Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis

Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.

Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease

Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.

Thirty-year Trend in Inflammatory Bowel Disease on Jeju Island, South Korea / 대한소화기학회지

Background/Aims@#Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing in South Korea. On the other hand, there are no reports of the incidence and prevalence of IBD specific to Jeju Island, prompting the necessity of this study. @*Methods@#In this retrospective design, the medical records of 453 patients diagnosed with IBD at Jeju National University Hospital from January 1990 to December 2019 were analyzed. @*Results@#Of the 453 IBD subjects (165 CD, 288 UC) included, the UC: CD ratio was 1.75:1. The incidence of IBD increased continuously from 0.19/105 in 1990 to 6.39/105 in 2017 and after that decreased to 4.92/105 in 2019. The male:female ratio was 2.24:1 for CD and 1.29:1 for UC. In the CD subjects, the disease activity included remission (33.3%), mild (25.5%), moderate (30.9%), and severe (6.1%). In UC subjects, the disease activity included remission (24.0%), mild (35.4%), moderate (28.8%), and severe (6.2%). According to the Montreal classification, the cases were as follows: CD: terminal ileum (22.4%), colon (9.7%), ileocolon (66.1%), and upper gastrointestinal involvement (27.3%), and perianal fistula/abscess was present in 43.6% of subjects before or at diagnosis: UC: proctitis (43.4%), left-sided colitis (29.1%), and pancolitis (23.3%) at diagnosis. @*Conclusions@#The incidence of IBD on Jeju Island has increased steadily for approximately 30 years but has exhibited a decline since 2017. Therefore, the incidence of IBD in Jeju is believed to have plateaued. Further study will be needed for clarification. (Korean J Gastroenterol 2023;81:243-252)

Calcium, Vitamin D, and Colorectal Cancer / 대한소화기학회지

Colorectal cancer has a high incidence and mortality worldwide, with Westernized lifestyles and diet being significant contributing factors. Vitamin D and calcium have been known to reduce the incidence of colorectal cancer by affecting cell differentiation, proliferation, and apoptosis. Despite observational studies which have suggested that a higher serum vitamin D level can lower the risk of colorectal cancer and improve survival rates, no large-scale randomized controlled trials to establish these benefits have been conducted to date. Calcium intake has also been found to have a beneficial role in reducing the incidence and improving survival rates of colorectal cancer in several observational studies. Moreover, intervention studies have proved its effect in preventing colorectal adenomas. However, there are few intervention studies that have identified the relationship of vitamin D and calcium with colon cancer. To elucidate the impact of vitamin D and calcium supplementation on colorectal cancer, well-designed and large-scale randomized controlled trials are necessary in the future.

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

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

Effective Eradication Regimen and Duration According to the Clarithromycin Susceptibility of Helicobacter pylori Determined Using Dual Priming Oligonucleotide-Based Multiplex Polymerase Chain Reaction

Background/Aims@#Dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR) has recently been used for both the detection of Helicobacter pylori and the identification of H. pylori 23S ribosomal RNA point mutations that cause clarithromycin resistance.The aim of this study was to investigate the duration of effective standard triple therapy in a clarithromycin susceptible group and of bismuth-based quadruple therapy in a resistant group based on DPO-PCR. @*Methods@#We retrospectively analyzed the electronic medical records of 184 patients who, between September 2019 and December 2020, received eradication therapy following detection of H. pylori, and the subsequent identification of the clarithromycin susceptibility of their H. pylori using DPO-PCR. Patients were treated with 7- or 14-day standard triple therapy in the clarithromycin susceptible group, whereas 7- or 14-day bismuth-based quadruple therapy in the clarithromycin resistance group. @*Results@#In the clarithromycin susceptible group, per-protocol analyses showed eradication rates of 87.5% (42/48; 95% confidence interval [CI], 77.1% to 95.8%) for 7-day therapy and 87.2% (41/47; 95% CI, 78.7% to 95.7%) for 14-day therapy (p=0.969). The eradication rates in the clarithromycin resistance group were 91.4% (32/35; 95% CI, 80.0% to 100.0%) for 7-day therapy and 90.3% (28/31; 95% CI, 77.4% to 100.0%) for 14-day therapy (p=0.876). There was no significant difference in the eradication rates, patient compliance, or rate of adverse events between the 7-and 14-day therapies for both groups. @*Conclusions@#Compared to the 14-day therapy, 7-day eradication therapy is sufficient after DPO-PCR-based clarithromycin susceptibility testing.

Treatment of Inflammatory Bowel Disease in Elderly Patients – What Are Different and What Should We Know? / 대한소화기학회지

As the incidence of inflammatory bowel disease (IBD) are increasing with an ageing population, the incidence and prevalence of IBD in the elderly continue to increase. Older IBD patients can be classified into two groups; elderly-onset IBD patients and elderly IBD patients who were diagnosed at a young age and transitioning into advanced age. Clinicians must consider elderly-onset specific phenotypes or prognosis and age-related concerns in the treatment of elderly IBD patients. There is a paucity of evidence whether there is a different disease process when IBD occurs in older age yet. Clinicians may expect similar therapeutic effects in older and younger patients in drug selection, but since older patients are often excluded from clinical trials, evidence to support this assumption is currently lacking. Also, the risk of side effects may be higher in elderly patients. Therefore, when making management decisions in the elderly, clinicians should assess an individual’s frailty rather than only considering an individual’s chronological and biological age. Knowing specific requirements for managing older IBD patients may help to make an appropriate therapeutic strategy for this patient group.

