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1.
J Asthma ; 60(3): 616-624, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35707873

RESUMO

OBJECTIVE: To assess the long-term safety of tezepelumab in Japanese patients with severe uncontrolled asthma. METHODS: This phase III, 52-week, open-label, single-arm study (NOZOMI, NCT04048343) evaluated the safety/tolerability of subcutaneous (SC) tezepelumab 210 mg every 4 weeks (Q4W) in Japanese patients aged 12-80 years with severe uncontrolled asthma using medium- to high-dose inhaled corticosteroids and at least one additional asthma controller medication, with/without oral corticosteroids. Exploratory outcomes included efficacy (asthma exacerbations, lung function, and asthma control), pharmacokinetic parameters, and immunogenicity. RESULTS: Among 65 patients (median age 52 years), 39 (60%) experienced 94 adverse events (AEs; predominantly nasopharyngitis [13/65]) of mild (49.2%), moderate (7.7%), or severe (3.1%) intensity. Two patients had transient injection site erythema related to tezepelumab. Four patients reported serious AEs unrelated to tezepelumab and one AE led to treatment discontinuation. AEs of special interest were infrequent and generally mild/moderate. Apart from a decrease in blood eosinophils (an expected pharmacodynamic effect), no notable trends/clinically relevant changes in hematology, clinical chemistry, or urinalysis parameters were observed. Among exploratory outcomes, tezepelumab was associated with a low annualized asthma exacerbation rate over the study period (0.11/patient-year), improved lung function (mean [standard deviation] change from baseline of 0.075 [0.226] L in pre-dose/pre-bronchodilator forced expiratory volume in 1 s), and better asthma control versus baseline (responder rate: 71.4% at Week 52). CONCLUSION: Tezepelumab 210 mg SC Q4W in Japanese patients with severe uncontrolled asthma showed safety/tolerability profiles similar to international data, with low exacerbation rates and improvements in lung function and asthma control.


Assuntos
Antiasmáticos , Anticorpos Monoclonais Humanizados , Asma , Humanos , Pessoa de Meia-Idade , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Método Duplo-Cego , População do Leste Asiático , Anticorpos Monoclonais Humanizados/uso terapêutico
2.
Int J Clin Oncol ; 28(10): 1398-1410, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37498492

RESUMO

BACKGROUND: Bladder cancer is the 10th most common cancer globally, with a growing incidence in Japan. Evaluation of molecular, genetic, and cellular biomarkers that predict treatment response and prognosis in patients with metastatic urothelial carcinoma (mUC) may help optimize sequential treatment strategies with chemotherapy and immune checkpoint inhibitors (ICIs). METHODS: This multicenter, retrospective cohort study, evaluated programmed death-ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and cancer-immune phenotype as predictive prognostic biomarkers following first-/second-line treatment in Japanese adult patients with mUC. The primary endpoint was prevalence of PD-L1 expression. Secondary endpoints were TMB, overall survival (OS), and progression-free survival (PFS) from initiation of first-line treatment, and exploratory endpoints were cancer-immune phenotype, OS, PFS, and treatment response according to potential biomarker status. RESULTS: Of the 143 patients included (mean age 71.7 years), PD-L1 expression was high in 29.4% of patients. Non-synonymous TMB was high in 33.6% and low in 66.4%. Cancer-immune phenotype was immune-desert in 62.9%, immune-excluded in 30.8%, and inflamed in 6.3%. Median OS and PFS following first-line treatment were 18.2 and 7.4 months, respectively. Overall response to second-line treatment was slightly better with high versus low/negative PD-L1 expression. PD-L1 expression and TMB were non-significant predictors of OS or PFS, whereas immune-excluded phenotype was associated with better OS in comparison with immune-desert phenotype. CONCLUSION: PD-L1 expression and TMB were non-significant predictors of prognosis after first-line treatment in Japanese patients with mUC, but cancer-immune phenotype may be an important prognostic factor in chemotherapy-ICI sequential treatment strategies. Clinical trial registration number UMIN000037727.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células de Transição , Neoplasias Pulmonares , Neoplasias da Bexiga Urinária , Adulto , Humanos , Idoso , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Carcinoma de Células de Transição/tratamento farmacológico , Antígeno B7-H1/genética , Estudos Retrospectivos , Mutação , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/patologia , Microambiente Tumoral
3.
Allergol Int ; 72(1): 82-88, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35977863

RESUMO

BACKGROUND: Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan. METHODS: NAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed. RESULTS: Overall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV1 was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was -1.12 (0.15) and -0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%). CONCLUSIONS: Tezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan.


