bluuebunny/crossref_metadata_2025 huggingface dataset:
P971 The relapse rates and dynamics of disease severity of inflammatory bowel disease after forced biologic treatment discontinuation: Taiwanese multicentre retrospective study
Authors: Le P H , Chang C H , Chou J W , Hsu H , Chen C M , Tu C H
Published: January 2024

Background

The reimbursement regulations in 2011 for inflammatory bowel disease (IBD) in Taiwan require patients (pts) to discontinue biologic treatment after using the medication for one year and pts can be retreated after ≥ 6 months of forced discontinue. This study aimed to evaluate relapse rates, predictors of relapse and dynamics of disease severity under Taiwan reimbursement policy.

Methods

This was a multicentre retrospective study using electronic medical record (EMR) database to identify the association between clinical variables and relapse after forced discontinuation in the real-world setting. Pts aged ≥ 20 years old with at least 6 months of biologic treatment were further analyzed to identify the disease severity prior to biologic treatment (closest endpoint before receiving 1st biologic), 1st forced discontinuation, 2nd biologic and 2nd forced discontinuation. EU PAS register number: EUPAS48289.

Results

We identified 455 newly diagnosed IBD pts from February 2008 to March 2020 in Taiwan. The percentage of relapse after biologic discontinuation was 47.0% (N=353), 41.4% (N=87), and 40.0%(N=15) for 1st, 2nd and 3rd biologic treatment cycle (TxC), respectively.

Among pts in the 1st biologic ST, 353 pts were identified who received at least 6 months of biological treatment. Only 87 (24.6%) pts were able to be re-treated for the 2nd biologic TxC under reimbursement criteria after forced biologic discontinuation.

Prior to biologic treatment, the use of anti-diarrheal symptom control treatment (HR: 1.452, p = 0.0186) and IBD-related surgery (HR: 1.434, p = 0.0216) were factors associated with an increased risk of relapse on 1st biological TxC. Pts who received the 1st biologic TxC and 2nd biologic TxC with a long biologic treatment duration at the end of treatment (HR: 0.998, p <0.0001); (HR: 0.998, p =0.0003) were less likely to experience relapse. Consistent results were found in the 3rd biologic TxC (HR: 0.963; p =0.0292) long biologic treatment duration was a protective factor against relapse.

The percentage of severe pts prior to biologic treatment was 43.7% and dropped to 11.4% after receiving the 1st biologic treatment. However, the percentage of severe pts increased to 32.0% at 1st forced discontinuation and further rose to 35.7% at 2nd forced discontinuation.

Conclusion

The predictors of relapse could assist physicians in clinical decision-making especially when pts faced with discontinuation. Proportion of moderate to severe disease severity decreased after receiving each TxC and due to forced discontinuation, half of the pts exhibited moderate to severe disease severity after forced discontinuation, suggesting that one year of treatment time was insufficient to reach the desired therapeutic goals.
P980 Dietary perceptions and practices in patients with Inflammatory Bowel Disease
Authors: Khemiri W , Ayari M , Ghannouchi A , Mtir M , Abdelaali Z E I , Douggui M H , Taieb J
Published: January 2024

Background

Patients with Inflammatory bowel disease (IBD) have a strong interest in the role that diet can play in the disease.However, studies evaluating the perception of diet in Tunisian patients are lacking.The aim of this study was to investigate the dietary beliefs and behaviours of adult patients with IBD.

Methods

We conducted a longitudinal study using a self-administered questionnaire distributed online to the «Association Tunisienne des Maladies de Crohn et de RCH» group. Through 17 items, we collected data assessing the dietary behaviours and beliefs of patients with Crohn's disease (CD) or ulcerative colitis (UC).

Results

A total of 121 patients (CD: 59%,UC 41%)were enrolled, with a mean age of 38.1±11.4 years and a sex ratio of M/F= 0.73.Twenty-three patients were active smokers. At the time of the enrollment, 26.4% of patients had an active disease. Eighty-three patients believed that diet was a trigger for the disease, with a male predominance(80% versus 60.8%, p=0.02) but no difference between the UC and CD groups was found(p=0.61). Fourty-one patients felt that diet was more important than medical treatment for disease control, with equal importance for 47 patients and no impact for 6 patients. Ninety-two patients thought that diet could induce a relapse of the disease, with 86.8% resorting to an exclusion diet, and 76% thought that a change in diet could induce remission of the disease. The most frequently avoided were spices(33.1%),and gluten(17.4%). Spicy foods were considered to be the main responsible for IBD flares by 90.1% of patients,followed by fast foods(75.9%), citrus fruits(70.4%) and legumes(64.7%). Respectively 57% and 34.7% of the patients believed that milk and dairy products could induce or worsen disease symptoms. Around half of our patients thought that pasta had no impact on the disease course, while rice was considered to be the major aliment able to prevent relapse and improve symptoms by 47.7% of patients. On the other hand, 52.2% of patients considered high fiber vegetables to be potentially responsible for relapses. Fourty-two percent of the patients believed that fruits could have a negative impact on IBD while 20.4% thought they have a positive effect. Around half the patients thought that red meats and coffee had no impact on the course of the underlying disease. Fifty-five percent of the patients believed that fasting could prevent relapses, while 53 patients felt that it had no significant effect. Half of our patients had at least once consumed nutritional supplements, with a medical prescription noted in 65.6%.