Next Generation Fecal Microbiota Transplantation

Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.

Next Generation Fecal Microbiota Transplantation

Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.

Treatment of Inflammatory Bowel Disease in Elderly Patients – What Are Different and What Should We Know? / 대한소화기학회지

As the incidence of inflammatory bowel disease (IBD) are increasing with an ageing population, the incidence and prevalence of IBD in the elderly continue to increase. Older IBD patients can be classified into two groups; elderly-onset IBD patients and elderly IBD patients who were diagnosed at a young age and transitioning into advanced age. Clinicians must consider elderly-onset specific phenotypes or prognosis and age-related concerns in the treatment of elderly IBD patients. There is a paucity of evidence whether there is a different disease process when IBD occurs in older age yet. Clinicians may expect similar therapeutic effects in older and younger patients in drug selection, but since older patients are often excluded from clinical trials, evidence to support this assumption is currently lacking. Also, the risk of side effects may be higher in elderly patients. Therefore, when making management decisions in the elderly, clinicians should assess an individual’s frailty rather than only considering an individual’s chronological and biological age. Knowing specific requirements for managing older IBD patients may help to make an appropriate therapeutic strategy for this patient group.

Optimal Laxatives for Oral Colonoscopy Bowel Preparation: from High-volume to Novel Low-volume Solutions / 대한소화기학회지

Optimal bowel preparation is essential for a more accurate, comfortable, and safe colonoscopy. The majority of postcolonoscopy colorectal cancers can be explained by procedural factors, mainly missed polyps or inadequate examination. Therefore the most important goal of optimal bowel preparation is to reduce the incidence of colorectal cancer. Although adequate preparation should be achieved in 85–90% or more of all colonoscopy as a quality indicator, unfortunately 20–30% shows inadequate preparation. Laxatives for oral colonoscopy bowel preparation can be classified into polyethylene glycol (PEG)-electrolyte lavage solution, osmotic laxatives, stimulant laxatives, and divided into high-volume solution (≥3 L) and low-volume solution (<3 L). The updated 2019 European Society of Gastrointestinal Endoscopy (ESGE) guideline is broadly similar to the 2014 American Society for Gastrointestinal Endoscopy (ASGE) recommendations and reaffirms the importance of split-dosing. However, new ESGE guideline, unlike the 2014 ASGE recommendation, suggests the use of high volume or low volume PEG-based regimens as well as that of non-PEG based agents that have been clinically validated for most outpatient scenarios. For effective, safe, and highly adherent bowel preparation, physicians who prescribe and implement colonoscopy should properly know the advantages and limitations, the dosing, and the timing of regimens. Recently many studies have attempted to find the most ideal regimens, and more convenient, effective, and safe regimens have been developed by reducing the dosing volume and improving the taste. The high tolerability and acceptability of the new low-volume regimens suggest us how we should use it to increase the participation of the national colorectal cancer screening program.

Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease

New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-to-target algorithms in order to optimize treatment results. The treatment of IBD has evolved with the development of tumor necrosis factor-α inhibitors beyond the conventional therapies. In spite of their long-term effectiveness, many patients do not respond to or cannot sustain treatment with these drugs, which have various side effects. Therefore, the development of new drugs targeting specific pathways in the pathogenesis of IBD has become necessary. Some novel biologics and small molecule drugs have shown potential in IBD clinical trials, providing safe and effective results. In addition, clinicians are now trying to target the dysbiotic microbiome of patients with IBD using fecal microbiota transplantation. New tools such as stem cells have also been developed. The available therapeutic options for IBD are expanding rapidly. In the next few years, physicians will face an unprecedented number of options when choosing the best treatments for patients with IBD. This review provides an overview of recent advances in IBD treatment options.

Dermatologic Manifestations in Inflammatory Bowel Disease / 대한소화기병학회잡지

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with an unknown etiology and pathogenesis. The incidence and prevalence of IBD are increasing rapidly in Korea. Approximately one-third of patients with IBD appear to develop extra-intestinal manifestations with the skin being one of the most commonly affected organs. They may precede, occur simultaneously, or follow the diagnosis of IBD. In addition, they may parallel with the luminal symptoms or independent from the disease activity of IBD. This review outlines the skin manifestations associated with IBD and discusses their management. Skin manifestations should be managed in close collaboration with a dermatologist.

Asian Physician's Perspectives on Biosimilars in Inflammatory Bowel Disease: Are We Ready to Use? / 대한소화기학회지

No abstract available.

