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Introduction: Anti-tumor necrosis factor (anti-TNF) therapy may improve insulin sensitivity, and its impact during pregnancy remains unclear. We aimed to assess the risk of gestational diabetes mellitus (GDM) associated with anti-TNF treatment among pregnant women with inflammatory bowel disease (IBD)., Methods: This nationwide cohort study included patients with IBD in Korea from 2010 to 2021. Anti-TNF exposure was identified from the last menstrual period (LMP) to LMP + 140 days. The development of GDM was assessed from LMP + 141 days to delivery. We performed overlap weighting to balance the covariates and used a generalized linear mixed model to measure the risk ratio (RR) and 95% confidence intervals (CIs). The anti-TNF group was compared with the unexposed group, as well as with the immunosuppressant, 5-aminosalicylate, and untreated groups., Results: A total of 3,695 pregnancies in women with IBD were identified, of which 338 (9.2%) were exposed to anti-TNFs. GDM was found in 7.1% of the pregnancies exposed to anti-TNFs as compared with 11.0% of those unexposed. The crude and weighted RRs for GDM risk were 0.64 (95% CI 0.43-0.96) and 0.68 (95% CI 0.55-0.84), respectively. The weighted RR when compared with the immunosuppressant, 5-aminosalicylate, and untreated groups was 0.70 (95% CI 0.41-1.18), 0.71 (95% CI 0.52-0.95), and 0.85 (95% CI 0.59-1.24), respectively., Discussion: This nationwide cohort reported a decreased risk of GDM among patients who used anti-TNFs during early pregnancy compared with those unexposed. GDM risk may become a consideration in the decision-making process when choosing treatment options for pregnant women with a risk factor for GDM., (Copyright © 2024 by The American College of Gastroenterology.)

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: This study aimed to evaluate the safety of biologics and small molecules for the treatment of inflammatory bowel diseases (IBD) in patients receiving antirejection therapies after organ transplants., Materials and Methods: We reviewed the medical records of patients with IBD who received organ transplants at the Asan Medical Center between January 1989 and December 2021. We compared the parameters of patients receiving biologics or small molecules to those of patients without those therapies., Results: This study included a total of 53 patients (ulcerative colitis, 41; Crohn's disease, 6; and gastrointestinal Behçet's disease, 6). Among them, 15 patients were receiving biologics or small molecules and 38 were not. During a mean follow-up of 119 months, the proportion of patients experiencing severe infections was significantly higher in those treated with biologics or small molecules than in those not treated. However, other safety outcomes (e.g., malignancies, adverse events, including organizing pneumonia or hepatic failure, and death) were not different between the two groups. Kaplan-Meier curve analysis revealed no significant difference in the safety outcome rate related to the use of biologics or small molecules. During follow-up, eight patients underwent bowel resections for IBD. The rate of bowel resection was not different between the two groups., Conclusion: The use of biologics or small molecules for patients with IBD who received organ transplants did not show a significant difference in safety outcomes. However, the possibility of severe infections must be considered., Competing Interests: The authors have no potential conflicts of interest to disclose, (© Copyright: Yonsei University College of Medicine 2024.)

Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive. In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD, intestinal tuberculosis, and intestinal Behcet's disease were analyzed using multiplexed immunohistochemistry. Additionally, a separate "vedolizumab (VDZ) cohort" established in ulcerative colitis patients who underwent endoscopic biopsy before VDZ administration was analyzed to predict response to VDZ. In the immunohistochemistry analysis, the cell density of T cell subsets, including PD-1 + cells, was investigated and compared between IBD and other inflammatory diseases (OID). Cell densities of PD-1 + cells (p = 0.028), PD-1 + helper T cells (p = 0.008), and PD-1 + regulatory T cells (p = 0.024) were higher in IBD compared with OID. In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1 + cells (p = 0.026), PD-1 + helper T cells (p = 0.026), and PD-1 + regulatory T cells (p = 0.041) than the no response group. PD-1 + immune cells may contribute to the diagnosis of IBD and could be used to predict response to VDZ in ulcerative colitis patients., (© 2023. The Author(s).)

Competing Interests: Competing interests: BDY has received research grants from Celltrion and Pfizer Korea; consulting fees from AbbVie Korea, BMS Pharmaceutical Korea, Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES, Pfizer Korea, Samsung Bioepis, Takeda and Takeda Korea; and speaking fees from AbbVie Korea, Celltrion, Cornerstones Health, Curacle, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea and Takeda Korea. None of these disclosures are directly associated with this study.

Background and Aims: Reduced body muscle mass is a poor prognostic factor for inflammatory bowel disease (IBD). In this study, we investigated the prevalence of sarcopenia at diagnosis and its clinical significance in Korean patients with IBD., Methods: The prevalence of sarcopenia in IBD patients between June 1989 and December 2016 was investigated using a well-characterized referral center-based cohort. Abdominopelvic computed tomography within six months from IBD diagnosis was used for the evaluation. Sarcopenia was defined as an L3 skeletal muscle index of < 49 cm 2 /m 2 for male and < 31 cm 2 /m 2 for female. The clinical characteristics and outcomes were evaluated with respect to sarcopenia., Results: A total of 1,027 patients (854 Crohn's disease [CD]; 173 ulcerative colitis [UC]) were evaluated. Sarcopenia was found in 56.8% of the population (CD, 57.5%; UC, 53.2%), and male were more likely to be sarcopenic (CD, 94.3%; UC, 91.6%). There were no significant differences in the cumulative risk of using steroids, immunomodulators, biologics, and bowel resections (or colectomy) with or without sarcopenia during follow-up (median: CD, 5.8 years; UC, 3.7 years). In sarcopenic patients with CD, there was a significantly higher cumulative risk of perianal surgeries than in non-sarcopenic patients with CD (Log-rank test; P = 0.001). However, the risk of perianal surgeries was not significant in multivariate analysis (Odds ratio 1.368; 95% confidence interval 0.782-2.391; P = 0.272)., Conclusion: Sarcopenia at diagnosis may have no significant prognostic value for medical treatment and bowel resection, but it may be associated with perianal CD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn's disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab., Methods: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes., Results: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission., Conclusions: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with ~370,000 EUR individuals (~30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Objective: Whether benefits and risks of intravenous (IV) infliximab combotherapy with immunosuppressants versus infliximab monotherapy apply to subcutaneous (SC) infliximab is unknown. This post hoc analysis of a pivotal randomised CT-P13 SC 1.6 trial aimed to compare SC infliximab monotherapy with combotherapy in inflammatory bowel disease (IBD)., Methods: Biologic-naïve patients with active Crohn's disease or ulcerative colitis received CT-P13 IV 5 mg/kg at Week (W) 0 and 2 (dose-loading phase). At W6, patients were randomised (1:1) to receive CT-P13 SC 120 or 240 mg (patients < 80 or ≥ 80 kg) every 2 weeks until W54 (maintenance phase), or to continue CT-P13 IV every 8 weeks until switching to CT-P13 SC from W30. The primary endpoint-non-inferiority of trough serum concentrations-was assessed at W22. We report a post hoc analysis comparing pharmacokinetic, efficacy, safety and immunogenicity outcomes up to W54 for patients randomised to CT-P13 SC, stratified by concomitant immunosuppressant use., Results: Sixty-six patients were randomised to CT-P13 SC (37 monotherapy, 29 combotherapy). At W54, there were no significant differences in the proportions of patients achieving target exposure (5 µg/mL; 96.6% monotherapy vs 95.8% combotherapy; p > 0.999) or meeting efficacy or biomarker outcomes including clinical remission (62.9% vs 74.1%; p = 0.418). Monotherapy and combotherapy groups had comparable immunogenicity (anti-drug antibodies [ADAs]: 65.5% vs 48.0% [p = 0.271], neutralising antibodies [in ADA-positive patients]: 10.5% vs 16.7% [p = 0.630], respectively)., Conclusions: Pharmacokinetics, efficacy and immunogenicity were potentially comparable between SC infliximab monotherapy and combotherapy in biologic-naïve IBD patients., Trial Registration: ClinicalTrials.gov: NCT02883452., (© 2023. The Author(s).)

