Inflammatory Bowel Disease In Japan Research Articles

Efficacy and Safety of Etrasimod in Patients with Ulcerative Colitis in Japan: Data from the Phase 3 ELEVATE UC 12 and ELEVATE UC 40 JAPAN Trials

Introduction: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the primary analysis of a phase 3 trial evaluating the efficacy and safety of etrasimod in patients from Japan with moderately to severely active UC. Methods: Patients from Japan who completed the 12-week ELEVATE UC 12 induction trial could enroll in the 40-week ELEVATE UC 40 JAPAN maintenance trial for a combined 52-week treatment period. Patients in this Japan cohort continued their baseline assigned treatment (etrasimod 2 mg QD or placebo) from ELEVATE UC 12. Efficacy was assessed at week 12 and week 52. Treatment-emergent adverse events (TEAEs) pooled from both trials were assessed up to 52 weeks of exposure. Results: The Japan cohort comprised 32 and 16 patients who received etrasimod and placebo, respectively. A numerically greater proportion of patients who received etrasimod versus placebo achieved clinical remission at week 12 (etrasimod: 14.3%; placebo: 7.1%) and week 52 (etrasimod: 25.0%; placebo: 7.1%); a similar trend was observed for all key secondary efficacy endpoints. TEAEs occurred in 84.4% (27/32) and 62.5% (10/16) of patients who received etrasimod and placebo, respectively. No new safety signals were detected. Conclusion: In these induction and maintenance trials evaluating etrasimod in patients from Japan with UC, numerically higher proportions of patients who received etrasimod versus placebo achieved efficacy endpoints. Efficacy and safety findings were consistent with those from the global ELEVATE UC trial populations.

Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan

BackgroundInterleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population. MethodsThe study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking. ResultsThe frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44–0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype. ConclusionIL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC.

Factors of Self-Care Agency in Patients with Inflammatory Bowel Disease in Japan

Introduction: Currently, no self-care measurement tool specific to inflammatory bowel disease (IBD) exists in Japan. The Instrument for Diabetes Self-care Agency (IDSCA) is a reliable and valid self-care measurement tool for patients with diabetes. Factors affecting self-care ability assessed by IDSCA appear to meet the requirements for patients with IBD. Therefore, we created a self-care ability measurement tool adapted from IDSCA as an original draft for the Instrument for IBD Self-care Agency and extracted factors and items required to measure the self-care ability of patients with IBD. Methods: An anonymous questionnaire survey was distributed among 226 patients. Exploratory factor analysis examined the relationship of factors from multiple perspectives, identified factors based on their content, and confirmed their internal consistency. Statistical analyses were performed using JMP® 14.0.0. Results: Five factors with 23 items were extracted from the IDSCA, including ability to build a human support system, ability to acquire knowledge, ability to maintain self-care, ability to self-manage, and ability to self-assess. Cronbach’s alpha was 0.765–0.861 for each factor and 0.904 for the entire scale. Conclusion: We could identify the self-care agencies of patients with IBD, including 5 factors and 23 items. Focusing on these self-care factors may provide critical information to guide nurses’ self-care interventions.

Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan.

Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. Among pregnant IBD patients, 74.4% received at least one medication from 90days before pregnancy to 90days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.

Assessing the economics of biologic and small molecule therapies for the treatment of moderate to severe ulcerative colitis in Japan: a cost per responder analysis of upadacitinib

Aim Patients with moderately to severely active ulcerative colitis have an increasing number of advanced therapy options including several biologics and Janus kinase inhibitors. Though data on efficacy and safety of these advanced therapies are available, less is known about the potential economic implications of their utilization in Japan. We evaluated the relative value of these advanced therapies in Japan using a locally developed cost per responder model. Methods A model was developed using relevant clinical endpoints and treatment costs to calculate cost per responder of all advanced therapies used for moderately to severely active ulcerative colitis treatment in Japan. Cost per responder was assessed in biologic-naïve and biologic-exposed populations, respectively. The model incorporated induction and maintenance therapy pathways as patients progressed through based on efficacy rates (clinical response, clinical remission and endoscopic improvement). Total costs for induction and maintenance included: drug acquisition, drug administration and serious adverse event management (as necessary) for responders, with additional rescue treatment cost only for non-responders. Results Upadacitinib showed lower cost per clinical response and cost per clinical remission across both biologic-naïve and biologic-exposed populations with only one exemption in cost per clinical remission in biologic-naïve population. In addition, upadacitinib demonstrated lower cost per endoscopic improvement in both populations. Janus kinase inhibitors outperformed with lower cost per responder than other mediations across all outcomes and patient populations with the exception of tofacitinib for clinical remission in biologic-exposed UC population. Limitations Comparative data used in this analysis have been derived from network meta-analysis, not from direct comparison. Conclusions The results of this cost per responder analysis suggest upadacitinib is a cost-effective option for the first- and second-line treatment of moderately to severely active ulcerative colitis in Japan.

