Search

Background This study aimed to investigate the adverse events (AEs) after SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) and to compare them with healthcare workers (HCWs). Methods We conducted a web-based survey on the local and systemic AEs experienced within 7 days of SARS-CoV-2 vaccination (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19) in IBD patients and HCWs between October 2021 and February 2022. The frequency of all AEs was compared between IBD patients and HCWs, and propensity score matching method was used to control confounding factors. Results A total of 336 IBD patients (139 Crohn’s disease [CD] and 197 ulcerative colitis [UC]) and 288 HCWs who completed the questionnaire had received the same type of vaccine for their first and second doses. Common local AEs in patients with IBD were injection site pain (78.9% and 70.8% after receiving first and second vaccine doses, respectively), swelling (35.4% and 31.5%), and induration (35.1% and 26.5%), and systemic AEs were fatigue (44.6% and 42.0%), myalgia (42.6% and 37.2%), and fever or febrile sense (29.5% and 32.1%). All severe AEs were rarely observed (0-3.9%). Hospital visits or hospitalizations associated with AEs were observed in 16 (4.8%) and 18 (5.4%) patients, respectively. A small number of patients reported deterioration of bowel frequency (CD: 10.1% and 12.2%, UC: 8.1% and 11.7%), abdominal pain (CD: 5.0% and 7.9%), and rectal bleeding (UC: 5.1% and 7.6%). About 30% of IBD patients reported a worsening of their sense of well-being. After propensity score matching, there was no significant increase in the frequency of AEs in IBD patients except for diarrhea (14.5% vs 4.8%, P = 0.005) and dyspepsia (15.2% vs 5.5%, P= 0.007) after first vaccination. Conclusion SARS-CoV-2 vaccination in patients with IBD was generally well-tolerated and severe AEs occurred rarely. Compared with HCWs, the frequency of AEs does not seem to increase except for diarrhea and dyspepsia.

Background Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response. Methods Mice were divided into three groups: control, colitis-induced, and SIRT7 inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups. Results The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice. Conclusion Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation.

Background There are insufficient studies on clinical outcome after surveillance of low grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD). We aimed to evaluate the clinical feature, frequency and risk factors of advanced neoplasia in IBD patients after diagnosis of LGD Methods From 2003 to 2020, medical records of 166 IBD patients from 6 university hospitals in Korea were reviewed retrospectively. All of the patients were diagnosed as LGD in surveillance. Patents’ baseline characteristics, disease status, polyp characteristics and treatment were evaluated. The frequency and risk factors of advanced neoplasia were also analyzed. Results Disease duration was 11.47 years (7.85-14.50), and follow-up duration was 3.74 years (1.95-7.58). Colitis associated LGD was noted in 56 cases (33.7%), Advanced neoplasia developed in 12 cases (6 large LGD, 3 tubulovillous adenoma, 3 high grade dysplasia) and all the cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo score and colitis-related dysplasia were more common than sporadic lesions (83.3% vs. 29.9%; P Conclusion Advanced neoplasia developed in 7.2% of IBD patients with LGD. Because most of advanced neoplasia developed from colitis-associated lesions, more careful examination is suggested in patients with colitis -associated LGD, especially with previous history, in surveillance colonoscopy.

Background Gut microbial dysbiosis has been suggested to contribute to pathogenesis of inflammatory bowel disease (IBD). Vedolizumab (VDZ), an α4β7 integrin blocker, has been used as an effective agent for patients with IBD. However, effect of VDZ on gut microbiome and its relationship with efficacy outcomes are still unclear. We investigated gut microbial change in patients with ulcerative colitis (UC) during VDZ treatment. Methods Patients with UC were prospectively enrolled and were given a 300 mg infusion of VDZ at weeks 0, 2, and 6 as an induction therapy and then every 8 weeks as a maintenance therapy. In cases of insufficient response, the interval of maintenance therapy was shortened to every 4 week infusion. Faecal samples were collected at weeks 0, 14, and 54 and 16S rRNA gene microbiome profiling analysis was performed. Clinical remission (CREM), clinical response (CRES), endoscopic mucosal healing (MH) and biochemical response (BioRES) were evaluated. Compositional differences in microbiome were analysed according to CREM, CRES, MH, and BioRES at weeks 0, 14, and 54. Results Faecal samples were collected from 27 patients and patients were classified according to their outcomes (Table 1). In the analyses regarding species richness (ACE, Chao1, Jackknife, The number of OTUs) and diversity indices (NPShannon, Shannon, Simpson, Phylogenetic Diversity), no significant difference was observed among groups at weeks 0, 14, and 54. There were no significant changes in microbial composition at week 14 and 54, respectively compared to basal level. However, compared to baseline, relative abundance of genus Prevotella showed significant differences between groups which achieved normalsation of C-reactive protein or not (p=0.0394) (Figure 1). In the linear discriminant analysis effect size (LEfSe) analysis, the genus Actinomyces and the species Actinomyces odontolyticus group increased in patients who had no response at efficacy outcomes (achievement of clinical remission, achievement of clinical response, achievement of endoscopic mucosal healing, normalisation of C-reactive protein, and normalisation of faecal calprotectin) at week 14, compared to week 0 (Fig 2A). The genus Clostridium_g24, the species Paraprevotella_uc and PAC001224_s were also significantly increased in the same patient group at week 54 (Fig 2B). Conclusion In UC patients treated with VDZ, microbial composition showed differences depending on the achievement of efficacy outcomes. Further studies regarding the causal relationship between microbial composition and outcomes are warranted with a larger number of patients.

