Capsule endoscopy in inflammatory bowel disease: when and how

( Ida Hilmi ),( Taku Kobayashi ) 대한장연구학회 2020 Intestinal Research Vol.18 No.3

Capsule endoscopy (CE) is emerging as an important investigation in inflammatory bowel disease (IBD); common types include the standard small bowel CE and colon CE. More recently, the pan-enteric CE was developed to assess the large and small bowel in patients with Crohn’s disease (CD). Emerging indications include noninvasive assessment for mucosal healing (both in the small bowel and the colon) and detection of postoperative recurrence in patients with CD. Given the increasing adoption, several CE scoring systems have been specifically developed for IBD. The greatest concern with performing CE, particularly in CD, is capsule retention, but this can be overcome by performing cross-sectional imaging such as magnetic resonance enterography and using patency capsules before performing the procedure. The development of software for automated detection of mucosal abnormalities typically seen in IBD may further increase its adoption. (Intest Res 2020;18:265-274)

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn’s disease in Asia

Choon Jin Ooi,Ida Hilmi,Rupa Banerjee,Sai Wei Chuah,Siew Chien Ng,Govind K Makharia,Pises Pisespongsa,Min Hu Chen,Zhi Hua Ran,Byong Duk Ye,Dong Il Park,Khoon Lin Ling,David Ong,Vineet Ahuja,Khean Lee 대한장연구학회 2019 Intestinal Research Vol.17 No.3

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn’s and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn’s disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.

Efficacy and safety of vedolizumab in ulcerative colitis in patients from Asian countries in the GEMINI 1 study

( Choon Jin Ooi ),( Ida Normiha Hilmi ),( Hyo-jong Kim ),( Umesh Jalihal ),( Deng-chyang Wu ),( Dirk Demuth ),( Dirk Lindner ),( Shashi Adsul ) 대한장연구학회 2021 Intestinal Research Vol.19 No.1

Background/Aims: The efficacy and safety of vedolizumab in moderate to severely active ulcerative colitis (UC) have been demonstrated in the GEMINI 1 study (NCT00783718). This post-hoc exploratory analysis sought to establish the efficacy and safety of vedolizumab in a subgroup of patients from Asian countries with UC from GEMINI 1. Methods: Efficacy outcomes of interest were clinical response, clinical remission and mucosal healing at week 6 (induction phase); and clinical remission, durable clinical response, durable clinical remission, mucosal healing and glucocorticoid-free remission at week 52 (maintenance phase). Differences in outcome rates between vedolizumab and placebo in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) were assessed using descriptive analyses, and efficacy and safety compared between Asian and non-Asian countries. Results: During induction, in Asian countries (n=58), clinical response rates at week 6 with vedolizumab and placebo were 55.2% and 24.1%, respectively (difference 31.0%; 95% confidence interval: 7.2%-54.9%). In non-Asian countries (n=316), response rates at week 6 with vedolizumab and placebo were 45.9% and 25.8%, respectively. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 8 weeks, vedolizumab administered every 4 weeks and placebo were 9.1%, 36.8%, and 31.6%, respectively; corresponding rates for mucosal healing were 45.5%, 47.4%, and 47.4%, respectively. Vedolizumab was well-tolerated; adverse event frequency was comparable in Asian and non-Asian countries. Conclusions: In patients from Asian countries, the efficacy and safety of vedolizumab in treatment of UC were broadly consistent with that in the overall study population. (Intest Res 2021;19:71-82)

Efficacy and safety of vedolizumab in Crohn’s disease in patients from Asian countries in the GEMINI 2 study

( Rupa Banerjee ),( Sai Wei Chuah ),( Ida Normiha Hilmi ),( Deng-chyang Wu ),( Suk-kyun Yang ),( Dirk Demuth ),( Dirk Lindner ),( Shashi Adsul ) 대한장연구학회 2021 Intestinal Research Vol.19 No.1

Background/Aims: The efficacy and safety of vedolizumab in moderate-to-severely active Crohn’s disease (CD) were demonstrated in the GEMINI 2 study (NCT00783692). This post-hoc exploratory analysis aimed to assess the efficacy and safety of vedolizumab in the subgroup of patients from Asian countries. Methods: During the induction phase (doses at day 1, 15), clinical remission, enhanced clinical response, and change in C-reactive protein at 6 weeks; during the maintenance phase, clinical remission, enhanced clinical response, glucocorticoid-free remission and durable clinical remission at 52 weeks, were the efficacy outcomes of interest. Efficacy and safety of vedolizumab compared to placebo were assessed in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) using descriptive analyses. Results: During the induction phase, in Asian countries (n=51), 14.7% of the vedolizumab-treated patients achieved clinical remission at week 6 compared to none with placebo (difference, 14.7%; 95% confidence interval, 15.8%-43.5%). In non-Asian countries (n=317), the remission rate at week 6 with vedolizumab was 14.5%. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks and placebo were 41.7%, 36.4%, and 0%, respectively; while enhanced clinical response rates were 41.7%, 63.6%, and 42.9%, respectively. During induction, 39.7% of patients with vedolizumab experienced an adverse event compared to 58.8% of patients with placebo, and vedolizumab was generally well-tolerated. Conclusions: This post-hoc analysis demonstrates the treatment effect and safety of vedolizumab in moderate-to-severely active CD in patients from Asian countries. (Intest Res 2021;19:83-94)