Background/aims: Chronic enteropathy associated with SLCO2A1 gene (CEAS), an inherited disease characterized by nonspecific intestinal ulcers, has emerged in the Japanese population via loss-of-function mutations in the SLCO2A1 gene. We aimed to investigate the clinical and genetic characteristics of Korean patients diagnosed with CEAS., Methods: From July 2018 to July 2021, we performed Sanger sequencing of the SLCO2A1 gene in 46 patients with chronic intestinal ulcers. CEAS was confirmed based on known SLCO2A1 mutations. We summarized the clinical characteristics of patients with confirmed CEAS., Results: Fourteen out of 46 patients (30.4%) had genetically confirmed CEAS, and two SLCO2A1 variants were detected (splicing site variant c.940+1G>A and nonsense mutation [p.R603X] in SLCO2A1 ). Twelve patients (85.7%) were females and the median age at diagnosis of CEAS was 44.5 years. All patients presented with abdominal pain, and 13 patients (92.9%) presented with anemia (median hemoglobin, 9.6 g/dL). Ten patients (71.4%) had hypoalbuminemia (median, 2.7 g/dL). The most commonly involved site was the ileum (13/14, 92.9%). Manifestations of primary hypertrophic osteoarthropathy (PHO), such as digital clubbing, pachydermia, and periostosis were observed in five patients (28.6%) and two male patients and one female patient satisfied all major PHO diagnostic criteria., Conclusions: The clinical and genetic characteristics of Korean patients with confirmed CEAS were similar to those reported in the literature. CEAS should be considered in the differential diagnosis for patients with unexplained chronic nonspecific ulcers of the small intestine.

We aimed to explore whether the imaging of antiporter system x C - of immune cells with (4 S )-4-(3- 18 F-fluoropropyl)-l-glutamate ( 18 F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18 F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x C - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18 F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18 F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18 F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18 F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68 + xCT + and CD3 + xCT + cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68 + xCT + cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system x C - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18 F-FSPG PET imaging of system x C - activity may noninvasively assess the IBD activity., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background/aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy., Methods: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients' medical records were reviewed, and data were collected using a web-based case report form., Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn's disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis., Conclusions: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

Background & Aims: In this nationwide population-based study, we investigated the risk of vertebral and hip fractures in patients with inflammatory bowel disease (IBD)., Methods: Using data from the Korean National Health Insurance claims database gathered between 2007 and 2016, we calculated the incidence rate ratios (IRRs) of vertebral and hip fractures in patients with newly diagnosed IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis) compared with an age- and sex-matched control population (matching ratio, 1:10; n = 186,871)., Results: During a median follow-up period of 4.5 years, the incidence rate and IRR of vertebral and hip fractures in patients with IBD were 2.88 per 1000 person-years and 1.24 (95% CI, 1.08-1.42), respectively. The cumulative risk of vertebral and hip fractures in IBD patients was 0.6%, 1.4%, and 1.9% at 2, 5, and 7 years after diagnosis, respectively, and this risk of fracture in IBD patients was higher than that in matched controls (P = .002). The use of corticosteroids further increased the risk of fractures in IBD patients (IRR, 1.37; 95% CI, 1.13-1.65) compared with matched controls. The risk of fractures was significantly higher in patients with Crohn's disease (CD) (IRR, 1.56; 95% CI, 1.19-2.04) than in matched controls, and this risk remained higher in patients with CD without corticosteroid exposure (IRR, 1.62; 95% CI, 1.12-2.34). The risk of fracture increased with age and was particularly high in females and in those with comorbidities., Conclusions: The risk of fractures was significantly high in newly diagnosed IBD patients, especially in those with CD regardless of corticosteroid exposure., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The present study investigated the risk of active tuberculosis in patients with inflammatory bowel disease (IBD) treated with vedolizumab or ustekinumab, in actual clinical settings in a country with an intermediate tuberculosis burden. The medical records of 238 patients with IBD who received vedolizumab or ustekinumab were retrospectively reviewed at a tertiary referral center in South Korea. All patients had ≥ 3 months of follow-up duration and underwent a latent tuberculosis infection screening test before initiation of the administration of these drugs. Of the 238 patients enrolled, 181 had Crohn's disease, and 57 had ulcerative colitis. During the median 18.7 months of follow-up, active tuberculosis did not develop in any patient treated with vedolizumab or ustekinumab. Therefore, we concluded that the risk of tuberculosis appears to be low in patients with IBD treated with vedolizumab or ustekinumab in South Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background/aims: The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort., Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015., Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68)., Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.

