Satoshi Motoya

Sapporo Kosei General Hospital · IBD center

Background and aims: Perianal lesion is a refractory phenotype of Crohn's disease (CD) with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. Methods: Patients newly diagnose...

Background Biologics are commonly used for the treatment of Crohn’s disase (CD); however, the proportion of biologics used and their initiation time from diagnosis differs widely between different regions. There is limited information about the patient characteristics and the treatment persistence of each initial biologics, and the treatment persis...

Background Ustekinumab (UST) is an interleukin-12/23 p40 antagonist approved for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the final efficacy and safety results of UST in the Asian subpopulation in the UNIFI long-term extension (LTE) through 4 years (Week [WK] 200). Methods Overall, 87 intravenous (IV)...

Background: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. Methods: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hosp...

Background: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease pat...

Background and aim: Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical...

[This corrects the article DOI: 10.1371/journal.pone.0201956.].

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. Ad...

The killer cell immunoglobulin-like receptor (KIR) recognizes human leukocyte antigen (HLA) class I molecules and modulates the function of natural killer cells. Despite its role in immunity, the complex genomic structure has limited a deep understanding of the KIR genomic landscape. Here we conduct deep sequencing of 16 KIR genes in 1,173 individu...

Background AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. Methods This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study wa...

Background The spread of coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide. The clinical background and clinical course of inflammatory bowel disease (IBD) among Japanese patients with COVID-19 remains unclear. Methods This study is an observational cohort of Japanese IBD patients diagnosed with COVID-19. Dat...

Background An association between shorter disease duration and improved clinical efficacy has been shown in post hoc analyses of clinical trial data with biological therapies in Crohn’s disease (CD). The efficacy and safety of risankizumab (RZB) as induction and maintenance therapy have been recently reported. Here, the efficacy of RZB stratified b...

Introduction: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. Methods: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the Intern...

Background and Aim To determine the efficacy and safety of vedolizumab treatment with or without concomitant immunomodulator use in Japanese patients with moderate-to-severe ulcerative colitis. Methods Among enrolled patients in a phase 3 study conducted in Japan (Clinicaltrials.gov, NCT02039505), data from patients allocated to 300 mg intravenous...

Background Information on patient demographics and disease characteristics at the time of Crohn’s disease (CD) diagnosis is considered to be an important aspect in the treatment and management of CD. However, reports on phenotypes, disease course, and treatment impact in newly diagnosed CD patients are limited. An interim analysis of a large regist...

Background Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients wit...

Background Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called “mesalamine allergy,” which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the gen...

Background and Aim: To evaluate the onset of symptomatic response with vedolizumab in patients with moderate-to-severe ulcerative colitis in Japan. Methods: Patients were randomized to receive vedolizumab 300 mg or placebo at Weeks 0, 2, and 6. Mayo subscores were analyzed in patients with baseline stool frequency (SF) ≥1 and rectal bleeding (RB)...

Background/aims: Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate...

Aims: We evaluated the efficacy of MMX mesalazine for the induction of remission in patients with UC who insufficiently respond to pH- or time-dependent mesalazine. Methods: Retrospective data were collected from active UC patients who switched to MMX mesalazine 4.8 g/day because of an insufficient response to 3.6 g/day of pH- or 4.0 g/day of time-...

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 tr...

This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June...

Background Adrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC. M...

Background This study clarifies the long-term effectiveness of ustekinumab based on real-life data from Japanese Crohn’s disease (CD) patients. Methods A total of 137 patients were included, and 124 patients (90.5%) were exposed to anti-tumor necrosis factor-α agents. Results The clinical remission rate at week 52 was 32.4% in moderate to severel...

Background & Aims We investigated the effects of inducing deep remission in patients with early Crohn’s disease (CD). Methods We collected follow-up data from 122 patients (mean age, 31.2±11.3 y) with early, moderate to severe CD (median duration 0.2 y; interquartile range, 0.1–0.5 y) who participated in the effect of tight control management on C...

Background Anti-tumour necrosis factor (TNF)-α agents are the mainstay of the long-term treatments for refractory ulcerative colitis (UC). However, there is no prospective randomised controlled trial evaluating if anti-TNF-α agents can be discontinued in UC patients in remission. Methods Patients with UC maintained in clinical remission with infli...

Background The optimal endoscopic target in early Crohn’s disease (CD) that limits long-term disease complications is unknown. Methods We analysed medical records from patients who had follow-up data since the end of CALM. Patients with Crohn’s disease endoscopic index of severity (CDEIS) scores at the end of CALM were included. The primary outcom...