Conclusion

Our study underlines the importance of a holistic approach to the treatment of IBD, taking into account both traditional medical treatments and appropriate dietary education.
P992 Nutraceutical treatment based on a multi-compound formulation composed of Hericium erinaceus, berberine, quercetin, niacin, and biotin could improve the oral 5-ASA effectiveness in mild-to-moderate ulcerative colitis: Results from a two-arm multicentric retrospective observational study
Authors: Gravina A G , Tursi A , Pellegrino R , Brandimarte G , D'Avino A
Published: January 2024

Background

The use of nutraceuticals as adjunctive therapy for ulcerative colitis (UC) is increasingly emerging. HBQ-Complex® (a compound consisting of Hericium erinaceus, berberine, and quercetin), when added to biotin and niacin (a compound called Enteroflegin®), has already shown promising results in ex vivo models of UC as well as in other gastrointestinal disorders such as symptomatic uncomplicated diverticular disease. This multicentric observational retrospective study aimed to weigh the effectiveness and safety of Enteroflegin® in mild-to-moderate UC as adjunctive therapy to oral 5-aminosalicylic acid (5-ASA).

Methods

Mild-to-moderate UC patients [i.e., with a partial Mayo score (PMS) between 2 and 7] on exclusive therapy with oral 5-ASA (i.e., without taking steroids, biologics, small molecules or other prebiotics/symbiotics/antibiotics) were divided into two groups and evaluated at baseline (T0), after three months (T1) and after six months (T2). One group of patients (G1) took 5-ASA plus two Enteroflegin® tablets for six months, while the other control group underwent only 5-ASA treatment (G2). PMS, faecal calprotectin and 5-ASA dose were collected at each time. Clinical response at T1 and T2 (i.e., reduction in PMS ≥ 2 from baseline) and clinical remission at T1 and T2 (i.e., PMS < 2) were the main outcomes of the study, including compound safety.

Results

One hundred thirty patients [median age 39.5 (30 - 55), BMI 24.4 (22.8 - 26.4) Kg/m2, median years since UC diagnosis 10 (3.2 - 18.4)] were retrospectively included. In the sample, 51.5% were male, 47.7% had left colitis, 55.4% had proctitis, and 5.4% had pancolitis. 96.2% were on mesalazine therapy. 40.8% of patients had a PMS consistent with moderate activity. The clinical response rate at T2 (69.4% vs 47.5%, p=0.01) and clinical remission at T1 (17.9% vs 4.2%, p=0.029) and T2 (38.9% vs 19.1%, p=0.03) were higher in G1 than in G2 group (Figure A, p < 0.05). The trend in calprotectin reduction was also more favourable for G1 throughout the study (Figure B, p < 0.05). A dosage of 5-ASA > 3.6 g (OR 4.269, 95% CI 1.322 - 13.79; p=0.015) per day, as well as the use of Enteroflegin® (OR 3.303, 95% CI 1.232 - 8.857; p=0.018), resulted as clinical remission at T2 (i.e., six months) predictors. No adverse events were reported.

Conclusion

The nutraceutical compound Enteroflegin®, when added to standard therapy with oral 5-ASA treatment in patients with mild-to-moderate UC, increased its real-life effectiveness without safety concerns.
P998 Phase 2 basket design study evaluating the efficacy and safety of an anti-TL1A antibody (TEV-48574) in moderate to severe ulcerative colitis or Crohn's Disease (RELIEVE UCCD)
Authors: Reinisch W , Stoyanov S , Raphael G , Barkay H
Published: January 2024

Background

TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). TEV-48574 is being evaluated in the first basket design trial in IBD. The basket design is uniquely suited for the efficient assessment of TEV-48574 as evidence suggests that TL1A signaling plays a key role in both ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signaling is not a primary driver but an amplifier of inflammation; thus, targeting TL1A should mitigate excessive immune responses while leaving baseline immunity intact. Originating in oncology trials, the basket trial design has emerged as a new efficient approach for testing treatment efficacy in different disease indications with potentially common molecular mechanisms. The basket design approach allows the evaluation of multiple indications in a single study design that provides adequate support for initiation of confirmatory studies. Additionally, the basket design allows for shared sites and institutional review boards, data collection and analyses under consistent conditions. Herein, we describe the phase 2b basket trial evaluating TEV-48574 in UC and CD (clinicaltrials.gov NCT05499130), currently ongoing along with a long-term extension study (LTE)(NCT05668013).

Methods

In this double-blind placebo-controlled global study, TEV-48574 or placebo is administered subcutaneously to adults (n = 240) diagnosed with moderate-to-severe IBD (UC (n = 120) or CD (n = 120)). Patients who meet pre-specified inclusion/exclusion criteria are randomized to either one of two TEV-48574 dose regimens or placebo in a 1:1:1 ratio (stratified by diagnosis (UC or CD) and previous exposure to advanced IBD therapy(biologics and small molecules)) for 14 weeks. Patients who complete the 14-week induction period have the option to enter the LTE, consisting of a 44-week maintenance period for responders and a re-induction period for non-responders. Primary efficacy endpoints are induction of clinical remission (a modified Mayo Score of ≤2 points for UC), and endoscopic response (a reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) of ≥ 50% from baseline) for CD, at week 14. A Bayesian approach will be used to compute posterior probabilities for the response endpoints within each indication. Additional endpoints include safety assessments, measures of clinical response, biomarkers, pharmacokinetics, and immunogenicity.