Background and Aims: The long-term outcomes of paediatric-onset inflammatory bowel disease [pIBD] in non-Caucasian populations are unknown. We therefore evaluated and compared the clinical features and long-term outcomes of pIBD with those of adult-onset IBD [aIBD] using a population-based cohort in the Songpa-Kangdong district of Seoul, Korea., Methods: Clinical characteristics and prognoses were compared between the two groups: pIBD [defined as <18 years of age at diagnosis] and aIBD [18-59 years of age at diagnosis]., Results: We identified 131 patients with pIBD (48 ulcerative colitis [UC], 83 Crohn's disease [CD]) and 1192 patients with aIBD [866 UC, 326 CD] during 1986-2015. Extensive colitis at diagnosis was more prevalent in pUC than in aUC [45.8% vs 22.3%, p < 0.001], and the overall exposure to corticosteroids, thiopurines and anti-tumour necrosis factor agents was higher in pUC than in aUC [p < 0.001]. The cumulative risk of colectomy was higher in pUC than in aUC during a median follow-up of 125.0 and 112.1 months, respectively [8.9% vs 1.8% at 10 years after diagnosis, p = 0.030]. Ileocolonic location and inflammatory behaviour at diagnosis were more common in pCD than in aCD; however, patients with pCD and aCD did not differ regarding treatment or disease course during a median follow-up of 137.2 and 120.9 months, respectively., Conclusion: Our study showed clear differences between pIBD and aIBD, especially in UC. pUC presents with more extensive diseases and may have a more severe disease course, as suggested by an earlier time to administering medications and performing colectomy., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/aims: Data on the immunoprotective status against measles, mumps, rubella, varicella zoster virus (VZV), hepatitis A virus (HAV), and Epstein-Barr virus (EBV) infection in patients with inflammatory bowel disease (IBD) are still lacking. Therefore, we investigated the seropositivity rates for viral infectious diseases and the associated factors in Korean patients with IBD., Methods: In this retrospective cohort study, serum immunoglobulin G antibody positivity rates against measles virus, mumps virus, rubella virus, VZV, HAV, and EBV viral capsid antigen (VCA) were measured in patients with Crohn's disease or ulcerative colitis (UC) who first visited the IBD clinic. Seropositivity rates and their associated factors were analyzed., Results: Between January 2016 and December 2018, 263 patients were enrolled (male, 167 [67.3%]; UC, 134 [50.9%]). The median age at serological test was 30 years (interquartile range, 22 to 46). The seropositivity rates were 84.0%, 85.2%, 66.5%, 87.4%, 50.0%, and 93.7% for measles, mumps, rubella, VZV, HAV, and EBV, respectively. Younger age at serological test was associated with seronegative status for measles (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.88 to 0.96), VZV (aOR, 0.83; 95% CI, 0.74 to 0.93), and HAV (aOR, 0.93; 95% CI, 0.91 to 0.95). Furthermore, IBD type-UC was associated with seronegative status against VZV (aOR, 0.33; 95% CI, 0.11 to 0.99)., Conclusion: Seropositivity rates for common viral infectious diseases in Korean patients with IBD were similar to those of the general population. In the younger age group, protective immunity against measles, VZV, and HAV is required, with proper vaccination, as necessary.

In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Abstract: This study aimed to evaluate self-reported vaccination rates, immunity, knowledge of and attitudes toward vaccination among Korean patients with inflammatory bowel disease (IBD) as well as to identify factors associated with proper vaccination.Between November 2013 and February 2015, consecutive patients with IBD were invited to complete a standardized questionnaire on vaccination. Moreover, immune status for common vaccine-preventable diseases was evaluated via serologic tests.A total of 310 patients with IBD were invited to the questionnaire survey and 287 patients (92.6%) who completed the questionnaires were finally enrolled (men, 188 [65.5%], median age at survey, 29.9 years [interquartile range, 22.3-39.2], ulcerative colitis: Crohn disease = 165:122]. Self-reported vaccine uptake rates were as follows: hepatitis A virus (HAV; 13.2%), hepatitis B virus (HBV; 35.2%), seasonal influenza (43.2%), pneumococcus (4.9%). Most of the patients (87.1%) did not know that proper vaccination has been recommended for patients with IBD. Up to 64.8% and 32.8% of patients were negative for IgG anti-HAV antibody and IgG HBV surface antibody, respectively. In a multivariable analysis, newspaper subscription (aOR [adjusted odds ratio] 2.185, 95% confidence interval [CI] 1.136-4.203, P = .019), ever recommendation of vaccination by a physician (aOR 2.456, 95% CI 1.240-4.862, P = .010), and use of anti-tumor necrosis factor agents (aOR 4.966, 95% CI 1.098-22.464, P = .037) showed a significant association with uptake of adult vaccines recommended for patients with IBD.Vaccine uptake rates, positivity of antibody to HAV and HBV, and knowledge of patients with IBD regarding vaccination were not sufficient. Proper educational information and recommendation from physicians could enhance awareness among patients with IBD about the need for vaccination and thereby improve vaccination rates.Trial registration number: NCT01984879., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Genome-wide association studies [GWAS] of inflammatory bowel disease [IBD] in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify two new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional dataset of 1726 cases and 378 controls., Methods: An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3195 cases and 4419 controls, followed by replication in an additional 1088 cases and 845 controls., Results: The meta-analysis of Korean GWAS identified one novel locus for ulcerative colitis at rs76227733 on 10q24 [pcombined = 6.56 × 10-9] and two novel loci for Crohn's disease [CD] at rs2240751 on 19p13 [pcombined = 3.03 × 10-8] and rs6936629 on 6q22 [pcombined = 3.63 × 10-8]. Pathway-based analysis of GWAS data using MAGMA showed that the MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14% of the variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population., Conclusions: The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment., Methods: The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn's disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group., Results: Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014-1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262-3.066, p = 0.862)., Conclusions: In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy., (© 2021. The Author(s).)

Methods: We retrospectively reviewed the medical records of IBD patients who visited Asan Medical center. We used a large, well-characterized referral center-based cohort. The clinical features of IBD patients with body mass index (BMI) over 30 and matched controls with BMI under 30 were compared., Results: Among the 6,803 IBD patients enrolled in the Asan IBD Registry between June 1989 and December 2016, we identified 16 patients with Crohn's disease (CD) and 27 patients with ulcerative colitis (UC) whose BMI was over 30 at the time of diagnosis. Their clinical characteristics and course were compared with those of 64 and 108 matched patients with CD and UC, respectively. There were no significant differences in the risk of using steroids (hazards ratio (HR) = 0.633 and P =0.254), immunomodulators (HR = 0.831 and P =0.517), and anti-tumor necrosis factor (TNF) therapy (HR = 1.539 and P =0.351) and risk of bowel resections (HR = 1.858 and P =0.231) between CD patients with BMI over 30 and those with BMI under 30; similarly, UC patients did not show significant differences in the risk of using steroids (HR = 0.613 and P =0.145), immunomodulators (HR = 0.492 and P =0.111), anti-TNF therapy (HR = 0.385 and P =0.095), and risk of colectomy (HR = 0.262 and P =0.104). In the subgroup analysis, under-weight UC patients had a higher cumulative probability of needing steroids (HR = 0.2510 and P =0.042), needing immunomodulators (HR = 0.097 and P =0.014), and a higher risk of receiving colectomy (HR = 0.024 and P =0.019) than obese UC patients., Conclusions: Obese IBD patients with CD or UC did not show significantly different clinical features from nonobese IBD patients., Competing Interests: The authors declare that there are no conflicts of interest to disclose., (Copyright © 2021 Seong Kyun Kim et al.)