Assuntos
Antiasmáticos , Asma , Adulto , Adolescente , Humanos , Criança , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/efeitos adversos , Broncodilatadores/uso terapêutico , Japão , Método Duplo-Cego , Resultado do Tratamento
4.
Mod Rheumatol ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37706527

RESUMO

OBJECTIVES: Evaluate the long-term safety and tolerability of anifrolumab 300 mg, alongside standard therapy, in patients from Japan with systemic lupus erythematosus (SLE) in the TULIP-LTE trial (NCT02794285). METHODS: TULIP-LTE was a 3-year, randomized, double-blind, placebo-controlled long-term extension (LTE) of the TULIP trials. The primary safety outcome included serious adverse events (SAEs) and AEs of special interest (AESIs) during the LTE period. Exploratory efficacy outcomes included SLE Disease Activity Index 2000 (SLEDAI-2K) scores and glucocorticoid use. We performed a post hoc subgroup analysis of patients who enrolled in Japan. RESULTS: Exposure-adjusted incidence rates of SAEs during the LTE and follow-up for patients receiving anifrolumab 300 mg (n=21) were 8.7 per 100 patient-years; AESIs included influenza (6.9) and herpes zoster (3.5). One of three patients receiving placebo had an SAE (13.9). One patient per group discontinued due to an AE. There were no deaths. During the TULIP+LTE period, patients receiving anifrolumab 300 mg (n=24) had sustained reduction from baseline in mean SLEDAI-2K scores and cumulative glucocorticoid dosage. CONCLUSIONS: Anifrolumab 300 mg showed a favourable benefit-risk profile for the long-term treatment of adult patients with moderate to severe SLE from Japan, with safety, tolerability, and efficacy profiles consistent with the overall population.

5.
Mod Rheumatol ; 33(1): 134-144, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35134970

RESUMO

OBJECTIVES: Evaluate the efficacy and safety of anifrolumab in the subpopulation of Japanese patients with systemic lupus erythematosus (SLE) in phase 3 TULIP-2 trial. METHODS: TULIP-2 was a 52-week randomized placebo-controlled trial (N = 362) that evaluated efficacy and safety of anifrolumab 300 mg IV every 4 weeks vs. placebo in patients with moderate to severe SLE who were receiving standard therapy. We performed a post hoc analysis of the primary and key secondary endpoints, and safety, of TULIP-2 in the Japanese subpopulation. RESULTS: In the Japanese subpopulation (anifrolumab, n = 24; placebo, n = 19), the proportion of patients who achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment response at Week 52 (primary endpoint) was greater in the anifrolumab group vs. placebo [50.0% (12/24) vs. 15.8% (3/19); treatment difference: 34.2%, 95% confidence interval 6.9, 61.5; nominal p = .014]. Improvement in skin activity and flare rates (key secondary endpoints) were favourable for anifrolumab vs. placebo. Consistent with the overall population, anifrolumab had an acceptable safety and tolerability profile. CONCLUSIONS: The efficacy and safety of anifrolumab 300 mg in Japanese patients with SLE was consistent with the demonstrated clinical profile of anifrolumab for the overall TULIP-2 population.


Assuntos
Lúpus Eritematoso Sistêmico , Tulipa , Humanos , População do Leste Asiático , Anticorpos Monoclonais Humanizados/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego
6.
Respir Res ; 23(1): 255, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123707

RESUMO

BACKGROUND: The benefit of prompt vs delayed treatment initiation with inhaled long-acting bronchodilators in reducing exacerbations in chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate if long-acting bronchodilator therapy initiation within 30 days of COPD diagnosis reduces exacerbation risk in patients with COPD. METHODS: This was a retrospective cohort study of patients with COPD based on claims and electronic medical records data extracted from the Real World Data database. The index date (day 0) was the date of the first confirmed inpatient or outpatient COPD diagnosis between January 1, 2005, and December 31, 2018. Patients with COPD without an asthma diagnosis and aged ≥ 40 years at the index date were included. Patients who initiated inhaled long-acting bronchodilator therapy within the first 30 days (day 0 to day 29) were categorized into the "prompt therapy" group and the rest into the "delayed therapy" group. Time from day 30 post-diagnosis to the first exacerbation and annual exacerbation rate (AER) were evaluated for the overall population and those stratified by COPD phenotype, including chronic bronchitis (CB) and emphysema. RESULTS: Compared with the delayed therapy group (n = 1516), time to first exacerbation was prolonged (hazard ratio 0.78; 95% confidence interval [CI] [0.70, 0.87]) and annual rates of moderate or severe exacerbations were lower (rate ratio 0.74; 95% CI [0.65, 0.84]) in the prompt therapy group (n = 1466). Similarly, time to first exacerbation was prolonged and AERs were lower in the prompt therapy group in the subgroups of patients with CB or emphysema. CONCLUSIONS: This is the first study to demonstrate a prolonged time to first exacerbation upon initiation of long-acting bronchodilators within 30 days of COPD diagnosis. A beneficial effect was also observed in patients with CB and emphysema. Our data support advising patients to initiate long-acting bronchodilators soon after COPD diagnosis.