Results

Conclusion

TEV-48574 is a potential novel treatment option for patients with UC and CD that may have dual antifibrotic and anti-inflammatory effects. The phase 2 basket study design offers an efficient approach to advance TEV-45874to confirmatory phase 3 studies.
P1006 Assessing sexual health care needs in patients with inflammatory bowel disease
Authors: Beattie W , Elford A , Segal J , Kaushik V , Downie A , Mitchell J , Al-Ani A , Prentice R , Christensen B
Published: January 2024

Background

Optimal care of inflammatory bowel disease (IBD) should encompass both physical and mental health. Sexual health is often overlooked, despite contributing significantly to patient quality of life. This study aims to further characterise the impacts of IBD on sexual health using an IBD specific scale and assess patient interest in accessing relevant expertise.

Methods

An electronic survey was emailed to patients with IBD at a tertiary public hospital using REDCap. Assessment of disease severity was based on clinical disease indices: Harvey Bradshaw Index (HBI) for patients with Crohn’s disease (CD); and the Simple Clinical Colitis Activity Index (SCCAI) for patients with ulcerative colitis (UC). The survey also contains de-identified demographic data, basic information about the participant’s IBD and questions derived from both the validated IBD-Specific Female Sexual Dysfunction and IBD-Male Sexual Dysfunction Scales. Comparisons of patient responses from those with clinically active versus inactive disease were made using Fisher’s exact test. Analysis was exploratory and no correction for multiple comparisons was made.

Results

A total of 101 participants took the survey, including 53 females and 48 males which comprised of 38 patients with UC, 57 with CD, three with indeterminate colitis (and three unsure of diagnosis). Age ranged from 18 to 81 years old with a median of 38; 90% of patients had a disease duration of at least 2 years. Patients with CD recorded a median HBI of five (interquartile range three to nine). Patients with UC recorded a median SCCAI of two (interquartile range one to four). Patients with clinically active CD trended toward more significant sexual dysfunction than those in remission across all domains in the sexual dysfunction scale. Patients with active CD were more likely to report that their disease had prevented engagement in sexual activity in the past year (p=0.04) and more likely to be afraid to participate in sexual activity (p=0.01) compared to those in remission. Patients with active UC were more likely to report that pelvic pain affected sexual activity (p=0.03) compared to those in remission. Regarding seeking additional support, 47% of all patients expressed interest in gaining assistance though only 20% have attempted to seek this advice. 36% of participants would wish to be contacted by their treating team if a sexual health service became available at their hospital.

Conclusion

Patients with more active IBD were more likely to report that their illness negatively impacts their sexual health. 74% of participants reported interest in accessing expert advice regarding sexual health, highlighting the need for services specifically addressing sexual health for IBD patients.
P1016 Real-world data on sequential therapy in moderate-to-severe UC: Unveiling second-line strategies after anti-TNF failure
Authors: Farkas B , Borsos M , Resál T , Bacsur P , Szepes Z , Savarino E V , Bertin L , Limdi J K , Sethi-Arora K , Miheller P , Vilmos F , Castiglione F , Bonacci L , Lukas M , Maharshak N , Berman G , Krznarić Ž , Wetwittayakhlang P , Lakatos P L , Seidelin J B , Attauabi M , Michalopoulos G , Ribaldone D G , Kagramanova A , Chashkova E , Sarlós P , Saibeni S , Shitrit A B G , Molnár T , Farkas K
Published: January 2024

Background

The development of anti-TNFs has brought major advances in the treatment of ulcerative colitis (UC). Yet, a significant proportion of patients do not respond favorably to first-line anti-TNF therapy, which may require the use of second-, third-, or fourth-line biologics or small molecules. Treatment selection and sequencing, however, remains a major unmet need.

Methods

We conducted a multicenter, retrospective study including patients with moderate-to-severe UC who failed first-line anti-TNFs, and received sequential therapy with biologics or small-molecules. The effectiveness of sequential therapy, more specifically second-line agents was determined and compared by treatment persistence and colectomy-free survival up to 3 years post-initiation, and assessed using Kaplan-Meier analyses. Multivariate Cox regression analysis was performed to identify the predictive value of various factors for colectomy and persistence.

Results

683 UC patients were included. The median follow-up time was 62 months (IQR: 36-98), during which 14.2% of patients required colectomy. The probability of colectomy-free survival was 97.5%, 93.9% and 92.3% at 1, 2, and 3 years. Persistence rates increased significantly with the number of therapy lines (P<.0001). The presence of deep ulcers at diagnosis (HR: 0.45; P=.009), prior cyclosporine use (CYA; HR: 0.41; P=.028), and low serum albumin at first-line therapy (HR: 0.92; P=.002) appeared to be predictive for colectomy. Following anti-TNF failure, significantly higher colectomy-free survival rates were observed over 3 years with ustekinumab (UST; P=.014; Figure 1a.), than with vedolizumab or tofacitinib. Second-line UST also showed superior persistence at 3, 6, 12, and 24 months (P=.049; Figure 1b.), but not at 36 months. Neither the risk of colectomy (P=.343), nor the rate of persistence with second-line therapy (P=.19) was influenced by the reason of first-line anti-TNF discontinuation. Prior CYA use (HR: 0.42; P=.047) negatively influenced persistence with second-line therapy.