Background A clinical decision support tool (CDST) has been developed and validated for predicting outcomes of vedolizumab (VDZ) therapy for patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively. We aimed to validate each CDST for predicting outcomes and need for drug optimisation in patients with inflammatory bowel disease (IBD). Methods We retrospectively analysed 166 patients with IBD (71 with CD, and 95 with UC) treated with VDZ from January 2017 through November 2021 at 6 tertiary referral centres in Korea. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CfCREM) and response (CfCRES), biochemical response (BioRES), endoscopic healing (EH), and need for drug optimisation by CDST-defined response groups (low vs. intermediate to high probability group with a cut-off of 13 points in CD, Table 1A, and 26 points in UC, Table 2A, respectively). CDST was evaluated by area under the receiver operating characteristics curve (AUC) and test performance. Results Patients were classified as low (27 with CD, and 28 with UC) and intermediate to high probability group (44 with CD, and 67 with UC). Among CD patients, there showed no significant difference in the response rate of any outcomes between CDST-defined groups. Among UC patients, the rates of CREM (41.0 vs. 18.5%, p=0.040) and EH (56.5 vs. 33.3%, p=0.045) at week 14 were higher among intermediate to high probability group. The rate of drug optimisation during maintenance therapy was also higher in low probability group (54.2 vs. 30.2%, p=0.038). At week 26, CDST for CD discriminated CfCREM with an AUC of 0.656 (sensitivity 87.5%, specificity 43.8%) (Table 1B). Meanwhile, CDST for UC identified CREM with an AUC of 0.606 (sensitivity 83.3%, specificity 37.9%) at week 14 (Table 2B). BioRES of FC was identified with an AUC of 0.649 (sensitivity 84.6%, specificity 45.2%) at week 26. BioRES of CRP was identified with an AUC of 0.660 (sensitivity 68.8%, specificity 63.2%) at week 26, and with an AUC of 0.642 (sensitivity 70.0%, specificity 58.3%) at week 54. Drug optimisation during maintenance therapy was identified with an AUC of 0.620 (sensitivity 54.2%, specificity 69.8%). Conclusion Both CDST for CD and UC can be used to help guide VDZ therapy for Korean patients to predict BioRES with a fair discriminant function and moderate sensitivity.

Background Although high and low volume polyethylene glycol(PEG) bowel preparations are recommended for patients with inflammatory bowel disease(IBD) before colonoscopy, sometime it is limited due to poor compliance. So, studies regarding novel low volume preparations in IBD are need, but, there is limited data. We aimed to evaluated the safety, tolerability and efficacy of oral sulfate tablet (OST) by comparison with 2L PEG and ascorbate (PEG/Asc) in patients with IBD. Methods One hundred ten patients with IBD were enrolled in this single-blind, multicenter, non-inferiority study. Patients were assigned either 2L PEG/Asc or OST to be administered in a split-dose regimen. OST patients were administered 14 tablets with more than 1L of free water in the evening, and the following morning. Colonoscopies were performed by blinded investigators. The primary efficacy endpoint was successful bowel cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded endoscopist in each hospital. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Flare up of IBD symptoms and mucosa change associated with preparation were also evaluated. Tolerability, in terms of taste and degree of resistance to drink was assessed with VAS score by interview before colnoscopy. Safety was assessed by spontaneously reported adverse events, solicited ratings of expected prep symptoms, and laboratory testing. Results The cleansing score at all the segment was significantly higher in OST group. A high rate of cleansing success was seen with OST (98.1%), which was noninferior to 2L PEG/Asc (98.1%). Proportion of patients with bubble score 0 was significantly higher in OST than 2L PEPG/Asc group (94.5% vs. 50.0%, p Conclusion Oral sulfate tablets achieved a high level of cleansing comparable with 2L PEG/Asc in patients with IBD. The risk of mucosal change or symptom relapse were not higher, on the other hand the degree of satisfaction was higher than 2L PEG/Asc. OST split method could be considered as one of the preparation method for patients with inactive IBD.

Background Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC. Methods A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms. Results Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98–1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98–1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90–1.02] and 0.96 [CI 0.92–1.00], respectively. Conclusion Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.