Background: Previous studies have shown vitamin D status to be associated with disease activity in patients with inflammatory bowel disease (IBD), but its influence on the clinical course of IBD has not been established., Aims: We aimed to analyze whether the serum 25-hydroxyvitamin D3 [25(OH)D] status is associated with clinical characteristics and affects the risk of surgery in patients with IBD., Methods: From the IBD registry of the Asan Medical Center, we identified all patients who had at least one 25(OH)D measurement; we then analyzed the association between clinical factors and 25(OH)D status. 25(OH)D was considered borderline deficient, deficient, and severely deficient at levels of < 30, < 20, and < 10 ng/mL, respectively., Results: We included 711 Crohn's disease (CD) and 764 ulcerative colitis (UC) patients who had not undergone surgery before 25(OH)D was measured. Both in CD and in UC patients, reduced 25(OH)D was associated with higher disease activity scores and CRP levels (p < 0.001). Severe 25(OH)D deficiency was associated with ileocolonic disease and complicated behavior in CD (p < 0.05) and was relevant to the disease extent in UC (p < 0.001). Additionally, severe 25(OH)D deficiency was associated with CMV colitis in patients with UC (p < 0.001). In multivariable analysis, severe deficiency of 25(OH)D was an independent risk factor for surgery in both CD (HR 1.93, 95% confidence interval [CI] 1.38-2.70) and UC (HR 2.77, 95% CI 1.14-6.74)., Conclusion: Severe 25(OH)D deficiency may be a marker of a more aggressive clinical course of IBD.

Backgrounds and Aims: We aimed to evaluate the safety of Bacille Calmette-Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease., Methods: Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30., Results: After receiving BCG vaccination at a median age of 6 months [range, 0.25-11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death., Conclusions: BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Incidence of inflammatory bowel disease (IBD) is increasing in newly industrialised countries (NICs); however, data on suboptimal response to anti-tumor necrosis factor (anti-TNF) agents are limited., Objectives: To assess incidence and indicators of suboptimal response to first anti-TNF therapy in IBD patients in NICs., Methods: A chart review was conducted in ten countries from Asia-Pacific (APAC), Latin America (LatAm), and Russia and the Middle East (RME) regions among patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD), initiating anti-TNF therapy in 2010-2015. The cumulative incidence of suboptimal response to anti-TNF therapy was assessed using the following indicators: dose escalation or discontinuation, augmentation with non-biologic therapy, IBD-related hospitalization, or surgery., Results: The study included 1,674 patients (570 UC; 1,104 CD). At 24 months, 32.9% of UC (APAC: 45.1%; LatAm: 38.2%; RME: 23.8%) and 41.2% of CD patients (APAC: 54.1%; LatAm: 42.5%; RME: 29.5%) had experienced suboptimal response. The most frequent first indicator was non-biologic therapy augmentation in LatAm (41.7%), IBD-related hospitalization in RME (UC: 50.7%; CD:37.3%) and in APAC for CD (39.1%), and anti-TNF discontinuation in APAC for UC (38.3%)., Conclusion: Suboptimal response to anti-TNF agents is common in IBD patients in NICs. Observed regional differences in the incidence and indicators may reflect local practice and anti-TNF restrictions in IBD management., Nct Registration Number: NCT03090139., Competing Interests: Declaration of Competing Interests Qasim M Rana Khan, Olga Fadeeva and Dirk Demuth are employees of Takeda Pharmaceuticals Company Ltd. Morgane Guennec and Cecilia Sison are employees of IQVIA, which was funded by Takeda Pharmaceuticals Company Ltd to conduct this study. Jesús K. Yamamoto-Furusho is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd; has received honoraria from AbbVie, Takeda, Janssen, Farmasa, Ferring, Alfasigma, Hospira, UCB, Danone, Almirall and Pfizer as a speaker, key opinion leader, and member of national and international advisory boards; has received research funds from Bristol, Shire, Pfizer and Takeda and former President of the Pan American Crohn's and Colitis organisation (PANCCO). Othman Al Harbi is a consultant or advisory committee/board member for AbbVie, Janssen, Pfizer and Takeda Pharmaceuticals Company Ltd. Alessandro Armuzzi is a consultant or advisory/board member for AbbVie, Allergan, Amgen, Biogen, Celgene, Celltrion, Ferring, Hospira, Janssen, Lilly, MSD, Mundipharma, Mylan, Pfizer, Roche, Samsung Bioepis, Sofar, and Takeda Pharmaceuticals Company Ltd; has received lecture fees from AbbVie, Amgen, AstraZeneca, Chiesi, Ferring, Hospira, Janssen, Medtronic, MSD, Mitsubishi Tanabe, Mundipharma, Nikkiso, Otsuka, Pfizer, Samsung Bioepis, Takeda, Tigenix, and Zambon; and research funding from MSD, Pfizer and Takeda. Webber Chan indicated no relevant financial relationships. Enrique Ponce de Leon is a consultant or advisory/board member for AbbVie, Janssen and Takeda Pharmaceuticals Company Ltd. Jiaming Qian is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd. Marina Shapina is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd. Murat Toruner is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd; has received consulting fees from AbbVie Turkey, MSD Turkey, Janssen Turkey, Takeda Turkey and has received lecture fees from AbbVie Turkey, MSD Turkey, Janssen Turkey, Takeda Turkey, Ferring Turkey and UCB Turkey. Chia-Hung Tu is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd. Byong Duk Ye has received a research grant from Celltrion and Pfizer Korea; is a consultant or advisory/board member for AbbVie Korea, Celltrion, Chong Kun Dang Pharm., Daewoong Pharma., Ferring Korea, Janssen Korea, Kangstem Biotech, Kuhnil Pharm., Medtronic Korea, Shire Korea, Takeda Korea, IQVIA, Cornerstones Health, Robarts Clinical Trials Inc. and Takeda; has received lecture fees from AbbVie Korea, Celltrion, Ferring Korea, Janssen Korea, Shire Korea, Takeda Korea, and IQVIA., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The introduction of anti-TNFs, such as infliximab (IFX), has revolutionized the treatment of immune-mediated inflammatory diseases. Anti-TNF agents have shown outstanding efficacy and long-term improvement of clinical outcomes, but the cost has been relatively high. Out of this concern, several 'biosimilar' drugs of anti-TNF agents have been developed. CT-P13, the first biosimilar of reference IFX, was approved by the European Medicines Agency and licensed by the US FDA for use in all indications of IFX. This updated review summarizes all aspects of CT-P13, including pharmacology and pharmacokinetics, and evaluates its efficacy, safety and immunogenicity for all indications based on the results of the latest clinical trials as well as on real-world experiences.