Conclusion

Despite multiple lines of sequential biological and small molecule therapy we found a low incidence of colectomy and a high rate of persistence. Following anti-TNF failure, regardless of its cause, UST might be the preferred second-line agent in moderate-to-severe UC.
P1018 Population pharmacokinetic and exposure-response analyses for efficacy and safety of risankizumab in subjects with moderately to severely active Ulcerative Colitis
Authors: Thakre N , Goebel A , D'Cunha R , Winzenborg I , Liu W , Pang Y
Published: January 2024

Background

Risankizumab (RZB) has been evaluated in subjects with moderately to severely active ulcerative colitis (UC) in the INSPIRE and COMMAND trials. Population pharmacokinetic (PPK) and exposure-response (ER) analyses were conducted at the end of Phase 2b and following Phase 3 to characterize RZB PK and its relationship with clinical efficacy and safety to support Phase 3 induction dose selection, and the final dose recommendations for induction and maintenance treatment.

Methods

PPK analyses in UC used a previously developed PPK model for Crohn’s disease with additional evaluation of covariates relevant to UC. ER relationships between RZB exposures and efficacy endpoints at the end of induction (Week 12), re-induction (Week 24; exploratory only) and maintenance (Week 52) periods were established using exploratory graphical analyses and logistic regression modeling. ER analyses for safety were performed for key variables through Weeks 12, 24 and 52 using graphical analyses.

Results

A two-compartment model with first-order absorption for SC administration and first-order elimination adequately described RZB PK. Among the various covariates assessed, body weight, baseline (BL) serum albumin, BL high-sensitivity C-reactive protein, BL fecal calprotectin, sex, advanced therapy IR status, BL pancolitis and corticosteroid use were statistically correlated with RZB clearance but their impact on exposure was not clinically relevant for efficacy.

ER analyses for efficacy using Phase 2b induction data showed that while incremental improvement in efficacy was predicted with doses increasing from 1200 to 1800 mg, the magnitude of difference in efficacy was modest especially for endoscopy-driven endpoints. Phase 3 ER analyses for efficacy showed statistically significant trends of exposure-dependent increase in efficacy following induction treatment with 1200 mg IV at Week 0, 4 and 8, with greater response rates observed with higher exposures across all evaluated endpoints at Week 12, in line with the results from Phase 2b. ER analyses for maintenance demonstrated an exposure-dependent increase in efficacy for Week 52 endpoints, with modest improvement in efficacy when increasing the dose from 180 mg to 360 mg, and largely overlapping confidence intervals. ER analyses for safety indicated no apparent exposure-dependent safety events over the induction or maintenance treatment.

Conclusion

The PPK and ER analyses of RZB in subjects with UC characterized the disposition of RZB and its relationship to efficacy and safety, as well as the lack of impact by intrinsic and extrinsic factors on PK and efficacy. Results supported the final dosing regimen recommendations for the treatment of moderately to severely active UC.
P1021 Comparison of subcutaneous and intravenous infliximab in patients with inflammatory bowel disease showed no differences in immunogenicity or treatment persistence at one year
Authors: Hancox S , Morda F , Black C , Selinger C
Published: January 2024

Background

The effectiveness of infliximab (IFX) in inflammatory bowel disease (IBD) can be impaired by the formation of anti-drug antibodies (ADA). Subcutaneous (SC) IFX has a different pharmacokinetic profile compared to intravenous (IV) administration. These differences may affect the risk of immunogenicity and we sought to explore this in a retrospective study.

Methods

We performed a retrospective study in Leeds, United Kingdom. Adult patients starting IFX for the first time between January 2019 and June 2022 were identified. All received standard induction with three IV doses followed by either: 1) maintenance SC IFX 2-weekly (standard practice from 2021), or 2) maintenance IV IFX (standard practice until 2021). We compared ADA levels, IFX trough levels and treatment persistence between groups after 12-months of treatment. ADA levels above 10 AU/ml were considered positive and ADA levels above 50 AU/ml as clinically relevant.

Results

After excluding 41 patients (16 stopped IFX after IV induction, 24 moved to SC after >4 IV doses, and 1 lost to follow-up), 101 patients receiving maintenance SC IFX were compared to 108 patients continuing with maintenance IV IFX. At 12-months, prevalence of ADA positivity was similar in both groups (48.1% SC vs 50.6%; p=0.775). Clinically relevant ADA levels (>50 AU/ml) were also similar (21.1% SC vs 26.5% IV; p=0.481). Additionally, there were no statistically significant differences in terms of detectable IFX trough levels and treatment persistence after 12-months of treatment between the two groups. Patients receiving combination therapy with IFX and immunomodulators showed a significant reduction in ADA formation irrespective of the route of IFX administration. 34.8% of patients receiving combination therapy had detectable ADA compared to 65.2% receiving IFX monotherapy (OR 0.28 (95% CI 0.13-0.58; p=0.001)). Treatment persistence was also significantly higher in those receiving combination therapy compared with monotherapy at 12-months (73.3% vs. 51.9%; p=0.004). The proportion of patients with detectable drug levels at 12-months was also higher with combination therapy (91.3% vs. 72.7%; p=0.005).