Hydroxyurea associated ileocecal valve ulcer: evidence for causality

( Thevaraajan Jayaraman ),( Ruveena Bhavani Rajaram ),( Gin Gin Gan ),( Ida Hilmi ) 대한장연구학회 2021 Intestinal Research Vol.19 No.4

Hydroxyurea is an antimetabolite drug that is commonly used in many hematological disorders. Ulcer formation in the gas-trointestinal tract is a rare phenomenon associated with this drug. We report a case of a 73-year-old woman who was found to have an isolated ileocecal valve ulcer while on hydroxyurea 1 g daily for essential thrombocythemia. A comprehensive evalua-tion ruled out all other causes. The cytoreductive therapy was switched to anagrelide and the endoscopic evaluation 6 months later showed complete healing of the ulcer. However, the hydroxyurea was resumed due to increasing platelet counts and intol-erance to dose increments of the anagrelide. Subsequently, the patient was found to have a recurrence of the ulcer. Apart from oral ulcers, there have also been reports of ulcers involving the small bowel and the colon associated with the use of hydroxy-urea. The pathophysiology of the non-oral gastrointestinal ulceration in relation to this drug is unclear. Withdrawal of the drug typically leads to complete resolution. Increasing awareness of the rare association between the use of hydroxyurea and non- oral gastrointestinal ulcers is essential for early detection to prevent related complications. (Intest Res 2021;19:468-471)

Diagnosis 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

( Han Hee Lee ),( Jae Jun Park ),( Bo-in Lee ),( Ida Hilmi ),( Jose Sollano ),( Zhi Hua Ran ) 대한장연구학회 2023 Intestinal Research Vol.21 No.3

Background/Aims: Inflammatory bowel disease (IBD) is no longer a rare disease in Asia, thus it needs to prepare recommendations relevant to Asian patients. This study aimed to identify disparities in the process of the diagnosis of IBD in Asian countries/regions. Methods: In line with the 2020 Asian Organization for Crohn’s and Colitis annual meeting, a multinational web-based survey about Asian physicians’ perspectives on IBD was conducted. Results: A total of 384 Asian physicians (99 in China, 93 in Japan, 110 in Korea, and 82 in other Asian countries/regions) treating IBD patients from 24 countries/regions responded to the survey. Most respondents were gastroenterologists working in an academic teaching hospital. About half of them had more than 10 years of clinical experience in caring for patients with IBD. The European Crohn’s Colitis Organisation guideline was used most commonly for the diagnosis of IBD except for Japanese physicians who preferred their own national guideline. The Mayo score and Crohn’s Disease Activity Index were the most commonly used activity scoring systems for ulcerative colitis and Crohn’s disease, respectively. Endoscopy, not surprisingly, was the main investigation in assessing the extent and activity of IBD. On the other hand, there were disparities across countries/regions with regard to the favored modalities of small bowel and perianal evaluation of Crohn’s disease, as well as the use of serologic markers. Conclusions: Results of the present survey revealed practical behaviors of Asian physicians in the diagnosis of IBD. Investigating the reasons for different diagnostic approaches among countries/regions might help us develop Asian guidelines further. (Intest Res 2023;21:328-338)

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

( Way-seah Lee ),( Najib Azmi ),( Ruey-terng Ng ),( Sik-yong Ong ),( Sasheela Sri La Ponnampalavanar ),( Sanjiv Mahadeva ),( Ida Hilmi ) 대한장연구학회 2017 Intestinal Research Vol.15 No.4

Anti-tumor necrosis factor (anti-TNF) is highly effective in inflammatory bowel disease (IBD); however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years). All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia). All 3 patients died within 1 year from the onset of the infection(s). We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD. (Intest Res 2017;15:524-528)

Asian Organization for Crohn’s and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment

( Dong Il Park ),( Tadakazu Hisamatsu ),( Minhu Chen ),( Siew Chien Ng ),( Choon Jin Ooi ),( Shu Chen Wei ),( Rupa Banerjee ),( Ida Normiha Hilmi ),( Yoon Tae Jeen ),( Dong Soo Han ),( Hyo Jong Kim ) 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn’s and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web- based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommenda-during anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment. (Intest Res 2018;16:4-16)

Asian Organization for Crohn’s and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management

Dong Il Park,Tadakazu Hisamatsu,Min-Hu Chen,Siew Chien Ng,Choon Jin Ooi,Shu Chen Wei,Rupa Banerjee,Ida Normiha Hilmi,Yoon Tae Jeen,한동수,Hyo Jong Kim,Zhi Hua Ran,Kaichun Wu,Jiaming Qian,Pin-Jin Hu,Katsu 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn’s and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web- based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

The association between new generation oral contraceptive pill and the development of inflammatory bowel diseases

Santosh Sanagapalli,Yanna Ko,Viraj Kariyawasam,Siew C Ng,Whitney Tang,Hithanadura Janaka de Silva,Minhu Chen,Kaichun Wu,Satimai Aniwan,Ka Kei Ng,David Ong,Qin Ouyang,Ida Hilmi,Marcellus Simadibrata,Pi 대한장연구학회 2018 Intestinal Research Vol.16 No.3

Background/Aims: To examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort. Methods: A prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn’s disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD. Results: Three hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77–3.13; P=0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P=0.049). Conclusions: In this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users.