Background and Aims: The phenotypic concordance among familial cases of inflammatory bowel disease (IBD) has been rarely reported. Thus, the present study aimed to evaluate the concordance regarding disease type and phenotypic features in a large cohort of Korean patients with IBD., Methods: A total of 6647 patients with IBD who visited the Asan Medical Center between June 1989 and September 2016 were enrolled in the study. When at least two familial cases existed in our cohort, they were included in the concordance analysis (κ index). The concordance between younger and older members for IBD type [Crohn's disease (CD) and ulcerative colitis (UC)] and phenotypic characteristics such as disease extent and location, disease behavior, the use of medication, and need for surgery were evaluated., Results: A positive family history of IBD was noted in 216 patients with CD (7.0%) and in 238 patients with UC (6.7%). Of all patients, 167 consanguineous pairs in 146 families were identified. The crude concordance rate for IBD type was 82.6% with a κ index of 0.656 [95% confidence interval (CI): 0.545-0.768, good concordance]. There was mild concordance for disease location in CD (κ = 0.256; 95% CI: 0.007-0.505) and for the use of antitumor necrosis factor agents in UC (κ = 0.354; 95% CI: -0.049-0.757). The concordance for IBD type and several phenotypes in first-degree relative pairs was better than that in the entire pairs., Conclusions: Disease type and phenotypic characteristics of patients with familial IBD may be anticipated., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database., Method: Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)-10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD-specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart-based diagnosis). A multiple sampling test verified the validation results from the entire study population., Results: A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD-10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91-94.7]; specificity, 98.1% [96.9-98.8]; positive predictive value, 97.5% [96.1-98.5]; negative predictive value, 94.5% [92.8-95.8]) with the lowest error rate (4.2% [3.3-5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P-value < 0.05., Conclusions: We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Little is known whether routine prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is needed in patients with inflammatory bowel disease (IBD) on immunosuppression, especially in Asian populations. We, therefore, sought to investigate the incidence and risk factors of PJP in patients with IBD in Korea., Methods: We investigated the incidence of PJP in patients with IBD and compared the characteristics of IBD patients with PJP episodes (IBD-PJP group) with those of matched controls (IBD-only group) using a large, well-characterized referral center-based cohort., Results: Among the 6803 IBD patients (3171 with Crohn's disease and 3632 with ulcerative colitis) enrolled in the Asan IBD Registry between June 1989 and December 2016, six patients (0.09%) were diagnosed with PJP. During the 57 776.0 patient-years of follow-up (median 7.2 years per patient), the incidence of PJP was 10.4 cases per 100 000 person-years, and none of these patients had received PJP prophylaxis. In case-control analysis, the IBD-PJP group (n = 6) showed significantly higher C-reactive protein level at diagnosis of IBD (P = 0.006), as well as higher exposure to corticosteroids (P = 0.017), than did controls (n = 24). In addition, the IBD-PJP group showed higher rates of double (50% vs 12.5%) or triple (33.3% vs 4.2%) immunosuppression than did controls, although these are not statistically significant., Conclusions: Although the incidence of PJP in Korean patients with IBD is low, careful monitoring is necessary for the early detection of PJP. In addition to the patients receiving double or triple immunosuppression, PJP prophylaxis should be considered especially in patients with severe disease activities requiring corticosteroids., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: These Asian Working Group guidelines on diet in inflammatory bowel disease (IBD) present a multidisciplinary focus on clinical nutrition in IBD in Asian countries., Methodology: The guidelines are based on evidence from existing published literature; however, if objective data were lacking or inconclusive, expert opinion was considered. The conclusions and 38 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required., Results: Diet has an important role in IBD pathogenesis, and an increase in the incidence of IBD in Asian countries has paralleled changes in the dietary patterns. The present consensus endeavors to address the following topics in relation to IBD: (i) role of diet in the pathogenesis; (ii) diet as a therapy; (iii) malnutrition and nutritional assessment of the patients; (iv) dietary recommendations; (v) nutritional rehabilitation; and (vi) nutrition in special situations like surgery, pregnancy, and lactation., Conclusions: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 38 recommendations.

Background & Aims: Few data are available on risk of herpes zoster (HZ) infection in Asian patients with inflammatory bowel diseases (IBD). We investigated whether patients with IBD in Korea have an increased risk of HZ and sought to identify risk factors for infection., Methods: We performed a nationwide population-based study and a hospital-based, nested case-control study. Using the 2009-2013 data from the Korean national health insurance claims database, we calculated incidence rates and standardized incidence ratios (SIRs) of HZ infection in patients with IBD compared with the entire Korean population. In the nested case-control study, within a hospital-based cohort, 300 patients with IBD and HZ infection were matched with 895 patients with IBD without HZ., Results: In the nationwide population-based study, the incidence rate and SIR of HZ infection in patients with IBD were 18.34/1000 person-years and 1.48 (95% CI, 1.42-1.54), respectively. The SIR for HZ infection was higher in patients with Crohn's disease than in patients with ulcerative colitis (1.90 vs 1.36; P < .001) and higher in male patients than female patients (1.63 vs 1.33; P < .001). The incidence rate of HZ increased with age (P trend < .001), whereas the SIR of HZ infection decreased with age (P trend < .001). In the nested case-control study, corticosteroid use was associated with HZ infection (for ulcerative colitis, adjusted odds ratio, 2.44; 95% CI, 1.18-5.05 and for Crohn's disease, adjusted odds ratio, 2.70; 95% CI 1.25-5.83)., Conclusions: In a population-based study in Korea, we found patients with IBD to have an increased risk for HZ infection-especially among patients who are male, younger, or have Crohn's disease. Corticosteroid use increases risk of HZ infection in patients with IBD., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino acids drive the risks of CD and UC in Asians. To define the roles of HLA for IBD in Asians, we fine-mapped HLA in 12 568 individuals from Korea and Japan (3294 patients with CD, 1522 patients with UC and 7752 controls). We identified that the amino acid position 37 of HLA-DRβ1 plays a key role in the susceptibility to CD (presence of serine being protective, P = 3.6 × 10-67, OR = 0.48 [0.45-0.52]). For UC, we confirmed the known association of the haplotype spanning HLA-C*12:02, HLA-B*52:01 and HLA-DRB1*1502 (P = 1.2 × 10-28, OR = 4.01 [3.14-5.12]).

