Background/Aims: Despite the advent of advanced therapies, cases of so-called “difficult-to-treat” (D2T) ulcerative colitis (UC) persist. This study aims to clarify the epidemiological and clinical characteristics of patients with D2T UC. Methods: We conducted a nested case-control study using the Medical Data Vision Claims Database in patients with UC who began an advanced therapy (biologics, advanced small molecules, calcineurin inhibitors) from January 2018 through April 2023. D2T UC patients were defined as having 2 or more switches of advanced therapies, or as undergoing surgery for UC, within 2 years after the first advanced therapy. Results: Four hundred and one (16.7%) and 1,996 patients (83.3%) met the definitions of patients with D2T UC and non-D2T UC, respectively. After 1:1 matching by index year, 355 patients per group were included in the analysis. Multivariate logistic regression analyses, including sensitivity analyses based on follow-up period after the first advanced therapy, showed that a prescribed corticosteroid dose of ≥ 30 mg/day during the 6-month baseline period was associated with D2T UC. In D2T UC patients, median duration of the first advanced therapy was 99 days, and median number of advanced therapies per year was 1.7. The first advanced therapy was continued for 2 years in 78% of patients with non-D2T UC. Conclusions The proportion of D2T UC patients among UC patients starting advanced therapy was 16.7%. The factor most associated with D2T UC was the need for a corticosteroid dose ≥ 30 mg/day during the 6 months before initiation of advanced therapy.

Background/Aims: Crohn’s disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan. Methods: In this retrospective observational study (2010–2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis. Results: Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%–69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types. Conclusions Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.

Background/Aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

Background/Aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. Conclusions Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified.

Background/Aims: The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. Methods: SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Results: Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). Conclusions These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

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.

Intestinal ultrasound (IUS) is a promising modality for the management of inflammatory bowel disease (IBD) and has the potential to particularly contribute in monitoring disease activity, an advantage crucial for optimizing the therapeutic strategy. While many IBD physicians appreciate and are interested in the use of IUS for IBD, currently only a limited number of facilities can employ this examination in daily clinical practice. A lack of guidance is one of the major barriers to introducing this procedure. Standardized protocols and assessment criteria are needed such that IUS for IBD can be considered a feasible, reliable examination in clinical practice, and multicenter clinical studies can be conducted for further clinical evidence of the application of IUS in IBD for best patient care. In this article, we provide an overview of how to start IUS for IBD and introduce basic procedures. Furthermore, IUS images from our practice are provided as a color atlas for understanding sonographic findings and scoring systems. We anticipate this “first aid” article will be helpful to promote IUS for IBD in daily practice.

Background/Aims: We aimed to evaluate the efficacy and safety of ustekinumab (UST) in the East-Asian population with moderate to severely active ulcerative colitis (UC). Methods: This sub-analysis was conducted on data from East-Asian patients included in the UNIFI program (NCT02407236). UNIFI consisted of two double-blind, placebo-controlled trials: an 8-week induction study and a 44-week randomized withdrawal maintenance study. Results: Of 133 East-Asian patients (Japanese: 107, Korean: 26) who underwent randomization, 131 completed induction study and 111 entered maintenance study. In the maintenance study, 78 patients were randomized. Patients who received UST 130 mg and UST 6 mg/kg showed numerically higher clinical remission at week 8 in the induction study (5/44 [11.4%] and 5/45 [11.1%], respectively) compared with those who received placebo (0/44, 0%). The proportion of patients achieved clinical remission at week 44 was numerically higher in the UST 90 mg q12w group (10/21, 47.6%), but similar in the UST 90 mg q8w group (5/26, 19.2%) compared to placebo (7/31, 22.6%). Serious adverse events were reported in 1 patient in UST 130 mg group, but no patient in UST 6 mg/kg group through week 8 in the induction study, and 1 patient in UST 90 mg q12w group and 5 patients in the UST 90 mg q8w group in the maintenance study. No deaths were reported in East-Asian patients throughout the study. Conclusions UST induction and maintenance treatments were effective in East-Asian patients with moderate to severe UC; the efficacy and safety profiles were consistent with the overall population.

Background/Aims: Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods: This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results: The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Conclusions Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.