Survey of Pharmacist-Led Medication Guidance for Patients with Inflammatory Bowel Disease in Japan.

In pharmacotherapy for inflammatory bowel disease (IBD), good medication adherence is necessary to control the condition. However, some patients show poor adherence. Pharmacists need to provide appropriate medication guidance to improve medication adherence. Community pharmacists often have to provide medication guidance in case of insufficient patient information because of varying affiliations. Therefore, to help improve medication adherence in patients with IBD and establish cooperation between community and hospital pharmacies, we investigated the awareness of IBD among pharmacists and the actual status of pharmacist-led medication guidance for patients with IBD. This study comprised a knowledge test for IBD and a survey of medication guidance for IBD in the form of questionnaires, which were administered to pharmacists using web forms. Community pharmacy affiliation (p < 0.01) and having no experience in medication guidance for IBD (p < 0.01) contributed to low scores in the IBD knowledge test. There was a difference in the correct answer rate for interactions or screening tests prior to medication administration between community and hospital pharmacists. Medication guidance consultations involving residual drug adjustment (p < 0.01), confirmation of symptoms (p < 0.01), prescription from other hospitals (p = 0.04), therapeutic effects (p = 0.04), and confirmation of medication adherence were more common among community pharmacists than among hospital pharmacists. Cooperation between community and hospital pharmacies was most commonly achieved through tracing reports or personal medication handbooks. Improving pharmacists' awareness of IBD and sharing information are important to facilitate cooperation between community and hospital pharmacists to improve medication adherence.

P312 Questionnaire survey for IBD patients in Japan; A Web-based J-CUP Survey

Abstract Background The prevalence of inflammatory bowel disease (IBD) in Japan has been increasing. We aimed to clarify the symptoms of patients with IBD in Japan using an internet-based questionnaire survey. Methods Overall, 805 patients with IBD were asked to complete an internet-based questionnaire addressing their history of disturbances in daily activities, prevalence of fecal urgency, incontinence, and treatment preferences. Results Responses were obtained from 447 patients with IBD (mean age: 54 years; 70% were men), comprising 363 patients with ulcerative colitis (UC) and 84 with Crohn's disease (CD). Notably, 16% of patients with UC and 35% with CD took over 1 year until the diagnosis of IBD, and 5% of patients with CD visited more than five medical institutions. Patients with CD were more likely to experience disturbances in their diet, work, travel, and outings than those with UC. Fecal urgency and incontinence were significantly more frequent in patients with CD than in those with UC (72% vs. 44%, and 50% vs. 26%, respectively). In contrast, 26% of the men and 37% of women with IBD had constipation. Acid reflux, sleep disorders, and depressive symptoms were present in approximately 30% of the patients. Oral administration was preferred. Conclusion Patients with IBD in Japan experience more severe disturbances in their daily activities, and these are more severe in those with CD than those with UC. In addition to fecal urgency and incontinence, care is required for constipation, acid reflux, sleep disorders, and depressive symptoms.