Background: We investigated the incidence of active tuberculosis among patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF) inhibitors, with or without latent tuberculosis infection (LTBI)., Methods: The study was performed at a Korean tertiary referral center between January 2011 and June 2017. In total, 740 patients with IBD who underwent LTBI screening tests and were followed-up for ≥ 1 year after TNF inhibitor treatment initiation were enrolled. LTBI was detected on the basis of tuberculin skin test results, interferon-gamma release assay results, chest X-ray findings, and previous tuberculosis treatment history. The patients were classified into LTBI (n = 84) or non-LTBI (n = 656) group. The risk of developing tuberculosis in each group was assessed on the basis of standardized incidence ratio (SIR) and 95% confidence interval (CI) for active tuberculosis., Results: Mean patient age was 33.1 years, and patients with Crohn's disease were predominant (80.7%). Within 1 year after the initiation of TNF inhibitor treatment, 1 patient in the LTBI group (1/84; 1.2%) and 7 patients in the non-LTBI group (7/656; 1.1%) developed active tuberculosis. The overall 1-year incidence of tuberculosis among the patients was significantly higher than that among the general population (SIR, 14.0; 95% CI, 7.0-28.0), and SIR was not affected by LTBI status (LTBI group: 14.5, 95% CI, 2.0-102.6; non-LTBI group: 14.0, 95% CI, 6.7-29.4)., Conclusion: Patients with IBD undergoing TNF inhibitor treatment showed a higher 1-year incidence of tuberculosis than the general population irrespective of LTBI status., Competing Interests: Disclosures: The authors have no potential conflicts of interest to disclose.

Background and Aims: Recent meta-analysis of genome-wide association studies have identified over 241 inflammatory bowel disease susceptibility loci. However, the known variants only account for a fraction of inflammatory bowel disease heritability. To identify additional susceptibility loci, we performed a trans-ethnic meta-analysis as well as an Asian-specific meta-analysis, using all published Immunochip association results of inflammatory bowel disease., Methods: An inverse-variance fixed-effects meta-analysis was carried out across Korean and East Asian Immunochip datasets of 4156 cases and 4904 controls [Asian ancestry]. A trans-ethnic meta-analysis of inflammatory bowel disease was performed together with the European datasets of 38 155 cases and 48 485 controls genotyped on the immunochip using a Bayesian approach, Meta-Analysis of Trans-ethnic Association studies [MANTRA]., Results: We identified seven novel associations, including three novel susceptibility loci at MYO10-BASP1, PPP2R3C/KIAA0391/PSMA6/NFKB1A and LRRK1 as well as four novel secondary associations within previously known loci at NCF4, TSPAN32, CIITA and VANGL2. The new loci further implicate alterations in B cell biology in Crohn's disease pathogenesis. The effects of five loci were universal across European and Asian ancestries, whereas the NCF4 and CIITA loci showed significant heterogeneity between European and East Asian populations. In addition, 103 previously known IBD loci showed supporting evidence of association with nominal significance [p < 0.05] in Asians., Conclusions: Our findings of new loci not previously associated with IBD support the importance of studying inflammatory bowel disease genetics in diverse populations.

Background and Aim: CDKN2A/CDKN2B locus on 9p21 is reported to be associated with various diseases, including cancer and cardiovascular and inflammatory diseases. Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent genome-wide association study (GWAS)., Methods: We examined the association of CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In silico study was performed at various levels for functional annotation of the causal variant. Co-localization of the GWAS association signals and the corresponding expression quantitative trait loci in IBD-related tissues was evaluated using eCAVIAR., Results: An expanded GWAS showed genome-wide significant association of rs3731257 at 9p21 with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, P combined  = 5.68 × 10 -9 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval = 1.15-1.28, P combined  = 8.85 × 10 -9 ) in the Korean population. Co-localization study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the locus in the small intestine., Conclusions: rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans, with a suggestive role for small intestine-specific gene regulation. Our findings suggested that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory condition of the gastrointestinal tract causing bowel damage, hospitalizations, surgeries, and disability. Although there has been much progress in the management of IBD with established and evolving therapies, most current approaches have failed to change the natural course. Therefore, the treatment approach and follow-up of patients with IBD have undergone a significant change. Usage of immunosuppressants and/or biologics early during the course of the disease, known as top-down or accelerated step-up approach, was shown to be superior to conventional management in patients who had been recently diagnosed with IBD. This approach can be applied to selected groups based on prognostic factors to control disease activity and prevent progressive disease. Therapeutic targets have been shifted from clinical remission mainly based on symptoms to objective parameters such as endoscopic healing due to the discrepancies observed between symptoms, objectively evaluated inf lammatory activity, and intestinal damage. The concept of treat-to-target in IBD has been supported by population-based cohort studies, post hoc analysis of clinical trials, and meta-analysis, but more evidence is needed to support this concept to be applied to the clinical practice. In addition, individualized approach with tight monitoring of non-invasive biomarker such as C-reactive protein and fecal calprotectin and drug concentration has shown to improve clinical and endoscopic outcomes. An appropriate de-escalation strategy is considered based on patient demographics, disease features, current disease status, and patients' preferences.

Background: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD., Methods: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents., Results: We included 314 CD (51 [16.2%] primary nonresponders and 179 [57.0%] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7%] primary nonresponders and 74 [51.0%] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response., Conclusions: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.

