Treatment Of Crohn Research Articles

P363 Multimodal dynamic ultrasound approach as predictor of response in patients with Crohn’s disease treated with ustekinumab

Abstract Background Early prediction of the response to biological drugs in Inflammatory Bowel Diseases (IBD) is of utmost importance to allow prompt optimization of therapeutic strategies. Ustekinumab (UST) is nowadays a milestone in the treatment of Crohn’s disease (CD), but potential markers predicting its long-term efficacy are still lacking. Multimodal ultrasound (US), encompassing B-mode US, color-Doppler and contrast-enhanced US (CEUS), is a promising non-invasive technique, providing complementary information to endoscopy, due to its ability to both assess transmural healing and quantify changes in bowel microvascularization over time. The main objective of this study was to evaluate the role of multimodal US in predicting endoscopic response to UST in patients with CD. The secondary aim was to develop an US score that allows an early detection of treatment response. Methods We conducted a prospective monocentric study in the IBD outpatient clinic of Policlinico Agostino Gemelli in Rome, enrolling consecutive patients with moderate to severe ileal CD, who were scheduled to begin UST therapy as per clinical practice. Demographic, clinical and laboratory data were collected. Clinical activity was defined according to Harvey-Bradshaw Index. A complete US evaluation including B mode, Doppler, dynamic CEUS and elastography was perfomed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each US parameter and their variations from baseline were correlated with endoscopic response (SES-CD reduction of at least 50% from baseline) and mucosal healing (SES-CD < 3) after 1 year. Results A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. Median values of US parameters at the various time points were significantly different in the group who achieved endoscopic response from non reponders’ group (Figure 1). The univariate analysis showed that the percentage changes between T3 and T0 of bowel wall thickness, Limberg score (LS), mean signal intensity, rise time, wash-in rate (WiR), C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome (table 1). At the multivariate logistic regression analysis, three independent predictors of endoscopic response were selected: male sex, ∆%LS, and ∆%WiR. Based on the above parameters, we developed an US score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Conclusion Multimodal ultrasound provides early predictors of the long-term therapeutic outcome in patients with CD treated with UST.

P802 Impact of early use of immunomodulator on the outcomes of Crohn's disease: A Systematic Review and Meta-Analysis

Abstract 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.

P765 A Novel Monoclonal Antibody Drug Candidate SPY001 Targeting Integrin ɑ4β7 for the Treatment of IBD Demonstrates Prolonged Half-Life in Non-Human Primates

Abstract Background Background: Antagonism of the interaction between the cellular adhesion integrin ɑ4β7 and endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) has proven to be relatively safe and effective in the treatment for Crohn’s disease (CD) and ulcerative colitis (UC). Additional benefit may be gained from an ɑ4β7 antagonist given via the subcutaneous (SC) route at extended intervals (eg, every 8 to 12 weeks) during maintenance therapy. Methods The humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase its serum half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. Half-life extension was evaluated via pharmacokinetic analysis in Tg276 transgenic mice (hemizygous for human FcRn) following a single intravenous bolus dose of SPY001 (10 mg/kg, 5 mg/kg, 1 mg/kg) and in cynomolgus monkeys following a single bolus dose of SPY001 (150 mg/kg), given by either intravenous (IV) and subcutaneous (SC) administration. PK simulations in humans were based on allometric scaling of SPY001 clearance observed in cynomolgus monkey and conducted in MATLAB. Results In Tg276 mice, the half-life of SPY001 was 10-11 days across all dose cohorts compared to approximately 3 days for vedolizumab. In cynomolgus monkeys, the half-life of SPY001 was 19-23 days following a single IV or SC infusion, a significant increase over the reported half-life of 10 days for vedolizumab in cynomolgus monkeys. Based on allometric scaling of the clearance of SPY001 observed in this study, predictive simulations of SPY001 PK in humans suggested that Q8W-Q12W SC dosing at 300 mg would be able to achieve a C6-wks, induction ≥ 35 mg/mL and Ctrough, ss ≥ 6 mg/mL for simulated patients covering a large range of body weights and albumin concentrations. Conclusion SPY001 is a novel humanized monoclonal IgG1 with an extended half-life over that of vedolizumab in Tg276 mice and cynomolgus monkeys. It offers the potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential.

