Background and Aims Patients with inflammatory bowel diseases may have higher incidences of non-melanoma skin cancers and non-Hodgkin lymphoma, potentially linked to underlying disease and treatments. This analysis assessed incidence rates of these malignancies in Japanese patients with ulcerative colitis or Crohn’s disease, and their association with thiopurine and/or anti-tumor necrosis factor-α treatment, using data from a nationwide administrative database in Japan. Methods Patients diagnosed with inflammatory bowel disease without malignancy were identified from the Medical Data Vision database. Incident cases of non-melanoma skin cancers and non-Hodgkin lymphoma diagnosed after prescription of thiopurine and/or anti-tumor necrosis factor-α were identified between April 2008 and January 2018. Age- and sex-adjusted incidence rate ratios were calculated relative to the total treated patient population. Results A total of 75 673 eligible patients were identified at the index date. Thiopurine prescription with or without anti-tumor necrosis factor-α agents increased incidence rate ratios for non-melanoma skin cancers relative to the overall population (3.39 and 4.03, respectively). There were no notable differences in non-Hodgkin lymphoma incidence relative to the total population in any treatment subgroup, regardless of prescription of thiopurine and/or anti-tumor necrosis factor-α (all incidence rate ratios, ~1). Conclusions There is no evidence for an increased incidence of non-Hodgkin lymphoma attributable to thiopurine or anti-tumor necrosis factor-α treatment in Japanese patients with inflammatory bowel disease. The impact of racial differences on non-Hodgkin lymphoma incidences should be considered. Thiopurine therapy may be a risk factor for non-melanoma skin cancers in Japanese patients.

Background Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is important to prevent relapse. Proton-pump inhibitors (PPIs) are used for both treatment and maintenance therapy of GERD. Recently, a potassium-competitive acid blocker vonoprazan was launched in Japan. We evaluated the comparative efficacy of vonoprazan and other PPIs for GERD maintenance. Methods A systematic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials. Double-blind randomized controlled trials (RCTs) of PPIs, vonoprazan, and placebo for GERD maintenance published in English or Japanese were selected. Among them, studies conducted at the recommended dose and for the recommended use, and containing information on maintenance rate based on endoscopic assessment, were included. The comparative efficacies of treatments were estimated by performing a Bayesian network meta-analysis, which assessed the consistency assumption. Outcomes were number or rate of patients who maintained remission. Results Of 4001 articles identified, 22 RCTs were eligible for analysis. One study published as an abstract was hand-searched and added. The consistency hypothesis was not rejected for the analysis. The odds ratio of vonoprazan 10 mg to each PPI was 13.92 (95% credible interval [CI] 1.70–114.21) to esomeprazole 10 mg; 5.75 (95% CI 0.59–51.57) to rabeprazole 10 mg; 3.74 (95% CI 0.70–19.99) to lansoprazole 15 mg; and 9.23 (95% CI 1.17–68.72) to omeprazole 10 mg. Conclusions The efficacy of vonoprazan in GERD maintenance treatment may be higher than that of some PPIs. However, a direct comparison of vonoprazan and PPIs is required to confirm these effects. Electronic supplementary material The online version of this article (10.1007/s00535-019-01572-y) contains supplementary material, which is available to authorized users.

Background: Helicobacter pylori infection increases the risk of stomach cancer; therefore, eradication therapy is recommended for infected individuals. Although several methods are recommended for the diagnosis and therapy of H. pylori infection, their frequency and effectiveness have not been fully investigated in Japan. Methods: A nationwide claims database including > 1.6 million patients (April 2008 -October 2016) in Japan was utilized. We analyzed the distribution of methods for H. pylori diagnosis and therapy, waiting period between eradication and diagnostic test, and success rate of primary therapy. Results: Data for 481,041 patients were extracted. After primary eradication therapy, urea breath test was used for > 80% of diagnoses, and antibody measurement for 0.7%. The success rate of primary eradication was > 80% for most diagnostic methods and 69.0% for antibody measurement; inappropriately-timed antibody measurement may have contributed to this disparity. The overall success rate of eradication therapy decreased from 2011 to 2014, but increased from 2015, coinciding with launch of the potassium-competitive acid blocker vonopra-zan, which showed a higher success rate of eradication than proton-pump inhibitors. Conclusions: Diagnostic tests of H. pylori infection mostly followed Japanese Society for Helicobacter Research guidance, although some antibody measurements were timed inappropriately. Vonoprazan appears to increase the success rate of primary therapy.