The biologics infliximab (IFX) and adalimumab (ADA) have high therapeutic efficacy for Crohn's disease, and are used to treat many patients. However, randomized controlled trials (RCT) have not been conducted to compare their efficacy in biologic treatment-naive patients. Although RCT are not feasible, we used the propensity score (PS) matching to...

Background: Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission. Methods: We conducted a multicenter, prospective, randomised-control trial of patients...

Introduction: The Asia-Pacific consensus on the management of gastroesophageal reflux disease (GERD) and the GERD treatment guidelines of 2015 drawn up by the Japanese Society of Gastroenterology were proposed, and GERD management in Asian regions was assumed to be performed based on these consensuses. In this environment, the current status of GE...

Background: Vedolizumab is a gut-selective humanized antibody that binds the α4β7 integrin. We evaluated efficacy and safety of vedolizumab in Japanese patients with moderate-to-severe Crohn's disease (CD). Methods: In this Phase 3, double-blind study (NCT02038920), 157 patients were randomized to receive intravenous vedolizumab 300 mg (n = 79)...

Background: The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. Methods: Thi...

Background The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of...

Background: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we st...

Background: Budesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide. Methods...

Background & aims: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC). Methods: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japa...

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor approved in Japan for the treatment of ulcerative colitis (UC). Differences in the safety profile of tofacitinib in Japanese patients versus the global population, such as a higher risk of herpes zoster, have been reported. Objectives: We conducted post hoc analyses of tof...

Background The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN...

[This corrects the article DOI: 10.1371/journal.pone.0212989.].

Background Vedolizumab safety and efficacy have been established in many populations all over the world, but have never been studied in Japan. We report results from a Phase 3, randomized, double-blind, placebo-controlled study of vedolizumab in Japanese patients with active ulcerative colitis (UC). Methods Patients with moderate-to-severe UC were...

Subgroup analysis of clinical response in the induction phase (at Week 10). (DOCX)

Study design. Footnotes: aThe blindness was maintained until after completion of the database lock at Week 60. bRandomization schedules were generated by sponsor-designated personnel and kept in a secure area. cDynamic randomization was performed with the previous TNFα antagonist use, concomitant immunomodulator use, concomitant corticosteroid use,...

CONSORT checklist. (DOCX)

Original study protocol (Japanese). (PDF)

Translated study protocol (English). (PDF)

Patient demographics and baseline characteristics (Patients who entered the maintenance phase). (DOCX)

Background/aims: Inhibition of α4β7 integrin has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the α4β7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments. Methods: In this randomized, doub...

Background The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. To study the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN UMIN000009596). Methods Pa...

Background There are few studies about the influence of small bowel capsule endoscopy (SBCE) findings on clinical outcomes in patients with Crohn’s disease (CD). In particular, the influence of the severity of SBCE findings on treatment intervention is unclear. The present study analysed the long-term outcomes of treatment intervention according to...

Background We aimed to describe the long-term impact of achieving endoscopic and deep remission among participants in the effect of tight control management on CD (CALM) trial. Methods We analysed medical records from patients with follow-up data since end of CALM. Patients were stratified by outcomes in CALM at 1 year: clinical remission (Crohn’s...

Background/Aims: To elucidate the current management of ulcerative colitis (UC)-associated cancer, a questionnaire-based survey was conducted to gather current opinions on colitis-associated cancer in different East Asian countries. Methods: The questionnaire, based on physicians, contains 9 questions focused on UC management and cancer surveillanc...

Objectives The prevalence of pediatric Crohn’s disease (CD) is increasing in Japan and other countries, and many patients are unresponsive to or do not tolerate current treatment options. This study aimed to investigate the efficacy, safety, and pharmacokinetic profile of infliximab (IFX) in pediatric patients with moderate-to-severe CD and inadequ...

Protocol summary in English. (PDF)

CONSORT 2010 checklist. (DOC)

Protocol in Japanese. (PDF)

Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well-established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino a...

[This corrects the article on p. 233 in vol. 16, PMID: 29743836.].

Background: Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 va...

Background: Dose escalation is often recommended for loss of response in anti-TNFα-treated patients with Crohn's disease (CD). This 52-week phase 3, multicenter study investigated the efficacy and safety of escalation to adalimumab 80 mg every other week (EOW) in Japanese patients with CD who lost response to maintenance adalimumab 40 mg EOW. Met...

Background/Aims Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy...

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 con...