Long-term safety and effectiveness of vonoprazan for prevention of gastric and duodenal ulcer recurrence in patients on nonsteroidal anti-inflammatory drugs in Japan: a 12-month post-marketing surveillance study.

BACKGROUND: This study assessed the safety and effectiveness of vonoprazan for prevention of duodenal and gastric ulcer recurrence in patients on long-term nonsteroidal anti-inflammatory drugs (NSAIDs) in routine clinical practice. RESEARCH DESIGN AND METHODS: This 12-month, prospective, observational study (145 sites, Japan, September 2016-April 2020) analyzed patients with a history of gastric or duodenal ulcer who started once-daily vonoprazan and were receiving NSAIDs for pain. The primary outcome was the incidence of adverse drug reactions (ADRs). RESULTS: Most patients (86.7% [1099/1268]) received vonoprazan for at least 6 months. Most patients (98.6% [1250/1268]) received the 10-mg dose of vonoprazan, 38.3% (486/1268) received cyclooxygenase-2 inhibitors, and 61.7% (782/1268) received other NSAIDs. The overall incidence of ADRs was 0.71% (9/1268). Most commonly reported ADRs were gastrointestinal (0.32%), nervous system (0.16%), and hepatobiliary system (0.16%) disorders. The overall incidence of gastric or duodenal ulcer recurrence was 1.04% (95% CI 0.56-1.78). CONCLUSIONS: No new safety concerns were reported for vonoprazan for prevention of secondary ulcer or bleeding in patients receiving long-term NSAIDs. Vonoprazan was effective for preventing NSAID-related peptic ulcer recurrence in this real-world study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03214198; Japan Pharmaceutical Information Center Clinical Trials Information: JapicCTI-163436.

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

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The results of this study suggest an association between the practice of SMN and positive QOL in patients with IBD in Japan.

A Systematic Review of Self-Management Interventions for Patients with Inflammatory Bowel Disease.

Introduction: Previous studies have reported the effectiveness of inflammatory bowel disease (IBD) self-management. However, it is unclear which types of self-management interventions are effective. We conducted a systematic literature review to clarify the status and efficacy of self-management interventions for IBD. Methods: Searches were performed in databases including Embase, Medline, and Cochrane Library. Randomized, controlled studies of interventions in adult human participants with IBD involving a self-management component published in English from 2000 to 2020 were included. Studies were stratified based on study design, baseline demographic characteristics, methodological quality, and how outcomes were measured and analyzed for statistically significant improvements in outcomes, such as psychological health, quality of life, and healthcare resource usage. Results: Among 50 studies included, 31 considered patients with IBD and 14 and 5 focused on patients with ulcerative colitis and Crohn's disease, respectively. Improvements in an outcome were reported in 33 (66%) studies. Most of the interventions that significantly improved an outcome index were based on symptom management and many of these were also delivered in combination with provision of information. We also note that among effective interventions, many were conducted with individualized and patient-participatory activities, and multidisciplinary healthcare practitioners were responsible for delivery of the interventions. Conclusion: Ongoing interventions that focus on symptom management with provision of information may support self-management behavior in patients with IBD. A participatory intervention targeting individuals was suggested to be an effective intervention method.

Safety and Effectiveness of Vedolizumab in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim Analysis of a Japanese Post-Marketing Surveillance Study.

INTRODUCTION: This ongoing post-marketing surveillance monitors the long-term safety and effectiveness of vedolizumab in routine clinical practice in patients with moderate-to-severe ulcerative colitis (UC) in Japan. This interim analysis assessed induction-phase data, covering the initial three doses of vedolizumab. METHODS: Patients were enrolled via a web-based electronic data capture system from approximately 250 institutions. Incidence of adverse events and treatment responses were assessed by the physicians after the patient had received three doses of vedolizumab or when the drug was discontinued, whichever occurred first. Therapeutic response was defined as any treatment response, including remission or improvement of complete or partial Mayo score, and was assessed in the total and stratified patient populations according to prior tumor necrosis factor alpha (TNFα) inhibitor treatments and/or baseline partial Mayo score. RESULTS: The total incidence of adverse drug reactions (ADRs) was 4.10% (11/268). Common ADRs were dizziness, nausea, and arthralgia, each reported in 0.75% of patients (2/268). Serious ADRs were herpes zoster oticus and UC, each reported in 0.37% of patients (1/268). Therapeutic response was reported in 84.5% (218/258) of all patients, 85.8% (127/148) of TNFα inhibitor-naïve patients, and 82.7% (91/110) of TNFα inhibitor-experienced patients. Among patients with partial Mayo score of ≥ 4 at baseline, partial Mayo score remission in patients without or with prior TNFα inhibitor treatment was 62.5% (60/96) and 45.6% (36/79), respectively. CONCLUSION: The results confirm a safety and effectiveness profile of vedolizumab consistent with that observed in previous trials. CLINICAL TRIAL REGISTRATION: JapicCTI-194603, NCT03824561.

Association between baseline cognitive symptoms and the subsequent presenteeism and global function in patients with major depressive disorder.

Cognitive symptoms in major depressive disorder (MDD) contribute to impaired functional abilities and work productivity, particularly presenteeism. We investigated the association between baseline cognitive symptoms and subsequent presenteeism, and global functional impairment in Japanese patients with MDD from PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan) - a 6-month, multicenter, epidemiological study data. A total of 518 patients initiating antidepressant monotherapy (first-line or switched from another drug) were enrolled. Assessments include Perceived Deficits Questionnaire - Depression (PDQ-D) for cognitive complaints, Sheehan Disability Scale (SDS) for global function (analysed n = 318), and Work Productivity and Activity Impairment Questionnaire for presenteeism (analysed n = 122). A strong association between changes in presenteeism and changes in SDS scores (r: total = 0.636; work/school = 0.686) was observed. After adjusting for sociodemographic and MDD-related factors, patients without cognitive complaints at baseline showed lower odds of impaired presenteeism at 6 months versus patients with cognitive complaints (0.243, 95% CI: 0.079 to 0.747, p = 0.014) and also in patients with first episode of MDD against with recurrent MDD (0.327 (95% CI: 0.136 to 0.787). Similarly, patients without cognitive complaints had healthier global functioning (lower mean SDS total score) than patients with cognitive complaints (8.3 vs 11.2; 95% CI, -5.189 to -0.578; p = 0.014). First depressive episode (lower risk of presenteeism), being male, and low baseline SDS total score (better global functioning) were also associated with improved outcomes. These results highlight the potential value of baseline PDQ-D scores in predicting subsequent workplace and global functioning in patients undergoing treatment for MDD.

Prediction of residual cognitive disturbances by early response of depressive symptoms to antidepressant treatments in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) frequently retain cognitive disturbances after recovery from mood symptoms. We investigated the relationship between early response of mood symptoms and/or remission, and residual cognitive disturbances after 6 months of antidepressant treatment. METHODS: 518 patients with MDD were followed up for 6 months after antidepressant treatment initiation (first-line or switch from a previous drug). Subjective and objective cognitive disturbances were assessed by the Perceived Deficits Questionnaire - Depression (PDQ-D) and digit symbol substitution test (DSST), respectively. Depressive symptoms, as well as remission and early response to treatment, were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS: Early response of depressive mood (≥50% reduction in MADRS score at month 1) was related with fewer residual subjective cognitive symptoms, as evaluated by the PDQ-D at month 6 (p<0.001). Likewise, early remission status at month 2 was inversely associated with PDQ-D scores at month 6 (p<0.001). Among patients with baseline DSST scores of ≥1 standard deviation below the norm, early response/remission was associated with better performance on the DSST at month 6 (p<0.05). LIMITATIONS: The cohort may not be representative of the general MDD patient population, and the possible influence of concomitant medications was not evaluated. CONCLUSIONS: These findings suggest that early improvements in depressive symptoms predict better cognitive outcomes in patients with MDD. Grouping of patients by mood and cognition status in early stages of antidepressant treatments may facilitate efforts to improve long-term functional outcomes.

Patient and Physician Perspectives of Depressive Symptoms and Expectations for Treatment Outcome: Results from a Web-Based Survey.

PURPOSE: A previous international study suggested that perceptions of depression symptoms, social function, and treatment expectations are different between patients/physicians. We aimed to examine whether such differences exist in Japan. METHODS: A web-based survey was conducted with patients who reported that they had been diagnosed with depression, and physicians who reported that they had treated patients with depression, in Japan. Questionnaires were designed to quantify patients' perceptions of symptoms, social function, and treatment expectations. Patients were categorized into three stages of disorder based on their reported current symptoms: severe symptomatic, mild symptomatic, and remission. Physicians were assigned up to three patients, were provided with patient information from the questionnaire completed by those patients, and finally the completed questionnaire forms for each patient. Agreement between the perceptions of the patients and physicians was examined for each stage. RESULTS: Of the 2618 eligible patients, 828 were assigned to 326 eligible physicians. Overall, we found small differences in the perceptions of depression treatment between patients/physicians. Slightly fewer physicians than patients reported physical symptoms (85% vs 91%; p=0.018) in the mild symptomatic stage. Fewer physicians than patients reported cognitive symptoms in the severe (82% vs 87%; p=0.029) and mild (54% vs 66%; p=0.003) symptomatic stages. Social function was deemed to be lower by physicians than by patients, across all stages of disorder (p<0.001). Regarding treatment expectations, more physicians than patients reported "return to a normal life" in the mild symptomatic (51% vs 35%, p<0.001) and remission stages (57% vs 36%, p<0.001), and more patients than physicians reported "reduction of side effects" in the severe (10% vs 4%, p=0.004) and mild (12% vs 5%, p<0.001) symptomatic disorder stages. CONCLUSION: These results suggest small differences in patient/physician perceptions of depression treatment in Japan. Discrepancies between patients'/physicians' perceptions may vary depending on the medical environment.

Health technology assessment in Japan: a work in progress.

Background: In Japan, pharmacoeconomic requirements for list-price adjustment were institutionalized in April 2019 following provisional implementation of a new Health Technology Assessment (HTA) program 2016-2019. Since April 2019, submission of cost-effectiveness evidence to the Central Social Insurance Medical Council (Chuikyo) as part of the Japanese Ministry of Health, Labour, and Welfare has been mandatory for selected pharmaceuticals and medical devices.Methods: Based on a review of publications and commentaries since April 2019, together with views from a group of experts on key issues to be addressed, this report provides an update on recent HTA developments and key challenges still to be addressed.Results and Discussion: Japan's new HTA program is a first step toward development of a universal healthcare system that can be sustainable for many years into the future. Currently, Japan's HTA program requires provision of incremental cost-effectiveness ratios (ICERs) as evidence, with quality-adjusted life years as the preferred outcome measure. Prices can be adjusted both upward and downward according to the degree of the ICER estimate. Japan is the first country to have adopted an algorithmic method for "ICER-based" pricing; however, HTA measures that extend beyond a single ICER estimate are needed to take full advantage of HTA in the future. In particular, generation of evidence of value should support changes to the healthcare system so that incentives for innovation are not diminished while industry and government are not overburdened by the generation or assessment of evidence. There is a need to ensure scientifically sound HTA expertise across all sectors in Japan, and therefore enhancement of HTA literacy and capability among healthcare professionals, academia, government, and industry should be a priority.