Conclusion

There were no significant differences in ADA levels, IFX levels, and treatment persistence between the SC and IV routes of IFX administration after 12 months of treatment. Concurrent use of immunomodulators was associated with reduced immunogenicity and better treatment persistence regardless of the route of maintenance IFX. Clinicians should advise patients on the benefits of immunomodulator combination therapy when initiating IFX regardless of route of administration.
P1029 Prevalance and risk factors of thromboembolism in Inflammatory Bowel Disease
Authors: Katı O , Bakkaloglu O K , Hatemi I , Celik A F , Seyahi E , Erzin Y
Published: January 2024

Background

Inflammatory bowel disease (IBD), as a chronic inflammatory condition, can affect atherosclerotic process, arterial events, and increase the formation of venous thromboembolism. The aim of this study was to determine the frequency of thromboembolism and the risk factors associated with acute thromboembolism in our IBD cohort.

Methods

A total of 3133 patients with 1414 Crohn's Disease (CD), 1667 Ulcerative Colitis (UC) and 52 Indeterminate Colitis who were admitted between 1999 and 2021 were retrospectively analyzed. Patients with acute arterial events and venous thromboembolism (n=39) during the follow-up period were compared with a control group (n=78) of the same gender and same diagnosis. Patients with Behçet's syndrome (n=126),systemic vasculitis (n=16) and hereditary thrombophilia (n=5) were excluded.

Results

Among 3133 IBD patients, number of patients with arterial events or venous thromboembolism at any time was 124, and the frequency was 3,95%. A total of 132 thromboembolic events, 86 arterial (65,2%) and 46 venous (34,8%) were recorded.Coronary artery disease was significantly higher in the UC group (2,3% vs. 1,2%; p=0.028). During follow-up, 40 acute thromboembolic events, 25 arterial and 15 venous, were seen in 39 patients (frequency 1,24%). There was no significant difference between the CD and UC groups in terms of acute thromboembolism (p=0.871). The presence of exacerbation, the presence of hospitalization, the number of priot hospitalizations and clinical activity at the last visit were associated with both arterial and venous thromboembolism; smoking history, age at diagnosis, body-mass index, non-mucosal CD (Montreal B2-B3) and higher basal CRP were associated with arterial thromboembolism only; higher CRP at the last visit, annual exacerbation frequency, presence of an additional inflammatory disease, presence of complications (surgery, abcess), longer total steroid traetment duration and also recent steroid therapy were associated only with venous thromboembolism. In regression analysis, recent steroid therapy and additional inflammatory disease were considered as independent risk factors for venous thromboembolism whereas age at diagnosis of IBD was considered as an independent risk factor for arterial events.

Conclusion

In addition to risk factors such as age, smoking and obesity, parameters indicating disease activity, inflammatory comorbidities and recent steroid therapy appear to be associated with acute thromboembolism in IBD patients.
P1036 Persistence of biologics and advanced small molecules in 4th, 5th and 6th line of therapy for inflammatory bowel disease: a cross-sectional retrospective study
Authors: Parigi T L , Massimino L , Carini A , Allocca M , D'Amico F , Furfaro F , Zilli A , Cagliani S , Errico C , Facoetti A , Nicolò S , Peyrin-Biroulet L , Danese S
Published: January 2024

Background

The choice of treatment for inflammatory bowel disease (IBD) with multiple prior drug failures, also known as difficult-to-treat (D2T) IBD, is an increasing challenge. We assessed the persistence of biologics and advanced small molecules, a surrogate for their efficacy, in patients with Crohn's disease (CD) and ulcerative colitis (UC) overall and in 4th, 5th and 6th lines of advanced treatment.

Methods

We retrospectively searched the electronic medical records of patients with IBD followed at the San Raffaele Hospital (Milan, Italy) up to 1 October 2023. Patients enrolled in clinical trials that changed disease management or receiving experimental drugs were excluded. Drug persistence was defined as the time from initiation to discontinuation of each treatment. Welch's ANOVA and Games-Howell's method for multiple comparisons were used.

Results

A total of 679 patients with moderate to severe IBD were included. 350 had CD, 326 UC, and 3 IBD-U. The mean disease duration was 11 years and 452 (66%) had received 5-aminosalicylates or antimetabolites as first maintenance treatment. Escalation to and changes between advanced treatments over time is summarised in Figure 1A. A greater use of anti-TNF agents was observed in the first lines of treatment whereas newer medications were proportionally more prescribed in refractory patients.

In the overall analysis, regardless of the line of treatment, there was no difference in drug persistence between agents at 12 months (p=0.62), with approximately half of the patients having discontinued the drug. Figure 1B

In subsequent lines of treatment, drug persistence decreased significantly in patients with CD (p=0.002). The trend was particularly pronounced from line 2, with a mean duration of 31 months, to line 7, with a mean duration of 11 months.

In UC, the reduction was less evident and borderline non-significant (p=0.05), although it suggests a decrease in drug efficacy as the disease progresses. Figure 2 A, B

In patients with D2T IBD, drug persistence in 4th, 5th and 6th line advanced treatment was similar for all agents (all p>0.05), indicating no clear advantage of one drug over the others. Figure 2 C, D, E

Conclusion

In CD, and possibly in UC, the persistence of patients on any advanced drug decreases with subsequent lines of treatment. None of the advanced agents showed a longer persistence time when used as a 4th, 5th or 6th line of treatment.
P1060 Diverting Ostomy for Crohn’s Pancolitis in Pediatric Patients
Authors: Kwon H
Published: January 2024

Background

Childhood-onset Crohn’s disease (CD) is characterized by extensive anatomic involvement, with high rates of panenteric CD. Given the fact that total colectomy for these patients result in permanent loss of colonic absorption of nutrients, ostomy can be a good surgical option for children with Crohn’s pancolitis requiring surgical intervention. The purpose of this study was to retrospectively review the outcome of diverting ostomy for Crohn’s pancolitis in children.

