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.

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: 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.

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.

BACKGROUND/AIMS: Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. METHODS: UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. RESULTS: A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). CONCLUSIONS: CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.
Colitis, Ulcerative ; Drug Compounding ; Humans ; Medication Adherence ; Mesalamine ; Patient Acceptance of Health Care ; Patient Compliance ; Prospective Studies ; Recurrence ; Tablets ; Ulcer ; Visual Analog Scale

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.
Adalimumab ; Asia ; Asian Continental Ancestry Group ; Biological Factors ; Biosimilar Pharmaceuticals ; Colitis ; Colitis, Ulcerative ; Consensus ; Cooperative Behavior ; Crohn Disease ; Gastroenterology ; Hepatitis B ; Humans ; Immunologic Factors ; Inflammatory Bowel Diseases ; Infliximab ; Pharmacogenetics ; Philippines ; Practice Guidelines as Topic ; Tuberculosis ; Ulcer