Epidemiological and clinical studies have suggested that the pathogenesis of inflammatory bowel disease (IBD) is strongly influenced by genetic predisposition. Beyond the limitations of linkage analysis, multiple genome-wide association studies, their meta-analyses, and targeted genotyping array techniques have broadened our understanding of the genetic architecture of IBD. Currently, over 200 single nucleotide polymorphisms are known to be associated with susceptibility to IBD and through functional analysis of genes and loci, a substantial proportion of pathophysiologic mechanisms have been revealed. However, because only a modest fraction of predicted heritability can be explained by known genes/loci, additional strategies are needed including the identification of rare variants with large effect sizes to help explain the missing heritability. Considerable progress is also being made on applying outcomes of genetic research in diagnostics, classification, prognostics, and the development of new therapeutics of IBD., Competing Interests: Declaration of interests The authors are supported by the European Union Seventh framework program 305479, the Leona M. and Harry B. Helmsley Charitable Trust and the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) DK062413. D McGovern is on the advisory board for Merck, UCB and has research support from Amgen. B Duk Ye is on the advisory board for Shire Korea, Abbvie Korea and acts as a consultant for Celltrion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Background and Aims: Previous studies on the difference in phenotypes and disease course between familial and sporadic inflammatory bowel disease (IBD) have been controversial, although family history is considered to increase the risk of developing IBD., Methods: The influence of family history on phenotype and disease course of IBD was analysed in 2805 Korean patients with Crohn's disease (CD) and 3266 with ulcerative colitis (UC). Familial IBD was defined as the existence of one or more first-, second- and/or third-degree relatives affected with CD or UC., Results: A positive family history of IBD was noted in 191 patients with CD (6.8%) and 212 patients with UC (6.5%). In the patients with CD, the probability of anti-TNF use was higher in the familial cases than in the sporadic cases (56.3 vs 43.4%, respectively, at 10 years, p = 0.019). When analysed after excluding patients who had undergone intestinal resection within 1 year of diagnosis, the cumulative probability of intestinal resection was higher in the familial cases than in the sporadic cases (55.0 vs 32.2%, respectively, at 10 years; p = 0.007). In multivariate analysis, family history was an independent risk factor for the time to first intestinal resection in patients with CD (hazard ratio: 1.61, 95% confidence interval: 1.13-2.29; p = 0.009). In patients with UC, younger age at diagnosis and more females were observed in the familial cases (p < 0.001)., Conclusions: The present study suggests the possibility of a more aggressive clinical course of CD in familial compared with sporadic cases., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Limited data are available regarding the pulmonary toxicity of anti-tumour necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD)., Methods: We retrospectively searched the IBD registry of Asan Medical Center in order to identify patients with lung injury following anti-TNF therapy., Results: Among 1002 patients who were treated using anti-TNF therapy, six cases (0.6%) of anti-TNF-induced lung injury (ATILI) were identified. ATILI was observed soon after the beginning of anti-TNF therapy (two to four doses of anti-TNF). All of these patients experienced improvements in their respiratory symptoms and radiographic findings once the anti-TNF therapy was discontinued. One patient who suffered ATILI following adalimumab was switched to subsequent infliximab and was without recurrence of ATILI., Conclusion: Clinicians should be vigilant regarding the possibility of ATILI in IBD patients treated with anti-TNF agents., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anti-tumor necrosis factor (anti-TNF) agents are widely used to treat patients with moderate-to-severe inflammatory bowel disease (IBD). We aimed to identify the risk factors for adverse skin lesions in patients with IBD receiving anti-TNF agents and assess the effect of concomitant use of azathioprine/6-mercaptopurine (AZA/6 MP)., Methods: A total of 500 patients (404 with Crohn's disease, 96 with ulcerative colitis) who received anti-TNF agents between June 2002 and July 2013 were identified and retrospectively investigated. We compared 47 patients with IBD with skin lesions with 443 patients with IBD without skin lesions to identify risk factors by univariate and multivariate analysis. The Kaplan-Meier method was used to estimate the cumulative incidence of adverse skin lesions in relation to the concomitant use of AZA/6 MP., Results: Eczematiform eruptions (n = 18, 38%) were the most common skin lesion type, followed by psoriasiform lesions (n = 13, 28%). A response to topical steroids was seen in 70% (33/47) of patients with skin lesions, and anti-TNF agents had to be discontinued in 9% (4/47). Concomitant use of AZA/6 MP decreased the risk of skin lesions in univariate (hazard ratio, 0.452; 95% CI, 0.251-0.814; P = 0.008) and multivariate (hazard ratio, 0.437; 95% CI, 0.242-0.790; P = 0.006) analysis. In addition, the cumulative incidence of adverse skin lesions was lower in patients on concomitant maintenance with AZA/6 MP (P = 0.009) than in those on anti-TNF monotherapy., Conclusions: Concomitant use of AZA/6 MP may decrease the occurrence of adverse skin lesions in patients receiving anti-TNF therapy.

Objective: Limited data are available on the incidence and risk factors of colorectal cancer (CRC) in Asian patients with inflammatory bowel disease (IBD)., Material and Methods: Information on 5212 Korean patients with IBD (2414 with Crohn's disease [CD] and 2798 with ulcerative colitis [UC]) was retrieved from the IBD registry of Asan Medical Center. Data on CRC incidence for the entire Korean population were derived from the Korean Statistical Information Service., Results: During 39,951 person-years of follow-up (17,679 for CD and 22,272 for UC), 30 patients (12 with CD and 18 with UC) developed CRC. The standardized incidence ratio (SIR) of CRC was 6.0 (95% confidence interval [CI], 3.10-10.48) for CD and 1.68 (95% CI, 1.00-2.66) for UC; it was 9.69 (95% CI, 5.01-16.93) for CD with colonic involvement and 4.31 (95% CI, 2.46-7.00) for extensive UC. The SIR was also increased in patients diagnosed with IBD at younger than 30 years old. CRC location was the low rectum in 11 of 12 CD patients (91.7%). The cumulative probability of rectal cancer was higher in CD patients with a perianal fistula than in those without a perianal fistula (p = 0.02)., Conclusions: A high prevalence of perianal fistulas in Korean CD patients may be the cause of the predominance of low rectal cancer in this population and the higher SIR of CRC in Koreans than in Westerners. In contrast, the SIR of CRC in Korean UC patients may be similar to that in Western UC patients.

Nontuberculous mycobacterial (NTM) disease and tuberculosis (TB) develop during anti-tumour necrosis factor (TNF)-α therapy. We compared clinical characteristics and outcomes between the two diseases. A total of 1165 patients were screened for TB and treated with TNF-α antagonists from July 2004 to July 2013 for the following conditions: inflammatory bowel disease (n = 422), rheumatoid arthritis (n = 320), and ankylosing spondylitis (n = 389). TB and NTM disease were diagnosed at baseline screening in four and three patients, respectively, and developed during anti-TNF-α therapy in 19 and six patients, respectively. The incidence rate of TB and NTM disease was 747.7 per 100 000 and 238.2 per 100 000 person-years, respectively. Patients with NTM disease were older, with a greater proportion of females. All cases of NTM disease involved the lung, with rheumatoid arthritis (83.3%) being the most frequent underlying disease. The most common radiological feature was consolidation in NTM disease, and honeycombing was present in two rheumatoid arthritis patients with NTM disease. The most common pathogen was Mycobacterium intracellulare (n = 3) followed by Mycobacterium avium (n = 2). Both the NTM and TB group showed favourable outcomes. The clinical characteristics differed between NTM disease and TB that developed on anti-TNF-α agents, but clinical outcomes were favourable in both diseases., (©ERS 2014.)