Methods

Children with Crohn’s disease involving total colon with or without small intestine who underwent surgery were included. Preoperative patient features including extent of disease using Paris classification, nutritional status and medications were recorded. Outcomes analyzed included postoperative medication changes, nutrition and growth changes, postoperative complications and need for further operative interventions.

Results

We identified 13 patients with a median age of 11 years (range 5 months-15 years), all of whom had pancolitis at the time of surgery. All 13 patients underwent stoma formation, initially. Three patients received colectomy after median 24 months. Takedown rate was 38% (n=5) and the time from stoma formation to takedown was median 13 months (range 10-34 months). Weight and height z-score have been improved after ostomy.

Conclusion

Children with CD pancolitis could benefit from diverting ostomy which offers an opportunity to spare the large intestine partially or completely which could improve nutrition and growth. Outcome comparison between diverting ostomy and colectomy should be discussed with larger study populations.
P1066 The real-life use of the Crohn's disease exclusion diet (CDED) in adults with mild-to-moderate Crohn's disease activity: an interim analysis of an open-label randomized controlled trial
Authors: Bodini G , Pasta A , Formisano E , Calabrese F , Apollonio M , Pisciotta L , Giannini E G
Published: January 2024

Background

The Crohn's Disease Exclusion Diet (CDED) is a validated dietary intervention characterized by a specific highly restrictive food regime which aim to induce remission and reducing inflammation in Crohn's disease (CD). In a previously randomized control trial (RCT), clinical remission was achieved in a range of 75-85% of patients after 6 and 12-weeks of CDED. We aim to provide an additional real-world evidence-based validation.

Methods

Interim analysis of an open-label randomized controlled trial of CD patients with mild-to-moderate clinical activity assessed by Harvey-Bradshaw Index (HBI) was performed. Demographical characteristics and medical history were collected at enrollment, while weight, body mass index (BMI), HBI, fecal calprotectin and serum inflammatory indices were assessed at baseline and after 12 and 24 weeks. Bioelectrical impedance analysis (BIA) was performed every 12-weeks in CDED group to test the safety. The primary endpoint was clinical remission (HBI<5) and was assessed in the intention-to-treat population.

Results

Twenty-four patients were randomized to receive CDED diet, while 21 were in control group. No significant differences among all parameters considered were observed at baseline. Five patients in CDED group discontinued diet because of intolerance at median of 5 weeks. At week 12, the median HBI was lower in CDED patients than in control patients (3, IQR 1-5 vs 5, IQR 4-6, respectively; p=0.001) resulting in more patients achieving clinical remission (17/24, 70,8% vs 8/21, 38,1%, respectively; p=0.027). No differences in fecal calprotectin and serum inflammatory indices were observed. The administration of CDED was associated with weight loss (72 to 69 kg, p=0.003), although BIA analysis showed a decrease in fat mass (18.2% to 15.5%, p<0.0001), while fat-free mass significantly increased (81.9% to 83.7%, p=0.001). No difference in body cellular mass was observed after 12-weeks of CDED.

Conclusion

The CDED is effective in inducing remission in mild-to-moderate clinical activity CD patients and seems to be safe and well-accepted.
P1068 Limited long-term efficacy of corticosteroids in microscopic colitis emphasizing the need for advanced therapies
Authors: Taelman T , Vermeire S , Ferrante M , Sabino J , Verstockt B
Published: January 2024

Background

Microscopic colitis (MC) is a chronic inflammatory bowel disease, characterized by chronic watery diarrhea, and consisting of 2 subtypes: collagenous (CC) and lymphocytic (LC) colitis. It mainly affects middle-aged adults, although it can occur at any age. The only approved therapy is budesonide, preferably administered in a tapering regimen given the high relapse rates. However, little is known about the long-term natural history of the disease.

Methods

All adult patients diagnosed with MC after clinical and histological assessment at our referral center between 2014 and 2022 were reviewed. Patients with follow-up less than 3 months or in whom no clear description of initiated therapy could be identified by retrospective chart review, were excluded for evaluation of long-term outcomes. Clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day. Data on relapse rates, subsequent therapies and surgery were collected.

Results

Three-hundred twenty-four patients were included, of whom 198 (CC 38.3%, LC 61.7%) were eligible for long-term assessment (Table 1) with a median follow-up of 3.7 [1.1 – 6.3] years. Median age at diagnosis was 63.4 [51.6-74.7] years. Concomitant diseases occurring in 3% or more included thyroid dysfunction (11.6%), coeliac disease (3.5%) and Parkinson’s disease (5.1%), which numerically was more prevalent in the LC (7.4%) than CC (1.3%) population (p=0.09). A minority of patients had a family predisposition of IBD (5.6%). Spontaneous clinical remission occurred in 37 (18.6%) patients, while 4 (2.0%) patients were treated with 5ASA. Most patients (79.3%) were treated with corticosteroids, resulting in 81.1% clinical remission within 3 months. Eighty-six patients (54.8%) flared upon steroid tapering and/or withdrawal requiring corticotherapy reinitiation, prolongation or dose intensification. Due to steroid resistance or dependency, subsequent treatment options included 5ASA (n=14), cholestyramine (n=11), methotrexate (n=6) and azathioprine (n=8), all with limited effect. More advanced therapies are being used, including anti-TNF agents (n=25), vedolizumab (n=9) and JAK inhibitors (n=8). Eighteen patients (9.2%) are currently on maintenance advanced therapies for MC. Two treatment-refractory patients underwent colectomy.

