The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), has been increasing over the last three decades in newly industrialized countries as they have become more Westernized, including Asian countries such as Korea, Japan, China, and India [1-4]. In a population-based study from Hong Kong, the incidence of IBD per 100,000 individuals, increased from 0.10 in 1985 to 3.12 in 2014 [5]. A Taiwanese retrospective study using a nationwide insurance database also reported a rapid increase in the incidence of IBD since 2001. 3 In addition, a recently published Korean population-based cohort study reported that the adjusted mean annual incidence rates of CD and UC per 100,000 inhabitants increased from 0.06 and 0.29 in 1986-1990 to 2.44 and 5.82 in 2011-2015, respectively [6].

The clinical characteristics and natural history of Asian patients with IBD have been reported to differ in many aspects from those of Western patients with IBD. In Asian patients with CD, a male predominance, less prevalent isolated colonic disease phenotype, and a higher prevalence of perianal fistulas/abscesses have been reported [6-11]. In Asian patients with UC, a higher proportion of proctitis has been observed [6]. However, regarding genetic susceptibility, NOD2, a well-known CD-susceptible gene in Western patients, did not show an association with CD in Asians, whereas TNFSF15 was reported to be more strongly associated with CD in Asian patients [12,13]. Moreover, a recently published Korean study identified 3 novel susceptible loci for IBD that have not been previously associated with IBD in Western populations [14].

To date, most of the widely accepted guidelines for the management of IBD have been published based on studies conducted mainly on patients with IBD in Western society [15-21]. Although some Asian countries have developed their own guidelines tailored to the situation of each country [22-26], there could be regional differences in the therapeutic strategies for IBD patients according to countries. Hence, in 2014, a web-based multinational survey on the current IBD treatments performed by medical doctors who treat IBD patients in Asian countries was conducted at the second annual meeting of the Asian Organization for Crohn’s and Colitis (AOCC) [27]. However, since 2014, advances in therapies, including newly developed biologics and small molecules, have emerged for IBD management, and many Asian countries have become more industrialized; thus, there is a need for an updated survey on the current status of IBD therapies in Asia.

Considering the above, the Korean Association for the Study of Intestinal Diseases (KASID) conducted an online survey on the current status of IBD therapy. Here, we evaluated the current treatment of IBD in Asian countries/regions based on data from a web-based multinational survey of medical doctors treating patients with IBD.

In the present study, we performed a web-based multinational survey of medical doctors regarding current IBD treatment strategies in Asian countries/regions. Overall, respondents from each Asian country/region implemented similar treatments for patients with IBD and the overall treatment was not different from the recommendations in Western guidelines [15-21]. However, some differences were observed in terms of detailed aspects, such as the preferred treatment strategy, available medications, and disease monitoring tools, when compared with treatments in Western countries and compared between Asian countries/regions. For example, therapies that are not commonly used in Western countries, such as treatment with tacrolimus for patients with acute severe UC and leukocytapheresis for patients with corticosteroid-refractory UC are being currently used by Asian doctors. Of note, compared with the previous AOCC survey performed in 2014, an increased use of biologics, including anti-TNF agents, was observed in the present survey [27]. Among respondents, more than 90% responded that anti-TNF agents were available for the treatment of IBD. In addition, although there were some differences between countries/regions, more than 50% responded that anti-integrin agents, anti-IL-12/23 agents, and JAK inhibitors were available for patients with IBD.