Assuntos
Bronquite Crônica , Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Administração por Inalação , Bronquite Crônica/tratamento farmacológico , Broncodilatadores , Enfisema/induzido quimicamente , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Enfisema Pulmonar/induzido quimicamente , Estudos Retrospectivos
7.
Int J Urol ; 29(10): 1120-1129, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35598101

RESUMO

OBJECTIVES: To investigate current patterns and outcomes of intravesical bacillus Calmette-Guérin treatment in Japanese patients with bladder cancer, including the proportion of patients completing induction therapy, and time to subsequent treatments. METHODS: This retrospective cohort study utilized administrative claims data from the Medical Data Vision Co., Ltd. database to identify patients with a diagnosis of bladder cancer who had received ≥1 prescription of intravesical bacillus Calmette-Guérin between April 2008 and September 2015, and had ≥1 database record dated ≥12 weeks after the initial bacillus Calmette-Guérin dose. Patients were followed until September 2018, the last date of available data, or in-hospital death. Patients receiving six doses of bacillus Calmette-Guérin at intervals of <21 days were considered to have completed induction according to guidelines. Time from initial bacillus Calmette-Guérin dose to subsequent bladder cancer treatment after the end of treatment was defined as the recurrence-free duration. RESULTS: Of 6140 patients identified (median age 73.0 years; 83.4% males), 4588 (74.7%) completed induction and 1552 (25.3%) did not. Median recurrence-free duration was 64.4, 77.7, and 31.6 months in the overall, complete-induction and incomplete-induction cohorts, respectively. Corresponding 3-year recurrence-free rate was 56.3%, 59.0%, and 48.2% in these groups. The rate of cystectomy was approximately 6% at 5 years in all cohorts. CONCLUSIONS: Approximately 75% of Japanese patients who undergo intravesical bacillus Calmette-Guérin treatment receive a guideline-compliant induction regimen, but outcomes were not satisfactory, highlighting the need for more effective treatments for non-muscle invasive bladder cancer.


Assuntos
Mycobacterium bovis , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Idoso , Vacina BCG/uso terapêutico , Feminino , Mortalidade Hospitalar , Humanos , Japão/epidemiologia , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico
8.
Cancer Sci ; 112(6): 2405-2415, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33728735

RESUMO

This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.


Assuntos
Antineoplásicos/administração & dosagem , Benzamidas/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Pirazinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Esquema de Medicação , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Japão , Leucemia Linfocítica Crônica de Células B/sangue , Linfoma de Célula do Manto/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Púrpura/induzido quimicamente , Púrpura/epidemiologia , Pirazinas/efeitos adversos , Pirazinas/farmacocinética , Análise de Sobrevida , Resultado do Tratamento
9.
Biosci Biotechnol Biochem ; 85(12): 2434-2441, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34506620

RESUMO

Rapeseed contains high levels of glucosinolates (GSLs), playing pivotal roles in defense against herbivores and pests. As their presence in rapeseed reduces the value of the meal for animal feeding, intensive efforts to reduce them produced low-seed GSL cultivars. However, there is no such variety suitable for the south part of Japan. Here, we tested the effects of cold oxygen plasma (oxygen CP) on seed germination and GSL and lipid content, in 3 rapeseed cultivars. According to the cultivars, oxygen CP slightly stimulated seed germination and modified the GSL levels, and decreased GSL levels in Kizakinonatane but increased those in Nanashikibu. In contrast, it negligibly affected the lipid content and composition in the 3 cultivars. Thus, oxygen CP modulated seed GSL levels without affecting seed viability and lipid content. Future optimization of this technique may help optimize rapeseed GSL content without plant breeding.