Conclusion

In this large single-center retrospective analysis, steroids confirmed their first line position to induce clinical remission in MC. However, more than 50% of patients relapsed upon steroid tapering and/or withdrawal, resulting in a substantial need for advanced therapy in this patient population. The long-term efficacy and safety of these advanced IBD therapies in MC should therefore be further investigated.
P1080 Real-world Study on Early Predictors of Infliximab Treatment Efficacy in Crohn's disease
Authors: Lv C , Chen Y , Yan F , Pi S , Liu Y , Chen R , Tang W , Zhang H
Published: January 2024

Background

Infliximab (IFX) can effectively induce and maintain the clinical remission of Crohn's disease (CD). However, a substantial number of CD patients experience primary or secondary nonresponse to IFX during treatment. Therefore, it is essential to identify early predictors of IFX treatment efficacy.

Methods

This study included 147 CD patients. Based on clinical outcomes, patients were categorized into IFX nonresponse and response group. We collected and compared laboratory data on blood routine examination, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin and post-induction IFX drug concentration and antibody levels in both groups. Logistic regression models were employed to identify potential factors associated with the risk of IFX nonresponse. Machine learning using random forest analysis was utilized to quantitatively assess the predictive features for IFX treatment efficacy and ROC curves was used to evaluate the model’s accuracy. Additionally, we performed HE staining and double immunofluorescence staining for CD64 and CD206 on intestinal biopsy tissues obtained before IFX treatment to compare the difference of macrophage subtypes between the nonresponse and response groups.

Results

Data from both cohorts revealed that patients in the IFX nonresponse group had lower drug concentration (P < 0.001), higher antibody levels (P < 0.001), and increasing ESR during the induction therapy (P < 0.001). Univariate and multivariate Logistic regression models demonstrated that IFX drug concentration and the ratio of ESR before and after induction therapy were associated with the risk of nonresponse. After the induction period, for each unit increase in drug concentration (1 μg/ml), the risk of IFX nonresponse decreased by 23% (RR= 0.77, 95% CI = 0.68-0.89), while each doubling of the ESR ratio after induction was associated with a 1.43-fold increase in the risk of nonresponse (RR= 2.43, 95% CI = 1.48-4.00). After combining data from the two cohorts, random forest machine learning analysis revealed that drug concentration below 1.5 μg/ml and an increase in ESR during induction could predict IFX nonresponse, with ROC curve areas of 0.740 and 0.651, respectively. Furthermore, immunofluorescence staining of intestinal mucosal biopsy tissues before IFX treatment showed a higher proportion of M1-type macrophages in the nonresponse group compared to the response group (P < 0.05).

Conclusion

Our study suggests that lower post-induction IFX drug concentrations and an increase in ESR during the induction phase are predictive of IFX nonresponse. Additionally, a higher proportion of M1-type macrophages in the intestinal mucosa before IFX treatment is associated with IFX nonresponse.
P1085 Machine learning to predict the efficacy of ustekinumab for ulcerative colitis
Authors: Morikubo H , Tojima R , Maeda T , Matsuoka K , Matsuura M , Miyoshi J , Tamura S , Hisamatsu T
Published: January 2024

Background

Ustekinumab (UST), an anti-IL12/23p40 monoclonal antibody, is now widely used for ulcerative colitis (UC). Meanwhile, there are no established models to predict the efficacy of UST for UC. We previously demonstrated that the machine-leaning approach was useful for finding predictors and developing a prediction tool in vedolizumab (VDZ) treatment for UC (Miyoshi et al. Sci. Rep. 2021). In this study, we aimed to develop a new prediction model for UST in patients with UC.

Methods

UC patients who started UST as a remission induction therapy in Kyorin University Hospital were enrolled as the training cohort (Cohort 1), and at Toho University Sakura Medical Center were enrolled as the test cohort (Cohort 2). Clinical information of 44 items including age, sex, past/concomitant therapy for UC, clinical and endoscopic activity for UC, blood sample, and so on, in week 0, and clinical activity for UC in week 22 were collected. The outcome was defined as steroid-free clinical remission (SFCR) in week 22. Clinical remission was defined as the Lichtiger index (LI) of four or lower. Patients who terminated UST or needed surgery before week 22 were regarded as not achieving SFCR. Random Forest was used for the clinical data in Cohort 1 to identify the promising predictors to achieve SFCR in week 22. Prediction models were developed with these predictors and their prediction ability was validated in Cohort 2.

Results

25 patients (SFCR/non-SFCR=13/12 patients) and 46 patients (SFCR/non-SFCR=27/19 patients) were enrolled as Cohort 1 and Cohort 2, respectively, in this study. First, we examined if a VDZ prediction model that we previously reported could work for predicting the UST efficacy. In Cohort 1, the model showed a positive predictive value (PPV) of 56.3% and a negative predictive value (NPV) of 62.5%. This supports the notion that a prediction model for UST should be different from that for VDZ. From the 44 clinical information, 10 clinical features with the highest contribution to SFCR with UST were detected in Cohort 1. These clinical features included serum albumin, monocyte fraction, height, MCV, total protein, LI, white blood cell count, MCHC, partial Mayo score, and CRP (Figure 1). With these 10 clinical features, the seven prediction models for UST were developed using different algorithms. These models were applied to Cohort 2 to validate the prediction ability. The model that showed the best prediction ability was a support-vector machine polynomial model with PPV 68.8% and NPV 71.4%, respectively.