Regarding the treatment of mild to moderate UC, the treatment strategies did not significantly differ between countries/regions: most participants chose treatments based on oral and topical 5-ASA administration, while systemic corticosteroids were preferred for patients with more extensive colitis. For treating severe UC, as previously mentioned, the use of biologics increased in the current AOCC survey compared to the previous survey. The increased use of biologics in IBD patients in Asian countries/regions was comparable to that observed in previous studies from Western countries. Targownik et al. [31] reported that the use of anti-TNF agents in a Manitoba cohort of Canada was significantly increased among IBD patients diagnosed between 2009 and 2013 than in those diagnosed between 2001 and 2005 (P=0.0048). Brunet et al. [32] also reported that the rate of treatment with biologics increased from 15.0% in 2011 to 18.7% in 2017 (P<0.001) among CD patients in Spain. In the current study, treatment with biologics or JAK inhibitors was the most preferred medication as the second-line therapy for acute severe UC: 82.8% in China, 47.2% in Japan, 89.1% in Korea, and 76.8% in other countries/regions responded that they chose biologics or JAK inhibitors. Compared with the previous AOCC survey performed in 2014 (in which 52.6% in China, 18.2% in Japan, 87.9% in Korea, and 54.3% in other countries/regions chose biologics), many more respondents preferred biologics in the new survey [27]. Considering that Asian patients with IBD have similar favorable treatment response to biologics as Westerners, use of biologics will increase further if the availability of these drugs improves in several Asian countries [33]. Interestingly, tacrolimus and biologics were preferred by 64.8% and 18.1% of Japanese respondents in the 2014 survey, whereas 46.2% and 47.2% preferred those in the current survey [27]. Although cyclosporine was reported to be as effective as infliximab in treating corticosteroid-refractory acute severe UC [34-36], only 5.0% of respondents chose cyclosporine. Overall, for treating corticosteroid-refractory UC, 89.1% of participants preferred biologics/JAK inhibitors, which is a higher proportion than that in the 2014 AOCC survey (44%) [27]. Among biologics/JAK inhibitors, anti-TNF agents (86.2%) were the most preferred agents, followed by anti-integrin agents (40.4%), JAK inhibitors (25.8%), and anti-IL-12/23 agents (18.8%), respectively.

Interestingly, there were some differences in treating patients with acute severe UC between Asian doctors. First, Korean doctors consulted surgeons more restrictively than doctors from other countries/regions. Although the reason for this result is not clear, cultural differences between Asian countries may contribute to this difference. One possible explanation for this difference is that the Confucianism, the basis of traditional Korean culture, might have made Korean patients reluctant to undergo colectomy. This might have affected Korean doctors to delay or avoid consulting surgeons as much as possible. In addition, there was a trend that some Korean doctors used systemic corticosteroids longer until the decision of corticosteroid-refractoriness: the proportion of doctors who used systemic corticosteroids for 6 to 9 days was higher in Korea than in other Asian countries/regions (33.6% vs. 19.3%, P<0.01). This might have come from some differences in treatment policies and guidelines between Asian countries. In Korean guidelines for managing UC, it is recommended to observe the response to systemic corticosteroids for 7 to 14 days before initiating other treatments in patients with moderate to severe UC. 36 Guidelines of other countries recommend a rather shorter period before initiating rescue therapy: 7 days in Japan versus 7 to 10 days in China [37,38]. The aforementioned reluctance to undergo colectomy might have also influenced on this result.

With regard to the treatment of patients with CD, anti-TNF agents were more frequently chosen for patients with moderate to severe CD (60.2% in colonic CD cases and 63.3% in small bowel CD cases) than for those with mild to moderate CD (27.9% in colonic CD cases and 28.6% in small bowel CD cases), with no significant differences between countries/regions. In addition, the preferred drugs were not significantly different according to disease location (small bowel CD vs. colonic CD) in both mild to moderate and moderate to severe CD patients. Interestingly, approximately 40% of mild to moderate CD patients and about 65% of moderate to severe CD patients were treated with oral 5-ASA, regardless of their disease location. A recent review on isolated colonic CD showed that 5-ASA was not beneficial in treating isolated colonic CD [39], whereas 2 studies published before 1990 showed a possible benefit of sulfasalazine for inducing remission of colonic CD [40,41]. However, the effectiveness of 5-ASA has not been confirmed in patients with small bowel CD [16]. Based on these results, the recently published American College of Gastroenterology guidelines and the British Society of Gastroenterology consensus guidelines do not routinely recommend the use of 5-ASA as a remission induction and maintenance treatment for CD [16,21]. The American Gastroenterology Association guidelines published in 2021 also did not recommend the use of 5-ASA for moderate to severe luminal CD, as the efficacy of mesalamine as an induction and maintenance therapy remains unclear [20]. Regardless of these recommendations, a recently published US study using claims database reported that 37.3% of patients with CD still received 5-ASA prescription; however, the prescription rate significantly declined from 2009 to 2014 [42]. Our results also suggest that a substantial proportion of Asian doctors still adhere to the traditional use of 5-ASA, despite the increasing emergence of more potent drugs such as biologics, and may represent a knowledge gap between evidence and clinical practice.