Assuntos
Glucosinolatos
10.
Allergol Int ; 69(1): 53-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31311707

RESUMO

BACKGROUND: The severe asthma and severe, uncontrolled asthma (SUA) populations in Japan are not well-studied. We investigated the prevalence of continuously treated severe asthma and SUA patients, their disease burden, and the treatment reality via a Japanese health insurance claims database. METHODS: Continuously treated asthma patients (patients prescribed inhaled corticosteroids for asthma ≥4 times in the past year) aged ≥17 years at the index date (latest visit between April 2014 and March 2015 for asthma treatment) were included in this analysis (KEIFU study, UMIN000027695). Asthma severity and control status at the index date were defined using modified criteria of ERS/ATS guidelines. Asthma hospitalization, oral corticosteroid (OCS) use, and total medical expenses were calculated using data up to 12 months post-index date. RESULTS: We identified 10,579 patients as continuously treated asthma patients. Of these, 823 (7.8%) had severe asthma; 267 (2.5%) and 556 (5.3%) patients had SUA and severe, controlled asthma (SCA), respectively. Compared with SCA and mild to moderate asthma patients, a greater percentage of SUA patients required hospitalization (13.7%, 6.2%, and 3.0%, respectively) and were prescribed OCSs (67.4%, 45.9%, and 16.2%, respectively). Yearly total medical expenses were also greater for SUA patients (mean [standard deviation]: 8346 [12,280], vs 5989 [10,483] and 3422 [8800] USD, respectively). CONCLUSIONS: The percentages of severe asthma and SUA patients continuously treated in Japan were obtained through this large-scale analysis using a health insurance claims database. SUA patients had greater medical and economic burdens, suggesting more appropriate treatment is required according to the treatment guidelines.


Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Efeitos Psicossociais da Doença , Adulto , Idoso , Asma/economia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
11.
Mod Rheumatol ; 30(1): 101-108, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30793642

RESUMO

Objectives: This study evaluated the safety and tolerability of anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, in Japanese patients with moderate-to-severe systemic lupus erythematosus (SLE).Methods: In this open-label, phase 2, dose-escalation study, patients received intravenous (IV) anifrolumab 100, 300, or 1000 mg every 4 weeks from days 29 to 337 (Stage 1). Patients who completed Stage 1 continued anifrolumab 300 mg every 4 weeks for 156 weeks (Stage 2). The primary objective was to evaluate the safety of anifrolumab for 48 weeks (Stage 1) and 156 weeks (Stage 2). The pharmacokinetics and pharmacodynamics of anifrolumab were also assessed.Results: Of 20 patients enrolled in Stage 1, 17 received IV anifrolumab 100 mg (n = 6), 300 mg (n = 5), or 1000 mg (n = 6). Adverse events (AE) and serious AE (SAE) incidences were similar between dose cohorts. SAEs occurred in 41% (Stage 1) and 33% (Stage 2) of patients; AEs leading to discontinuation occurred in 24% (Stage 1) and 22% (Stage 2) of patients. Anifrolumab had non-linear pharmacokinetics after the first and last dose and dose-dependently suppressed the IFN gene signature.Conclusion: Anifrolumab was well tolerated among Japanese patients with moderate-to-severe SLE.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Receptor de Interferon alfa e beta/imunologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Japão , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Mod Rheumatol ; 30(1): 93-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30791804

RESUMO

Objectives: To evaluate the safety of sifalimumab in Japanese patients with systemic lupus erythematosus (SLE).Methods: This phase 2, open-label study consisted of a 52-week initial stage (Stage I) and a long-term extension (Stage II). In Stage I, sequential cohorts of patients received ascending doses of sifalimumab (intravenous [IV] 1.0, 3.0, and 10.0 mg/kg or subcutaneous 100 mg every 2 weeks; IV 600 and 1200 mg every 6 weeks). In Stage II, patients enrolled before June 2012 received the same dose of sifalimumab as during Stage I for up to 157 weeks or sifalimumab 600 mg IV every 4 weeks if they enrolled later. The safety of sifalimumab was assessed by adverse events (AEs).Results: Thirty patients enrolled in Stage I and 21 patients entered Stage II. The majority of patients experienced AEs (96.7% in Stage I and 100% in Stage II); most were mild or moderate in severity. Serious AEs occurred in 30.0% and 57.1% of patients in Stage I and II, respectively; most were instances of SLE flares. The proportion of patients in Stage I and II who had AEs leading to discontinuation was 10.0% and 28.6%, respectively.Conclusion: Sifalimumab was well tolerated in Japanese patients with SLE.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Interferon-alfa/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
BMC Cardiovasc Disord ; 18(1): 139, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29973147