Conclusion

We developed a new prediction model for the middle-term efficacy of UST in patients with UC. Further studies are needed to develop a prediction model for each molecular-targeted drug.
P1102 Adherence to a Mediterranean dietary pattern in patients with Crohn's disease in remission is associated with lower fecal calprotectin levels
Authors: Mor-Sasson L , Sarbagili-Shabat C , Sherf-Dagan S , Aviv Cohen N , Ron Y , Hirsch A , Thurm T , Maharshak N , Fliss-Isakov N
Published: January 2024

Background

The Mediterranean Diet (MD) was recently found to be beneficial for Crohn’s Disease CD patients in various stages of the disease. The MD emphasizes the intake of foods that are fiber-rich and high in polyphenols, along with avoidance of ultra-processed foods (UPF) and a low intake of red meat. Previous data show that these dietary patterns could promote gut health and mucosal healing. However, little is known about the overall adherence to the MD and its association with biochemical activity in CD patients in remission. Therefore, we aimed to assess overall adherence to the MD and to investigate the association between adherence to the MD and fecal calprotectin (FC) levels in patients with CD in clinical remission and fecal biochemical inactivity.

Methods

A cross-sectional analysis of a prospectively maintained database of patients with CD in clinical remission [Harvey-Bradshaw Index (HBI)<5] and fecal biochemical inactivity (FC <250µg/g). FC levels of ≤150µg/g was further categorized as significant biochemical inactivity.

Patients were assessed for their medical status, clinical and biochemical disease activity, and nutritional intake by using a Food Frequency Questionnaire (FFQ). The Israeli Mediterranean dietary screener (I-MEDAS) was used to assess adherence to the MD. A positive score for each food component was assigned when a specific cut-off criterion was met. For overall adherence to the MD, the median score of the study sample was used as a cut-off for the classification of “adherence” or “non-adherence”.

Results

A total of 88 patients were included in this analysis. A high proportion of patients qualified for a positive score for low consumption of butter and margarine (96.6%), salty snacks (94.3%), and savory pastries (83.0%), while a low proportion of patients qualified for a positive score for high intake of whole grains (8.0%), fish (20.9%), fruit (9.1%), and legumes (28.4%) (Figure 1). Twenty-nine patients (32.9%) were adherent to the MD. This group of patients had higher rates of significant biochemical inactivity (i.e., FC≤150µg/g), compared to non-adherent patients (96.6% vs. 79.7% respectively, p=0.036) and lower occurrence of soft/liquid stool (p=0.044). Furthermore, low intake of savory pastries and red/processed meat was associated with significant biochemical inactivity [p=0.026 and p=0.020, respectively.

Conclusion

Overall adherence to the MD among patients with CD in clinical remission and biochemical inactivity is relatively low, with a low intake of beneficial food groups on one hand, and a low intake of UPF on the other hand. Adherence to the MD was associated with lower FC levels. Future studies should examine the long-term effects of the MD on the maintenance of clinical and biochemical remission.
P1103 Incidence of Crohn's disease in patients with perianal fistula surgery
Authors: Kim S , Kim S P , Park Y , Kim S H , Kim Y E , Choi H , Oh S , Yu C S , Yoon H J , Kim K
Published: January 2024

Background

Perianal fistula (PAF) is one of the most common complications of Crohn's disease (CD) and is more frequent in Asian countries. However, there is a lack of data about the prevalence of CD in patients with PAF. We aimed to investigate CD incidence and risk factors in patients who underwent anal fistula surgery.

Methods

National health insurance service databases from 2013-2017 were used to identify patients with PAF surgery. The case definition comprises operation codes or diagnosis-related groups of anal fistula. The incidence of CD was investigated among the patients who underwent PAF surgery. We analyzed the risk factors associated with Crohn's disease in patients who received anal surgery. The time interval from surgery to CD diagnosis and the cumulative incidence of PAF after diagnosis of CD were investigated.

Results

172,397 PAF surgeries were performed during the study period (male 146,643, female 25,754). The incidence of PAF surgery in the general population was 6.77 (95% CI 6.73-6.8) per 10,000 person-years. (11.48 (11.42-11.54) for males, 2.03 (2.00-2.05) for females). The rate of CD was higher in a person who had undergone multiple PAF surgeries, females, and teenagers. More than 50% of teenagers who received three or more PAF surgeries were diagnosed with CD. The median time from PAF to a diagnosis of CD was 14.4 months (4-40.4 months). The prevalence of PAF at CD diagnosis was 48.2% (male 52.8%, female 36.8%), and the cumulative incidence rate at the 5-year follow-up was 61.4% (male 67.6%, female 43.6%).

Conclusion

This study reveals the relationship between CD and PAF surgery in Korea. The incidence of CD in patients with PAF is relatively high, and children, women, and patients with multiple surgeries are more likely to be accompanied by Crohn's disease. These features could be used to monitor the patient to allow timely diagnosis of CD.