Inflammatory Bowel Disease In Japan Research Articles

Living with Ulcerative Colitis in Japan: Biologic Persistence and Health-Care Resource Use

Objective: The aim of the study was to improve understanding of adherence and persistence to biologics, and their association with health-care resource utilization (HCRU), in Japanese patients with moderate to severe ulcerative colitis (UC). Methods: Data were from Medical Data Vision, a secondary care administrative database. A retrospective, longitudinal cohort analysis was conducted of data from UC patients initiating biologic therapy between August 2013 and July 2016. Data collected for 2 years prior (baseline) and 2 years after (follow-up) the index date were evaluated. Patients completing biologic induction were identified, and adherence/persistence to biologic therapy calculated. HCRU, steroid, and immunosuppressant use during baseline and follow-up were assessed. Biologic switching during the follow-up was evaluated. Descriptive statistics (e.g., means and proportions) were obtained and inferential analyses (from Student’s t tests, Fisher’s exact tests, χ² tests, the Cox proportional hazard model, and negative binomial regression) were performed. Results: The analysis included 649 patients (adalimumab: 265; infliximab: 384). Biologic induction was completed by 80% of patients. Adherence to adalimumab was higher than that to infliximab (p < 0.001). Persistence at 6, 12, 18, and 24 months was higher with infliximab than with adalimumab (p < 0.05). Overall, gastroenterology outpatient visits increased, and hospitalization frequency and duration decreased, from baseline to follow-up. UC-related hospitalizations were fewer and shorter, and endoscopies fewer, in persistent than in nonpersistent patients, although persistent patients made more outpatient visits than nonpersistent patients. Hospitalization duration was lower in persistent than nonpersistent patients. Approximately 50% of patients received an immunosuppressant during biologic therapy; 5% received a concomitant steroid during biologic therapy. Overall, 17% and 3% of patients, respectively, received 2nd line and 3rd line biologics. Conclusions: Poor biologic persistence was associated with increased non-medication-associated HCRU. Effective treatments with high persistence levels and limited associated HCRU are needed in UC.

Ulcerative colitis-related severe enteritis: an infrequent but serious complication after colectomy.

After colectomy for ulcerative colitis (UC), very severe and sometimes lethal enteritis can develop. However, the clinical features remain uncertain because of the low incidence, diversity of symptoms, and undefined diagnostic criteria. The aim of this study was to define postoperative ulcerative colitis-related severe enteritis (UCRSE) and to investigate its clinical features. A retrospective multicenter study was performed as a survey ofmajor medical facilities utilizing surgical supplies for inflammatory bowel disease in Japan from 2001 to 2014. UCRSE was defined as a case with massive intestinal bleeding, intestinal perforation, high-output stoma, and/or a requirement for medications, such as steroids and biologics. Patients with gastroduodenal lesions or pouchitis alone were excluded. The incidence, symptoms, involvement of bacteria, cytomegalovirus reactivation, treatment, and prognosis were examined for patients with UCRSE after colectomy. Forty-two (0.8%) out of 5284 cases met the criteria for UCRSE. Major symptoms were massive intestinal bleeding (76.2%), which required a median of 3850 (560-18900) mL blood transfusion; high-output stoma (38.1%) with excretion of fluid of 5000 (2000-7800) mL/day; and intestinal perforation (7.1%). Hypovolemic shock (35.7%) and/or disseminated intravascular coagulation (31.0%) developed as serious complications. Tests for cytomegalovirus reactivation were positive in 26.2% of cases. The presence of pathogenic bacteria was confirmed in only 5 cases. Corticosteroids or infliximabs were effective in half of the patients. Thirteen cases (31.0%) were treated surgically and 22 cases (56.4%) required maintenance therapy. The mortality rate was 11.9%. UCRSE is a rare but serious complication after colectomy and is sometimes life-threatening.

Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry.

Background/Aims There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children.Methods This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data.Results A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn’s disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturing/non-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01).Conclusions Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.

Very early-onset inflammatory bowel disease in Japan: A nationwide survey.