Long-term efficacy of vedolizumab therapy in patients with Crohn’s disease

Introduction: Currently, the possibilities in the treatment of Crohn’s disease (CD) are expanding. Various classes of genetically engineered biological therapy are available for the treatment of inflammatory bowel diseases (IBD). Vedolizumab, having a selective nature of action, has a higher safety profile of the drug, which suggests lower immunogenicity and, as a consequence, long-term efficacy. Materials and methods: A retrospective study was conducted on the basis of the National Medical Research Centre of Coloproctology named after A. N. Ryzhikh, which included 54 patients treated with vedolizumab. In the course of the work, the survival of therapy was evaluated, as well as the influence of demographic characteristics, localization, phenotype of the disease and other factors on the effectiveness of therapy. Results: The study showed 86.0% (95% CI 72.8-93.1) survival of therapy for 15 months and 75.9% (95% CI 58.8-86.7) for two years. No statistically significant differences were obtained when assessing the effect of gender, comorbidity, lesion localization, disease phenotype, smoker status and the use of glucocorticosteroids during vedolizumab induction. During the analysis, it was revealed that significant factors affecting the effectiveness of therapy are the age of CD debut less than 21 years and the SES-CD index index more than 7, as well as previous therapy with the use of two or more anti-TNF drugs. Discussion: Despite the small sample size, the findings allow us to predict the effectiveness of therapy, which may affect survival.

Autologous stem cell transplantation with low-dose cyclophosphamide to improve mucosal healing in adults with refractory Crohn’s disease: the ASTIClite RCT

Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of < 150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm [38 in 13 (100%) patients] than in the usual-care arm [16 in 4 (40%) patients]. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died. Conclusions Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use. Limitations The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive. Future work Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohn’s disease, including those with a stoma or multiple previous resections. Trial registration This trial is registered as ISRCTN17160440 and EudraCT 2017-002545-30. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 3. See the NIHR Funding and Awards website for further award information.

Infliximab monitoring in Crohn’s disease: a neural network approach for evaluating disease activity and immunogenicity

Background: The treatment for Crohn’s disease (CD) has increasingly required the use of biological agents. Safe and affordable tests have led to the active implementation of therapeutic drug monitoring (TDM) in clinical practice, which, although not yet widely available across all health services, has been proven effective. Objective: To analyze serum infliximab (IFX) and antidrug antibody (ADA) levels in CD patients, compare two tests, as well as construct a prediction of neural network using a combination of clinical, epidemiological, and laboratory variables. Design: Cross-sectional observational study. Method: A cross-sectional observational study was conducted on 75 CD patients in the maintenance phase of IFX treatment. The participants were allocated into two groups: CD in activity (CDA) and in remission (CDR). Disease activity was defined by endoscopic or radiological criteria. Serum IFX levels were measured by enzyme-linked immunosorbent assay (ELISA) and rapid lateral flow assay; ADA levels were measured by ELISA. A nonparametric test was used for statistical analysis; p value of ⩽0.05 was considered significant. Differences between ELISA and rapid lateral flow results within the measurement range were assessed by the Wilcoxon test, Passing–Bablok regression, and Bland–Altman method. Prediction models were created using four neural network sets. Neural networks and performance receiver operating characteristic curves were created using the Keras package in Python software. Results: Most participants exhibited supratherapeutic IFX levels (>7 mg/mL). Both tests showed no difference in IFX levels between the CDA and CDR groups ( p > 0.05). The use of immunosuppressive therapy did not affect IFX levels ( p > 0.05). Only 14.66% of patients had ADA levels >5 AU/mL, and all ADA-positive participants exhibited subtherapeutic IFX levels in both tests. The median results of both tests showed significant differences and moderate agreement ( r = −0.6758, p < 0.001). Of the four neural networks developed, two showed excellent performance, with area under the curve (AUCs) of 82–92% and 100%. Conclusion: Most participants exhibited supratherapeutic IFX levels, with no significant serum level difference between the groups. There was moderate agreement between tests. Two neural network sets showed disease activity and the presence of ADA, noninvasively determined in patients using IFX by presenting an AUC of >80%.