N13 Sexual satisfaction and its associated factors among patients with inflammatory bowel disease in Japan

Abstract Background Patients with inflammatory bowel disease (IBD) frequently experience fatigue and depression, which can lead to difficulties in their sexual lives, such as decreased motivation for sexual activity. Despite indications of sexual dysfunction and dissatisfaction, few studies have explored these issues. This study aims to clarify sexual satisfaction among patients with IBD and its related factors and to determine the percentage of respondents who were unwilling to answer the question about sexual satisfaction and their characteristics. Methods We consecutively recruited 500 patients from the specialized IBD clinic, of which 492 (206 with Ulcerative colitis and 286 with Crohn’s disease) valid responses were used in the study. To assess sexual satisfaction, we employed a 5-point scale using the "I am satisfied with my sex life" item from the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F). We collected information on patient characteristics (sex, age, occupation, marital status, disease duration, and sleep deprivation status). Additionally, we obtained data from the FACIT-F regarding non-response to sexual satisfaction, emotional well-being (EWB), and the Fatigue subscale (FS). Furthermore, we collected information on disease severity from the medical records, including the partial Mayo Score (pMayo) and Crohn's Disease Activity Index (CDAI). Results Out of 492 patients who participated in the study, 319 (64.8%) provided responses, while 173 (35.2%) did not respond to the sexual satisfaction question. The distribution of responses was as follows: “not at all” (11.0%), “a little bit” (9.7%), “somewhat” (24.7%), “quite a bit” (12.2%), “very much” (7.1%). In the bivariate analyses of sexual satisfaction and related factors, four variables showed a significant relationship: age (rs=-0.19, p=0.001), sleep deprivation status (p=0.003), EWB (rs =0.30, &amp;lt;0.001), and FS (rs =0.34, p&amp;lt;0.001). Multiple logistic regression analysis of the factors influencing non-response preferences revealed that female gender (OR=2.41, 95%CI= 1.55-3.75) and older age (OR=1.04, 95%CI=1.02-1.06) were statistically significant. Conclusion Chronic conditions, such as depression, fatigue, and sleep deprivation, can affect the sexual satisfaction of patients with IBD, even during periods of remission. A substantial percentage of respondents were unwilling to answer questions regarding sexual satisfaction among Japanese patients with IBD. Hence, healthcare providers should consider offering support for sexual issues, recognizing the discomfort some individuals may feel in discussing such intimate matters.

P760 Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: A final report of effectiveness and safety data

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present the final analysis of a 60-week post-marketing surveillance (PMS) study of tofacitinib in patients (pts) with UC in Japan. Methods A final analysis of safety and effectiveness data from a PMS study was conducted (final data as of 30 September 2022). All pts with UC in Japan receiving tofacitinib were registered. All adverse drug reactions (ADRs) during tofacitinib treatment were recorded. Data were excluded for 13 pts from 2 hospitals that did not obtain pt consent and were therefore not permitted for publication. In the risk-management plan, several ADRs were identified as clinically important events or as potential risks, for which all treatment-period data were used to calculate cumulative incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure). Effectiveness was assessed by partial Mayo score as observed. Results In total, 2043 pts receiving tofacitinib were enrolled in the PMS study, of whom 1982 and 1969 were included in the final safety and effectiveness analyses, respectively. In total (safety analysis set), 60.5% of pts were male and mean age was 42.5 years, with 2706.4 PY of exposure. ADRs and serious ADRs were observed in 462 (23.3%) and 46 (2.3%) pts, respectively; one death occurred due to an intestinal abscess (not related to study drug per investigator’s assessment). Herpes zoster (HZ; non-serious/serious) was the most commonly reported infection (89 pts [4.5%]). The IRs of malignancy, cardiovascular events and venous thromboembolic events were all &amp;lt;0.5 per 100 PY of exposure (Table). At Week 60, 735 of 870 ongoing pts (84.5%) were in remission (Figure). Overall, 1038/1982 pts (52.4%) discontinued treatment, most commonly due to inadequate clinical response (508/1038 pts [48.9%]). Conclusion In this final analysis, the overall safety profile during the treatment period from PMS reports of tofacitinib in pts with UC in Japan was generally comparable with tofacitinib safety data previously reported in PMS reports from Japan and worldwide,1 and in the tofacitinib UC clinical programme.2 However, rates of HZ were higher in this final analysis than in the tofacitinib UC clinical programme.2 Tofacitinib was effective in Japanese pts with UC in a clinical practice setting. The majority of pts with evaluable partial Mayo scores achieved remission during the 60-week observation period, consistent with previously reported data from the tofacitinib UC clinical programme.2

A Continuous Registry of Medical Record, Patient Input, and Epidemiological Data of Patients With Ulcerative Colitis: a Multicentre, Prospective, Observational Clinical Registry Study in Japan.