RESUMO

BACKGROUND: The EPICOR Asia (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) study (NCT01361386) was an observational study of patients hospitalized for acute coronary syndromes (ACS) enrolled in 218 hospitals in eight countries/regions in Asia. This study examined costs, length of stay and the predictors of high costs during an ACS hospitalization. METHODS AND RESULTS: Data for patients hospitalized for an ACS (n = 12,922) were collected on demographics, medical history, event characteristics, socioeconomic and insurance status at discharge. Patients were followed up at 6 weeks' post-hospitalization for an ACS event to assess associated treatment costs from a health sector perspective. Primary outcome was the incurring of costs in the highest quintile by country and index event diagnosis, and identification of associated predictors. Cost data were available for 10,819 patients. Mean length of stay was 10.1 days. The highest-cost countries were China, Singapore, and South Korea. Significant predictors of high-cost care were age, male sex, income, country, prior disease history, hospitalization in 3 months before index event, no dependency before index event, having an invasive procedure, hospital type and length of stay. CONCLUSIONS: Substantial variability exists in healthcare costs for hospitalized ACS patients across Asia. Of concern is the observation that the highest costs were reported in China, given the rapidly increasing numbers of procedures in recent years. TRIAL REGISTRATION: NCT01361386 .


Assuntos
Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/terapia , Disparidades em Assistência à Saúde/economia , Custos Hospitalares , Hospitalização/economia , Avaliação de Processos em Cuidados de Saúde/economia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Idoso , Ásia/epidemiologia , Feminino , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Arch Biochem Biophys ; 605: 129-40, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27021583

RESUMO

In this work, we have studied the action of dielectric barrier discharge (DBD) plasma irradiation using various feeding gases on seeds of Raphanus sativus L. and analysis their growth. Our experimental data shows that Air, O2, and NO(10%)+N2 feeding gases plasma irradiation enhanced plant growth, whereas N2, He and Ar feeding gases plasma irradiation had little influence on plant growth. Moreover, humid air plasma irradiation was more effective in growth enhancement than dry one. More than 2.3 times faster growth was observed by 3 min air plasma irradiation with 40-90% relative humidity. The reactive species generated by plasma in gas phase were detected using optical emission spectroscopy and in liquid phase by electron spin resonance (ESR) spectroscopy. We concluded that OH and O radicals were key species for plant growth enhancement.


Assuntos
Gases em Plasma , Raphanus/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Ar , Campos Eletromagnéticos , Espectroscopia de Ressonância de Spin Eletrônica , Umidade , Radical Hidroxila/química , Nitrogênio/química , Oxigênio/química , Espécies Reativas de Oxigênio/química
16.
Invest New Drugs ; 32(5): 946-54, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24875132

RESUMO

BACKGROUND: AZD8931 is an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), human EGFR 2 (HER2) and HER3. This two-part Japanese study (NCT01003158) assessed the safety/tolerability of AZD8931 monotherapy in patients with advanced solid tumors and in combination with paclitaxel in female patients with advanced breast cancer. METHODS: Monotherapy part: ascending doses of AZD8931 (40/60/80 mg twice daily [bid]) for 21 consecutive days. Combination part: AZD8931 40 mg bid and paclitaxel 90 mg/m(2) (on days 1, 8 and 15 of a 28-day cycle). RESULTS: Seventeen patients received AZD8931: 11 received AZD8931 monotherapy (40/60/80 mg [n = 3/4/4]) and six AZD8931 40 mg bid plus paclitaxel. No dose-limiting toxicities were observed for AZD8931 alone or combined with paclitaxel. The most frequent adverse events (AEs) were diarrhea, paronychia, pustular rash and dry skin (each n = 8) with AZD8931 monotherapy and diarrhea, stomatitis, rash, alopecia, epistaxis and neutropenia (each n = 4) with combination therapy. Grade ≥3 AEs were reported for one, two and four patients in the 40 mg, 60 mg and combination groups, respectively. AZD8931 was rapidly absorbed with a half-life of 12 h. There was no evidence of pharmacokinetic interaction between AZD8931 and paclitaxel. Two patients (one in each part) had unconfirmed and confirmed partial responses, with a duration of 42 and 172 days, respectively. CONCLUSION: Although maximum tolerated dose was not confirmed for AZD8931, based on overall incidence of rash and diarrhea AEs in the 80 mg group, doses up to 60 mg bid as monotherapy and 40 mg bid combined with paclitaxel are the feasible AZD8931 doses in Japanese patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-3/antagonistas & inibidores , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Quinazolinas/sangue , Quinazolinas/farmacocinética
17.
J Asthma Allergy ; 17: 45-60, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38268535