Very early-onset inflammatory bowel disease is defined as inflammatory bowel disease diagnosed before 6years of age. Very early-onset inflammatory bowel disease has various differential diagnoses, including primary immunodeficiency disorders, and is known to be resistant to conventional treatment. Therefore, global attention is required to manage this challenging condition. We conducted a retrospective epidemiological survey of the number of patients, final diagnosis, and examinations performed to diagnose very early-onset inflammatory bowel disease in Japan. A primary questionnaire about the number of very early-onset bowel disease cases and its diagnosis was administered to 630 pediatric facilities nationwide in Japan. A secondary survey about the examinations performed to achieve diagnosis was sent to the facilities that responded to the first survey. The answering rate was 92.2% (581/630 facilities); 81 facilities had 225 very early-onset bowel disease patients undergoing their care during the past 68months. Twenty-six patients (11.6%) were diagnosed with immunodeficiency-associated inflammatory bowel disease. The answering rate of the secondary survey was 70.4% (57/81 facilities). Colonoscopy, esophagogastroduodenoscopy, and small bowel imaging were performed for 99.4%, 67.5%, and 28.8% of patients, respectively. Genetic analysis was performed for 26.9% (43/160 patients) of patients, and 51.2% (22/43) of patients were diagnosed with immunodeficiency-associated inflammatory bowel disease. Approximately 40 patients are diagnosed yearly in Japan. Imaging studies, especially for small bowel lesions, can be challenging for this unique group of patients. However, a comprehensive approach including immunological and genetic analyses appears useful for diagnosing immunodeficiency-associated inflammatory bowel disease.

A Multicenter Prospective Survey on Early-Onset Inflammatory Bowel Disease in Japan

Introduction: The incidence of early-onset inflammatory bowel disease is increasing in Japan. Objective: This study aimed to analyze the treatment and progress of early-onset inflammatory bowel disease. Methods: This prospective survey evaluated the data of 43 patients aged <8 years who were diagnosed with inflammatory bowel disease (IBD) from the time of diagnosis to 36 months after registration. Results: A total of 12 patients with Crohn’s disease (CD), 21 with ulcerative colitis (UC), and 3 with unclassified IBD were enrolled. The mean disease onset age was 3 years and 7 months. Colon and anal lesions were present in 100 and 50% of patients with CD, respectively. Granulomas were detected in 5 patients (41.7%). Dietary elimination including elemental diet was performed in all patients. Eleven patients (91.7%) were in remission by initial induction therapy, and 72.7% maintained remission for 36 months. Three patients (14.3%) with UC had familial history, 71.4% had pancolitis-type UC, and 66.7% exhibited disease of moderate severity. Colectomy was performed in 4 patients (21.1%). Eighteen patients (85.7%) were in remission by initial induction therapy; however, only 15.8% maintained remission for 36 months. Anal complication was more prevalent in infantile-onset IBD than in childhood-onset IBD (p = 0.014). Conclusions: Among Japanese patients aged <8 years who were diagnosed with IBD, colitis-type disease was more common in CD and pancolitis was more common in UC. As the courses of several patients were severe, identifying primary immunodeficiency appears to be necessary to confirm background disease.

Quality of Life and Eligibility for Specific Financial Assistance for Medical Expenses: A Cross-Sectional Web-Based Survey among Patients with Inflammatory Bowel Disease in Japan

Specific financial assistance for people with rare and intractable diseases is part of Japan’s public health system. This survey aimed to clarify the relationship between eligibility for this specific financial assistance and quality of life (QOL) among individuals with inflammatory bowel disease (IBD) in Japan. A nationwide, web-based survey was conducted in Japan among 300 people with IBD. Questionnaire items covered socioeconomic characteristics and QOL, assessed with the five-dimension, five-level EuroQol (EQ-5D-5L). The percentage of respondents who were ineligible for specific financial assistance was 11.0% among those with Crohn’s disease (CD) and 34.0% among those with ulcerative colitis (UC). For those with CD, the median EQ-5D-5L utility weight did not differ significantly between the non-assistance and assistance groups (p = 0.2222). For those with UC, the median EQ-5D-5L utility weight was significantly higher in the non-assistance group than in the assistance group (p = 0.0034). The present study demonstrated that the revision of the law on intractable and rare diseases has not had a negative influence on the QOL of patients with IBD in Japan. Based on our findings, further research on patient-reported outcomes among individuals with IBD may be necessary to inform health policy makers.