Background/aims: The aim of this study was to analyze the actual application patterns of how Korean diagnostic guidelines for inflammatory bowel disease (IBD) were applied in clinical practice., Methods: Questionnaires regarding guidelines for ulcerative colitis (UC), Crohn's disease (CD), intestinal Behçet's disease (BD) and intestinal tuberculosis (TB), were distributed during the 2011 Korean Association for the Study of Intestinal Disease annual conference, and e-mail survey was additionally conducted. Forty eight questionnaires were collected., Results: Most of responders (79.2%) were working at secondary (≥500 beds) or tertiary referral centers. For the necessity of guidelines, 93.8% of responders gave positive answers in UC; 95.8% in CD; 81.3% in BD; 91.7% in TB. Of the clinicians, 95.8%, 91.7%, 64.6%, 77.1% had read UC, CD, BD and TB guideline, and 87.0%, 93.2%, 90.3%, and 92.0% replied that diagnostic guidelines for UC, CD, BD and TB were helpful in practice, respectively. Practice patterns were changed in 39.1%, 33.2%, 41.9%, and 54.1% of responders by UC, CD, BD and TB guidelines, respectively. For the needs of update, 58.7% of responders answered 'yes' in UC, 54.5% in CD, 51.6% in BD and 48.7% in TB. There were differences between recommendations and practice patterns, including colonoscopy surveillance in UC, radiological examinations for small bowel in CD and for intestinal obstruction in UC, or biopsy method in UC, CD and TB, and diagnostic criteria in BD., Conclusions: Although most of responders perceived the Korean diagnostic guidelines for IBD, there were differences between recommendations of guidelines and actual practice patterns. Therefore, the publicity and revision of diagnostic guidelines are important to reconcile theory and practice.

The risk of lymphoproliferative disorders (LPDs) has been reported to be increased in autoimmune diseases and chronic inflammatory diseases. Similar with other chronic inflammatory diseases such as rheumatoid arthritis, there is a concern about the risk of LPDs in patients with inflammatory bowel disease (IBD). Generally, in IBD patients, the risk of LPDs appears to be similar with or very slightly higher, compared to the general population. The association of therapeutic agents with the risk of LPDs is difficult to evaluate due to multiple other potentially involved factors and co-treatment with other agents. To date, data show that thiopurine is associated with a moderately increased risk of LPDs in patients with IBD. Evidence regarding the risk of LPDs in IBD patients using methotrexate is not sufficient, but the risk of LPDs seems low. The responsibility of anti-TNF-a agents on the risk of LPDs is difficult to determine, because most of IBD patients receiving anti-TNF-a agents are co-treated with thiopurines. Attention should be given to the high risk of hepatosplenic T-cell lymphoma in young male patients treated with anti-TNF-a agents together with thiopurines. The risk and benefit of immunosuppressive therapy for IBD should be carefully evaluated and individualized considering the risk of LPDs.

Caspase recruitment domain (CARD)-containing protein 8 (CARD8) is a potential candidate risk gene for inflammatory bowel disease (IBD) because of its role as a component of the NALP3 inflammasome and as an inhibitor of nuclear factor-kappa B. Previous studies examining the association of a CARD8 single-nucleotide polymorphism (SNP) (rs2043211, p.Cys10X) with IBD yielded mixed results in Caucasians that may result from interaction with NALP3 or NOD2 (nucleotide-binding oligomerization domain 2) variants. To understand the genetic association between CARD8/NALP3 and IBD in Koreans, we investigated seven CARD8, four NALP3 and four NOD2 SNPs in 650 Crohn's disease (CD), 660 ulcerative colitis (UC) patients and 688 controls from the Korean population. rs2043211 of CARD8 showed significant association with UC (P = 0.011; odds ratio = 1.50, 95% confidence intervals = 1.12-2.00, P = 0.006 under recessive model). In contrast, an SNP in intron 1, rs1972619, was associated with CD only (P = 0.033). None of the NALP3 or NOD2 SNPs was significantly associated with CD or UC in the Korean populations. The stop allele of rs2043211 was associated with higher serum interleukin-1β levels only in female patients with UC (P = 0.027). Our data suggest that CARD8 variants might have roles in the pathogenesis of CD and UC in Koreans.

Summary: Background: The impact of continuing or stopping 5‐aminosalicylates (5‐ASA) after commencing anti‐tumour necrosis factor (anti‐TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear. Aims: To compare the outcomes of patients with IBD who stopped or continued 5‐ASA after starting anti‐TNF therapy. Methods: We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5‐ASA within 90 days of anti‐TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD‐related hospitalisation, or intestinal surgery. Results: Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5‐ASA within 90 days of starting anti‐TNF therapy. During a median 4.3‐year follow‐up, discontinuation of 5‐ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93–1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5‐ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups. Conclusions: In this nationwide population‐based study, discontinuing 5‐ASA after starting anti‐TNF therapy was not associated with an increased risk of adverse events in patients with IBD. [ABSTRACT FROM AUTHOR]

Summary: Background/Aim: We aimed to validate clinical decision support tools (CDSTs) to predict real‐life effectiveness of vedolizumab (VDZ) in patients with inflammatory bowel disease. Methods: We retrospectively enrolled patients with Crohn's disease (CD) or ulcerative colitis (UC) treated with VDZ at 10 tertiary referral centres in Korea between January 2017 and November 2021. We assessed clinical remission (CREM) and response (CRES), corticosteroid‐free clinical remission (CSF‐CREM) and response (CSF‐CRES), biochemical response based on C‐reactive protein (BioRES[CRP]) and faecal calprotectin (BioRES[FC]), endoscopic healing (EH), and the need to optimise or switch drugs based on CDST‐defined response groups. Additionally, the area under the receiver operating characteristics curve (AUC) for the CDSTs was calculated. Results: We included 143 patients with CD and 219 with UC. We observed incremental trends on CSF‐CRES at week 14 (W14) (ptrend = 0.004) and decreasing trends for the need to optimise or switch drugs (ptrend = 0.016) in CD from the low to high probability groups. Except for CSF‐CREM at W54, we noticed incremental trends for all clinical responses at W14, W26 and W54 (ptrend <0.001) in UC. W26 and W54 BioRES[CRP] and W14 EH also showed increasing trends (ptrend <0.05) in UC. With increasing probabilities of response, drug optimisation or switching was less frequently required in UC (ptrend = 0.013). With 26 points cut‐off, CDSTs effectively identified W14 CSF‐CRES, W26 BioRES[CRP], BioRES[FC] and W54 BioRES[CRP] in UC, all with AUCs >0.600, whereas CDSTs showed poor accuracy in CD. Conclusions: CDSTs for VDZ had acceptable accuracy in predicting effectiveness outcomes including clinical and biochemical outcomes in UC. However, their utility in CD was limited. [ABSTRACT FROM AUTHOR]