This registry aims to allow for a prospective non-interventional observational study of ulcerative colitis. This will facilitate monitoring of the current state of ulcerative colitis in Japan and improving the long-term disease course and adverse events associated with current treatment options. Inclusion of patients from five centres in Japan is planned. The study is expected to take place from July 15, 2020, to November 30, 2024. Background, demographics, and medical history/information will be collected from electronic medical records at enrolment. Medical information including medications, laboratory data, and disease activity will be collected automatically from electronic medical records throughout the study. Patient-reported quality of life data will be collected directly from patients via smartphone. Efficacy endpoints (clinical remission rate, clinical improvement rate, and endoscopic healing rate) and safety endpoints (incidence of adverse events and specific ulcerative colitis-related events) will be collected according to treatment administered. Treatment categories include no treatment, 5-aminosalicylic acids, corticosteroids, immunomodulators, immunosuppressants, anti-tumour necrosis alpha agents, cytapheresis, Janus kinase inhibitors, anti-integrin antibodies, and anti-interleukin-12/23 antibodies. The dataset will include cross-sectional and longitudinal data and is expected to capture the state of ulcerative colitis in Japan. Patients will be included on a large scale, and the registry will be established automatically from electronic medical records and direct patient input, facilitating the accurate recording of medical information for patients with ulcerative colitis in Japan and minimizing limitations intrinsic to databases that require manual data entry, such as the burden on participating investigators and entry of data with errors/typos.

Patients' Preference on Advanced Therapy and Follow-Up Procedure for Inflammatory Bowel Disease in Japan: A Web-Based 3A Survey.

With the recent increase in number of drugs for treating inflammatory bowel disease (IBD), it has become important to select treatments acceptable to patients. Endoscopy and biomarkers from blood and stool samples are used to evaluate IBD disease activity. This study aimed to clarify the acceptability of usage of advanced therapy and examination methods in patients through an internet-based survey. Patients with inflammatory bowel disease were asked via the internet to participate in a survey on the acceptability of nine therapies and three examination methods. The respondents rated acceptability on a scale of 1-10 and specified the most preferred option. Responses were obtained from 388 patients with ulcerative colitis and 82 with Crohn's disease; 14.5% and 11.5% of the patients underwent intravenous infusions and subcutaneous injections, respectively. Once-daily oral administration had the highest acceptability score, which was significantly different from other administration usages (p < 0.0001), regardless of prior treatment history. Oral administration was preferred by 88.9% of patients. The ranking of examination methods from most to least acceptable was blood tests > endoscopy > stool tests, with significant differences among all groups (p < 0.0001). Blood testing (76%) and stool testing (4.5%) were the most and least preferred methods, respectively. The most acceptable usage of advanced therapy in patients with inflammatory bowel disease was once-daily oral administration. Treatments that are effective, safe, and acceptable to patients should be selected, and examination methods acceptable to patients should be used.

Questionnaire Survey for Inflammatory Bowel Disease Patients in Japan; A Web-Based Japan, Crohn's Disease, Ulcerative Colitis, Patients Survey.

The prevalence of inflammatory bowel disease (IBD) in Japan has been increasing. We aimed to clarify the symptoms of patients with IBD in Japan using an internet-based questionnaire survey. Overall, 805 patients with IBD were asked to complete an internet-based questionnaire addressing their history of disturbances in daily activities, prevalence of fecal urgency, incontinence, and treatment preferences. Responses were obtained from 447 patients with IBD (mean age: 54 years; 70% were men), comprising 363 patients with ulcerative colitis (UC), and 84 with Crohn's disease (CD). Notably, 16% of patients with UC and 35% with CD took over 1 year until the diagnosis of IBD, and 5% of patients with CD visited more than 5 medical institutions. Patients with CD were more likely to experience disturbances in their diet, work, travel, and outings than those with UC. Fecal urgency and incontinence were significantly more frequent in patients with CD than in those with UC (72% vs. 44%, and 50% vs. 26%, respectively). In contrast, 26% of the men and 37% of women with IBD had constipation. Acid reflux, sleep disorders, and depressive symptoms were present in approximately 30% of the patients. Oral administration was preferred. Patients with IBD in Japan experience more severe disturbances in their daily activities, and these are more severe in those with CD than those with UC. In addition to fecal urgency and incontinence, care is required for constipation, acid reflux, sleep disorders, and depressive symptoms.