Frontiers and challenges in diagnosis and treatment for Crohn's disease -from epidemiology to treatment

Frontiers and challenges in diagnosis and treatment for Crohn's disease -from epidemiology to treatment

Treatment of Crohn’s disease with complex fistula disease using an exclusion diet

Exclusive Enteral Nutrition (EEN) is considered the standard of care for the treatment of children with Crohns Disease (CD) but it is rarely used in adults. The main reason for this might be severe dietary restrictions, resulting in a reduced quality of life and a lack of compliance with the diet. The development of less restrictive dietary strategies has improved therapy adherence and thus also the success of the therapy in recent years. The therapy of fistulas in CD is generally considered difficult and nutritional therapy for fistulas has not been systematically investigated. We present the case of a patient with fistulizing CD. Immunosuppressive therapy with a biological was complicated by urothelial carcinoma, and an alternative treatment had to be found. In our patient, Crohns Disease Exclusion Diet (CDED) and Partial Enteral Nutrition (PEN) resulted in normal stool consistency and frequency, and one and a half years after the start of the exclusion diet, the patient remains in clinical remission.

Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience.

Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

S70 Real-World Experience and Perspectives on the Treatment of Crohn’s Disease: Results From a Health Care Provider Survey

S70 Real-World Experience and Perspectives on the Treatment of Crohn’s Disease: Results From a Health Care Provider Survey

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review.

Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.

Injection of Freshly Collected Adipose Tissue for the Treatment Complex Cryptoglandular Anal Fistula: Case Report

AbstractIntroduction Perianal fistula is a common colorectal disease which is caused mainly by cryptoglandular disease. Although most cases are treated successfully by surgery, management of complex perianal fistulas (CPAF) remains a challenge with limited results in recurrence and sometimes associated with fecal incontinence. The CPAF treatment with autologous adipose-derived mesenchymal stem cells (ASCs) had become a research hotspot. The technique started to be used in the treatment of Crohn's disease (CD) fistulas, where the studies showed safe and goods result from the procedure. Cultured ASCs have been used but this approach requires the preceding collection of adipose tissue, time for isolation of ASCs and subsequent in vitro expansion, need for laboratory facilities, and expertise in cell culturing. These factors have been getting over by using the commercially available alternative, allogenic ASCs. Treatment with allogeneic ASCs has shown good results in patients with CD fistulas, however with the disadvantage of being expensive. Objective To show that the injection with freshly collected adipose tissue is an alternative to treatment with autologous or allogenic ASCs with several advantages. Methods: In this case report, we show our first experience in the treatment of CPAF with the application of collected adipose tissue in a tertiary referral hospital from Belo Horizonte, Brazil. Results The patient had a good postoperative recuperation with a complete fistula healing after 8 months without adverse effects. Conclusion Injection with freshly collected adipose tissue is a promising and apparently safe sphincter-sparing technique in the treatment of CPAF.

The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn's Disease with Infliximab.

Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn's disease (CD). We evaluated Clearance, another PF of PK origin, either alone or in combination with concentrations. They were evaluated from two cohorts, the first designed to receive standard dosing (n = 37), and the second designed to proactively target therapeutic IFX concentrations (n = 108). Concentrations were measured using homogeneous mobility shift assay. Clearance was estimated using the nonlinear mixed effects methods with Bayesian priors. C-reactive protein-based clinical remission (<3 mg/L in the absence of symptoms) was used for the disease control outcome measure. Longitudinal changes in disease control due to factors including time, IFX concentration, and Clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and Clearance. The results indicated that lower baseline Clearance and proactive dosing associated with enhanced disease control during induction (p < 0.01). Higher IFX concentrations and lower Clearance measured at the second, third, and fourth infusion yielded improved disease control during maintenance (p < 0.032). During maintenance, the association with disease control was better with Clearance than with concentrations (∆OFV = -19.2; p < 0.001), and the combination of both further minimized OFV (p < 0.001) with markedly improved clinical yield in the presence of both PF of PK origin. We conclude that the combination of IFX concentration and Clearance are better predictors of therapeutic outcome compared with either one alone.