PGI30 WEB-BASED RESEARCH OF QUALITY OF LIFE OUTCOME AND STATUS OF MEDICAL EXPENSE SUBSIDY FOR INTRACTABLE DISEASE FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN JAPAN

The medical expense subsidy for intractable diseases is part of the public health system for economic aid among patients with intractable diseases in Japan. We aimed to clarify the actual status of the medical expense subsidy for intractable diseases and quality of life (QOL) between Japanese patients with inflammatory bowel disease (IBD) who receive the subsidy and patients who are ineligible for this support. This nationwide survey was conducted in Japan, using a web-based questionnaire. We surveyed 200 patients with ulcerative colitis (UC) and 100 patients with Crohn’s disease (CD). The survey was conducted until data were collected for a predetermined number of patients. Survey questions covered age, sex, marital status, income, medical expense subsidy status, actual treatment status, and EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), which was used to assess QOL. The proportion of responders diagnosed with CD and UC who were ineligible to receive the subsidy was 11.0% and 34.0%, respectively. Median EQ-5D-5L scores were not significantly higher in the non-subsidy group than the subsidy group (0.87:0.78–1.00 vs. 0.82:0.75–0.79, P=0.282) in CD-diagnosed responders. In UC-diagnosed responders, scores were significantly higher in the non-subsidy group than in the subsidy group (0.89:0.87–1.00 vs. 0.89:0.78–1.00, P=0.003). Additionally, the introduction of biologic therapies was 8-fold higher in responders with CD than in those with UC (60.0% vs. 7.5%, P<0.001). In the present study, we demonstrated the health-related utility of patients with IBD, according to status of the intractable disease medical expense subsidy and socioeconomic factors. The introduction of biologic therapies was related to subsidy status. Patients who do not have active disease and do not receive active treatment have been excluded from the current subsidy system. We consider that the current subsidy system has not decreased QOL for patients with IBD in Japan.

Patients' Preference of Topical Therapy for Ulcerative Colitis in Japan: A Web-based 3T Survey.

The therapeutic drugs available for ulcerative colitis (UC) have recently increased. However, use of topical therapy for UC in Japan has not been determined. This study aimed to investigate real-world use of topical therapy for UC in Japan using a web-based survey designed for UC patients. A web-based questionnaire on UC management was administered to 773 patients over a 2-day period in September 2019. The responses regarding topical therapy use were analyzed. Questionnaire responses were obtained from 323 UC patients. Of these, the mean disease duration was 12.2 years, and 220 patients (68.1%) had used topical therapy, of whom 68 (21.1%) were currently using this treatment. The frequency of using the prescribed topical therapy was appropriate in 36.8% of patients, only when needed in 38.6%, and rarely in 24.5%. Among all topical therapy users, 64.4% reported that budesonide foam was easy to use, which was significantly higher than the rates for mesalazine suppositories (43.6%), mesalazine enemas (12.9%), and glucocorticoid enemas (13.9%; P < 0.05). Regarding treatment effects, 68.9% of patients were satisfied with the budesonide foam, which was a significantly higher rate of satisfaction than those for mesalazine suppositories (44.6%), mesalazine enemas (30.2%), glucocorticoid enemas (36.1%), and glucocorticoid suppositories (41.9%; P < 0.05). Although topical therapy use was common in this Japanese UC population, patient adherence was not very high. Of all the topical therapy types, budesonide foam, which has recently become available, was rated highly by these patients.

