to less surgeries in each patient and a reduction in long-term post-surgery complications (short-bowel syndrome, abdominal adhesions, eventrations, etc).
P892 Do anti TNF alpha drugs reduce cardiovascular risk in Crohn's disease ?
Authors: Fissah M , Rechach A , Charifi M , Menzou F , Djouhri M , Taharboucht S , Karch A , Talbi L , Touati N , Chibane A
Published: January 2024

Background

We now know that Crohn's disease (CD) is characterised by a higher cardiovascular risk, despite the low frequency of traditional risk factors. Arterial stiffness (AS) and its relationship with chronic inflammation seem to explain this paradox. Given that inflammation plays an important role in AS, reducing it should make it possible to reduce this stiffness. This led us to evaluate the effect of anti TNF alpha on AS

Methods

This was a prospective observational study involving 118 patients with CD, 63 of whom were taking anti TNF alpha (Adalimumab, Infliximab). AS was assessed by pulse wave measurement (aPWV) using a validated Sphingmocor Syndney device at the time of recruitment and during patient follow-up. Statistical analysis was performed using SPSS statistical software and Student's t-test for paired samples.

Results

The mean age was 37 years [19-67], sex ratio = 1.5, 22.2% were active smokers, 62.9% of patients were in a flare and 43.3% had had at least two relapses in the year prior to recruitment, median duration of disease was 30 months. The mean duration of follow-up was 9 months [6-24]. The reduction in aPWV was highly significant for patients on anti-TNF alpha therapy, whether with flexible or rigid arteries: the mean aPWV was 7.67+/-1.4 vs 7.08+/-1.07 for patients on anti-TNF alpha therapy, with a p=2*10-5. The aPWV was 8.49+/-1.07 vs 7.42+/- 0.44 for patients with rigid arteries with a p= 3*10-4.

Conclusion

Treatment with Anti TNF alpha appears to slow down aPWV in Crohn's disease, and may therefore be a good way of reducing the cardiovascular risk and the risk of developing cardiovascular disease in Crohn's disease.
P895 Analysis of the efficacy of intravenous ustekinumab maintenance treatment in patients with refractory Inflammatory Bowel Disease
Authors: López-Sáez B , Brunet-Mas E , Melcarne L , Puy A , Lario S , Ramirez-Lázaro M J , Llovet L P , Garcia-Sagué B , Frisancho L E , Altadill A , Villoria A , Calvet X
Published: January 2024

Background

Ustekinumab (UST) is a monoclonal antibody that inhibits the p40 subunit of IL-12 and IL-23, approved for the treatment of Crohn's Disease (CD) and Ulcerative Colitis (UC). Its administration is intravenous during induction and subcutaneous during maintenance. Several studies have assessed the efficacy of reinduction and intensification of this treatment in patients with loss of response. However, there are few studies evaluating the effectiveness of intravenous UST for maintenance.

The aim of the study is to evaluate the efficacy and safety of maintenance with intravenous UST in patients with Inflammatory Bowel Disease (IBD).

Methods

Observational, retrospective, and single-center study. All patients receiving maintenance with intravenous UST until June 2023 were reviewed. Clinical response was evaluated with Harvey-Bradshow Index for CD and partial Mayo for UC. Biochemical response was evaluated with calprotectin and C-reactive protein.

Results

A total of 29 patients with IBD (24 CD and 5 UC) were included. The mean follow-up of patients was 449 days (74-948). The cohort's characteristics are summarized in Table 1.

In all cases, intravenous maintenance was performed with UST 130mg/4 weeks. In 4 cases (13.8%), maintenance was initiated directly with intravenous UST. In 9 (31%) patients due to primary failure to UST and in 16 (55.2%) patients due to secondary failure.

The clinical response to intravenous UST maintenance in patients with CD at week 8 and 16 and at one year of follow-up was 87.5% (n=21/24), 83.3% (n=20/24), 73.3% (n=11/15) respectively. For UC, the response was 60% (n=3/5) at week 8 and 16 and at one year. The drug survival was 723 days (± 74) (Figure 1). No predictive variable for treatment response was identified. Two patients (both with CD) experienced recurrent respiratory infections as an adverse effect, without the need to discontinue UST.