Changes in surgery rates among hospitalized patients with inflammatory bowel disease in Japan from 2015 to 2019: A nationwide administrative database analysis.

Treatment of inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), has advanced with the application of biologics or Janus kinase inhibitor (JAKi); however, some patients still need surgery. We assessed time trends of surgery and biologics or JAKi variety in Japan. Patients hospitalized due to IBD were analyzed using Diagnosis Procedure Combination data between 2015 and 2019. Longitudinal trend analysis was performed for demographics, and interrupted time-series analysis was performed to examine the association between surgery rates and an increase in the types of biologics or JAKi. Totally, 37867 cases with UC and 35493 cases with CD were analyzed. Over 5years, the surgery rate decreased in both UC and CD. The proportion of biologics and JAKi usage increased in UC and stabilized in CD. Between decreasing surgery and expanding treatment options of biologic or JAKi, interrupted time-series analysis results showed no significant correlation (level change in UC, -1.13, 95% confidence interval [CI]: -2.11 to -0.16, P=0.0235; slope change in UC, -0.05, 95% CI: -0.26 to 0.16, P=0.6372; level change in CD, -0.55, 95% CI: -1.82 to 0.71, P=0.3815; slope change in CD, -0.22, 95% CI: -0.63 to 0.19, P=0.2892). In Japan, from 2015 to 2019, the use of biologics or JAKi increased for UC and slightly decreased for CD, while the number of surgeries decreased in both. Our findings suggest that more widespread use of biologics or JAKi therapy could reduce surgeries in patients with IBD.

Differences in Coronavirus disease - 19 vaccination related side effects in patients with ulcerative colitis and Crohn's disease in Japan.

It has been recommended that individuals with inflammatory bowel disease (IBD) be vaccinated against Coronavirus disease -19 (COVID-19). Recently, we documented the incidence of side effects (SEs) after COVID-19 immunization among individuals with IBD in Japan. However, the study did not show differences between the types of IBD or the patients' clinical backgrounds. In this survey, we aimed at investigating whether the frequency of SEs differed among patients with IBD. A cross-sectional survey was conducted among adult patients with IBD at Kobe University between March 2022 and September 2022. Total 195 patients, including 134 with ulcerative colitis (UC) and 61 with Crohn's disease (CD), completed the questionnaire and were included in the analysis. Of these, 92.3%, 91.3% and 44.1% received the initial, second and third dose of the COVID-19 vaccine, respectively. The frequency of local symptoms following the initial, second and third dose of thevaccine was comparable between patients with UC and CD (69.6% vs. 72.7%, 64.2% vs. 69.1% and 63.5% vs. 73.9%, respectively). Muscle pain after the initial and second doses of the COVID-19 vaccine was more common among patients treated with corticosteroids (58.1% vs. 37.6% and 60.0% vs. 31.8%, p < 0.05). Female sex, younger age and current or former smoking were associated with an increased incidence of fever or chills after the initial dose of thevaccine (p < 0.05). In contrast, corticosteroid use was identified as a factor associated with an increased incidence of muscle pain after the initial dose of vaccine (p < 0.05). The use of corticosteroids could increase the risk of muscle pain following COVID-19 vaccination. Additionally, factors such as female sex, younger age and current or former smoking can affect the incidence of fever or chills. This information should encourage patients with IBD to get vaccinated against COVID-19.

A web-based survey on self-management for patients with inflammatory bowel disease in Japan.