Background and Aim Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton‐pump inhibitors (PPIs) are recommended as a first‐line therapy to treat GERD. Recently, a new potassium‐competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD. Methods We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double‐blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta‐analysis to assess the consistency assumption. Results Of 4001 articles identified in the database, 42 studies were eligible. One study was hand‐searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79–7.06), 3.94 (1.15–14.03), 2.40 (0.90–6.77), and 2.71 (0.98–7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs. Conclusions This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.

Background and Aim It is unclear how adding an anti‐tumor necrosis factor alpha agent to immunomodulator (IM) treatment, as a step‐up strategy, affects long‐term outcomes in ulcerative colitis. This retrospective study investigated persistence associated with biologic anti‐tumor necrosis factor alpha agents combined with IMs versus biologic monotherapy in patients with ulcerative colitis. Methods This was a longitudinal cohort study of patients in the Japan Medical Data Center claims database who had been newly prescribed infliximab or adalimumab as induction (completed) and maintenance (2010–2016). Biologic persistence (i.e. no switch/discontinuation during maintenance) was compared among patients prescribed biologic monotherapy (Bio) and those prescribed a biologic combined with an IM, as step‐up (Bio + prior IM) or simultaneously (Bio + IM). Results Three hundred and sixty‐nine eligible patients were analyzed (233, 78, and 58 in the Bio, Bio + prior IM, and Bio + IM subgroups, respectively). Multivariate analysis showed a lower probability of nonpersistence during maintenance for infliximab‐treated patients in the Bio + prior IM versus Bio subgroup (hazard ratio: 0.53; 95% confidence interval: 0.29–0.99; P = 0.045). No such effect was seen in adalimumab‐treated patients (P = 0.222) or in the overall population (P = 0.398). The probability of nonpersistence during maintenance in the Bio + IM subgroup was not significantly different from that in the Bio subgroup in either the biologic subpopulation or in the overall population. Conclusions Adding infliximab to an existing IM results in a lower probability of nonpersistence compared with infliximab monotherapy in ulcerative colitis patients. This effect is not seen in adalimumab‐treated patients.

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Background and Aim Intestinal strictures in Crohn's disease (CD) have a high rate of repeated surgery. As alternatives to surgery, endoscopic balloon dilatation (EBD), immunomodulators (IMs), and antitumor necrosis factor alpha (anti‐TNFα) have been proposed. We aimed to assess the effectiveness of the combined therapy with anti‐TNFα and EBD in preventing intestinal stricture recurrence and surgery in patients with CD. Methods This retrospective cohort study included patients from the nationwide administrative database in Japan who were hospitalized and underwent at least one EBD between 1 April 2010 and 31 March 2017. The effectiveness of anti‐TNFα was evaluated by performing survival analysis for the primary outcome. We selected the inverse probability of treatment weighting method for adjustment of covariates. As an exploratory analysis, we evaluated the association of anti‐TNFα initiation timing with intestinal stricture recurrence. Results The anti‐TNFα exposed group had a significantly lower risk of intestinal stricture recurrence than that of the anti‐TNFα nonexposed group (hazard ratio = 0.38, 95% confidence interval 0.31–0.48, P < 0.001). Surgery‐free rate was shown to have the same tendency. Anti‐TNFα therapy initiation before or after EBD resulted in a lower risk of intestinal stricture recurrence than that of simultaneous treatment. Conclusion The combined therapy with anti‐TNFα and EBD could have preventive effects for intestinal stricture recurrence and surgery in hospitalized patients with CD. In particular, anti‐TNFα initiation may be recommended before or after EBD, not immediately after EBD. With respect to EBD, it is important to clarify the effectiveness of combination therapy with several new medication treatments, such as biologics.

Antiplatelet agents including low-dose aspirin (LDA) or adenosine diphosphate (ADP) receptor antagonists are widely used for the prevention of cardiovascular events. However, antiplatelet agents increase the risk of bleeding associated with mucosal breaks in the gastrointestinal (GI) tract [1,2]. Because GI bleeding is independently associated with mortality and ischemic compilations, and temporary cessation of antiplatelet agents increases the risk of mortality, GI bleeding prevention is important during therapy [2-5]. Concomitant use of a proton pump inhibitor (PPI) is regarded as appropriate in patients with multiple risk factors for GI bleeding who require antiplatelet therapy [6]. Risk factors for GI bleeding include a history of bleeding or other complications of peptic ulcer disease [7,8], advanced age, use of steroids or non-steroidal anti-inflammatory drugs (NSAIDs) [9-15], and concomitant use of 2 antithrombotic agents [i.e. dual antiplatelet therapy (DAPT)] [1,16-19]. Vonoprazan (TAK-438) belongs to a class of acid-inhibitory agents known as potassium-competitive acid blockers (P-CABs), which reversibly inhibit H + , K +-ATPase independently of acid pH