Conclusion

Maintenance treatment with intravenous UST can be useful and safe in patients with severe IBD and/or failure of subcutaneous UST maintenance.
P898 Hesitancy on COVID-19 Vaccination Among Patients with Inflammatory Bowel Disease in South Korea: A Multicenter Survey
Authors: Kang S B , Moon H S , Jung Y , Kim D S , Koo H S , Huh K C
Published: January 2024

Background

Despite many clinicians recommending COVID-19 vaccination to patients with inflammatory bowel disease (IBD) due to high susceptibility, COVID-19 vaccine hesitancy was a worldwide phenomenon. Although previous studies to identify the cause of this vaccine hesitancy are being published, few studies have been done on COVID-19 vaccine hesitancy among IBD patients in South Korea. Therefore, the aim of our study was to find out the factors that cause vaccine hesitancy in patients with IBD in South Korea.

Methods

An electronic survey was conducted on IBD patients with receiving treatment at 5 hospitals in Daejeon-Chungchung province from September 2022 to January 2023. Basal characteristics, factors for vaccine hesitancy was evaluated. Survey was designed as a voluntary and anonymous manner.

Results

A total of 272 patients participated in the survey, of which 119 patients had Crohn’s disease (CD) and 153 patients had ulcerative colitis (UC). COVID-19 vaccine hesitancy tended to decrease with age (r=-0.158, p=0.011). In IBD medication, comparing patient group using 5-aminosalisylic acid and using biologics, hesitancy was higher in the biologics group (p=0.017). Hesitancy was high in patients who preferred Moderna (p=0.049). 102 patients answered that the cause of vaccine hesitancy was concern about safety of vaccines, with the largest share.

Conclusion

The study found that the main reason of hesitancy was concerns about the safety of the vaccine. Hesitancy tended to decrease with age and was higher in patients using biologics. This study may be helpful to educate patients with more specific targets to prepare for the current COVID-19 as well as other possible future pandemics.
P901 Extended induction response over time in patients with moderately-to-severely active Ulcerative Colitis treated with mirikizumab in the LUCENT-1 and -2 trials
Authors: Rubin D T , Charabaty A , Jairath V , Walter J , McGinnis K , Moses R , Maier S , Escobar R , Baygani S , Zaremba-Pechmann L , Kobayashi T
Published: January 2024

Background

The safety and efficacy of mirikizumab (miri), an anti-IL-23p19 antibody, for moderately-to-severely active ulcerative colitis (UC) have been shown in Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092).1 Extended induction with 3 additional intravenous (IV) doses of miri induced clinical response at Week (W)24 in more than 50% of patients who did not initially achieve clinical response to induction with miri at W12.2 Among the clinical non-responders, some had achieved partial response at W12 (Table 1). We assessed response over time in clinical non-responders at the end of induction who received extended induction with miri for an additional 12W.

Methods

In LUCENT-1, patients (N=1281) were randomly assigned 3:1 to receive miri 300mg or placebo IV at W0, W4, and W8. Patients not achieving clinical response with miri 300mg IV at W12 of LUCENT-1 (n=272) received extended induction treatment with open-label miri 300mg IV at W12, W16, and W20 (LUCENT-2). Symptomatic remission, symptomatic response, bowel urgency (BU) remission, and BU change from baseline at W16 and W20 are reported (definitions in Table 1) in addition to the previously disclosed outcomes at W24. For categorical variables, number and percentage of patients who are responders/remitters were presented. For continuous variables, mean change from baseline with standard deviation (SD) was used. Missing data were imputed as non-response.

Results

Among patients who were clinical non-responders to 12W of initial induction treatment (n=272), 53 (19.5%); 73 (26.8%); 101 (37.1%) achieved symptomatic remission and 144 (52.9%); 169 (62.1%); 197 (72.4%) patients achieved symptomatic response at W16, W20, and W24, respectively. Among miri induction non-responders with Urgency Numeric Rating Scale (NRS) score ≥3 at induction baseline (n=256), 10.9% achieved BU remission at W16, 14.8% at W20, and 19.9% at W24. There was a 1.8±2.4 (mean±SD) point reduction in Urgency NRS scores at W16, 2.1±2.5 reduction at W20, and 2.5±2.7 reduction at W24 (Table 1).

Conclusion

Among patients who were clinical non-responders to induction at W12, more than 50% achieved clinical response after 3 additional induction doses with miri. A proportion of patients benefited earlier from extended induction at W16 and W20, respectively, regarding symptomatic response and remission, and BU outcomes. The results demonstrate continued symptomatic improvement and further support the potential benefit of extended induction treatment.