Efficacy of early biologic therapy versus late/conventional therapy in children and adolescents with Crohn's disease: A systematic review and meta-analysis.

The objective of this study was to estimate the effectiveness of early biologics compared to conventional treatment in the management of Crohn's disease among pediatric and adolescent patients. A comprehensive literature search was conducted in four electronic databases to identify relevant studies published from inception to 2023. The inclusion criteria comprised randomized controlled trials (RCTs) and cohort studies that reported on the efficacy and clinical outcomes of early biologic therapy compared to late/conventional therapy in children with Crohn's disease. The quality of the studies was assessed using the Cochrane Risk of Bias tool and the Newcastle Ottawa scale. A total of 13 studies (2 RCTs and 11 cohort studies), involving 861 patients, were included in the meta-analysis. The results demonstrated that early biologic therapy was associated with a significantly higher rate of clinical remission (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.10-1.54), lower relapse rates (RR 0.33, 95% CI 0.21-0.53), and improved mucosal healing (RR 1.47, 95% CI 1.10-1.97) compared to late/conventional therapy. However, it should be noted that there was evidence of publication bias among studies reporting clinical remission. In conclusion, early biologic therapy is significantly more effective in achieving clinical remission (within two years of diagnosis), promoting mucosal healing, and reducing relapse rates in pediatric and adolescent patients with Crohn's disease, compared to late/conventional therapy. These findings emphasize the importance of initiating biological therapy early in the treatment of Crohn's disease in this patient population.

The impact of medication belief on adherence to infliximab in patients with Crohn's disease.

Objective: Crohn's disease (CD) is an incurable chronic disease that requires long-term treatment. As an anti-tumor necrosis factor (TNF) agent, Infliximab (IFX) is widely used in the treatment of Crohn's disease, while the adherence is not high. The purpose of this study was to investigate the adherence to IFX among CD patients in China and evaluate the association between medication belief and IFX adherence. Methods: Demographic data, clinical information and patients' medication beliefs were collected using an online questionnaire and reviewing electronic medical records (EMRs). The Beliefs about Medicines Questionnaire (BMQ)-specific was used to assess medication beliefs which contains the BMQ-specific concern score and the BMQ-specific necessity score. An evaluation of adherence factors was conducted using univariate and multidimensional logistic regression analyses. Results: In all, 166 CD patients responded the online questionnaire among which 77 (46.39%) patients had high adherence. The BMQ-specific concern score in patients in low adherence was 30.00 and in high adherence patients was 27.50, and patients with lower BMQ-specific concern score had higher adherence (p = 0.013). The multiple regression analysis showed that the BMQ-specific concern score (OR = 0.940, 95% CI: 0.888-0.996) significantly affected the IFX adherence in CD patients. Otherwise, gender, marital status, time spent on the way (including the waiting time in infusion center) and accommodation to the center were also the influencing factors of adherence. Conclusion: The IFX adherence to CD in China was not high. Medicine concerns may be predictive factor of adherence. Education, the duration of IFX therapy and experience of adverse effects were not significantly associated with IFX adherence. By enhancing knowledge and relieving medicine concerns, we may increase patients' adherence to IFX.

Application of TIGIT combined with interleukin-6 detection in the evaluation of Crohn's disease status