RESUMO

Introduction: This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. Methods: This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. Results: In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. Conclusion: No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

18.
Leuk Lymphoma ; : 1-9, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38952054

RESUMO

This report focuses on part 3 of a multicenter, open-label, phase 1 study (NCT03198650) assessing the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of acalabrutinib plus obinutuzumab in Japanese patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL). Ten patients were included; median age was 68 years. With a median treatment duration of 27.2 months, treatment-emergent adverse events (AEs) occurred in all patients (grade ≥3, 70%), and the most common AEs were anemia and headache (40% each). One patient had a grade 4 AE of neutropenia (the only dose-limiting toxicity). PK results suggested no marked effects of concomitant obinutuzumab treatment on the exposure of acalabrutinib. PD assessment indicated that combination therapy provided >98% Bruton tyrosine kinase (BTK) occupancy. Overall response rate (ORR) was 100% with median duration of response (DoR) and median progression-free survival (PFS) not reached. Treatment with acalabrutinib plus obinutuzumab was generally safe and efficacious in adult Japanese patients with TN CLL.

19.
Cancer ; 119(4): 704-13, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22972694

RESUMO

BACKGROUND: The increasing costs associated with large-scale adjuvant trials mean that the prognostic value of biologic markers is increasingly important. The expression of nuclear antigen Ki-67, a marker of cell proliferation, has been correlated with treatment efficacy and is being investigated for its value as a predictive marker of therapeutic response. In the current study, the authors explored correlations between Ki-67 expression and tumor response, estrogen receptor (ER) status, progesterone receptor (PgR) status, and histopathologic response from the STAGE study (S_tudy of T_amoxifen or A_rimidex, combined with G_oserelin acetate to compare E_fficacy and safety). METHODS: In a phase 3, double-blind, randomized trial (National Clinical Trials identifier NCT00605267), premenopausal women with ER-positive, early stage breast cancer received either anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before surgery. The Ki-67 index, hormone receptor (ER and PgR) status, and histopathologic responses were determined from histopathologic samples that were obtained from core-needle biopsies at baseline and at surgery. Tumor response was determined by using magnetic resonance imaging or computed tomography. RESULTS: In total, 197 patients were randomized to receive either anastrozole plus goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor response was better for the anastrozole group compared with the tamoxifen group both among patients who had a baseline Ki-67 index ≥20% and among those who had a baseline Ki-67 index <20%. There was no apparent correlation between baseline ER status and the Ki-67 index in either group. Positive PgR status was reduced from baseline to week 24 in the anastrozole group. CONCLUSIONS: In premenopausal women with ER-positive breast cancer, anastrozole produced a greater best overall tumor response compared with tamoxifen regardless of the baseline Ki-67 index.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/metabolismo , Adulto , Anastrozol , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Método Duplo-Cego , Feminino , Gosserrelina/administração & dosagem , Gosserrelina/uso terapêutico , Humanos , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Terapia Neoadjuvante , Nitrilas/administração & dosagem , Nitrilas/uso terapêutico , Valor Preditivo dos Testes , Pré-Menopausa , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Tamoxifeno/administração & dosagem , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/uso terapêutico
20.
Lancet Oncol ; 13(5): 466-75, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22512843

RESUMO

BACKGROUND: Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting. METHODS: Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0-2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3-6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588. FINDINGS: Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2-8·5] vs 2·6 months [1·6-2·8]; hazard ratio [HR] 0·42, 95% CI 0·33-0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of 147 in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]), and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%] of 147 in the gefitinib group, none of 148 in the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%) patients given placebo had serious adverse events. Three deaths were thought to be related to treatment with gefitinib: one from interstitial lung disease; one from lung infection; and one from pneumonia. INTERPRETATION: Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients. FUNDING: AstraZeneca.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quinazolinas/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Método Duplo-Cego , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
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