References:

1. D’Haens G, et al. N Engl J Med 2023;388(26):2444-2455.

2. D’Haens G, et al. J Crohns Colitis 2023;17(Supplement_1):i682-i683.
P920 Efficacy and Drug Adherence Rates of Anti TNF Drugs in patients with Crohn's Disease: A Single Tertiary IBD Center Cohort
Authors: Eroglu Z , Yilmaz V , Guvenir T , Er R E , Toruner M
Published: January 2024

Background

In the last 2 decades, the introduction of biological therapies has been a significant milestone in the management of inflammatory bowel diseases. Despite the recent emergence of new biological therapies and small molecules, Anti-TNF agents still play a crucial role in treatment and still being used as first line biologic treatments rather than anti-integrins and anti-cytokines in quite a number of countries.Although many studies have been conducted previously to compare the efficacy of these drugs, there is still not a clear conclusion. In this study, we aimed to compare the persistence of infliximab (IFX) to adalimumab (ADA) in the treatment of Crohn's at a tertiary IBD center.

Methods

This was a retrospective cohort analysis of patients with Crohn's disease either received adalimumab or infliximab as a first line biologic treatment. A total of 411 patients were included to this analysis. Demographic information such as gender, age, montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes.

Results

Out of the 411 patients included in the study, 165 had used infliximab, and 246 had used adalimumab as a first-line treatment. Age and gender of the patients in both groups did not differ from each other statistically. 87% of the patients treated with adalimumab and 84% of the patients treated with infliximab were thiopurine experienced. Montreal classification differed between two groups (in IFX group, 60% of the patients had either sticturing or penetrating behaviour where as in ADA group, only 46% of the patients had either sticturing or penetrating behaviour, p<0.05). In ADA group, only 48% of the patients were receiving concomitant azathioprine treatment where as in IFX group, 60% of the patients were receiving concomitant azathioprine treatment. Primary non-response rates were not different between IFX and ADA group, 4.5% vs 4.6% respectively. In addition, clinical response rates after first year were 73.8% and 72.8% respectively. Drug persistency rates of adalimumab and infliximab in moderate to severe ulcerative colitis patients were not statistically different from each other (Figure 1).

Conclusion

In conclusion, it seems that there is no difference in drug persistence rates and in efficacy rates of the medications between infiximab and adalimumab treated moderate to severe Crohn's disease patients. Although disease character and concomitant treatment presence differ between two groups, these differences did not show any significant effect.
P922 A multicenter retrospective real-world study to determine the optimal cases of vedolizumab-treated UC patients
Authors: Kobayashi T , Hisamatsu T , Ishiguro K , Hirose L , Hibi T
Published: January 2024

Background

Vedolizumab (VDZ) is a gut-selective monoclonal antibody approved for ulcerative colitis (UC). This real-world study aimed to evaluate the effectiveness of VDZ in the treatment of UC, with the goal of further treatment optimization.

Methods

In this multicenter, retrospective, observational chart review, 370 patients with UC who received at least one dose of VDZ in clinical practice at 16 tertiary hospitals in Japan were enrolled. Comprehensive analyses of predictors of 2- and 54-week remission, drug persistence, and the development of loss of response were performed.

Results

Lower partial Mayo scores and lower Mayo endoscopic subscores were significantly associated with 2-week remission in the multivariate analysis. More 2-week remitters achieved clinical remission at Week 52 than non-2-week remitters. Clinical remission rates were significantly higher in biologic-naïve than in biologic-non-naïve patients across Weeks 2 to 54. Higher clinical remission rates at Week 54 were significantly associated with lower baseline disease severity and no prior anti-tumor necrosis factor alpha (anti- TNFα) treatment. Among patients with prior anti-TNFα treatment, longer duration of anti-TNFα treatment was associated with higher clinical remission rates at Week 54 (28.1%, 32.7%, and 60.0% for ≤3 months, >3 to <12 months, and ≥12 months, respectively, p=0.001 between groups). In addition, clinical remission rate at Week 54 was higher in patients who had loss of response to anti-TNFα treatment than in those who had primary nonresponse (54.4% vs 24.6%; p=0.001). The 54-week persistence rate was 64.5%. Concomitant use of tacrolimus (OR 2.76, 95% CI 1.00, 7.62, p=0.05) and shorter disease duration (median:7.8 years), (OR 0.33, 95% CI 0.13, 0.82 for ≥7.8 years vs <7.8 years p=0.017) were associated with loss of response to VDZ in the multivariate analysis, but prior use of anti- TNFα treatment was not.

Conclusion

This retrospective study confirms favorable outcomes with VDZ in patients without prior exposure to anti-TNFα treatment. However, among patients with history of anti-TNFα- exposure, better outcomes were observed among those who experienced loss of response than those with primary nonresponse, as well as those who had a longer duration of anti-TNFα treatment.