Unraveling the Pathogenesis of Inflammatory Bowel Disease and Search for New Therapeutic Medicines

The breakdown of the intestinal mucosal barrier has been shown to play a key role in the pathogenesis of intestinal immune-related disorders such as inflammatory bowel disease (IBD). IBD is a chronic inflammatory disorder with intermittent episodes of remission and relapse, and the incidence of IBD in Japan has risen dramatically in recent decades. Although sustained clinical remission has recently been recognized as an important goal of IBD therapy, there are not many treatment options to maintain long-term remission. Intestinal macrophages play pivotal roles in the regulation of immune homeostasis and inflammation in the intestine. Resident intestinal macrophages can regulate themselves and other immune cells, primarily through the spontaneous secretion of interleukin-10 (IL-10). We reported that the enhancement of IL-10 production by intestinal macrophages has the potential to be a novel therapeutic mechanism for maintaining the remission of IBD. Thus, to develop new therapeutic medicines for IBD, we screened the Wakanyaku Library derived from medicinal herbs for the ability to enhance IL-10 production by intestinal macrophages. Some compounds were identified with the potential to enhance IL-10 production by intestinal macrophages and thereby maintain long-term remission in IBD. This review focuses on our recent findings on the role of intestinal macrophages in the pathogenesis of IBD and developing a novel therapeutic strategy aimed at maintaining remission in IBD.

Vedolizumab good value in ulcerative colitis in Japan

Vedolizumab good value in ulcerative colitis in Japan

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan

BackgroundVedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC.ObjectiveThe aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective.MethodsA hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually.ResultsOver a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated.ConclusionOur analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan.Electronic supplementary materialThe online version of this article (10.1007/s40273-019-00841-1) contains supplementary material, which is available to authorized users.

I. The Patients with Inflammatory Bowel Disease in Japan Increasing Rapidly Concerning Metabolic Disorders

I. The Patients with Inflammatory Bowel Disease in Japan Increasing Rapidly Concerning Metabolic Disorders

Health-related quality of life outcomes and economic burden of inflammatory bowel disease in Japan.

PurposePrevious Japanese studies have not compared health-related quality of life (HRQoL), work productivity and activity impairment, health care resource utilization (HRU), and costs in inflammatory bowel disease (IBD) patients with non-IBD controls, leading to insufficient evidence regarding IBD’s true burden. The aim of this study was to examine the impact of IBD on patient-reported outcomes and costs among Japanese adults (≥18 years).Patients and methodsThis retrospective cross-sectional study used data from the 2012–2014 Japan National Health and Wellness Survey (N=83,505). HRQoL (SF-36v2), work productivity and activity impairment (work productivity and activity impairment-General Health Questionnaire), HRU, and annual costs were compared between respondents with IBD (n=441) and non-IBD controls (n=82,944), and within IBD subtypes (Crohn’s disease [CD] and ulcerative colitis [UC]) using chi-square and ANOVA tests.ResultsMental Component Summary (MCS), Physical Component Summary (PCS), and health state utility (Short-Form-6 Dimensions [SF-6D]) scores were significantly lower in IBD respondents than in controls (differences of 2.2 points, 2.6 points, and 0.041 points, respectively; all P<0.001). However, only differences in SF-6D scores reached the minimally important difference threshold. Furthermore, IBD-diagnosed respondents reported greater absenteeism, presenteeism, overall work productivity loss and activity impairment, and HRU than controls (all P<0.001). Consequently, direct and indirect costs were 3-fold and 1.5-fold higher in IBD-diagnosed respondents than in controls (both, P<0.001). Additionally, CD-diagnosed respondents had lower MCS, PCS, and SF-6D scores (all P<0.01) and higher direct costs (P<0.001) than UC-diagnosed respondents.ConclusionIBD and its subtype CD were associated with lower HRQoL, greater impairment to work and non-work activities, HRU, and costs among Japanese adults. This reinforces the general consensus that IBD patients, specifically those diagnosed with CD, require support from their family and society to combat the disease.

A Retrospective Study of Catheter-Related Thrombosis Using the Central Vein Catheters for the Ulcerative Colitis Patients

Leukocyte apheresis is a therapeutic option for moderate-to-severe active ulcerative colitis in Japan. It causes fewer complications, however, leukocyte apheresis requires the use of a relatively large caliber of peripheral venous line for hemodialysis. We reluctantly used a large caliber catheter with a double-lumen into the central vein.

Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

The Correlation between Sexuality and Family Functioning among Patients with Inflammatory Bowel Disease in Japan

Purpose: The objective of this study was to examine the correlation between the sexuality of patients with Inflammatory Bowel Disease and family functioning. Methods: The study took the form of a self-administered questionnaire survey, utilizing the Sexuality Satisfaction Index for IBD (SEXSI-IBD) for measuring sexuality and the Survey of Family Environment Survey of Family Environment (SFE) for measuring family functioning. SEXSI-IBD consists of 28 items and five domains, and SFE consists of 30 items and five domains. The participants were recruited at 15 self-help groups and 14 hospitals. Results: Of 146 participants, 48.6% were male and 52.4% female, with an average age of 41.1 years. A significant correlation was observed between the item average score of SEXSI-IBD and Overall Satisfaction Score (OSS) of SFE. Significant correlations were observed in two domains of the SEXSI-IBD, “Daily interaction” and “Sexual communication,” and in all five domains of the SFE. In particular, for “Daily interaction,” the strongest correlation was observed in the SFE’s “Macro system” and “Family internal environment system.” A correlation was observed between the “Physical contact importance” in SEXSI-IBD and the “Macro system” in the OSS of the SFE. Conclusions: Sexuality correlates with family functioning not only in the family internal environment system but also in the family external environment system. Through an approach aimed at elevating the degree of satisfaction for sexuality, it becomes possible to improve family functioning and realize a sense of family well-being.

Burden Of Ulcerative Colitis In Japan

Burden Of Ulcerative Colitis In Japan

The relationship between socio-demographic factors, health status, treatment type, and employment outcome in patients with inflammatory bowel disease in Japan

BackgroundInflammatory Bowel Disease (IBD) constitutes a huge burden for patients and studies show that IBD patients have difficulties remaining in employment. Because there is no data about the unemployment of IBD patients in Japan.MethodsWe surveyed a representative sample of 1068 Japanese IBD patients regarding their employment status.ResultsWe found that the labor force participation rate is lower and unemployment higher for patients with IBD compared to the general population. Factors associated with unemployment in the IBD sample are older age, female gender, and the prevalence of depression.DiscussionIBD constitutes a high burden for patients in Japan regarding employment outcome.

Genetic polymorphisms of MAFK, encoding a small Maf protein, are associated with susceptibility to ulcerative colitis in Japan.

AIMTo investigate whether single nucleotide polymorphisms in maf protein K (MAFK), which encodes the MAFK, lead to increased susceptibility to ulcerative colitis in the Japanese population.METHODSThis case control study examined the associations between MAFK single nucleotide polymorphisms (rs4268033 G>A, rs3735656 T>C and rs10226620 C>T) and ulcerative colitis susceptibility in 174 patients with ulcerative colitis (UC) cases, and 748 subjects without no lower abdominal symptoms, diarrhea or hematochezia (controls). In addition, as the second controls, we set 360 subjects, who have an irregular bowel movement without abnormal lower endoscopic findings (IBM controls).RESULTSThe genotype frequency of rs4268033 AA and allelic frequency of the rs4268033A allele were significantly higher in the UC cases than in both controls (P = 0.0005 and < 0.0001, P = 0.015 and 0.0027 vs controls and IBM controls, respectively). Logistic regression analysis after adjustment for age and gender showed that the rs4268033 AA and rs3735656 CC genotypes were significantly associated with susceptibility to UC development (OR = 2.63, 95%CI: 1.61-4.30, P = 0.0001 and OR = 1.81; 95%CI: 1.12-2.94, P = 0.015, respectively). Similar findings were observed by the comparison with IBM controls. In addition, the rs4268033 AA genotype was significantly associated with all phenotypes of UC except early onset. There was no significant association between rs10226620 and ulcerative colitis.CONCLUSIONOur results provide the first evidence that MAFK genetic polymorphisms are significantly associated with susceptibility to UC development. In particular, rs4268033 is closely associated with an increased risk for the development of UC.

PGI36 - Real World use of Biologics Therpies for Patients with Ulcerative Colitis in Japan

PGI36 - Real World use of Biologics Therpies for Patients with Ulcerative Colitis in Japan