Treatment of patients who do not respond to anti-TNF agents is challenging for physicians. In the present study, we evaluated the treatment strategies of clinicians for non-responders to anti-TNF agents. In this situation, the most preferred strategy was to check the patients’ serum levels of anti-TNF agents and anti-drug antibodies (40.9%). Compared with a previous questionnaire-based study published in 2014 that reported that dose escalation was the preferred strategy for Asian patients with initial loss of response to anti-TNF agents [43], anti-TNF TDM appears to be the preferred trend for the treatment of Asian patients with IBD. However, in Japan, only 6.5% of respondents preferred to check anti-TNF levels, and empiric dose escalation or shortening of drug intervals were the most preferred strategies (46.2%). This disparity is likely due to differences in the availability of TDM of anti-TNF agents in each country/region. Over 90% of the Chinese clinicians responded that checking serum levels of anti-TNF agents and anti-drug antibodies was an option in their practice, whereas the corresponding proportion was approximately 32% in Korea and less than 15% in Japan. Considering that reactive TDM of anti-TNF agents was recently adopted as a treatment strategy [21,23,44-47], there seems to be heterogeneity in the availability of anti-TNF TDM as a therapeutic strategy. As treatment strategies differ between countries/regions, it will be helpful to determine the most suitable therapeutic sequence for Asian IBD patients with anti-TNF-failure by comparing therapeutic outcomes.

The widespread use of imaging modalities and fecal calprotectin for monitoring disease activity during the treatment of CD is intriguing. In the previous AOCC survey performed in 2014, clinical disease activity index assessment, colonoscopy, and blood tests were the preferred methods for disease activity monitoring, and only 11% and 6% of respondents used CTE and MRE, respectively [27]. In the present survey, although clinical disease activity index assessment, colonoscopy, and blood tests were still preferred (each modality was selected by 85.4%, 83.6%, and 81.8% of respondents, respectively), the use of CTE and MRE increased to 43.0% and 47.4%, respectively. In addition, fecal calprotectin was preferred by 59.6% of respondents. In particular, the increased use of MRE was prominent, and this result suggests that more Asian doctors are now aware of the clinical significance of monitoring transmural disease activity in patients with CD with less exposure to radiation. Additionally, there was a difference in the use of disease monitoring tools in CD patients between Japan and other Asian countries/regions: Japanese doctors used fecal calprotectin (11.8%) more restrictively, whereas favoring capsule endoscopy (43.0%) and wired enteroscopy (33.3%). These results are likely due to differences in the medical environments of each Asian country/region (e.g., the use of fecal calprotectin was not approved for Japanese patients with CD when this survey was conducted).

Lastly, for treatment of postoperative CD patients with moderate to severe endoscopic recurrence who have been treated with an anti-TNF agent, the most preferred strategy was dose escalation or shortening interval of patient’s anti-TNF agent (50.5%), followed by switching to anti-IL-12/23 agents (44.0%), switching to anti-integrin agents (35.4%), and employing combination therapy with thiopurines (34.6%). Compared to the previous AOCC survey, where the respondents equally preferred the addition of thiopurines, dose escalation, or interval shortening of anti-TNF agents, the current survey results showed more diverse responses. This variation could be due to the introduction of novel biologics with new mechanisms of action [27]. It will be necessary to evaluate whether these changes in therapeutic strategies for CD patients with postoperative endoscopic recurrence will lead to better outcomes.

This study had several limitations. First, although doctors from 24 Asian countries/regions participated in this survey, approximately 80% of respondents were from China, Japan, or Korea. Therefore, our results may be biased towards East Asian countries/regions. Second, because most of respondents (87.2%, 335 of 384) were working in academic teaching hospitals, our results could be partially different with IBD treatment patterns of primary or secondary level centers. Third, we could not include or adjust for the heterogeneous health care system and services of each Asian country/region. Fourth, although we presented the overall treatment situation in Asian countries/regions, the detailed differences between our results with those from Western countries/regions could not be evaluated as this survey was conducted on Asian doctors only.

However, our study has some strengths, as it is the latest study reflecting real-life treatment situations conducted among a large number of doctors from over 20 Asian countries/regions. We also incorporated questions regarding medications available in each country/region. In addition, our study attempted to evaluate the temporal trends in the treatment of IBD in Asian countries/regions by repeating similar questionnaires asked in the previous AOCC survey performed in 2014 [27].

In conclusion, the present survey of 384 Asian doctors demonstrated that the treatment strategies for IBD in Asian countries/regions were generally comparable. However, some differences were observed in the detailed management strategies between countries/regions. In addition, compared with the previous survey performed in 2014 [27], a trend of increased use of drugs with higher efficacies, such as biologics, and more objective disease monitoring tools, including fecal calprotectin, CTE, and MRE, was identified. Therefore, it is necessary to establish the most suitable therapeutic strategy for Asian patients with IBD while considering Asia-specific medical circumstances.