Background We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes. Methods This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose. Results 267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p Conclusion CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.

Background Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pre-treatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. Methods We performed a multicentre, prospective study of patients with IBD at 5 tertiary medical centres in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2–2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/μL, levels of haemoglobin 10 g/dl, or platelet counts below 100 K/μl. Results Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (p = .005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22–0.81; p = 0.009), pre-treatment genotype analysis (HR, 0.37; 95% CI, 0.18–0.77; p = 0.008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19–0.59; p < 0.001) independently decreased risk of myelosuppression. Pre-treatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. Conclusion In a randomised controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leucopoenia significantly reduced the proportion of patients with myelosuppression during treatment.

Background Despite its increasing incidence, large-scale data regarding the demographics and characteristics of paediatric inflammatory bowel disease (IBD) at diagnosis in Korea is scarce. We aimed to compare the differences of paediatric Crohn’s disease (CD) and ulcerative colitis (UC) at diagnosis in Korea. Methods This analysis was conducted using data from a multicentre, registry-based, retrospective cohort study conducted at five centres in Korea between 2013 and 2018. Baseline demographics, clinical characteristics, results from laboratory, endoscopic, radiologic examinations were compared between paediatric CD and UC patients who were Results A total 307 patients were included in this analysis. Among them 227 patients were diagnosed with CD (73.9%), and 80 patients (26.1%) with UC. The male to female ratio was 2.49:1 for CD, and 1.29:1 for UC (p = 0.019). Median age at diagnosis was 14.4 years (IQR 12.4–16.2) for CD, and 14.4 (11.7–16.5) for UC (p = 0.962). Symptoms at presentation that were dominant in CD patients compared with UC patients were abdominal pain (76.2% vs. 51.2%, p < 0.001), weight loss (51.5% vs. 22.5%, p < 0.001), perianal fistulas (18.9% vs. 0%, p < 0.001), perianal skin tags (15.9% vs. 1.2%, p < 0.001), fever (20.3% vs. 6.2%, p = 0.007), and oral ulcers (13.7% vs. 3.8%, p = 0.026), while hematochezia was the only dominant symptom in UC patients compared with CD patients (86.2% vs. 30.8%, p < 0.001). White blood cell counts, platelet counts, ESR, CRP were significantly higher, and serum albumin level was significantly lower in CD patients. ASCA was positive in 44.5% and 16.2% of CD and UC patients, respectively (p < 0.001), and ANCA was positive in 15.0% and 58.8% of CD and UC patients, respectively (p < 0.001). Terminal ileal involvement on endoscopy was prominent in CD (62.1% vs. 16.2%, p < 0.001), while rectal involvement was more prominent in UC (52.4% vs. 83.8%, p < 0.001). Small bowel involvement and perianal perforating diseases on radiologic exams were also more prominent in CD. Conclusion Clinical symptoms, laboratory test results, radiologic findings, endoscopic findings were significantly different between paediatric Crohn’s disease and ulcerative colitis at diagnosis in Korea. A large-scale study on a nationwide basis is expected to better clarify this difference in the future.

Background Recent researches reported that inflammatory bowel disease (IBD) in Asia has become more prevalent. Since IBD is chronic inflammation disorder and its relapse is frequent, obtaining and maintaining remission is important. As our knowledge on the pathogenesis of IBD deepened, many immunosuppressants and biological agents were introduced and confirmed to be both safe and effective. However, biologics known as anti-tumour necrosis factor (anti-TNF) agents was reported to lose response over time in 23–46% of patients. Therefore, combination therapy adding immunomodulator drug such as azathioprine was introduced and showed better outcome by optimising biologic pharmacokinetics and minimising immunogenicity. Adversely, rates of tuberculosis are increased, but there is no large population data estimating and comparing these risk in combination therapy. Methods We used 2008–2016 data of the South Korean Health Insurance and Review Agency (HIRA), and odd ratio (OR) for tuberculosis in IBD patients who underwent anti-tumour necrosis factor (TNF) agent, azathioprine, or combination therapy. Results Between 2008 and 2016, 47,760 patients were newly diagnosed as IBD, 29,440 as UC and 15,320 as CD. We compared the risk of tuberculosis according to the medication divided into 5 groups; infliximab only, azathioprine only, combination of azathioprine and infliximab, azathioprine monotherapy and infliximab monotherapy, and azathioprine and infliximab whether simultaneously or separately. We also compared the risk between male and female. Hazard ratio of tuberculosis in infliximab monotherapy, azathioprine, and combination therapy in IBD patients were 1.132, 1.256, and 2.118, respectively. Conclusion Our study shows that Korean IBD patients are at risk for tuberculosis, and this results may highlight the importance of screening for tuberculosis in IBD patients.

Background The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC). Methods We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method. Results A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p < 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p < 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis. Conclusion Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.