Dermatologic Manifestations in Inflammatory Bowel Disease / 대한소화기학회지

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with an unknown etiology and pathogenesis. The incidence and prevalence of IBD are increasing rapidly in Korea. Approximately one-third of patients with IBD appear to develop extra-intestinal manifestations with the skin being one of the most commonly affected organs. They may precede, occur simultaneously, or follow the diagnosis of IBD. In addition, they may parallel with the luminal symptoms or independent from the disease activity of IBD. This review outlines the skin manifestations associated with IBD and discusses their management. Skin manifestations should be managed in close collaboration with a dermatologist.

In Vivo Endoscopic Removal of Ancylostoma duodenale in a Patient with Abdominal Pain

A 20-year-old Cambodian male living in Korea for 2 years as a foreign worker visited our gastroenterology outpatient clinic. He had a small farm in Cambodia. He complained of postprandial upper abdominal pain with nausea and vomiting for 2 years. Gastroduodenoscopy showed hyperemic mucosa near the major papilla in the duodenum and two small and slender reddish worms. These were removed with endoscopic biopsy forceps. Under microscopy, these were identified as Ancylostoma duodenale by the characteristic morphology of 2 pairs of cutting teeth in the buccal cavity and 3 lobes in the copulatory bursa. After removal of two worms, his symptom improved. Soil-transmitted helminths (STH) present a global health problem. In the Republic of Korea, STH, including hookworms, were highly prevalent until the 1970s. With mass fecal examination followed by selective mass chemotherapy with anthelmintics from 1969 to 1995, the prevalence of STH has rapidly decreased since the 1980s. Since 2004, no hookworms have been found in nationwide surveys on the prevalence of intestinal parasitic infection. Therefore, we report a case of in vivo endoscopic removal of A. duodenale in a patient with abdominal pain.

Evolving Therapeutic Strategies in the Inflammatory Bowel Disease / 대한소화기학회지

It is important to have effective therapeutic strategies and goals in clinical practice and research of inflammatory bowel disease. Conventional end points for clinical trials in Crohn's disease and ulcerative colitis have been based on composite indices, such as the Crohn's Disease Activity Index and the Mayo Clinic Score. Although these indices have been shown to reduce the intestinal injury to some extent, satisfactory results have not been obtained in improving the quality of life of patients. Recently, alternative measures of outcome and definitions of response are being developed beyond symptoms. Mucosal healing as a clinical response and treatment goal has showed better long-term outcomes. Patient-reported outcomes (PROs) are emerging instrument directly created by patient to quantify symptoms. Coprimary realistic treatment ‘target’, comprising mucosal healing and PROs, can offer a clinically valid endpoint and can be readily applied in practice compare to existing composite indices. ‘Treat-to-target’ algorithm based on mucosal healing and PROs, in which therapy is progressively intensified until a specific personal treatment goal is reached, could improve quality of life of patient by reducing disease-related disability. Furthermore, histologic remission is an area of increased research focus and has the potential to guide treatment decisions in the future.

Colonoscopy: Is It Safe Test for Screening of Colorectal Cancer? / 대한소화기학회지

No abstract available.

Impact of inflammatory bowel disease on daily life: an online survey by the Korean Association for the Study of Intestinal Diseases

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disabling gastrointestinal disorder that diminishes the quality of life of the affected individuals. Limited data are available regarding the impact of IBD on the daily life of Koreans. METHODS: Self-administered, computer-aided, internet-based questionnaires were distributed to members of a Korean patient organization for IBD from March to April 2013, by the Korean Association for the Study of Intestinal Diseases. RESULTS: A total of 599 patients with IBD (387 with Crohn's disease [CD] and 212 with ulcerative colitis [UC]) were enrolled. The majority of patients (81%) expressed feelings of fatigue, weakness, and being worn out in their daily lives during times of flare; this percentage was reduced to 61% during remission. Respondents were absent from work or school for an average period of 18 days because of illness, within the first 6 months; the majority of respondents (64%) felt stressed about their absence. Forty-six percent of the respondents reported having received unfair comments at work, or having suffered discrimination. Forty-seven percent of the respondents felt that IBD had negatively affected their income and earnings. Compared with patients with UC, those with CD reported a more frequent negative impact of IBD on work, or more economic burden. More than half of the respondents (61%) reported that IBD had prevented them from making or keeping friends. CONCLUSIONS: IBD significantly impacts daily life, including work, education, and social relationships. Treatment that addresses the full spectrum of life of a patient would be more effective.

Endoscopic Ultrasound-Guided Perirectal Abscess Drainage without Drainage Catheter: A Case Series

A perirectal abscess is a relatively common disease entity that occurs as a postsurgical complication or as a result of various medical conditions. Endoscopic ultrasound (EUS)-guided drainage was recently described as a promising alternative treatment. Previous reports have recommended placement of a drainage catheter through the anus for irrigation, which is inconvenient to the patient and carries a risk of accidental dislodgement. We report four cases of perirectal abscess that were successfully treated with only one or two 7 F double pigtail plastic stent placements and without a drainage catheter for irrigation.