To explore the application of IL-6, PCT, T lymphocyte subsets and TIGIT expression on T lymphocytes in the evaluation of Crohn's disease status. Using a cross-sectional study, total of 119 confirmed patients with Crohn's disease who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from June 2020 to December 2022 were selected. The age range was 18-59 years old, and the median age (interquartile range) was 37 (29, 45) years old, including 57 cases in active disease group (30 males, 27 females), 62 cases in disease remission group (33 males, 29 females); 50 healthy control groups (27 males, 23 females), the age range was 19-60 years old, and the median age (interquartile range) was 38 (31, 46) years old. The level of IL-6 was detected by flow fluorescence microsphere method, the concentration of PCT was detected by immunochromatography, and the levels of T lymphocyte subsets and TIGIT were detected by flow cytometry. The differences and correlations between the detection indicators in each group were compared, logistic regression was used to analyze the factors influencing the progression of Crosne's disease and the clinical value of each detection indicator was analyzed by ROC curve. The results showed that there were no statistically significant differences in age and gender among the control group, the remission group, and the active group (H=1.422,χ2=0.020;P=0.491, P=0.990); in the active group, IL-6 was 17.55(9.67, 21.72)pg/ml, PCT was 0.38(0.14, 0.43)ng/ml, CD3+CD4+ was 35.47%±6.01%, CD3+CD8+ was 30.50%±5.20%, TIGIT was 25.08%±6.30%; in the remission group, IL-6 was 8.46(5.21, 10.04) pg/ml, PCT was 0.26(0.11, 0.35) ng/ml, CD3+CD4+ was 37.62%±4.86%, CD3+CD8+ was 28.30%±5.28%, TIGIT was 34.22%±5.45%; in the control group, IL-6 was 6.13(3.57, 8.12)pg/ml, PCT was 0.17(0.10, 0.21)ng/m, CD3+CD4+ was 39.74%±3.94%, CD3+CD8+ was 26.59%±4.50%, and TIGIT was 37.64%±6.22%.There were significant differences in IL-6, PCT, CD3+CD4+%, CD3+CD8+%, and TIGIT among the three groups(H=58.688, H=18.003, F=9.600, F=8.124, F=65.059;P<0.001, P<0.001, P<0.001, P<0.001, P<0.001), Among them, IL-6 and TIGIT in the active group were significantly different from those in the remission group (P<0.001, P<0.001), and only TIGIT was significantly different between the remission group and the control group (P=0.007);Spearman correlation analysis showed that the expression of TIGIT on T lymphocytes was negatively correlated with the levels of IL-6; the results of Logistic regression analysis showed that IL-6, PCT and TIGIT were independent factors affecting the progression of Crohn's disease;Comparing the ROC curves of the active group and the remission group, found that TIGIT was significantly different from PCT, CD3+CD4+, CD3+CD8+(Z=4.011, Z=4.091, Z=4.157; P<0.001, P<0.001, P<0.001), no statistical difference with IL-6 (Z=1.193, P=0.233). Selected the combined detection of IL-6 and TIGIT with the best AUC area and Youden index, which shows that the clinical value is improved, the AUC area of IL-6+TIGIT was significantly different from that of IL-6 (Z=2.674, P=0.008). In summary, TIGIT of T lymphocytes and IL-6 detection may be valuable in the diagnosis and treatment of Crohn's disease, and the combined detection of TIGIT and IL-6 may be meaningful for evaluating the status of Crohn's disease.

Treatment of inflammatory bowel disease-Asian perspectives: the results of a multinational web-based survey in the 8th Asian Organization for Crohn's and Colitis meeting.

As the characteristics of inflammatory bowel disease (IBD) differ between Asians and Westerners, it is necessary to determine adequate therapeutic strategy for Asian IBD patients. We evaluated the current treatment of IBD in Asian countries/regions using a web-based survey. The Korean Association for the Study of Intestinal Diseases conducted a multinational web-based survey for current IBD care in Asia between September 16, 2020, and November 13, 2020. A total of 384 doctors treating IBD patients from 24 Asian countries/regions responded to the survey. Anti-tumor necrosis factor (TNF) agents, anti-integrins, and anti-interleukin-12/23 agents were available for use by 93.8%, 72.1%, and 70.1% of respondents in Asian countries/regions. Compared with a previous survey performed in 2014, an increased tendency for treatment with biologics, including anti-TNF agents, was observed. In the treatment of corticosteroid-refractory acute severe ulcerative colitis, 72.1% of respondents chose anti-TNF agents, followed by tacrolimus (11.7%). In the treatment of corticosteroid-refractory Crohn's disease, 90.4% chose anti-TNF agents, followed by thiopurines (53.1%), anti-interleukin-12/23 agents (39.3%), and anti-integrin agents (35.7%). In the treatment of Crohn's disease patients refractory to anti-TNF agents, the most preferred strategy was to measure serum levels of anti-TNF and anti-drug antibodies (40.9%), followed by empiric dose escalation or shortening of dosing intervals (25.3%). Although there were some differences, treatment strategies for patients with IBD were mostly similar among Asian doctors. Based on the therapeutic outcomes, it is necessary to identify the most appropriate therapeutic strategy for Asian IBD patients.