Self-management (SMN) is a recognized component of care for chronic conditions, yet its importance in the context of inflammatory bowel disease (IBD) is unclear. This study evaluates the status of SMN and its relationship with quality of life (QOL) in Japanese patients with IBD. A web-based survey was conducted among adult (≥20 years old) Japanese patients with ulcerative colitis (UC) or Crohn's disease (CD). Registered members of an online IBD information platform completed a 45-item survey covering demographics, diet, treatment, physical condition, stress management, financial concerns, support services, and QOL. SMN was operationally defined by dietary and lifestyle behaviours, and contingency analysis was used to test for associated factors. Individual-level contributions to SMN were identified with logistic regression. There were 372 responses to the survey (211 with UC, 161 with CD). Approximately 60% of participants practiced SMN and these patients were 4-24% more likely to report positive QOL than those who did not. SMN was more common in patients with CD than those with UC. SMN practice was also associated with IBD-related hospitalisation/surgery and consultation with others about IBD (e.g. physicians, nurses, patients). The results of this study suggest an association between the practice of SMN and positive QOL in patients with IBD in Japan.

Association of ulcerative colitis symptom severity and proctocolectomy with multidimensional patient-reported outcomes: a cross-sectional study

BackgroundThe YOu and Ulcerative colitis: Registry and Social network (YOURS) is a large-scale, multicenter, patient-focused registry investigating the effects of lifestyle, psychological factors, and clinical practice patterns on patient-reported outcomes in patients with ulcerative colitis in Japan. In this initial cross-sectional baseline analysis, we comprehensively explored impacts of symptom severity or proctocolectomy on nine patient-reported outcomes.MethodsPatients receiving tertiary care at medical institutions were consecutively enrolled in the YOURS registry. The patients completed validated questionnaires on lifestyle, psychosocial factors, and disease-related symptoms. Severity of symptoms was classified with self-graded stool frequency and rectal bleeding scores (categories: remission, active disease [mild, moderate, severe]). The effects of symptom severity or proctocolectomy on nine scales for quality of life, fatigue, anxiety/depression, work productivity, and sleep were assessed by comparing standardized mean differences of the patient-reported outcome scores.ResultsOf the 1971 survey responses analyzed, 1346 (68.3%) patients were in remission, 583 (29.6%) had active disease, and 42 (2.1%) had undergone proctocolectomy. A linear relationship between increasing symptom severity and worsening quality of life, fatigue, anxiety, depression, and work productivity was observed. Patients with even mild symptoms had worse scores than patients in remission. Patients who had undergone proctocolectomy also had worse scores than patients in remission.ConclusionsUlcerative colitis was associated with reduced mood, quality of life, fatigue, and work productivity even in patients with mild symptoms, suggesting that management of active ulcerative colitis may improve patient-reported outcomes irrespective of disease severity. (UMIN Clinical Trials Registry: UMIN000031995, https://www.umin.ac.jp/ctr/index-j.htm).

Trends in the prevalence and incidence of ulcerative colitis in Japan and the US

PurposeTo estimate and compare annual prevalence and incidence, and demographic characteristics of patients with ulcerative colitis (UC) in Japan and the United States (US).MethodsAll patients with UC were identified from large employment-based healthcare claims databases (Japan Medical Data Center [JMDC] in Japan and IBM MarketScan Commercial Claims and Encounters database [CCAE] in the US), from 2010 to 2019. Cases were confirmed using International Classification of Disease-9/10 codes with/without Anatomical Therapeutic Chemical codes. Annual age-standardized prevalence and incidence rates were estimated for the JMDC by direct standardization using the CCAE as the standard population.ResultsPatients with UC were younger in Japan than in the US and men were affected more than women, whereas the reverse was true in the US. Annual prevalence per 100,000 population increased significantly from 5 in 2010 to 98 in 2019 in Japan and from 158 to 233 in the US. Prevalence increased in men more than in women and in all age groups in Japan, whereas increases were observed similarly in men and women, and in the 6 to < 65-year age groups in the US. Annual incidence per 100,000 person-years increased significantly over time in both sexes and in all age groups in Japan, with higher increases in women and in ≥ 18 year-olds. UC incidence rates did not change over time in the US.ConclusionTen-year trends in epidemiology of UC differ between Japan and the US. The data point to a growing disease burden in both countries that warrants investigation of measures for prevention and treatment.

Cost-Effectiveness Analysis of Tofacitinib Compared with Biologics in Biologic-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan.

Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). The objective of this study was to evaluate the long-term cost-effectiveness of tofacitinib versus current biologics, considering combinations of first-line (1L) and second-line (2L) therapies, from a Japanese payer's perspective in patients with moderate-to-severe active UC following an inadequate response to conventional therapy and in those who were naïve to biologics. A cost-effectiveness analysis was conducted during the time horizon specified in the Markov model, which considers a patient's lifetimeas 60 years and an annual discount rate of 2% on costs and effects. The model compared tofacitinib with vedolizumab, infliximab, adalimumab, golimumab, and ustekinumab. The time of active treatment was divided into induction and maintenance phases. Patients not responding to their biologic treatment after induction or during the maintenance phase were switched to a subsequent line of therapy. Treatment response and remission probabilities (for induction and maintenance phases) were obtained through a systematic literature review and a network meta-analysis that employed a multinomial analysis with fixed effects. Patient characteristics were sourced from the OCTAVE Induction trials. Mean utilities associated with UC health states and adverse events (AEs) were obtained from published sources. Direct medical costs related to drug acquisition, administration, surgery, patient management, and AEs were derived from the JMDC database analysis, which corresponded with the medical procedure fees from 2021. The drug prices were adjusted to April 2021. Further validation through all processes by clinical experts in Japan was conducted to fit the costs to real-world practices. Scenario and sensitivity analyses were also performed to confirm the accuracy and robustness of the base-case results. In the base-case, the treatment pattern including 1L tofacitinib was more cost-effective than vedolizumab, infliximab, golimumab, and ustekinumab for 1L therapies in terms of cost per quality-adjusted life year (QALY) gained (based on the Japanese threshold of 5,000,000 yen/QALY [38,023 United States dollars {USD}/QALY]). The base-case results demonstrated that the incremental costs would be reduced for all biologics, and decreases in incremental QALYs were observed for all biologics other than adalimumab. The incremental cost-effectiveness ratio (ICER) was found to be dominant for adalimumab; for the other biologics, it was found to be less costly and less efficacious. The efficiency frontier on the cost-effectiveness plane indicated that tofacitinib-infliximab and infliximab-tofacitinib were more cost-effective than the other treatment patterns. When infliximab-tofacitinib was compared with tofacitinib-infliximab, the ICER was 282,609,856 yen/QALY (2,149,157 USD/QALY) and the net monetary benefit (NMB) was -12,741,342 yen (-96,894 USD) with a threshold of 5,000,000 yen (38,023 USD) in Japan. Therefore, infliximab-tofacitinib was not acceptable by this threshold, and tofacitinib-infliximab was the cost-effective treatment pattern. The current analysis suggests that the treatment pattern including 1L tofacitinib is a cost-effective alternative to the biologics for patients with moderate-to-severe UC from a Japanese payer's perspective.

Computational Simulation Model to Predict Behavior Changes in Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Analysis of Two Regional Japanese Populations.

Managing inflammatory bowel disease (IBD) is a major challenge for physicians and patients during the COVID-19 pandemic. To understand the impact of the pandemic on patient behaviors and disruptions in medical care, we used a combination of population-based modeling, system dynamics simulation, and linear optimization. Synthetic IBD populations in Tokyo and Hokkaido were created by localizing an existing US-based synthetic IBD population using data from the Ministry of Health, Labor, and Welfare in Japan. A clinical pathway of IBD-specific disease progression was constructed and calibrated using longitudinal claims data from JMDC Inc for patients with IBD before and during the COVID-19 pandemic. Key points considered for disruptions in patient behavior (demand) and medical care (supply) were diagnosis of new patients, clinic visits for new patients seeking care and diagnosed patients receiving continuous care, number of procedures, and the interval between procedures or biologic prescriptions. COVID-19 had a large initial impact and subsequent smaller impacts on demand and supply despite higher infection rates. Our population model (Behavior Predictor) and patient treatment simulation model (Demand Simulator) represent the dynamics of clinical care demand among patients with IBD in Japan, both in recapitulating historical demand curves and simulating future demand during disruption scenarios, such as pandemic, earthquake, and economic crisis.

Expert consensus on vaccination in patients with inflammatory bowel disease in Japan

Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients’ IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice.