Non-acquired immunodeficiency syndrome defining malignancies in people living with haemophilia and human immunodeficiency virus after direct-acting antiviral era.

Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.

Disease and treatment burden of patients with haemophilia entering the explorer6 non-interventional study.

OBJECTIVES: We aimed to characterise baseline disease and treatment burden in a large population with haemophilia A/B, both with (HAwI/HBwI) and without (HA/HB) inhibitors. METHODS: The prospective, non-interventional explorer6 study included patients ≥12 years old with severe HA, severe/moderate HB or HAwI/HBwI of any severity, treated according to local standard of care (excluding previous/current exposure to concizumab or emicizumab). Baseline characteristics and historical clinical data were collected and patient-reported outcomes, including treatment burden, were assessed. RESULTS: The explorer6 study enrolled 231 patients with haemophilia (84 HAwI/HBwI) from 33 countries. At baseline, patients with HA/HB treated with prophylaxis had the lowest median annualised bleeding rates (ABRs; 2.0), irrespective of haemophilia type; of these patients, 27.5% (HA) and 31.4% (HB) had target joints. Patients with HAwI/HBwI treated episodically reported the highest treatment burden. Of these patients, 28.5% (HAwI) and 25.1% (HBwI) performed sports activities in the month before screening. CONCLUSION: Despite receiving routine clinical care, historical and baseline information from patients enrolled in explorer6 showed that patients with HA/HB treated episodically and patients with HAwI/HBwI had higher ABRs, higher treatment burden and participated in sports less than those with HA/HB treated with prophylaxis. Emerging treatments could be beneficial in addressing these unmet medical needs.

Preference of treatment characteristics among people with haemophilia or their caregivers, and physicians in the Japanese healthcare environment.

INTRODUCTION: Studies of treatment preferences in haemophilia have been conducted in many countries. This study is the first to examine treatment characteristic preferences among people with haemophilia (PWH) and their caregivers, and physicians in Japan. AIM: To examine current treatment preferences of PWH and their caregivers, plus those of physicians at haemophilia treatment centres (HTCs) and non-HTCs for different treatment characteristics in Japan. METHODS: Physicians listed on a survey panel were invited to participate in the survey and to refer PWH and caregivers to participate in the survey. Web-based surveys were conducted to examine physician and PWH/caregiver background, prophylaxis background, prophylaxis goals, understanding of haemophilia treatment products, important information sources, preferences while choosing prophylaxis products, understanding of the patient's condition, and potential product switching. A discrete choice experiment exercise was included in the survey. RESULTS: A total of 107 physicians and 44 PWH/caregivers participated in the study. Key treatment goals of physicians included optimisation of haemophilia management. PWH/caregivers were focused on quality of life and reduced treatment burden. Consistent differences in haemophilia treatment strategies at HTCs and non-HTCs were observed for prescribed treatments, preferences in choosing prophylaxis products, understanding of patients' condition, and reasons for potential product switch. CONCLUSION: Our study utilises real-world survey data and presents preferences for haemophilia treatment characteristics among physicians, PWH and their caregivers in Japan, which could encourage improvements in individualised treatment and disease management. Alignment between treatment approaches at HTCs and non-HTCs could facilitate improvements in the quality of care for PWH across Japan.

Factors Associated with Neutralizing Antibody Responses following 2-Dose and 3rd Booster Monovalent COVID-19 Vaccination in Japanese People Living with HIV.

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4+ count, CD4+/CD8+ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4+ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH.

Safety of recombinant activated factor VII for treatment of breakthrough bleeds in patients with congenital haemophilia A and inhibitors receiving emicizumab prophylaxis: Review of the real-world evidence.

BACKGROUND: Emicizumab is used as a subcutaneous prophylaxis for prevention of bleeding episodes in patients with haemophilia A (HA) with and without inhibitors. While low bleeding rates were observed in clinical trials, patients still experience breakthrough bleeds (BTBs) with emicizumab in the real-world. Current guidelines recommend use of recombinant activated factor VII (rFVIIa) for treatment of BTBs in patients with inhibitors. Due to thrombotic events observed in the HAVEN 1 study, activated prothrombin complex concentrate (aPCC) should be used with caution. OBJECTIVES: The objective of this review is to identify and discuss real-world data on the frequency of BTBs and the safety of concomitant rFVIIa use in patients with inhibitors on emicizumab prophylaxis. METHODS: A search of the following databases was conducted on 15 July 2022: BIOSIS Previews® , Current Contents Search® , Embase® , MEDLINE® . Search terms included 'real world', 'haemophilia A', and 'emicizumab'. RESULTS AND CONCLUSIONS: Eleven relevant publications were identified (seven original research articles and four congress abstracts). The frequency of BTBs specifically for HA patients with inhibitors was described in three publications with 5%-56% patients on emicizumab reporting ≥1 bleeding episode. Treatment of these BTBs appeared to be managed according to relevant guidelines. Importantly, no thrombotic complications occurred during concomitant rFVIIa use. Due to the nature of real-world studies, direct comparison of the results between studies is limited. However, real-world data show that BTBs in inhibitor patients during emicizumab prophylaxis can be safely treated with rFVIIa.

Association of physical activity with bleeding events and safety in patients with haemophilia A starting emicizumab prophylaxis: an interim analysis of the TSUBASA study.

INTRODUCTION: Little information exists on the relationship between bleeding outcomes and physical activity in patients with haemophilia A (PwHA). AIM: This interim analysis of the TSUBASA study (UMIN-CTR ID: UMIN000037448) evaluated the association of physical activity with bleeding and safety in PwHA starting emicizumab. METHODS: PwHA without factor VIII inhibitors were recruited. Physical activity and bleed data were obtained using an electronic patient-reported outcome application and wearable activity tracker. Adverse events (AEs) were documented. RESULTS: At data cut-off (31-May-2021), 107 PwHA were enrolled, with a median (range) age of 35 (0-73) years. Physical activity data were obtained for 74 participants. Of these, 47 (63.5%) recorded a total of 396 exercise events. The most common exercise events were walking (32.4%), cycling (14.9%), and football (5.4%). Two (0.5%) exercise events in the same individual were associated with bleeding (running, weight training). The safety analysis population consisted of 106 participants treated with emicizumab (median observation period: 241.5 days). Twenty-one (19.8%) participants experienced a total of 39 AEs. Five (4.7%) experienced a serious AE, none of which was emicizumab-related, and three (2.8%) experienced an adverse drug reaction. CONCLUSIONS: PwHA receiving emicizumab in the TSUBASA study experienced minimal bleeding associated with physical activity. TRIAL REGISTRATION: Trial registration: UMIN-CTR ID: UMIN000037448.

Haemophilia and cardiovascular disease in Japan: Low incidence rates from ADVANCE Japan baseline data.

INTRODUCTION: With the increasing life expectancy of people with haemophilia, the risk of cardiovascular disease (CVD) and thrombotic events has become a growing concern. Longitudinal studies on the incidence and risk factors of CVD in this population are limited, and optimal prevention and treatment strategies are yet to be established. AIM: This study aimed to present the baseline data of a prospective longitudinal study focusing on a subset of Japanese patients with haemophilia, specifically investigated the incidence, risk factors and treatment modalities for CVD and thrombotic diseases in people aged 40 years in Japan over 10 years through the ADVANCE Japan study. METHODS: The ADVANCE Japan study is a prospective multicentre cohort study involving 600 adult individuals with haemophilia A/B aged 40 years in Japan. The primary endpoint was the incidence of CVD, with secondary endpoints encompassing anticoagulant use, mortality rates, and comparison with the general population. RESULTS: Baseline data from the 600 participants revealed that thrombotic events occurred in 13 individuals (2.2%), mostly in those with haemophilia A. Atrial fibrillation was observed in 11 participants (1.8%). Hypertension and dyslipidaemia were identified as the prevalent risk factors. Various prophylactic treatments were employed, and no severe bleeding events were observed during the study period. CONCLUSION: This study provides vital baseline data for a 10-year prospective investigation of CVD and thrombotic disease risk in people with haemophilia. These findings will contribute to refining prevention and treatment approaches and improving patients' quality of life.

Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. METHODS: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. RESULTS: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. CONCLUSIONS: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Clinical significance of human neutrophil antigen-1 antibodies in children with neutropenia.

Primary autoimmune neutropenia in young children is characterized by chronic neutropenia and positivity for antibodies against human neutrophil antigens (HNAs). This study analyzed the clinical characteristics of 402 children with neutropenia to identify differences between those with and without HNA-1 antibodies (HNA1abs). HNAabs in sera were detected by granulocyte immunofluorescence testing using flow cytometry. Relative fluorescence intensity (RFI) values were used to divide patients into positive (PG, n = 302), borderline (BG, n = 34), and negative (NG, n = 66) groups. The antibodies reacted to HNA-1a alone (59%), HNA-1b alone (1%), and HNA-1a/1b (40%). The PG had a significantly lower absolute neutrophil count before definitive diagnosis and a 1.6- to 2-times greater risk of hospitalization during neutropenia than the other groups. The median duration of neutropenia was longest in the PG at 25 months, followed by 20 months in the BG and 14 months in the NG. This large-scale cohort characterizes clinically distinct groups using the RFI value for HNA1abs in young children with neutropenia. Detection of HNA1abs may aid in understanding the clinical characteristics of children with neutropenia.

Relationship between CD4+ T-cell counts at baseline and initial periodontal treatment efficacy in patients undergoing treatment for HIV infection: A retrospective observational study.

AIM: To retrospectively investigate the relationship between the CD4+ T-cell counts at baseline and the efficacy of the initial periodontal treatment of patients undergoing treatment for human immunodeficiency virus (HIV) infection using the periodontal inflamed surface area (PISA). MATERIALS AND METHODS: Thirty-three patients with chronic periodontitis who had undergone periodontal examination at baseline and after the initial periodontal treatment were enrolled. PISA was calculated from the periodontal probing depth and bleeding on probing, and the ratio of PISA after treatment to that at baseline (PISA response ratio) was calculated. Groups with a response ratio of <1 and ≥1 were defined as the improvement and the non-improvement groups, respectively. RESULTS: PISA after the initial periodontal treatment significantly decreased compared with that at baseline (p < .05). A weak negative correlation was found between the PISA response ratio and CD4+ T-cell counts at baseline (p < .05). The CD4+ T-cell counts at baseline were significantly higher in the improvement group than in the non-improvement group (p < .05). Multivariate analysis revealed that the CD4+ T-cell counts at baseline was an independent factor that affects the PISA (p < .05). CONCLUSIONS: The higher the CD4+ T-cell counts at baseline in patients undergoing treatment for HIV infection, the more effective the initial periodontal treatment.

Association of demographics, HCV co-infection, HIV-1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV-1 Surveillance Network.

INTRODUCTION: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas. METHODS: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/µl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%. RESULTS: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/µl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07_BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis. CONCLUSIONS: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing.

The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs.

Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, NAb prevalence in the target population is vital in designing clinical trials with AAV vectors. Hence, updating the seroprevalence of anti-AAV NAbs, herein we analyzed sera from 100 healthy individuals and 216 hemophiliacs in Japan. In both groups, the overall seroprevalence against various AAV serotypes was 20%-30%, and the ratio of the NAb-positive population increased with age. The seroprevalence did not differ between healthy participants and hemophiliacs and was not biased by the concomitant blood-borne viral infections. The high neutralizing activity, which strongly inhibits the transduction with all serotypes in vitro, was mostly found in people in their 60s or of older age. The multivariate analysis suggested that "60s or older age" was the only independent factor related to the high titer of NAbs. Conversely, a large proportion of younger hemophiliacs was seronegative, rendering them eligible for AAV-mediated gene therapy in Japan. Compared with our previous study, the peak of seroprevalences has shifted to older populations, indicating that natural AAV exposure in the elderly occurred in their youth but not during the last decade.

Clinical conditions and risk factors for inhibitor-development in patients with haemophilia: A decade-long prospective cohort study in Japan, J-HIS2 (Japan Hemophilia Inhibitor Study 2).

BACKGROUND: Inhibitor-development is a serious complication in patients with haemophilia (PwH). Previous studies reported that therapeutic and genetic factors could be associated with these alloantibodies. Relevant clinical features such as genetic-background and different treatment regimens in Japan remain unclear, however. AIMS: To analyse a nation-wide Japanese registry for PwH, and to examine risk factors for inhibitor-development. METHODS AND RESULTS: Newly diagnosed patients with haemophilia A (PwHA) or haemophilia B (PwHB) without inhibitors after 2007, and with treatment records traceable from 0 to 75 exposure days (ED), were enrolled in the Japan Hemophilia Inhibitor Study 2 (J-HIS2) initiated in 2008. Of 417 patients (340 PwHA, 77 PwHB) from 46 facilities, 83 (76 PwHA, 7 PwHB) were recorded with inhibitors by July 2020. Inhibitors were observed in 31.0% of severe PwHA, 8.0% moderate and 1.6% mild and in 17.1% of severe PwHB. The majority of inhibitors (89.7% in severe PwHA and 71.4% in severe PwHB) were detected on or before 25ED (median 12ED in PwHA and 19ED in PwHB). Genotyping in these severe patients identified an association between inhibitor-development and null variants of F8 (P < .01) or F9 (P < .05). A lower incidence of inhibitors was recorded in severe PwHA treated with prophylaxis than in those treated on-demand (P < .01). A past-history of intracranial-haemorrhage appeared to be associated with inhibitor-development, while FVIII-concentrates infusion and routine vaccination on the same day was not related to inhibitor-development. CONCLUSION: The J-HIS2 study has identified significant clinical variables associated with inhibitor-development in Japanese PwH, consistent with other global studies.

Outcomes of Patients Who Undergo Transfusion of Fresh Frozen Plasma: A Prospective, Observational, Multicentre Cohort Study in Hiroshima, Japan.

PURPOSE: Given the chronic shortage of blood for transfusion in Japan, promotion of appropriate use of fresh frozen plasma (FFP) urgently needs to be addressed by the national blood project in Japan. Whether FFP transfusions are administered appropriately in Japan is currently unclear. In this study, we aimed to investigate the outcomes of patients who undergo FFP transfusion and the appropriateness of use of FFP. PATIENTS AND METHODS: This multicentre, prospective, observational cohort study was conducted from September 2017 to April 2019 at the 15 medical institutions in Hiroshima Prefecture that are the top providers of FFP. All patients who underwent FFP transfusion during the study period were included, relevant data being extracted from the medical records. The indications for FFP transfusion were classified in accordance with the Guidelines of the Ministry of Health, Labour and Welfare of Japan. Factors associated with patient outcomes at day 28 after FFP transfusion were subjected to multivariable logistic regression analysis. RESULTS: In total, data of 1299 patients were eligible for analysis. At least 63.8% of indications for FFP were in accordance with the guideline for FFP transfusions. The mortality rate at day 28 after FFP transfusion was 16.2%. Older age (65-74 years: adjusted odds ratio [AOR]=4.3, ≥75 years: AOR=4.1), non-perioperative use (AOR=4.5), coagulopathy associated with liver damage (AOR=2.7), large volume of FFP transfused (AOR=2.5), and lack of improvement in blood coagulation following FFP transfusion were independently and significantly associated with death within 28 days after FFP transfusion. CONCLUSION: Our findings do not support the simple conclusion that FFP transfusions contribute to prognosis. However, given that coagulopathy in patients with end-stage liver disease is infrequently improved by FFP transfusion, "inappropriate" use of FFP should be avoided. It is important to promote appropriate use of FFP so as not to waste blood resources.

Allogeneic hematopoietic cell transplantation using fludarabine plus myeloablative busulfan and melphalan confers promising survival in high-risk hematopoietic neoplasms: a single-center retrospective analysis.

OBJECTIVES: Optimal selection of pretransplant conditioning is crucially vital for improving survival and quality-of-life of patients who receive allogeneic hematopoietic cell transplantation (allo-HCT), particularly in those with high-risk diseases. In this study, we evaluated the efficacy and safety of recently-developed reduced-toxicity myeloablative regimen that combines fludarabine, intravenous busulfan, and melphalan (FBM). METHODS: We conducted a single-center retrospective analysis of 39 patients (23 with myeloid neoplasms and 16 with lymphoid neoplasms), with a median age of 50 (range, 17-68) years, who underwent their first allo-HCT using the FBM regimen. Graft types were bone marrow in 11, peripheral blood in 11, and cord blood in 17 patients. Cyclosporine- or tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was administered. The primary end point of the study was the overall survival rate at 2-year after transplantation. RESULTS: After a median follow-up of 910 days for the surviving patients, 2-year overall survival was 62% for the entire cohort; 73% in the low-to-intermediate-risk group and 44% in the high-to-very high-risk group classified by the refined CIBMTR Disease Risk Index. Cumulative incidences of engraftment, grade II-IV acute GVHD, chronic GVHD, relapse, and non-relapse mortality were 95%, 56%, 56%, 31%, and 17%, respectively. CONCLUSION: These results suggest that our FBM regimen can be applied to allo-HCT using various graft types and yields acceptable outcomes with relatively low non-relapse mortality in both myeloid and lymphoid neoplasms. Also, we observed a promising survival in the group of patients with high-risk diseases, warranting more accumulation of patients and longer follow-up.

Budget impact analysis of Jivi (damoctocog alfa pegol, Bay 94-9027) in severe hemophilia A in Japan.

OBJECTIVE: Hemophilia A (HA) is a genetic bleeding disorder characterized by a deficiency of clotting factor VIII (FVIII) requiring lifelong prophylactic treatment typically with conventional standard half-life recombinant FVIII (rFVIII). Lifelong prophylaxis impacts budget, patient adherence, and long-term outcomes. The consequent economic and treatment burden may be reduced by using novel extended half-life rFVIII. The objective of this analysis was to estimate the budget impact of introducing Jivi (damoctocog alfa pegol, BAY 94-9027), hereafter referred to as BAY 94-9027, as an on-demand and prophylactic treatment for severe HA from a Japanese payer's perspective. METHODS: A global budget impact model was adapted to the Japanese setting using data obtained via a targeted literature review of Japanese sources. The model considered a five-year time horizon for a market without and with BAY 94-9027. Using annual per-patient costs, the total cost of on-demand and prophylactic treatment of adolescent and adult patients with severe HA (without inhibitors) were analyzed. The model used summary of product characteristics (SmPC) and clinical trial dosing, and unit costs from the National Health Insurance (NHI) drug price database. Comparators considered in the model comprised of currently available products in Japan. Projected BAY 94-9027 uptake ranged from 4% to 9% over the five years (2020-2024). RESULTS: Introduction of BAY 94-9027 for the treatment of severe HA is estimated to decrease the overall budget by 1.5%, with a cost saving of approximately $67 million USD (¥7.4 billion JPY) over five years. Estimated cost savings associated with BAY 94-9027 ranged from $1.4 million USD (¥156 million JPY) in 2020 to $23 million USD (¥2.6 billion JPY) in 2024 for the Japanese healthcare system. LIMITATIONS: There were limitations associated with the study. The Japanese guidelines consulted during the targeted literature review of national data sources in Japan were based on global data as reference sources. Also, studies reporting the bleeding rate, dosing guidelines, and economic burden in the Japanese population identified by the targeted literature review were limited hence global studies were used and may not have been representative of the Japanese population. CONCLUSIONS: BAY 94-9027 can reduce total severe HA treatment costs, driven by lower annual rFVIII utilization, and a narrow weekly dosing range compared to competitor products in the Japanese market.

Brief HIV stigma scale for Japanese people living with HIV: validation and restructuring using questionnaire survey data.

This study aimed of validating a ten-item HIV stigma scale that was originally developed in the U.S.A. and adapting it for Japanese adults with HIV. To adapt the HIV stigma scale for Japanese adults with HIV, a forward-backward translation method was employed. We assessed its validity and reliability using questionnaire survey data collected from 463 Japanese adults with HIV between August 2017 and February 2018. Although the validity was acceptable, the internal consistency in two subcategories in the Japanese version of the HIV stigma scale was low (ω: 0.63, 0.60). Therefore, we performed exploratory factor analysis, which suggested a different model consisting of two subcategories. Then, we assessed the reliability and validity of the scale. The omega values were between 0.83 and 0.89, the absolute correlations (|r|) to other psychological scales for external validity were between 0.34 and 0.51, and the non-response rates for feasibility were between 0.9 and 1.8. The Japanese version of the HIV stigma scale therefore had sufficient reliability and validity. This questionnaire may help identify individuals that need increased care, which may improve their quality of life.