Real-World Persistence of Ustekinumab in the Treatment of Inflammatory Bowel Disease.

There is an urgent need to understand the long-term real-world effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD), fistulizing CD (FCD), and ulcerative colitis (UC). Persistence on treatment is commonly used as a surrogate measure of real-world treatment response. This study aims to estimate the long-term real-world persistence of UST in adult patients with CD, FCD, and UC. A retrospective study was conducted in patients with CD, FCD, and UC treated with UST through a national patient support program in Canada. Treatment persistence was described using the Kaplan-Meier method, and the impact of patient characteristics on persistence was explored through stratified analyses and multivariable Cox proportional hazards models. Persistence rates for 8724 patients with CD were 82.9%, 71.4%, 64.1%, and 59.7% at 1, 2, 3, and 4years, respectively. Similarly, persistence rates for 276 patients with FCD were 84.1%, 70.9%, 64.9%, and 63.1% at 1, 2, 3, and 4years, respectively. Persistence rates for 1291 patients with UC were 76.5% at 1year and 69.5% at 1.5years. When stratified by prior IBD-indicated biologic experience, persistence was numerically higher in biologic-naïve patients across all disease cohorts. A Cox proportional hazards model confirmed that this difference was significant in patients with CD (hazard ratio: 0.72; confidence interval: [0.65-0.79]). This study estimated long-term persistence in a large population of patients with IBD. At 1year, over three-fourths of patients remained on UST treatment in all disease cohorts, and over half of patients remained on treatment at 4years in CD and FCD patients. Biologic-naïve status was significantly associated with higher persistence in patients with CD.

Treatment of perianal fistulas in Crohn’s disease - review of literature and current recommendations

Introduction: Crohn's disease is an idiopathic inflammatory disorder of unknown etiology, associated with genetic, immunological, and environmental factors. The incidence of this disease continues to rise in developed countries. In almost 25% of patients, perianal fistulas occur during the course of the disease, which are difficult to treat and significantly impair the patient's quality of life.&#x0D; Aim of the study: To summarize the current state of knowledge on the treatment of Crohn's disease with perianal fistulas, with a particular focus on biological therapies and stem cell treatments.&#x0D; Methods and Materials: A systemic review was conducted using PubMed, Google Scholar, and ScienceDirect databases and it was limited to studies published in last 5 years. The search strategy was based on following terms: "Crohn's disease", "perianal fistula", "biological treatment", and "inflammatory bowel disease".&#x0D; Results: In recent years, there has been intensive research into new treatment options for perianal fistulas in Crohn's disease. Infliximab remains the first-line therapy, best controlled by monitoring the drug concentration in the serum. Alternatively, other drugs such as ustekinumab and vedolizumab may be considered. The combination of biological and surgical treatment is a recognized standard of care and modern, minimally invasive techniques that preserve sphincters, such as the FiLaC™ laser procedure, are increasingly being used. A novel and very promising therapeutic approach is based on mesenchymal stem cells, which may offer hope for patients who do not improve with standard treatment.&#x0D; Conclusion: Perianal disease in patients with Crohn's disease poses a significant therapeutic challenge and has a substantial negative impact on the physical and emotional well-being of patients. Despite the existence of various therapeutic options, a certain percentage of patients still fails to achieve clinical remission. Further research into new therapies is necessary.

SUPERIOR PERSISTENCE WHILE ON LABELED MAINTENANCE DOSE AMONG BIO-NAÏVE PATIENTS WITH CROHN’S DISEASE INITIATED ON USTEKINUMAB COMPARED TO ADALIMUMAB

Treatment of Crohn’s disease (CD) may require biologics. Dose escalation may be necessary to maintain efficacy, while adverse events or non-response may lead to treatment discontinuation. This analysis aimed to generate real-world evidence of persistence to ustekinumab versus adalimumab while on labeled maintenance dose (United States [US] prescribing information) among bio-naïve patients with CD in the US.